key: cord- - q vm ek authors: parakh, ankit; kumar, amit; kumar, virendra; kumar dutta, ashok; khare, shashi title: pediatric hospitalizations associated with pandemic influenza a (h n ): an experience from a tertiary care center in north india date: - - journal: indian j pediatr doi: . /s - - - sha: doc_id: cord_uid: q vm ek objectives: to describe our experience in children hospitalized with the pandemic influenza a (h n ) from northern india. methods: the retrospective case study was conducted at the pediatric ward and pediatric intensive care unit (picu) dedicated to the children (aged years or younger) with influenza-like illness (ili) with positive laboratory test results for pandemic h n by reverse-transcriptase polymerase-chain-reaction assay. results: between august and january , a total of children were hospitalized with suspected h n influenza with category “c” as described by the government of india. twenty five patients were positive for h n and for seasonal influenza a. the most common presentation (h n positive) was with fever ( %), cough ( %), coryza ( %), respiratory distress ( %), vomiting ( %) and diarrhea ( %). one child presented with hypernatremic dehydration and seizures (serum sodium meq/l). of the h n positive hospitalized children, ( %) had respiratory failure and required picu admission, ( %) required mechanical ventilation, and ( %) died. the major radiological findings were bilateral pulmonary infiltrates and consolidation. all patients were treated with oral oseltamivir suspension or capsule as per appropriate weigh band and supportive care as required. two deaths were caused by refractory hypoxemia and one by refractory shock. conclusions: the exact incidence of pandemic h n influenza on morbidity and mortality is difficult to calculate since only category “c” patients were screened. the pandemic influenza a virus appeared in mid-march and spread rapidly to involve a large part of the world. the first case in the indian subcontinent was reported on may [ ] . in a matter of few weeks it spread to large parts of the country. after the reports of the epidemic the government of india, anticipating the spread of the pandemic, initiated the containment phase. on th june the who raised level of pandemic alert from phase to phase , considering community-level outbreaks in at least country in ≥ who regions [ ] . this observational retrospective analysis describes our experience in children hospitalized with the pandemic influenza a (h n ) virus in a tertiary care hospital in north india. we conducted a retrospective analysis of case records involving hospitalized children with influenza like illness (ili) in whom h n influenza was diagnosed on reverse-transcriptase polymerase-chain-reaction assay. as per the directions of the director general health services (dghs), ministry of health and family welfare (mohfw), government of india, a screening center, pediatric ward and pediatric intensive care unit (picu) dedicated to the children with influenza-like illness (ili) aged years or younger hospitalized was started at kalawati saran children's hospital (ksch), new delhi, india (referral center for positive patients). it is only exclusive hospital for children in north india in the government sector and caters to the national capital region of delhi and the neighboring states. all patients with ili were referred to the screening center. patients were categorized into category a/b/c as per the guidelines of the mohfw for home isolation, testing treatment, and hospitalization (revised and released on th october ) [ ] as described in table . these guidelines were released at the time when the pandemic was underway, there was sustained human-to-human transmission and containment was not possible. the patients who were in category "a" or "b" were managed on a domiciliary basis with instructions for follow up. oral oseltamivir was given as per the guidelines. telephonic calls were made after and h to assess the clinical course. patients with category "c" symptoms were admitted. detailed history (including travel history, any contacts, and previous premorbid conditions) and clinical examination (including anthropometry) was done for all patients. relevant routine investigations, chest radiographs and blood cultures were done. a naso-pharyngeal swab was taken at the time of admission and stored in the appropriate transport media for category "c" patients. all samples were sent for rt-pcr the next morning to the national center for disease control (ncdc) delhi. all patients were treated with oral oseltamivir suspension or capsule as per appropriate weight band for days and supportive care as required as per standard guidelines [ ] . children who tested positive for h n and those awaiting results were kept in separate cubicles. children who tested positive were isolated in the wards with the parents for days. the statistical analysis was done using the spss version . software. data are presented as numbers (percentages), mean (sd) or median (range) as appropriate. the clinical characteristics of children positive for pandemic h n and negative for h n but positive only for influenza a were compared using fisher's exact test for dichotomous variables and the wilcoxon rank-sum test for continuous variables. a two-tailed p-value, . was considered statistically significant. from august through january , a total of children were screened in the screening center of which were category "a" and were category "b". one hundred children were hospitalized with ili, suspected h n influenza with category "c" symptoms. twenty five patients were positive for h n and for seasonal influenza a. further details are described for these children only. figure depicts the pandemic curve for the entire season for the hospitalized patients. the median age of the h n positive patients was months ( mo- yrs) and ( %) were females. the majority of the patients were between - years. eight ( %) children had moderate and another eight ( %) had severe malnutrition in the h n positive group as compared to children with seasonal flu only two ( %) had moderate and none had severe malnutrition. all patients presented with similar features of fever, cough, and coryza. vomiting and diarrhea were also present in a substantial number of patients. one child presented with gastroenteritis like illness with hypernatremic dehydration and seizures (serum sodium meq/l). one patient had underlying pulmonary tuberculosis and another had acyanotic congenital heart disease. baseline characteristics and details of clinical signs and symptoms of both groups are summarized in table . baseline characteristics were similar in both groups. contact history was positive in patients with positive h n . although ( %) children had respiratory distress at presentation, only ( %) had respiratory failure at presentation. these seven ( %) were admitted to the picu and four ( %) required mechanical ventilation. three ( %) patients expired. two deaths were caused by refractory hypoxemia and one by refractory shock. one patient who expired had underlying pulmonary tuberculosis. one child required picu care and expired with seasonal influenza a. the details of the patients who died are described in table and the age related severity of illness in fig. . the major radiological findings were prominent peribronchial markings with hyperinflation ( %) and bilateral, symmetric, and multifocal areas of consolidation, often associated with ground-glass opacities in ( %). nodular opacities, reticular opacities, pleural effusion, or lymphadenopathy were not observed in any patient. all children with hypoxemia and picu admission had extensive involvement on the chest radiographs. chest radiographs were normal in the seasonal influenza group except one child who expired had bilateral, symmetric, and multifocal areas of consolidation. blood cultures were negative in all patients. rest patients were discharged in healthy conditions with instructions for follow up. no significant adverse events were observed with the drug. most patients received antibiotics since bacterial disease could not be excluded with the clinical picture and reports were available only after - days. our study summarizes the clinical characteristics of pandemic h n virus infection in north indian children during the peak of the pandemic. our results are in variance with the earlier indian report by saha et al done during the containment phase which was suggestive of a very mild disease with no picu admissions and no deaths [ ] . the difference could be due to the categorization of patients which was not suggested earlier or change in the intensity of the evolving pandemic. similar study from argentina including a total of hospitalized children with h n influenza, ( %) were admitted to a picu, ( %) required mechanical ventilation, and ( %) died [ ] . recently published results from canada including children also show similar results but mortality in only children [ ] . in another study from canada, a total of children were admitted to picu's. one or more chronic comorbid illnesses were observed in . % of patients. mechanical ventilation was used in % of children, children ( . %) had acute lung injury on the first day of admission. the picu mortality rate was % ( of patients) [ ] . kumar et al have described hospitalized children from wisconsin, us. picu admissions were in . %, % required ventilation, . % required ecmo and . % died. bacterial coinfections occurred in . % and % of patients received antibacterials [ ] . similar reports are also available from australia [ ] and china [ ] . the slightly higher mortality in our study (although sample size was small) could be possibly attributed to underlying malnutrition, delayed presentation to health care facilities in developing countries and better intensive care facilities including ecmo in the developed world. the association of severe malnutrition and higher mortality in children with pandemic h n has not been described elsewhere in literature. recent reports suggest that pandemic h n can also present with unusual complication like myopericarditis [ ] , benign acute myositis [ ] , guillain-barre syndrome [ ] and neurological features [ ] . there are a few drawbacks in the study. firstly, being a hospital based (tertiary referral hospital) and not a community based study there would be a bias towards sicker cases. secondly, since only category "c" patients were tested for pandemic h n virus as per the national guidelines, the exact incidence of h n influenza on morbidity and mortality is difficult to calculate. present data could not be compared to seasonal influenza from the previous years since there is poor routine surveillance from india, although it appears to be statistically similar with our small cohort. thirdly, the sample size was small and hence the predictors of severe disease or mortality could not be evaluated using a regression model. also very few patients had underlying problems and hence whether the disease would have a greater impact on some conditions is difficult to predict. fourthly, we could not study other viruses which could be co-morbid or could be there in the negative group both for h n and seasonal influenza a. their contribution cannot be ruled out. since this group would be very heterogeneous it was not compared. our data reiterates the fact that influenza can present with a wide spectrum of disease from very mild self limiting upper respiratory tract infection to very severe fatal pneumonias. children presenting with rapidly developing pneumonias with typical radiological finding (bilateral, symmetric, and multifocal areas of consolidation) should be evaluated for influenza and not just be treated for pyogenic infections. where in the algorithm of diagnosis of pneumonias should a rt-pcr be incorporated would have to be decided, the investigation being expensive and available in only specialized laboratories at present. also, routine surveillance for seasonal influenza should be enhanced in developing countries like india. contributions ankit parakh: patient management, acquisition of data, literature search, statistical analysis, interpretation and writing. amit kumar: patient management, interpretation and writing. virendra kumar: concept, design and final critical review. he will act as the guarantor. ashok kumar dutta: critical reappraisal and writing. shashi khare: performance of the rt-pcr for h n . ministry of health and family welfare, india. information on swine flu. new delhi: mohfw, accessed world health organization. influenza a (h n ): pandemic alert phase declared, of moderate severity. geneva: who ministry of health and family welfare, india. information on swine flu. new delhi: mohfw, accessed ministry of health and family welfare, india. information on swine flu. new delhi: mohfw, accessed swine-origin influenza a (h n ) in indian children pediatric hospitalizations associated with pandemic influenza a (h n ) in argentina pandemic influenza in canadian children: a summary of hospitalized pediatric cases critical illness in children with influenza a/ph n infection in canada. pediatr crit care med clinical and epidemiologic characteristics of children hospitalized with pandemic h n influenza a infection pandemic (h n ) : a clinical spectrum in the general paediatric population analysis of children with novel influenza a (h n ) virus infection cardiac tamponade and heart failure due to myopericarditis as a presentation of infection with the pandemic h n influenza a virus benign acute myositis associated with h n influenza a virus infection guillain-barré syndrome in children aged < years in latin america and the caribbean: baseline rates in the context of the influenza a (h n ) pandemic neurological sequelae of influenza a (h n ) in children: a case series observed during a pandemic role of funding source none. key: cord- -kcs oukj authors: gupta, amitesh; pradhan, biswajeet; maulud, khairul nizam abdul title: estimating the impact of daily weather on the temporal pattern of covid- outbreak in india date: - - journal: earth syst environ doi: . /s - - - sha: doc_id: cord_uid: kcs oukj the covid- pandemic has spread obstreperously in india. the increase in daily confirmed cases accelerated significantly from ~ additional new cases (anc)/day during early march up to ~ anc/day during early june. an abrupt change in this temporal pattern was noticed during mid-april, from which can be inferred a much reduced impact of the nationwide lockdown in india. daily maximum (t(max)), minimum (t(min)), mean (t(mean)) and dew point temperature (t(dew)), wind speed (ws), relative humidity, and diurnal range in temperature and relative humidity during march to june , over major affected cities are analyzed to look into the impact of daily weather on covid- infections on that day and , , , , days before those cases were detected (i.e., on the likely transmission days). spearman’s correlation exhibits significantly lower association with ws, t(max), t(min), t(mean), t(dew), but is comparatively better with a lag of days. support vector regression successfully estimated the count of confirmed cases (r( ) > . ) at a lag of – days, thus reflecting a probable incubation period of ± days in india. approximately % of total cases were registered when t(max), t(mean), t(min), t(dew), and ws at – days previously were varying within the range of . – . °c, . – . °c, . – . °c, . – . °c, and . – . m/s, respectively. thus, we conclude that coronavirus transmission is not well correlated (linearly) with any individual weather parameter; rather, transmission is susceptible to a certain weather pattern. hence multivariate non-linear approach must be employed instead. in human history, it is apparent that pathogens have caused devastating consequences in social wellbeing and economies (briz-redón and serrano-aroca ). the recent novel coronavirus disease is one prominent example of such a disastrous event that has grasped the world. the earliest outbreak of covid- caused by severe acute respiratory syndrome coronavirus- (sars-cov- ) happened in wuhan, hubei province, china during the late december, , (guan et al. ; wu and mcgoogan ; zhu et al. ; zu et al. ) . because of humanto-human transmissibility of the virus by contact, droplets and fomites (wang et al. a, b) , the transmission of this disease has become progressively more unpredictable and populations have become more vulnerable. considering the rapid spread of the virus, the world health organization (who) declared an international public health emergency on january , , and later on march , , who declared this disease to be a global pandemic, due to the exponential surge in the total number of infections. up to june , , a total of , , cases have been affirmed with . % of these resulting in deaths worldwide (https :// www.world omete rs.info/coron aviru s). despite the fact that india registered its first case on january , , the real outbreak occurred from march , onwards, and as of june , , a total of , cases have been confirmed; however, the death rate ( . %) is much lower than in the rest of the world. clinical investigations of covid- identified respiratory droplets as the most common agent of infection (ge et al. ; huang et al. ) and the symptoms are also quite analogous to other coronavirus diseases such as mers and sars (holshue et al. ; perlman ; tan et al. ; wang et al. c) . who also reported that the sars-cov- virus initially causes respiratory disease, presents as a wide range of illness from asymptomatic or mild through to severe disease and death. thus, the covid- disease has close similarities in its presentation to influenza (https ://www.who.int/weste rnpac ific/news/q-a-detai l/). environmental factors, such as daily weather and longterm climatic conditions, may affect the epidemiological dynamics of this type of infectious disease (dalziel et al. ; yuan et al. ). daily air temperature and relative humidity may impact on the transmission of coronavirus by affecting the persistence of the viral infections within its transmission routes (casanova et al. ) . a few studies accounting for climate and weather conditions found that these factors considerably affect the spatial distribution of the disease, along with its incubation period (bedford et al. ; lemaitre et al. ; sooryanarain and elankumaran ) . many years ago, bull ( ) was the first to report that the mortality rate of pneumonia is intimately associated with changes in weather conditions. other studies have revealed that among different climatic variables, air temperature affects influenza epidemics mostly in tropical regions (tamerius et al. ) , whereas the mid-latitude temperate regions experience influenza epidemics mostly during winter months (bedford et al. ; sooryanarain and elankumaran ) . nevertheless, the response of covid- transmission to weather patterns remains debatable, since studies carried out in different countries suggested an existing correlation between weather and the covid- pandemic (ficetola and rubolini ; liu et al. ; ma et al. ; oliveiros et al. ; qi et al. ; tosepu et al. ). contradictorily, a few studies have reported that meteorological observations are not correlated with the outbreak pattern (jamil et al. ; mollalo et al. ; shi et al. ; xie and zhu ) . studies carried out by (wang et al. a, b) suggested that the spread of disease would decrease with an increase in temperature. based on the usa model, a reduction of transmission in warmer conditions had been predicted for india (gupta et al. a) . however, in view of the long-term climate record, it was found that comparatively hot areas in india are possibly going to be more affected by this disease (gupta et al. b ). on the basis of regional data for several provinces in india, goswami et al. ( ) reported on the inconsistency of the weather-infection interrelationship in india. besides, the incubation period of covid- may also vary spatially. the who reported an incubation period of - days for covid- based on worldwide observation (world health organization ) while the national health commission in china had initially estimated an incubation period of - days for china (https ://www.aljaz eera.com/news/ / /china s-natio nal-healt h-commi ssion -news-confe rence -coron aviru s- .html). the centres for disease control and prevention in united states of america estimate an incubation period of - days (https ://www.cdc.gov/coron aviru s/ -ncov/sympt oms-testi ng/sympt oms.html). on the other hand, some studies reported an incubation period of around days (bai et al. ; guan et al. ) . covid- has already made a significant indirect impact through reduction in anthropogenic activities on several environmental aspects in the indian context (gupta et al. c) , however, only a few studies have investigated the impact of daily weather on covid- transmission nationwide, and since the incubation period of this disease in india is also not mentioned anywhere to date, there is a need for a comprehensive study about the impact of weather patterns on covid- transmission in the indian scenario. thus, the present study is aimed at understanding the temporal patterns of the outbreak, any abrupt changes and the influence of daily weather conditions on the daily count of infected cases in india. we have also attempted to estimate the incubation period of covid- based on five different timeframes: precisely on the day of the case detected, and with leads of , , , , and days prior to the case detection. india, the largest country in south asia, extends from ° n to ° n, and from ° e to ° e, comprising a land area of . million sq. km. with a total population of more than . billion (census of india website ). the data of daily covid- cases were collected from the official website of the ministry of health of india (https ://www. mohfw .gov.in). among a total of districts in india, districts have reported multiple confirmed cases. several studies have reported that the disease spreads faster in the cities where population density is very high (casanova et al. ; ahmadi et al. ; bonasera and zhang ; kang et al. ; rocklöv and sjödin ) . thus, among 'million cities' (where the total population is more than one million) in india, cities have been selected for this study, from where more than % of the total cases in india have been reported up to june , (fig. ) . the daily weather data were collected from https ://www.wunde rgrou nd.com. figure shows the prevailing daily weather conditions in terms of maximum, minimum and mean temperature of air, diurnal range in air temperature, dew point temperature, average relative humidity, diurnal range in relative humidity, and wind speed, in those cities. since all the selected cities are located in different bio-climatic zones having different temperature characteristics (gupta ) , the variations in meteorological observations will also help to identify how spatially varying weather conditions influence the pattern of covid- transmission in india. the nonparametric mann-kendall (mk) method (kendall ; mann ) was applied to the daily data of covid- confirmed cases during march to june , to detect statistically significant trends. the mk test takes as published in partnership with ceccr at king abdulaziz university the null hypothesis (h ) that there is no trend in the count of confirmed cases of infections; while the alternate hypothesis (h ) is that there is a trend (increasing or decreasing) over time. the mathematical expressions for calculating mk statistics s, v(s) and standardized test statistics z are as follows: where, x i and x j are the daily observations, t is the length of the time series, t p is the number of ties for the pth value. positive z values designate an increasing trend and negative z values signpost a negative trend. for |z|> z −α/ , h is accepted with rejection of h , considering the critical value of z −α/ to be . for a p value of . . the statistic s is closely related to the kendall's τ which is given by: sen's slope (sen ) is widely employed to estimate the magnitude of trends. where d is the slope, x j and x k represent the corresponding data values at time j and k, ( ≤ k < j ≤ n), n is the number of the variables. a positive q i value denotes an increasing trend; a negative q i value signifies a decreasing trend. in this study, the mk test and sen's slope estimator were implemented to investigate the trend of daily transmission over selected cities as well as all over the whole country. this helped to establish whether the temporal pattern of transmission varied in different cities with respect to the countrywide pattern or not. originally developed by (pettitt ) , the non-parametric pettitt test is an effective method of identifying the change in the temporal trend in any time-series, because of its sensitivity to breaks in the middle of temporal records (gao et al. ; hänsel et al. ; jaiswal et al. ; mallakpour and villarini ; wijngaard et al. ) . in this method, s is evaluated for all random variables from to t; then the most prominent change point is determined as that where the value of |s| found to be largest: at a particular time t, the change point is detected when k t is clearly different from zero at any particular level, where the significant level is estimated by: the change point can be evaluated as statistically significant only when the estimated p value becomes less than the pre-assigned significance level, i.e., α. growth rate denotes the magnitude of alteration of any particular variable within a definite time period. here, growth rate between march and june , for the overall country and for each selected city was calculated using following formula: here, nf refers to the number of covid- cases recorded on the st day of record,ne refers to the number of covid- cases recorded on the last day of the study period (june , ), and n refers to the number of days between the first day of covid- case detection and the last day of the study period. the doubling time denotes the time taken for a count to be doubled. here doubling time for the overall country and for each selected city was calculated using following formula: spearman's rank correlation coefficient (r s ) calculates the association between the number of daily new cases and other input parameters. it summarizes how well the association between daily transmission and weather parameters can be quantified. the coefficient can be calculated via following equation: where, n represents the number of alternatives, and d i is the difference between the ranks of two parameters. all the above mentioned statistics were based on a % confidence level. published in partnership with ceccr at king abdulaziz university support vector machine (svm) is an extensively utilized machine learning technique. it is performed on the basis of statistical auto-adaptation and the structural risk minimization principle (tien bui et al. ) . by creating a hyperplane, the nonlinearity in the input dataset is reshaped into a linear entity ). the key factor behind this data transformation is a kernel function. using the assigned training dataset, svm puts the original input into a higher dimensional feature space, then finds the supreme fringe of separation among the observations, and constructs a hyperplane at the centre of that extreme margin (marjanović et al. ( ), tehrany et al. ( ) . however, the accuracy of estimation depends on the kernel type selected during the training of the model (yao et al. ). the radial basis function (rbf) kernel produces more exact results and is preferred over the linear, polynomial and sigmoid kernels, due to its higher capability in interpolation (song et al. ). in the present study, the log-transformed values of daily covid- cases were estimated using several daily weather parameters, along with the elevation and population of those cities (eq. ). where, nc is the number of new confirmed case, t max is maximum air temperature (°c), t min is minimum air temperature (°c), t mean is mean air temperature (°c), t range is temperature range (°c), t dew is dew point temperature (°c), h avg is average relative humidity (%), h range is range of relative humidity (%), ws is wind speed, ele is elevation (m), pop is total population. the total dataset was divided into a : ratio, where % of observations were used as a training dataset and the rest were used for testing. the accuracy of estimation was evaluated in terms of r , root mean square error (rmse) and mean bias (mb). all the analyses were done using r programs. (fig. ) . one of major reasons behind the initial slow growth rate might be surmised to be that the original virus had been transmitted through an infected immigrant; moreover, very few tests conducted throughout the country during march (fewer than , tests/day). analysis also reveals that within this days study period, the percentage growth rate for the overall country was . %, whereas among the selected cities, mumbai had the highest growth rate ( . %) while jaipur had the smallest growth rate ( . %). basically, the growth rate was higher in the cities, which had a higher rate of acceleration in covid- cases. on the other hand, the doubling time of covid- cases for mumbai ( . days) and chennai ( . days) was very close to the countrywide situation ( . days). hyderabad registered the slowest doubling time of . days. this shows that the daily count of covid- cases was doubling in less than days throughout the country, which is also a measure of the drastic adverse situation in india. from fig. , it can be seen that an average of / tests results were confirmed for infection during the entire study period. however, this positive rate was / during the month of march; later, it rose to / and / during april - , and may -june , , respectively. this shows that the probability of detecting confirmed cases also increased published in partnership with ceccr at king abdulaziz university each week, which may be evidence of community transmission. the trend of daily new cases in the major affected cities (fig. ) also indicates the large increase in daily transmission from may onwards. figure also shows that cities located at a lower elevation and having higher population registered a higher growth rate of transmission, thus agreeing with an early observation by (gupta et al. d) . of the five megacities in india, just three (delhi, mumbai, and chennai) are the only cities where the count of daily infected cases exceeded . one of the probable reasons behind such spikes in transmission rate might be the allowance to migrants to return to their native places, which instigated large crowds in various cities and gathering in transport hubs, as reported in many local and national newspapers, thus resulting in such an unforeseen increasing rate of transmission all over the country. the spearman correlation analysis (table ) shows that there were mostly significant but still predominantly low fig. the daily trend of confirmed case in selected cities are shown. inset is a scatter graph depicting the growth rate of transmission with respect to the population and elevation of those cities correlations between the number of daily new cases and the various weather conditions. among the eight weather parameters, the correlation for t range is non-significant over all time spans. hence, the diurnal range of temperature is not significantly associated with the spread of covid- cases in india. h avg is associated significantly positively on the day of detection up to days lag (i.e., when transmission presumably occurred). however, h range is significantly negatively associated for - days prior to detection. following the observations over the selected cities located in different geographical parts of the country, it is uncertain whether the higher humidity could reduce the infectivity of the coronavirus by reducing the suspension time of virus. this suggests that the role of humidity is quite complex and needs to be investigated further. on the other hand, all the temperature parameters (t max , t min , t mean , t dew ) are proportionately associated with covid- transmission. the analysis also indicates that t max , t min , t mean , t dew and ws on the day of the detection have the lowest correlations, which improves up to its peak at a time lag of days. in other words, the maximum, minimum, mean and dew point temperature along with wind speed at days prior to detection are closely allied with the number of infections. this suggests the interesting inference that weather conditions days prior to the detection of infections had provided favorable conditions for virus transmutability. surprisingly, perhaps, t min is found to be better related than t mean t max t dew . therefore, places with higher minimum temperature are more susceptible to covid- transmission in india. a significant positive correlation between ws and daily transmission at a lag of days infers that the virus might be able to transmigrate in high winds. since most of the weather parameters are better correlated with the daily confirmed cases at a time lag of days, this indicates an approximate incubation period of around days for this disease in the indian scenario. therefore, considering the lag period of days, the correlation analysis for each selected city (table ) shows that cities located away from the coast such as delhi, indore and jaipur have better association with temperature parameters (t max , t min , t mean , t dew ) than the coastal cities such as mumbai, chennai and kolkata. however, ws is relatively better correlated with covid- cases in coastal cities than in the other cities. interestingly, rh avg and rh range are also significantly related with covid- cases in coastal cities only, while cities located in the interior did not exhibit any significant correlation. that is why on the country-wide scale, correlations between covid- cases and rh parameters were reporting as non-significant. hence, a higher humidity with a higher wind speed could be favourable for virus transmissibility; while a higher temperature might favor virus transmission in semi-arid and interior areas. this also suggests that the geographical location of the cities plays a crucial role in the association of weather parameters with covid transmission, which makes this interrelationship even more complex. figure and table show the validation of estimated daily confirmed cases for all time spans using the non-linear multivariate support vector regression model with rbf kernel. the model performance in terms of r , rmse, and mb are presented in table . this shows that the svm-based unlike most studies, the present study investigated the impact of various weather parameters which include maximum, minimum, mean, and dew point temperature, temperature range, average humidity, humidity range and wind speed on the same day, as well as with time-lags of , , , , and days prior to detection of the confirmed cases of covid- in the indian context. additionally, the daily trends of confirmed cases in nine of the most affected cities in india, along with a comparison of the entire country, have also been inspected in this study. the analyses revealed that the count of confirmed cases is not well correlated with any individual meteorological parameter because simple correlation depicts a linear relationship only. rather than that, covid- cases are significantly associated with a very certain range of temperature parameters and wind speed. thus, much better than linear correlation, the nonlinear svm-based regression approach efficiently resolved this complex association and was able to estimate the daily cases of infection quite accurately with the help of the daily weather inputs. however, the positive correlation between daily transmission and air temperature, as well as wind speed, indicates that the daily transmission in highly populated areas in india has consequently increased during the current summer days of . an approximate incubation period of ± days can also be identified from the data, which is a little longer than what who had estimated early in march. therefore, in the prevailing weather conditions in india, the sars-cov- can be disseminated into the surrounding environment for around weeks after being ingested from any other infected source. the covid- pandemic has resulted in a state of recrudescence in india. the daily confirmed cases have been rising at an acceleration rate of ~ anc/day since march , with a doubling rate of . days. this rate of acceleration all over the country reached approximately anc/ day during the starting of june. initially, out of each . influence of weather parameters on count of confirmed cases with a lag of - days tests revealed positive results during the first week of march, but the positive test rate escalated to / tests in the first week of june. on the other hand, reduced strictness in subsequent phases of lockdowns, along with the allowing of interstate migration, had inevitably caused an easy pathway for transmission, hence resulting in an intractable circumstance all over the country. the cities with larger populations are cataloguing a higher rate of increase in daily cases. moreover, a step-change in the rising trend over all the major affected cities has also been noted during mid-april, i.e., at the boundary between the first and second lockdowns. this signifies that the imposed lockdown was unsuccessful in reducing the covid- transmission in india, unlike in e.g., south korea, japan, and iran. nonetheless, this study has limitations, since we were unable to include many other major affected cities due to lack of meteorological data availability. moreover, the number of immigrants from abroad or other cities who were quarantined was not available; these might have enhanced the exactitude of the current analysis. funding this research was supported by the centre for advanced modelling and geospatial information systems (camgis), faculty of engineering and information technology, in the university of technology sydney (uts). conflict of interest the authors declare no conflict of interest. open access this article is licensed under a creative commons attribution . international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes 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in india with covid- : challenges ahead and possible way-outs date: - - journal: j revenue pricing manag doi: . /s - - -z sha: doc_id: cord_uid: jik j coronavirus outbreak has been highly disruptive for aviation sector, threatening the survival and sustainability of airlines. apart from massive losses attributed to suspended operations, industry foresee a grim recession ahead. restrictive movements, weak tourism, curtailed income, compressed commercial activities and fear psychosis are expected to compress the passenger demand from to %, endangering the commercial viability of airlines operation. fragile to withstand the cyclic momentary shocks of oil price fluctuation, demand flux, declining currency, airlines in india warrants for robust structural changes in their operating strategies, business model, revenue and pricing strategies to survive the long-lasting consequences of covid- . paper attempts to analyze impact of lockdown and covid crisis on airlines in india and possible challenges ahead. study also suggests the possible way-out for mitigating the expected losses. the world, at present is combating with pandemic covid- . emerged from wuhan (china) in december , within few months it has taken countries across the globe into its clutches. with reported cases on january , the infected cases have crossed . million as on july . india is no different; with cases reported as on february, the number has surpassed , , whilst three extended phases of lockdown. the magnitude of virus contagion spread in the absence of any antidote developed so far has left the countries across the world with quarantine as the only remedy, despite of its drastic consequences on the economy. aviation sectors is perhaps worst hit with covid impact. the preventive restrictive movements have drastically dented the airlines and allied services with huge losses. airlines passengers' services in india remain suspended for sixty day ( march to may ), bringing massive loss to the industry. according to dgca, six days suspended operations of march leads to % decline in passenger traffic (from . million reported in march to . million in march ). as per crisil infrastructure advisory report, the expected revenue loss to the indian aviation sector due to lockdown amounts to billion; inter se, airlines account for % losses, followed by allied servicesground handling, etc. capa india estimates the industry staggering losses of to billion in april-june quarter, assuming operations to remain suspended till june . this imply loss of . to billion for per day of extended lockdown. in addition to the above losses, the industry foresees grim recession ahead. restrictive movements and destinations, truncated consumable income, decline in tourism, and fear psychosis are expected to significantly curtail the passenger traffic for the current fiscal or perhaps longer. india is the third largest domestic civil aviation market in the world (ibef, report). however, thin profit margins, high operating cost, inflated taxes and cut-throat price war make it one of the toughest aviation market (saranga and nagpal ) . the cost structure of airlines in india is believed to be highly bloated with atf taxes, landing and parking charges, which are perhaps highest in india. the industry is exposed to high operating leverage. the airlines operating cost structure consists of nearly to % of fuel cost, % lease rental, nearly % for other operating expenses (including general administrative, operating expenses such as flight equipment, maintenance, overhaul, user charges including landing, airport charges and air navigation charges (dgca report). other than fuel cost, maintenance of aircraft, selling & distribution cost, and parking & landing charges, rest other expenses are fixed and are to be honored irrespective of flight operations. burden of fixed charges-lease rental, interest charges, and crew salaries keep the airlines on their toes for managing cashflows. the high operating cost and cut-throat competition compel the airlines to struggle with low margins. the airlines demand in india is highly price elastic (wang et al. ). entry of lowfrill competitors has changed the airlines price dynamics of pricing the services that were earlier based on additional frills (saranga and nagpal ) . any hike in the expenses, prima-facie, is a pinch on the airlines margin as ugly fare wars restrict to surpass the uncertain hike in costs on ticket prices. commercials of airlines revolve around available seat kilometers (ask)-capacity, revenue per kilometer (rpk)-income earned, passenger load factor (plf)-capacity utilized, break-even load factor (belf)-operating cost per ask over operating revenue per rpk. higher the distance flown, more is the opportunity for the airlines to spread the operating fixed cost over longer distance and thereby reducing their adjusted operating cost. in this backdrop, improving plf by offering lucrative offers is prevalent trend in the industry. as provided, the airlines in india performed at decent capacity of nearly % in the month of january, . in the month of february, irrespective of low demand, the spicejet, go air, indigo, air asia, vistara have managed high plf by providing attractive offers (fig. ) . higher plf, however, does not implies profitability. it only represents the successful selling of available seats. operating viability requires the plf to exceed belf. the irony is that despite of heavy demand, the airlines strive hard for making break-even due to tough competition. in the dilemma of managig operating cash flows, the cash stripped airlines with overmounted fixed operating costs emphasize on selling more seats, ignoring the break-even. as provided in the fig. , only five airlines operate above belf during fy - , with the safety margins from . to . %, whilst rest all were in red. the covid outbreak has added financial woes of the sector. with the dwindling demand anticipations, capacity utilization certainly will be a major challenge ahead for airlines sustainability. hitherto combating for break-even, low passenger traffic possibly restrain the airlines from recovering their variable expenses, thereby obstructing the commercially viability of their operations. present study attempts to analyze the financial impact of covid outbreak on airlines and challenges ahead. possible suggestion for sustainable operations of airlines are suggested. findings are expected fig. plf of airlines in india during january and february . source dgca https ://www.ibef.org/indus try/india n-aviat ion.aspx#:~:text=india 's% avi ation % ind ustry % is% exp ected ,aviat ion% nav igati on% ser vices % by% https ://www.dnain dia.com/busin ess/repor t-the-cost-of-flyin g-high- to contribute in the restructuring of the airlines for operating viability and sustainability. airline industry has been one of the fastest growing industry globally in terms of demand as well as capacity (lee ) . over the past century, commercial aviation has been observed as integral part of economic prosperity, stimulating trade, cultivating tourism development. its relative affordability in recent years has inculcated it in people's lifestyles (o'connell ) . aviation sectors economic contribution (direct, indirect, induced and tourism concomitant) in global gdp is estimated as usd . trillion (atag ). notwithstanding the growth in demand as well as capacity, the sectors has always been financially challenging struggling with thin margins (o'connell ), vulnerable to fuel prices, foreign exchange, interest rates and high competition (merkert and swidan ; stamolampros and korfiatis ) . the industry has been exposed to dynamic external environment, regulations, technology, customers preference, intense competition, labor cost, fuel prices and security measures and so forth (riwo-abudho et al. ) . airline industry performance is contingent to macro-predictability, micro-uncertainty and macro environmental factors (mhlanga ) . airlines industry has always been exposed to exogenous events. terrorist attack of / has put the industry into depression making number of airlines bankrupt. those who rescued from the effect have been grabbed with the oil crisis of (yang ) . the entry of low cost carriers (lcc) in triggered turnaround changes in the industry in terms of pricing strategies and well as competition level (belobaba ) . the lccs pricing and revenue management strategies threaten the commercial viability of traditional model, compelling the changes in conventional airline revenue management practices (michaels and fletcher ). the paper examines how they differ in their approach, how airlines are responding and what constitutes an effective response in the changed airline business world. this includes consideration of all the marketing levers (product, price, promotion and distribution) in an integrated way, as well as developments needed in the core revenue management systems themselves (michaels and fletcher ) . online bookings, access to airline tickets on internet has made price competitiveness as an important parameter of airline's success (ratliff and vinod ) . india airlines market despite of being the fastest growing market (mahtani and garg ) , has been one of the toughest aviation markets in the world, due to high fuel prices, overcapacity and intense price competition (saranga and nagpal ) . notwithstanding the extensive infrastructural development supported by government, airlines in india often combat financial distress with the changing dynamics of internal and external environment (mahtani and garg rapid transformation with the liberalization of indian aviation sector (singh ) . india began to relax controls on its airline industry in , allowing willing entrants to add system's capacity. however, financial performance of the airlines remains challenging owing to inappropriate policies, restricted capacity allocation on profitability basis (hooper ) . liberalization of air travel services and the advent of low-frill airlines have changed the panorama of indian civil aviation in terms of demand as well as supply (ohri ; srinidhi ) . reformation of regulatory policies resulted in three-fold increase in the number of scheduled airlines and a five-fold increase in the number of aircraft operated (o'connell and williams ) . the increased interconnectivity within the global airline markets has altered the dynamics of external environment and internal operations (riwo-abudho et al. ; singh ) . success and survival in this milieu warrants for coherent strategies adapting with market flavor (pathak ) . entry of the lccs in india in , with first 'no-frills' airlines-air deccan has changed the dynamics of indian domestic aviation market (sakariya et al. ). low-cost carrier (lcc) by enhancing affordability of air travel has stimulated the demand for air travel in india (krämer et al. ; wang et al. ). undoubtedly, low-frill operation has proved to be a successful business model in the industry (alamdari and fagan ) . budget airlines and small chartered airlines witnessed more efficient in the system (dhanda and sharma ; jain and natarajan ; saranga and nagpal ) and dominated the indian airline market (deeppa and ganapathi ; wang et al. ) . the lcc in india have managed to achieve significant operational efficiencies with the rigid cost structure, heavy taxes, high landing and parking charges, undesirable regulatory factors (saranga and nagpal ) . india's low cost carriers show better scale efficiency vis-à-vis their full service competitors (sakthidharan and sivaraman ) . low cost airlines have been witnessed advantageous in utilizing their capacity compare to the full service airlines which strives hard to attain break-even capacity (thirunavukkarasu ) . however, the inexorable rise of lcc has made the industry more volatile (doganis ) . intense competition and enhanced capacity have made cost effectiveness as the daring need for survival and sustainability. financial performance of airlines is vulnerable to both internal conditions of the company and as well the external environment. operating factors, namely, operating revenue per air kilometers, capacity, cost structure, load factor dictate the operational output of the airlines and their commercial stability. from the external environment, atf prices largely affect airlines profitability in india. also, annual inflation and gdp growth rate in the country has a major influence on the sustainability of the airlines in india (mahtani and garg ) . with uncontrollable cost behavior, tight margins and cut-throat market, survival and subsistence of airlines largely depends on its ability to maximize their customer base (singh ) . fierce competition compel the airlines to optimizes their revenues (josephi ; krämer et al. ). in the backdrop of covid pandemic outbreak, the globally airline industry has been adversely affected. airlines in india which have been observed vulnerable to withstand the cyclic economic disruption (of fuel prices, inflation, devaluation of currency and demand shock), certainly be entering into a tough time with extremely low demand and ever mounting losses. present study attempts to analyze the financial impact of covid pandemic on airlines in india and possible impact of their financial strengths and weakness. further study suggests possible way-outs of sustaining operating viability. the indian aviation industry is characterized by high fixed costs of nearly to %. these costs include lease rental, employees cost, interest charges. per day of suspended operations has hit the industry at the rate of - crore loss per day. table exhibits fixed-cost information pertaining of four key airlines of india for last three years (fy to ). the costs mentioned signify the charges that are to be met irrespective of the business operations. the increasing pattern of expenses over years, prima-facie, signify the expanded operations' size over years. ceteris paribus, no significant change in the operations size and cost for the fy - , per day loss of suspended operations for interglobe aviation accounts for crores, followed . crores for spicejet, . crores for go airlines and . crores for air asia (based on the - estimates). in capital intensive industries, such as airlines, liquidity plays an important role in boosting profits (merkert and swidan ) . perhaps the cash rich airlines are in better position to negotiate with the suppliers-oil companies, lessor, bankers, employees for favorable deals and heavy discounts. airlines in india suffers from weak liquidity. cash burn rate of airlines in india during the years to is provided in table . the cash burn rate indicates the number of days for which a company can sustain its operations with the available cash reserves. the data contained in table , suggests few days of cash back-up available to most of the airlines, excluding interglobe aviation which is exhibiting consistent pattern of satisfactory cushion of more than a quarter. the aggregated cash reserves of interglobe aviation as on december were reported to be . crores . assuming, . crores of daily fixed cost (refer table ), the reserves of crores possibly have been wiped out amid seventy days of lockdown. remaining cash balance of . crores suggest the probability of days of survival, based on estimated burn rate of . per day. however, for other airlines resuming operations with insufficient operating cash seems to be a challenge. in the backdrop of tight liquidity, thin margins and high burn rate, the airlines have always been fragile to withstand the normal demand shocks, oil price fluctuation, depreciating currency, etc. industry has vouched the devastating impact of these events ranging deep losses to airlines bankruptcy. table exhibits onwards financial performance of airlines in india in terms of profits margins, rate of returns, assets turnover ratio and interest coverage ratios. as provided, the profit margins of the airlines are highly thin and unsatisfactory to insulate the firms from sudden shocks. median net profit margin − . , prima-face, corroborate that net profits of all the airlines in india are occasionally positive. there appears only three airlines, interglobe, go air, and blue dart (cargo airline) with positive net profit margin in all the five years. in terms of magnitude, the net profit margin . to % and ebit margin of to % does not seems satisfactory to justify the corpus invested and the risk involved there in. oil price hike of has plunged the sector into deep losses. interglobe aviation that appears to be best performer of the industry has experienced deep shrinkage in its net profit margin of from to . % (table ). unable to take the hit, loss running jet airways blown out of the race with its operations meeting grinding halt in april . previously also, industry has a history of several starts and may failures; east west airlines and damania airways in s, kingfisher airlines in are classic instances of airlines financial failure. table exhibit the altman z-score of select four airlines. altman z-score model (altman ) was developed by edward altman in . it gauges the likelihood of bankruptcy of business concern within two years, using multiple corporate income and balance sheet values. z-scores are used to predict corporate defaults and an easy-to-calculate control measure for the financial distress status of companies. the z-score is calculated using liquidity, profitability, leverage and turnover parameters. (altman ) . here x working capital/total asset, x retained earnings/total asset, x ebit/total x market capitalization/ book value of debt, x total sales/total assets. score below . signifies high probability of bankruptcy; . to . is considered as grey zone and score of above . is considered as safe zone. this model was applicable for manufacturing sector. for predicting the bankruptcy of service sector firms in emerging market modified atman score was proposed (altman ). as per the model, z − score = . + . x + . x + . x + . x , here x working capital/total assets, x retained earnings/ total assets, x ebit/total assets, x market capitalization/ book value of debt. score above . is considered safe zone, . to . as moderate risk and score below . indicates high risk of bankruptcy. table exhibits the altman z-score of airlines in india computed using traditional altman model and modified altman model for emerging market. in the backdrop of unavailability of market capitalization information of all the airlines, the enterprise value minus book value of debt is considered as value of equity. the findings of both the models lend credence to the sustainability of indigo aviation and spicejet. nevertheless, the decline in the scores is very likely, due to deteriorated finances amid lockdown and grim prospect of passenger demand ahead. covid- pandemic has proven highly disruptive. it has wreaked havoc with the global economy, economically, socially and financially (laing ; wren-lewis ). the aftermath of the disasters is perhaps more threatening, endangering the survival and sustainability of various businesses. airline industry is worst hit sector, which is expected to lose usd . billion in , the highest loss the sector has ever witnessed (iata). owing to the restricted movements and destinations, the industry expects severe decline in its passenger load (thams et al. ) , perhaps, a significant parameter of airlines profitability (baltagi et al. ; clark and vincent ; sibdari et al. ) . as provided in fig. , month of march has witnessed sharp decline in plf of airlines all across the globe. other than the loss amid suspended operation, the future prospect of the industry seems more dreadful for sustainable operations of airlines. in the backdrop of aggressive multiplication in covid cases, the likelihood of normal passenger traffic seems distant. restricted movements, fear psychosis, declined tourism, reduced commercial activities, curbed disposable income is expected to have significant impact on passenger airlines demand. tourism sector is considered as significant driver/ stimulator of airlines business (bieger and wittmer ) . an important aspect of international traffic to and from india pertains to trend in foreign tourist arrivals in india. the months from april to july are generally observed as peak season for the airlines, with the maximum passenger load factor (plf). in the fy - , yoy growth in plf is positive only in the month of april & july. as per the dgca report, % of international passenger traffic during fy was attributed to tourism sector. in view of expected decline in tourism amid covid pandemic, the airline business foresees a major disruption ahead. according to icao united aviation study, depending upon the duration and intensity of outbreak, control measures and economic and psychological impact, the global pink cells portray risky zone and green cells represent safe zone as per altman z-score airlines industry may witness decline of to % seats offered, reduced passenger traffic from to million and gross operating revenue loss of approximately usd to million for the year . as per the report, the estimated decline is the worst ever observed before during any of the crisis, economic or otherwise (fig. ) . airlines in india are vulnerable to high operating leverage (sakthidharan and sivaraman ) . operating leverage signifies an ability of a firm to use its fixed operating expenses to magnify the impact of change in its sales on its operating profit. degree of operating leverage (dol) is calculated as total contribution /total ebit. high the degree of operating leverage, higher will be the magnifying impact of increased operations/sales on ebit (chen et al. ; garcía-feijóo and jorgensen ; mandelker and rhee ) . for instance, times of dol implies that if sales increase by % than ebit will increase by × , i.e., times. it is worth mentioning, that use of fixed operating cost signifies the risk in operations; the risk of repaying the fixed charges in case income fall short of expectations (gahlon ; mcdaniel ) . performance of high levered firms significantly reduced compared to their competitors in industry downturns due to enhanced cost of financial distress (gonzález ). in the backdrop of severe downturn expected in the industry, the highly levered airlines in india are likely to suffer heavy losses. table exhibits the degree of operating leverage of four airlines in india and the consequences on the ebitda of the airlines, with the different expectations of possible decline in sales amid covid impact. the rationale of including select airlines for analysis is the unavailability of the data for the year . as provided, air asia (india) is in losses; go air, spicejet and intergloble are reflecting alarming degree of operating risk. high the dol, higher will the expected losses. with . times of dol, ebitda of interglobe aviation is expected to decline by . times with % dip in its revenue, i.e., from . lac crores of ebitda to negative- . lac crores. social distancing practices initiated by regulatory authorities and airlines to prevent infection outbreak will be financial hit on airlines pocket (iata economics ). declined plf coupled with cost of social distancing is expected to threaten the commercial viability of airlines operations. measures such as leave empty seats between passengers in the aircraft will reduce the seating capacity by to %. in india, dgca laid down social distancing norms and sanitization norms for airlines to be followed during passengers handling, sanitizing aircrafts, checkpoints and baggage, ppe kits, medical team, etc. this cost will further dig the profitability of the airlines. the dgca advisory of blocking middle seat, will compressed the seat offering capacity of airlines to %. plf is an important driver of airline financial performance. based on a sample of airlines, on average, airlines break even at a load factor of %. notwithstanding the high plf of to %, airlines are witnessed struggling for breakeven. as per iata analysis, out of the sample of airlines across globe, only airlines will manage break-even below %. in the present scenario, where airlines plf is expected to decline by to %, the financially feasibility of airlines operations seems scary. additionally, the cost of implementing other social distancing and sanitization norms will further enhance the airlines' costing. airlines perhaps find it difficult to cover the variable cost of their operations. post-lockdown world will be not be the business as usual. the airline industry combat with covid- and its after effects seems taxing and perhaps long drawn-out. the sustainability and survival of airlines warrants for turnaround changes in their strategies and business model to strengthen their financial stamina. overcapacity, intense competition and high operating cost are the major factors affecting airlines performance. to overcome the present challenge of covid crisis, optimal utilization of resources, cooperation rather than competition, and cost optimization seem to be the possible way-outs for sustaining with commercially viable take-off on rough terrain. air cargo business despite of being a least preferred choice of airlines compared to passenger business, has an important role to play in the airline's profitability. threatening subsistence with the growing challenges of the industry warrants for major structural changes in the present business model. accommodating the cargo business in the existing business model perhaps be an effective steps towards the improved performance (reis and silva ) . the globalization of the supply chain has resulted in competitive pressure on the air cargo industry. with independent and improved supply chain strategies, airlines can positioned themselves in the global supply chain market (hong et al. ) . high degree of cargo business is evident to improve the operational efficiency of combination as well as cargo airline (hong et al., ) . airlines with a high share of cargo business in their overall operations are significantly more efficient than airlines ( hong and zhang ) . however, challenges for handling cargo makes it less attractive to airlines compared to passenger business. combination airlines use the belly space of passenger aircrafts to substantiate the cargo. these airlines often experience the problem of freight orders exceeding the airline's fixed capacity, particularly for hot selling routes (feng et al. ) . in present scenario, where a severe decline in passenger traffic as well as restricted destinations is expected amid infection paranoia, cargo business perhaps can be used a rescue boat to safeguard the airlines from expected the crash landing. it is a saying in management accounting, that in short-term if profits can't be maximized, focus should be on minimizing the losses. for optimum capacity utilization, cargo-cum-passenger model can be an effective way-out. at present nearly % of freight business in india is done through belly cargo. only blue dart is fully dedicated airlines for freight cargo business (fig. ) . in view of restricted passenger movements, from january onwards airlines across the globe have started engaging passenger aircrafts entirely for cargo (fig. ) . indigo followed by spicejet have also joined the race. figure portray the average seat capacity of scheduled airlines in indian during fy - . as provided, most of the airlines have the average capacity of to . with the expected - decline in passenger traffic in current fiscal, accommodating cargo load for unutilized seats can mitigate the revenue losses of the airlines. amid low passenger traffic, dedicating small aircrafts (with less seating capacity) for passenger business relatively will be more financially viable for the airlines. big aircrafts can be temporarily converted in cargo planes for carrying supplies. depending upon the cargo load, large capacity planes can be fully dedicated or utilized as passenger cum cargo planes. in view of dgca advisory to leave middle seat vacant, some temporary arrangements for accommodating cargo in provided space can be worked out. for instance, vacant seat can be used for carrying passenger's luggage and the side carriers can be utilized for lesser weights parcels. also, the space used for accommodating passengers' check-in luggage can be utilized for cargo business. the passenger cabin can be restructured in such a manner that its front and back seats can be used for passenger traffic and middle space can be utilized for cargo services. airline industry is known for ugly competition and fare wars that perhaps has been the prime reason for their meagre profit margin (eng and vichitsarawong ) . in the backdrop of trimmed passenger traffic expected for upcoming months, pooling of resources perhaps can be useful step in this direction. airlines industry needs to adapt cooperation model instead of competition. alliance in the airline industry is a widely used strategy to stimulate competition (cobeña et al. ) . alliances are useful rescue for the firms with vulnerable strategic positions either because of competition or when they are attempting pioneering technical strategies (eisenhardt and schoonhoven ) . they enhance value by facilitating optimal utilization of pooled resources (das and teng ) . the alliance, perhaps, can be better way-out for balancing these demand and supply fluctuations. alliance for aircraft sharing can possibly assist the airlines in optimizing their aircraft capacities and mitigating their operating losses. the covid economic impact on aviation is extreme and perhaps uncertain. higher the reduction in plf, more difficult will be the attainment of break-even for the airlines. the lockdown of two months with zero revenue and spiraled fig. cargo business using passenger flights during january to april . source icao https ://www.hindu stant imes.com/busin ess-news/india -s-domes ticair-traffi c-to-fall-to- -mn-this-fisca l-repor t/story -ynobz buttd z g d sn fm.html using passenger planes for carrying cargo in belly space fixed charges, particularly, loan instalments and lease rental, perhaps has drained out the liquidity of airlines. with the trimmed air traffic estimated in the coming months, there seems meagre probability of recovering the past losses. with the reduced plf the recovery of variable cost of operating a flight will be challenging, threating the operation viability of airlines. figure portray projection done by icao regarding commercials of aviation sector. as provided, in all the situations the operating losses are confirmed, with the only difference in the magnitude of losses from high to low. in the given situation, bailout package, particularly, waivers of interest charges pertaining to lockdown period, reduced landing and parking charges, atf taxes, seems essential for the stability of the sector. the cost waivers by reducing operating cost of airlines will enhance the airlines probability of attaining break-even. in fact, in view of dipped consumable income, the reduced cost possibly be a relief for passengers in terms of affordable flying. air travelers rate assurance (singh, ) and financial conditions of airlines significantly affect the quality of air travel. product quality decreases when airlines are in financial distress (phillips and sertsios ) . given the deteriorating finances and demand crunch ahead, airlines service quality and safe operations may be compromised. further, the reasonable ticket cap as a safeguard to airlines as well as passengers' interest may be implemented. present paper attempts to analyze the vulnerability of airlines in india to withstand covid- after effects. lockdown of two months has been drastic for the fragile airlines business distressed with thin margins, liquidity crisis, over mounting fixed cost and debt. zero revenue, albeit spiraling fixed expenses has been a drain on the cash reserves of airlines dragging them towards insolvency. above all, the sector is viewing grim recession ahead. in this backdrop, the operation viability of airlines seems conditional on the recovery of variable expenses. sustainability of airlines warrants of turnaround changes in their revenue strategies and operating models. focus on minimizing losses rather than profit maximization possibly can help the airlines to combat current situation. impact of the 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distress in airline companies in india using fuzzy ahp framework the impact of the degrees of operating and financial leverage on systematic risk of common stock operating leverage and operating risk flying with(out) a safety net: financial hedging in the airline industry impacts of the macro environment on airline performances in southern africa: management perspectives competing in an lcc world the routledge companion to air transport management transformation of india's domestic airlines: a case study of indian airlines, jet airways, air sahara and air deccan discussion paper: airport privatization in india survival lessons from a dying kingfisher how do firm financial conditions affect product quality and pricing? future of revenue management: airline pricing and revenue management: a future outlook assessing the air cargo business models of combination airlines kingfisher's acquisition of air deccan: altering india's lcc scenario? the case centre impact of operating cost components on airline efficiency in india: a dea approach drivers of operational efficiency and its impact on market performance in the indian airline industry on the impact of jet fuel cost on airlines' capacity choice: evidence from the u.s. domestic markets competitive service quality benchmarking in airline industry using demand model for air passenger traffic on international sectors airline service quality and economic factors: an ardl approach on us airlines tourism & hospitality: an initial assessment of economic impacts and operational challenges for the tourism & hospitality industry due to covid- an analysis on domestic airlines capacity performance in india key determinants of airline pricing and air travel demand in china and india: policy, ownership, and lcc competition airlines' futures key: cord- -mx ycsvo authors: momaya, kirankumar s. title: return from covid- : thinking differently about export competitiveness and sustainability date: - - journal: jgbc doi: . /s - - - sha: doc_id: cord_uid: mx ycsvo times are really tough for millions across the world, and more so for poor populations in emerging countries, due to the strategic discontinuity called covid- . this perspective editorial urges to think differently in addressing issues such as the covid- pandemic. starting from an analogy of ‘signals from nature’, it gives a brief background about the relationship between competitiveness and sustainability. the classical method of situation-actor-process—learning-action-performance (sap-lap) is adapted for the context of an experimental bottom-up micro-pilot to ‘return from covid- ’. glimpses of emerging findings from the pilot project in the context of academic institutions are shared. topics for urgent and mid-term studies in the given context are listed, focusing on implications for the rebound of export activity. we will discuss ways for leaders to enhance export competitiveness despite covid- . this article contributes to the literature by extending sap-lap in an alternative micro-situation for an optimistic scenario. mother nature has for decades been very accommodating to the greed of many, but recent crises signal that 'limits to growth' (meadows et al. ) may have been reached quite a while ago. responses to silent crises such as pollution and climate change have been too slow, and the most powerful countries often threaten to withdraw from collective organizations. however, responsible cities or states may proactively start to address challenges. for instance, leaders in london, new york and tokyo have taken several initiatives to stabilize population, de-congest, reduce pollution and help the city on the journey of rejuvenation. leaders in indian cities have also tried, but may be less proactive and effective. a crisis such as covid- can be interpreted as a signal from mother nature that we need to rethink with a clean slate about the fundamentals of economy, development and sustainability. while most of us see many challenges arising from covid- , some of us should also be able to sense the signals and see opportunities to review directions. in an indian context, examples of macro challenges include finding incomes for youth and experienced workers (e.g. made jobless due to crisis), restarting supply chains to fill voids and restoring health (not only physiological, but psychological as well). similarly, examples of competitiveness challenges at a firm level include regaining customers (particularly international ones at better price points), and innovating to address problems, even if we assume that operational challenges can be managed-which may not be true for many firms. proactive firms or organizations can reboot ideation by asking tougher questions, such as the following in the context of the indian institute of technology bombay (iitb): • how long will the air in cities remain reasonably clean? can it become even worse in mumbai post-lockdown for reasons such as the following: • many people are adopting road travel, as trains-the backbone of public transport-in mumbai are considered less safe in such a crisis. • how can mumbai trains achieve new levels of hygiene to be among the safest public transport in india, not only from covid- , but other types of infectious diseases (e.g. tuberculosis) as well? • when can we dream of bicycling beyond the iitb campus-a paradise for walkers and bicyclists-and attend meetings within a - -km range from iit bombay, riding on bicycles in case public transport systems become less safe due to such viruses? • how can we pilot greener labs or gemba that are more resilient, to help 'return from crisis' at even better sustainability? • what types of new service or product development (nsd or npd) and organizational innovations should be piloted at iits to enhance contributions to society, industrial competitiveness (momaya et al. ) and exports in an x/ scenario of resources (e.g. only / resource available)? the low sustainability of popular schools of development and economics has been highlighted by many in india, and is now confirmed by strategic discontinuities (sds) such as covid- . mahatma gandhi long ago rejected the westerndominant design of development and took several initiatives with holistic approaches balancing socioeconomic, health, political and other dimensions (e.g. गां धी १९२१). most of the large asian countries that broke out into higher orbits significantly adapted some development model, and if not, invented their own. similarly, new thinking is needed on the competitiveness front to minimize losses for firms, ventures, clusters and cities from such strategic discontinuities (sds). paradigms such as industrial organization (io) and the porter diamond (porter ) will remain popular, but may be of limited use to address the survival crisis of competitiveness being faced by a large number of start-ups, micro-, small and medium enterprises (msmes), ventures and even focal firms (momaya ) . for instance, it is forecasted that more than % of the indian population will fall below the poverty line as a result of covid- (cii ). the huge task of lifting them out of poverty again will be daunting; what took decades to build will be wiped out with just one crisis, and india may not have the resilience of countries such as japan and korea needed to recover. developing countries such as india do not have deep pockets, and indebtedness can skyrocket for individuals, msmes, firms, cities and even countries that fail to sustain competitiveness. this indicates that popular models of development and competitiveness are less sustainable. alternative thinking on competitiveness has begun to yield more flexible and useful frameworks. for instance, models such as abcd [advantages,benefits, constraints, disadvantages] (yin et al. ) have higher utility due to simplicity. the competitiveness assets-processes-performance framework (app) (momaya ) has a very strong 'process' facet that can help prioritize linkages of different factors (e.g. competitiveness asset factors such as human and financial resources) to sustain performance on key factors of survival (e.g. employee satisfaction, cashflow) and prepare firms to scale up on other factors, including performance, once the firm has navigated through multiple valleys of death (mvod). apart from sound foundations, attempts have been made to incorporate the best elements of classical theories such as the resource-based view (rbv) and the dynamic capabilities view (dcv) in a competitiveness app framework, and such approaches are being tested in a variety of industries, from mature (e.g. engineering construction, bhattacharya et al. ) to emerging ventures (e.g. software, shee et al. , ambastha et al. telecom, mittal et al. ; nanotechnology, momaya ) . the sustainability dimension of competitiveness is also important, but may need to wait a bit, as return from covid- has become the first priority for most governments, industry associations, firms and even institutes. let's make some sense of examples of brutal facts to understand weak signals. examples of signals from nature or facts: • cities and towns are getting choked with traffic, solid and liquid waste, increasing pollution • shrinkage or disappearance of lakes, ponds, forests, flora, fauna and other forms of life • worsening fiscal and trade balance (if not savings, investments, information, knowledge, technology, etc.) • pollution of core or surrounding cities and towns (from air and water to solid waste) • lack of balance: e.g. in levels of self-sufficiency, low energy in the context of the background highlighted above, we want to address practical questions such as: • what are the advantages and limitations of bottom-up or grassroots projects that can help increase the confidence and motivation of associates? • what can we learn from such micro-projects? how can we share them to benefit many? considering the urgency of the situation, we adopted an action research approach (kemmis et al. ) as a research method to address the situation and improve the classical sap-lap framework (sushil ) . sap-lap is a very useful holistic framework that has been evolving through applications in diverse contexts, including one related to technology management and competitiveness (e.g. sahoo et al. ) . since a key objective of our action research (ar) is to address problems created by the strategic discontinuity, we explored various types of sap-lap models. in this way, we aimed to evolve a specific model for problem solving, building on tools such as problem structuring (momaya et al. ) . the model will be an exploratory one (versus normative, sushil ) for managerial inquiry (and later, case development) for a specific context of the 'group on competitiveness' (goc). we take into consideration the six components of sap-lap (please refer to details of each component in the appendix) and plan to make a method contribution by extending sap-lap. we plan to consider a future scenario of changed situations to sharpen priorities among actors and actions for higher feasibility. among different types of action research (ar), we adapted selected elements of canonical ar with a focus on problem solving. researcher intervention to improve situations in times of crisis such as covid- also envisage change (e.g. wong and davison ) through action research on multiple dimensions: • flexibility and resilience to get up and 'return from crisis' with better performance. • it is a cooperative project, where the goc intends to contribute significantly to recovery of research processes at multiple levels, from goc to other research groups at the management school-our clients for internal counselling. since the crisis has hit at a time when the school is in 'silver jubilee' year, the time is right for deep thinking. • in terms of theory, we will build on problem solving theory, particularly structured methods such as problem structuring that are found to have flexibility to interface well with the sap-lap framework, e.g. through actorbased root cause analysis (rca) (for an example in a very related context of iits, please see momaya et al. ) to enhance the feasibility of actions. • we focus on the collaborative aspect of canonical ar. the actors here are researchers at the management school, particularly associates of the goc, who have shown a keen interest in actively participating in the project. we also plan to emphasize improving rigour (the other element of canonical ar, davison et al. ; wong and davison ). since it was not possible to meet associates in person, alternative e-meeting approaches were adopted to coordinate actions during the lockdown. for documenting the situation, processes, etc., we employed and extended a powerful structured sap-lap approach (sushil ) that has been widely used. we attempt to extend the sap-lap framework by: • testing its utility in a sharper focus on the micro-context of small groups • evolving an alternative situation as a guide to concentrate on future actions and performance. we used an optimistic scenario of a future situation. the covid- tsunami that swept across the world will be felt for decades. with cases close to five million, the death toll has surpassed , (as of may and we are still countig; worldometers ). the big question is why the developed countries were so ill-prepared, and have seen more than deaths each (e.g. germany , france , , uk , and usa , ; as of may , , worldometers ). a glimpse of patterns of new cases in selected large countries is given in fig. . a comparison of patterns among the largest countries (by size of the economy) provides some useful findings. the scale of the y-axis-daily new cases, considered a good proxy for effectiveness-gives a clue to different scales of impact in these countries. the usa has been the worst affected in this early phase, with new cases per day peaking at close to , and very slow declines; the death toll in the usa is higher than that during ww ii. japan was able to contain the peak below , a more than -fold difference compared with the peak in the usa, after factoring in the population difference. patterns are quite different for india, japan and the usa; china may remain an exception. india's peak has not yet been reached. the focus on saving human lives in india seems to be quite different from the focus in the usa (more focus on economy), but india may have to endure massive economic losses for much longer. china may remain an exception; it was able to contain the pandemic dragon much more rapidly. within india, megacities are the worst affected, and patterns are quite divergent and dynamic. population densities in megacities are reaching alarming levels, and they can become easy victims of such pandemics. mumbai and pune seem to be the worst affected among the diverse patterns in the selected megacities, with at least times the number (from confirmed cases to deceased) as compared with bengaluru, indicating the massive challenges these cities are going to face. hence, our focus is on mumbai-the city where the action research pilot was undertaken-in this study (table ) . having waited patiently for the year -the milestone year of vision by the most popular president of india, dr. a. p. j. abdul kalam (e.g. kalam and rajan ) -the group on competitiveness (goc) at iit bombay was overwhelmed by such a tsunami, but recovered quickly to stand up again and start walking. with students having to leave labs and campus, and offices under threat of lockdown, it was considered wise to shift the base of the goc to home. thinking soon started on ideas to preserve food and information and communications technology (ict) infrastructure for digital work. the first pilots were on the research front, where a commitment was made to continue research, and even do much better than last year in terms of output. several initiatives were established, involving members, for the evolution of 'return from covid- '. only a glimpse of one such project is given in the appendix. let me list key learnings here: • as we started rationing food, we realized how much wastage we had. we hope to cut monthly expenses by at least %. • we do not necessarily require so many physical assets such as buildings and cars. we have started pilots to test efficiency with much less asset use with minimum forex. such steps can help us on a path towards better balance, if not 'आत्मनिर्भ रता' that is recalled in crisis. • balance is important, as we swing from physical to digital; otherwise unexpected effects may occur, and worsen the situation. for instance, e-learning is picking up massively in covid- times. even though some focal institutes in india are capable of creating relevant local content and exchanging it to earn some forex, the net forex and trade competitiveness index (tci) can go markedly negative as the costs of digital platforms can rise stead- ily. as there are business oligopolies in the usa (e.g. the big five tech companies, rayport et al. ) , costs can be very high. because concepts such as swadeshi take too long to diffuse (and penetrate in india, unlike in the usa/eu/east asia), many institutes or universities can become stranded in high-risk zones of digital dependence without affordable indigenous options. the side effects such as lifestyle diseases and digital addiction that many of can get into may require massive doses of bitter treatments (e.g. digital detox) to return to a normal condition. • there is so much to be done from a researcher perspective to learn from crisis and pilots. one of the things we focused on was a platform called the international journal of global business and competitiveness (jgbc). we contacted many members of the editorial board, review board and authors to reconnect and link with emotionally. based on suggestions received, work has started on improvements on regular issues and on several supplementary or special issues, including one related to covid- . we clustered emerging topics of high importance in two sections for quick attention of leaders. • many businesses have seen massive erosion of the top line, with grave implications for profits, corporate social responsibility (csr) and sustainability activities. other businesses have or may fold. in such situations, the survival facet of competitiveness becomes crucial. starting from survival of oneself (from such viruses or other infectious pathogens) and family, employees, suppliers and local stakeholders should get higher priority. the factors and criteria of competitiveness (momaya ) that become more useful in such a crisis era can be an urgent topic for study. • people are the heart of business. studies that address questions such as the following can be useful: • how can employees be motivated to evolve productive and healthy work schedules and environment, while keeping morale of family members high? • how can they be enabled digitally for task delivery, cooperative work and even speed learning of essential skills? what are the trends in the availability of affordable indigenous tools for that? • capabilities and the maturity of people are tested in such trying times. even when managers are less mature, top leaders need to demonstrate resilience, restraint and responsibility. how do frameworks such as p-cmm [people-capability maturity mode] (e.g. ambastha ) need to be adapted for such a crisis? • leadership in discontinuity is a very different ball game. popular theories and frameworks in developed countries are often not working in their own countries; expecting them to work in complex emerging countries such as india is less realistic, even after adaptation. for instance, the healthcare system in india is highly fragmented and fragile. how do we rebuild more internationally competitive and flexible systems that provide exciting opportunities for study and action pilots? here, concepts such as lean or agile development or start-up can be tested. • on a different plane, leadership in discontinuity needs to be quite creative and one that forges 'human cooperation', perhaps the most powerful force on this planet (kalam and tiwari ) . how can we cultivate such leaders and how can we evolve cooperative strategies (e.g. momaya ) remain an exciting perennial topic? • megacities such as mumbai and pune may have to bear the worst, as densities are high or growing rapidly. they may run out of leaders who are capable of rebooting msmes and firms to restart supply chains. the situation may be tougher for mumbai, as its value chains and industry value system are less digitized, for example with respect to bengaluru. questions such as how to redirect one's thinking towards more sustainable systems-e.g. decongestion for flexibility to face larger crises-can provide exciting opportunities for study. • msmes are worst hit by the discontinuity, but one with a competitiveness orientation can survive and rebound. many sme exporters do not have money even to pay wages, and their supply chains need to be rebooted in the face of very limited resources, including cash flow and other financial assets. trust plays a key role in such trying times. identifying, selecting and reviewing best practices in local contexts can provide useful learning (for examples from india, see cii bp). • prolonged lockdowns and related uncertainty are testing the mettle of even enduring industrial houses, and sme sustainability will require outside-the-box ideas and actions. studies that explore best or next practices of sustainability in both the near and long term can be very useful. • goals such as 'स्वस्थ समु ह' (healthy groups), institutes and cities demand paradigm shifts to break out from vexing myths. balance between 'उपचार एवं व्ापार' is difficult to define and evaluate, but provides exciting topics of research for some exceptionally enduring researchers. globalization has received a major blow due to the crisis. while several countries including china and korea are flexible enough to redirect their focus, studies are needed to understand issues such as what can be done by large emerging countries such as india to reboot their export supply chains to meet the urgent need for medical supplies, food, and other humanitarian needs of poorer countries. • repeated pump-priming of the financial system is leading to precarious economies in many countries. time will demand cooperative strategies, particularly between large democratic countries such as india and japan, in banking, financial services, insurance, manufacturing and emerging industries (e.g. bansal et al. ; momaya momaya , every crisis provides clues that can translate to opportunities for action, if proactive individuals and firms are open to listening to weak signals (schoemaker and day ). the covid- crisis is similarly providing clues to enormous opportunities for building health and values such as discipline to cope with a discontinuity. india had never faced such a challenge of a potential loss of thousands of lives despite efforts by so many, but the country has responded quite well to government calls for collective initiatives such as the janata curfew (swayam-shisht). institutes such as iit bombay also responded proactively for safety of thousands of students and implemented lockdowns, while many faculty also proactively began working from home. the core contribution of this article-extending a flexible paradigm to address issues arising from strategic discontinuities-also evolved from pilots in crisis times. let me give a glimpse of an action agenda for associates and readers of jgbc from the learning from pilots. when facing issues regarding balance in nutrition, it is still possible to increase immunity-a key defence for coping with viruses such as coronavirus or anything else that may follow. practices such as 'य़ोग और प्ाणायाम' (yoga and pranayam) can help improve our health to face such crises. since the crisis has exposed the limitations of so-called global supply chains (gscs) (e.g. griffith and myers ) , we must learn to take help from local supply chains, even when we cannot ride off the gscs. for those keen to evolve their research for the post-covid- era, i urge them to evolve linkages-at the early stage of research conceptualization-of the problems of functional areas (e.g management, operations, hr, finance) with the needs of competitiveness, as thousands of micro, small and medium enterprises (msmes), ventures, start-ups and even established firms will struggle to survive due to gaps in their understanding about competitiveness. while collective bottom-up initiatives take time to surface, the power of individual efforts should not be underestimated. for instance, most of the innovative firms in japan were born from such passionate individuals and teams during the crisis of ww ii. we hope to bring you more exciting stories about the return from covid- to next steps in the coming issues of jgbc. until then, visit regularly or follow our micro-projects (e.g. on researchgate) to receive updates about calls for papers (cfps), seminars, boot camps and other action workshops. let me close this perspective editorial by refreshing our collective memory with the words of the great saint tiruvalluvar, in the current context: those who strive with strong unwavering mind will leave misfortune's fate behind.-tirukkural (verse ; tiruvalluvar ) the topic of 'revitalise from viruses' is very vast; we will focus on questions related to internationalisation and export competitiveness. this can spark different thinking and learning that can be implemented in relevant time horizons, including today. please reflect on these questions or suggestions in context of small organizational unit in your firm or other export-oriented firm of your choice. . accepting such crisis due to virus or other pathogens (नवषाणु ) as a new normal, evolve a plan to help yourself, family, friends and other groups to live with it safely. learn to evolve safety norms and processes (e.g. use of apps such as arogya setu, when going closer to risky zones) to enhance protection and options to recover faster, when caught by the pathogen. . plethora of guidance and 'rules or regulations' coming from different bodies can create a lot of complexity and chaos. try to simplify your choices and processes to minimize adverse impacts on productivity and quality. . plan pilots to increase sustainability of your activities by thinking such as glocal (global thinking with local sustainable actions). . review patterns of forex spend and earning to calculate trends of net forex and trade competitiveness index (tci) for the firm. generate ideas and start pilots to improve net forex. . explore projects on "return from viruses" to open dialogue with professionals who are trying to share their views, resources and research on the topic and link such projects with other similar projects to enhance awareness, immunity and revitalise self and others. • an optimistic scenario • faculty propose challenge projects to reboot activities and take new projects, e.g. e-seminars (later e-mdps with face-to-face components and boot camp) • alternative gemba piloted close to residences to minimize transport disruptions with testing for creative nature-friendly space for several weeks; elements of sustainability of such lab are being identified and characterized • digitalization and experience of virtual work may reduce load on physical infrastructure, permitting more executives to be associated • cooperative head involves key stakeholders to evolve better strategic intent • digitally savvy associates ready to facilitate e-learning to face such abrupt disruption to academics due to lockdown • an enduring associate trained to handle less prepared associates; e.g. with their issues related to hardware (hw), access to software (sw) • pilots of alternative labs done to learn when access to lab is not possible during lockdowns • even higher goals (at least % high in and % high in over levels, particularly in terms of research output) are set to see that the ambitious plans for are not disturbed even with dispersion of the team • two associates trained to do pilots to address less availability of indigenous sustainable tools (or time for their adaptation) the above -to -year example scenario of the situation is quite short-term, mainly focusing on firefighting. we need to also work a bit on medium-and long-term (e.g. - years) scenarios when the focus can be on structural factors of competitiveness of groups that demand such horizons. challenges for indian software firms to sustain their global competitiveness. singapore management building competitiveness through people cmm: a case of implementation in tata capital exploring cooperative strategies between india and japan: a view on banking industry enablers of sustaining competitiveness: a case of growth strategies of top international construction companies competitiveness of india inc.-india @ : forging ahead, confederation of indian industry principles of canonical action research manufacturing competitiveness: research opportunities note of exit strategy of lockdown, federation of indian chambers of commerce and industry (ficci) trusteeship the performance implications of strategic fit of relational norm governance strategies in global supply chain relationships india : a vision for the new millennium transcendence: my spiritual experiences with pramukh swamiji the action research planner: doing critical participatory action research limits to growth: the -year update longitudinal and comparative perspectives on the competitiveness of countries: learning from technology and the telecom sector international competitiveness: evaluation and enhancement evaluating country competitiveness in emerging industries: learning from a case of nanotechnology city clusters and break-out in corporate competitiveness institutional growth and industrial competitiveness: exploring the role of strategic flexibility taking the case of select institutes in india the past and the future of competitiveness research: a review in an emerging context of innovation and emnes the competitive advantage of nations: with a new introduction the powers that be: google, apple, facebook, amazon, and microsoft strategic technology management in practice: dynamic sap-lap analysis of an auto component manufacturing firm in india how to make sense of weak signals flexibility and competitiveness: case of software/services firms in india saint tiruvalluvar and his message of life as dharma sap-lap models knowledge sharing in a global logistics provider: an action research project worldometer coronavirus cases the success factors of korean global start-ups in the digital sectors through internationalization our sincere thanks to anonymous reviewers for constructive suggestions for improvement. i acknowledge active participation of researchers padmanav adhikari, sneha bhat, interns harshil misra, neha tale, chaitanya johari, rishabh thapliyal and other members of the group on competitiveness (goc), iit bombay in the pilot. we thank sjm school of management for infrastructure support. partial financial support for activities related to this research from wadhwani foundation through industrial research and consultancy centre (ircc), indian institute of technology bombay is acknowledged. this section gives a glimpse of extending a popular approach, situation-actors-processes-learning-action-performance (sap-lap, sushil ) by applying it to a challenging context of crisis. we contribute to the method by 'lean application' of the framework for a micro-context. here is just a glimpse of elements of sap-lap analysis. key: cord- -q gb qkq authors: singh, b. p. title: forecasting novel corona positive cases in indiausing truncated information: a mathematical approach date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: q gb qkq novel corona virus is declared as pandemic and india is struggling to control this from a massive attack of death and destruction, similar to the other countries like china, europe, and the united states of america. india reported cases novel corona confirmed cases as of april , and out of which cases were reported recovered and deaths occurred. the first case of novel corona is reported in india on january , . the growth in the initial phase is following exponential. in this study an attempt has been made to model the spread of novel corona infection. for this purpose logistic growth model with minor modification is used and the model is applied on truncated information on novel corona confirmed cases in india. the result is very exiting that till date predicted number of confirmed corona positive cases is very close to observed on. the time of point of inflexion is found in the end of the april, means after that the increasing growth will start decline and there will be no new case in india by the end of july, . a novel corona virus is responsible for epidemic popularly known as covid- is a new strain that has not been identified previously in humans. who declared covid- a pandemic on march , . [ ] the virus that caused the incidence of severe acute respiratory syndrome (sars) in in china, middle east respiratory syndrome (mers) in in saudi arabia and the virus that causes covid- are genetically related to each other, but the diseases they caused are quite different. [ ] these viruses, in general, are a family of viruses that target and affect mammal's respiratory systems. the sars corona virus spread to humans via civet cats, while the mers virus spread via dromedaries. in case of the novel corona virus, typically happens via contact with an infected animal, perhaps the common carriers are bats initial reports from seafood market in central wuhan, china. novel corona virus is spreading throughout the world at alarming speed. worldwide it has exploded to cases and caused deaths by april , . [ ] developed countries like italy, spain, france and united state of america etc. are struggling to overcome from the pressure created by novel corona virus. india with a huge population about . billion, amongst majority of the people are living in poor hygienic condition and the medical facilities like number of doctors and hospitals are less in india as compared to developed countries indicates that the situation of india will become very critical but comparatively better public health system and political control in india than the above developed countries. india reported cases novel corona confirmed cases as of april , and out of which cases were reported recovered and deaths occurred. the first case of novel corona is reported in india on january , when a student returned from wuhan, china. [ ] the government of india was quick to launch various levels of travel advisories beginning from february , , with restrictions on travel to china and nonessential travel restrictions to singapore, south korea, iran and italy. [ ] the efforts to control by the hon'ble prime minister narendra modi ji through janata curfew (public curfew) on march , , can be seen as the beginning of wide-scale public preventive measures. india has launched several social distancing measures and personal hygiene measures during the second week of march. [ ] since huge population of about . billion, thus india has chosen a flexible strategy of largescale quarantine and limited testing because of less number of testing kits and also the cost of testing is too much. the country is relying on the people power; thousands of health-care workers are working out across the country to trace and quarantine people who might have had contact with those with novel corona. people are typically only tested if they develop symptoms. countries such as south korea isolated infected people based on widespread testing, but some scientists say that india's mass surveillance approach could achieve a similar goal, and be relevant for other low and low-middle income countries facing kit shortages. under the lockdown, people are allowed out for essentials, such as food and medical care, but in most states people under quarantine are closely monitored by social workers and cannot leave their homes in some places. if public health workers do not trace all infected individuals during the lockdown, india will need to continue its period of stringent physical distancing. for the spread of novel corona virus, when disease dynamics are still unclear, mathematical modeling helps us to estimate the cumulative number of positive cases in the present scenarios. now india is interring in the mid stages of the epidemic. it is important to predict how the virus is likely to grow amongst the population. a mathematical modeling approach is a suitable tool to understand the dynamics of epidemic. in the study some mathematical approach to understand the dynamics of novel corona virus in india has been discuss. we obtained the truncated information on cumulative number of corona positive confirmed cases in india from march to april , from covid india.org. [ ] all cases are laboratory confirmed following the case definition by the govt. of india. some studies modeled the epidemic curve obeying the exponential growth. [ , ] the nonlinear least square framework is adopted for data fitting and parameter estimation for -ncov at this early stage. in this study first exponential and then logistic growth curve has been used to model the novel corona epidemic, since epidemics grow exponentially not linearly. but it is surprising that exponential growth curve always provide increasing number of daily new cases. there is no saturation point. another deterministic model used for understanding the dynamics of epidemic is the sir model, which has been used to accurately predict incidence like sars. in the sir model, we need to know the input parameters first the stats we feed into the model. [ , , ] the first one is r called the basic reproduction number. it is essentially the number of new cases a single infected person will cause during their infectious period. it is one of the most important parameters for assessing any epidemic. corona virus has an r ~ . . in contrast, the h n virus had an r ~ . in the swine flu epidemic. [ ] the r will inform us about how many people will get infected with one infected person. other one is the case fatality rate (cfr), which is the percentage of infected people that will die due to the infection. the cfr for corona virus has been reported between . - %. the lower values are more appropriate in resource better settings of medical facility. but sir model assumes that every person is moving and has equal chance of contact with each and every other person among the population irrespective of the space or distance between different people. it is assumed that the transmission rate remains constant throughout the period of pandemic. also this model considered to have the same transmission rate for who have been diagnosed and are in quarantine or those who have not been quarantined. the harmonic analysis methods and dynamic model estimates show that the number of covid- infected would be (if there were infected individuals as of march , , who was not taking any precautions to spread), , (if there were ) and , (if there were ). [ ] a growth curve is an empirical model of the evolution of a quantity over time. growth curves are widely used in biology for quantities such as population size in population ecology and demography for population growth analysis, individual body height in physiology for growth analysis of individuals. growth is also a key property of many systems such as an economic expansion, spread of an epidemic, the formation of a crystal, an adolescent's growth and the condensation of a stellar mass. this is the simplest growth model, in which population grows at a constant rate over time. linear growth is described by the equation . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint where t p represents the numbers or size of the system at time t,  t p represents the system's numbers or size of the system one time unit later, and a is the system's (linear) growth rate. many times this model fails to explain natural phenomenon. exponential growth (unlimited population growth) another simple model describes exponential growth, in which population grows at a constant proportional rate over time. the relation may be expressed in either of two forms, depending on whether reproduction is assumed to be continuous or periodic. [ ] exponential growth results in a continuous curve of increase or decrease, whose slope varies in direct relation to the size of the population. with the current incidence of the novel corona virus going on, we hear about exponential growth. in this study, an attempt has been made to understand and analyze the data through exponential growth curve. the reason for using exponential growth curve for studying the pattern of novel corona virus incidence is that epidemiologists have studied these types of happenings and it is well known that the first period of an epidemic follows exponential growth. the exponential growth function is not necessarily the perfect representation of the epidemic. i have tried to fit exponential curve first, and at the next point to study the logistic growth curve because exponential curve is only fit the epidemic at the beginning. at some point, recovered people will not spread the virus anymore and when someone is or has been infected, the growth . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . will stop. logistic growth is characterized by increasing growth in the beginning period, but a decreasing growth after point of inflexion. for example in the corona virus case, the maximum limit would be the total number of exposed people in india because when everybody is infected, the growth will be stopped. after that the increasing rate of curve starts to decline and reach to the minimum. in the figure , predicted values of the cumulative number of novel corona positive cases obtained by method and is drawn along with observed cumulative number of novel corona positive cases. bothe the methods provide moderately good estimates but the tendency of both the curves are unlimited increasing. the rate of growth of method is slightly lesser than the rate of growth of method . the number of total infected cases by april , would be about (method ) and (method ). if we do not adjust the method for tablighi spread then the total infected cases by april , would be about . thus we can obtain the effect of tablighi spread is about percent. the logistic model reveals that the growth rate of the population is determined by its biotic potential and the size of the population as modified by the natural resistance, or, in other words, by all the various effects of inherent characteristics, that are density dependence. [ ] natural resistance increases as population size gets closer to the carrying capacity. logistic growth is similar to exponential growth except that it assumes an essential sustainable maximum point. in exponential growth curve, the rate of growth of y per unit of time is directly proportional to y but in practice the rate of growth cannot be in the same proportion always. the logistic curve will continue up to certain level, called the level of saturation, sometimes called the carrying capacity, after reaching carrying capacity it starts declining. the factor y is called the momentum factor which increases with time t and the factor ) ( y k  is known as the retarding factor which decreases with time. a system far below its carrying capacity will at first grow almost exponentially however, this growth gradually slows as the system expands, finally bringing it to a halt specifically at the carrying capacity. [ , ] the logistic relationship can be expressed as . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . and are the number at given time and respectively provided that y y y t t t t t t t    . you may also estimate the parameter a and b by method of least square after fixing k. to predict confirmed corona cases on different day, logistic growth curve has been also used and found very exciting results. the truncated information on confirmed cases in india has been taken from march to april , . the estimated value of the parameters are as follows k= . , a= . and b=- . , with these estimates predicted values has been obtained and found considerably lower values than what we observed. on april and , the number of confirmed corona cases are drastically increasing in some part of india due to some unavoidable circumstances thus there is an earnest need to increase carrying capacity of the model, thus it is increased and considered as and the other parameters a and b are estimated again which are a= . and b=- . . the predicted cumulative number of cases is very close to the observed cumulative number of cases till date. the time of point of inflexion is obtained as . i.e. days after beginning. we have taken data from march , so that the time of point of inflexion should be april , and by may , there will be no new cases found in the country. the distribution of the new cases is in the red color in the figure , which is quite normal and obvious. as mentioned in the above paragraph method provided natural estimate of the total infected cases by may , is . this estimate is obtained when no preventive measure would be taken by the government of india. the testing rate is lower in india than many western countries, so our absolute numbers is low, when government initiate faster testing process then we have observed more number of cases and fount this logistic model fail to provide cumulative number of corona confirm cases after april , thus there is a need to modify this model. in order to the modification i have taken natural log of cumulative number of corona confirm cases instead of cumulative number of corona confirm cases as taken in the previous model. this model provides the carrying capacity is about cases and time of point of inflexion april , . the present model provides reasonable estimate of the cumulative number of confirmed cases till date (see appendix and figure ) and by the end of july, there will be no new cases found in the country. india is in the comfortable zone with a lower growth rate than other countries studied. our mathematical model shows that, the epidemic is likely to stabilize with cases by the end of july, . a study advocated of days single lockdown i.e. lockdown up to may , reduce infected cases below but our study contradict it. [ ] the government has adopted a strategy of large scale quarantine and limited testing to flatten the epidemic curve and reduce the death rate. the projections produced by the model and after their validation can be used to determine the scope and scale of measures that government need to initiate. in conclusion, if the current mathematical model results can be validated within the range provided here, then the social distancing and other prevention, treatment policies that the central and various state governments and people are currently implementing should continue until new cases are not seen. the spread from urban to rural and rich to poor populations should be monitor and control is an important point of consideration. mathematical models have certain limitations that there are many assumptions about homogeneity of population in terms of urban/rural or rich/poor that does not capture variations in population density. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint covid- ) -events as they happen who statement regarding cluster of pneumonia cases in wuhan, china coronavirus update (live): covid- virus outbreak -worldometer. available at india covid- tracker: a crowdsourced initiative consolidated travel advisory in view of covid- revised strategy of covid testing in india a preliminary analysis of the epidemiology of influenza a (h n ) v virus infection in thailand from early outbreak data simple framework for real-time forecast in a data limited situation: the zika virus (zikv) outbreaks in brazil from to as an example healthcare impact of covid- epidemic in india: a stochastic mathematical model prudent public health intervention strategies to control the corona virus disease transmission in india: a mathematical model-based approach age-structured impact of social distancing on the covid- epidemic in india gupta mohak corona virus in india: make or break modelbased retrospective estimates for covid- or coronavirus in india: continued efforts required to contain the virus spread methods and materials of demography on the rate of growth of the population of the united states since and its mathematical representation date observed predicted % lci % uci new cases residual march - - - - - - - - - - - - - - - - - april - key: cord- -p vqpazu authors: tsai, theodore f.; rao, raman d.s.v.; xu, zhi yi title: immunization in the asia-pacific region date: - - journal: plotkin's vaccines doi: . /b - - - - . - sha: doc_id: cord_uid: p vqpazu nan and inactivated vero cell-derived je vaccines from china, japan, and korea, regionally; live attenuated hepatitis a vaccine from china, regionally; live attenuated and inactivated pandemic and seasonal influenza vaccines from india and china, internationally; and oral cholera vaccine from vietnam, internationally). previously, asian manufacturers did not themselves market novel vaccines in europe or the united states, choosing to distribute their innovative products, such as acellular pertussis and live attenuated varicella vaccines, through multinational companies. however, an increasing global integration is taking place, as multinational companies acquire asian manufacturers (e.g., sanofi-aventis, france, acquired shantha biotechnics, india); asian companies acquire or obtain technologies and distribution rights from european countries (e.g., inactivated polio vaccine by serum institute of india ltd. acquiring bilthoven biologicals, netherlands; astellas, japan, acquiring recombinant influenza hemagglutinin from protein sciences, u.s.; thai government pharmaceutical organization acquiring chimeric je vaccine from sanofi-pasteur, france; and biological evans, india, acquiring je vaccine from intercell ag, austria); and vaccine codevelopment is agreed between entities in developed and asian countries (e.g., genetically modified, inactivated hiv vaccine codeveloped by sumagen, korea, and the university of western ontario, canada; mycobacterial proteinag a candidate tuberculosis vaccine codeveloped by tianjin cansino biotechnology, china, and mcmaster university, canada; universal influenza vaccine codeveloped by xiamen wantai and sanofi-pasteur, france; and novel pneumococcal conjugate vaccine codeveloped by sk chemicals, korea and sanofi-pasteur, france). , , the role of asian companies as developers and providers of neglected and improved vaccines for the region and, for developing countries more generally, is an emerging trend as illustrated by the joint research activity agreement between the national research council, canada, and the chinese national biotec group that covers development of h. influenzae type a and hib bivalent conjugate vaccine, novel mucosal adjuvants and therapeutic vaccines against helicobacter pylori infection, and cell culture manufacturing platforms for viral and vectored vaccines. a korean-manufactured biosimilar (generic) biological, infliximab, now is licensed in europe, a step toward commercial expansion of asian region-manufactured biologicals to developed countries. the emergence of asia as the base of new multinational vaccine companies with broad development, production, and distribution capabilities is on the horizon, even as consolidation of existing companies occurs elsewhere. [ ] [ ] [ ] the broad income range within countries in the region results in large population segments that have sufficient means to pay for vaccines out-of-pocket. even among countries that otherwise qualify economically for gavi funding (e.g., india), substantial numbers of families can avail themselves of vaccines not covered by the national epi, resulting in a two-tiered system of vaccination, paralleling the public-private dichotomy of healthcare delivery in general. practitioners serving these and expatriate families generally follow current u.s., european, or australian vaccine recommendations, or some modification of those schedules. five je vaccines have been developed and licensed in asian countries. the widely used first-generation inactivated suckling mouse brain (smb)-derived vaccine is being replaced rapidly in economically disadvantaged countries by the chinese developed and manufactured live attenuated or inactivated vaccine (sa - - strain) grown in primary baby hamster kidney (phk) cells and in higher-income countries with vero cell-derived inactivated vaccines (licensed in the united states, australia, canada, and europe, as well as several asian countries) or a replicating chimeric yellow fever-je virus recombinant vaccine (manufactured in thailand). details are provided in chapter . to control cases and occasional outbreaks of the far eastern subtype of tickborne encephalitis virus in northeastern china, the changchun biologicals institute developed a formalininactivated vaccine, derived from a human isolate, senzhang strain, and grown in phk cell cultures. related vaccines prepared from central european strains and distributed in europe are described in chapter . the kyasanur forest disease virus (kfdv) is a highly pathogenic member of the family flaviviridae causing a zoonosis, kfd, that is transmitted by the bite of infective ticks (haemaphysalis spinigera) primarily in its nymphal stage, and characterized by acute febrile illness with severe hemorrhagic manifestations. it was first described from outbreaks centered in karnataka state, india, among herders and villagers with forest exposure and was considered to be localized in the shimoga district area of the state. however, since first being reported in , the virus has been found in other areas of india including the kutch and saurashtra parts of gujarat state, andaman islands and west bengal. it is estimated that close to cases of kfd occur in india every year and, from to , among confirmed cases, were fatal. following the outbreak in india various vaccines including a formalin inactivated russian spring summer encephalitis virus, a russian spring-summer encephalitis virus-based mouse-brain vaccine, and a live attenuated vaccine that was serially passaged in tissue culture were tried but with limited success. finally, a formalin inactivated vaccine with the kfd virus grown in chicken embryo fibroblasts was tested in a large field trial from to among inhabitants of affected villages. the disease attack rates reported were . % ( / ) among persons receiving one dose and . % ( / , ) among recipients of two doses, respectively, compared to an attack rate of . % ( / , ) in unvaccinated persons, for vaccine efficacies of . % and . %, respectively. the vaccine was subsequently commercialized and is produced by the state institute of animal health and veterinary biologicals, hebbal, bangalore, and has been central to kfd prevention efforts in the state of karnataka. annual vaccinations have been done since in the shimoga and adjacent districts wherein two doses of the vaccine were administered in individuals to years of age at an interval of month. periodic boosters were also administered after to months. however, recent observations suggest a lower field effectiveness than had been reported previously, especially following a single dose, while overall coverage has also been low. between and , effectiveness among individuals perceptions of the value of vaccines and their risks also range widely, regionally and within individual countries, from largely enthusiastic acceptance and even demand for additional routine vaccinations (e.g., for je vaccine in southern and southeast asia) to a degree of skepticism equal to, if not more deeply and widely held, than vaccine hesitancy in europe and the united states. within the last years, japan discontinued routine childhood vaccine programs for combination measles-mumps-rubella, influenza, and je, and withdrew recommendations for the human papillomavirus (hpv) vaccine for adolescents, owing in several of instances, to incorrectly thinking that coincidental adverse events were causally related. the requirement for subcutaneous, as opposed to im administration for all vaccines, exemplifies the misattribution of adverse reactions, arising in this case from an extrapolation of muscle contractures resulting from repeated im administration of antibiotics, to other intramuscularly administered products, including vaccines. , the extrapolation has had unintended consequences of impeding the licensure of vaccines with newer adjuvants with mechanisms of action that require im administration. with the global spread of information, concerns over the thimerosal content of childhood vaccines and vaccine-associated autism have been as active a parental concern among middle-class families in developing countries as elsewhere. parental refusal of routine je vaccination in korea and significant declines in vaccine coverage occurred in a different context after seven cases of temporally related cases of anaphylactic shock and neurological disease, including five deaths, occurred in . the cases could not be excluded as causally related to administration of the mousebrain-derived vaccine, prompting a national debate and establishment of a vaccine adverse events reporting scheme, a national vaccine injury compensation system, and introduction of a live attenuated je vaccine derived from a nonneural tissue substrate. from this mosaic, we describe some common themes, highlighting representative approaches and unique issues that hold a wider interest. because they are covered elsewhere in this volume, we have not reviewed specific vaccines of regional concern (e.g., pandemic influenza and je vaccines) or vaccination topics common to developing countries (e.g., initiatives surrounding injection safety, measles and neonatal tetanus elimination, and polio eradication, nor financing mechanisms). we concentrate, instead, on other aspects of vaccine development and implementation, organized by the steps of vaccine development, approval, production, recommendation, and delivery. we also focus on childhood vaccines and vaccination and on selected countries in the region. japan is acknowledged as the innovator of several vaccines now used internationally, including acellular pertussis and live attenuated varicella vaccines, but other novel vaccines have been developed by japan, china, india, australia, and vietnam for region-specific needs (table . ). these include vaccines for je, hantaan (htn)-and seoul (seo) virus-related hfrs, russian spring-summer encephalitis, kfd, cholera, severe acute respiratory syndrome, and q fever. in addition, novel attenuated strains of measles, mumps, hepatitis a, rotavirus, and intranasally delivered pandemic h n virus have been derived for products distributed principally within the region. additional novel vaccines for hepatitis e and ev-a have potential for broader use internationally, an indicator of the region's transition from a provider of fill-finish and manufacturing capacity to a full-fledged participant in biotechnology research and clinical development. text continued on p. the reasons for low vaccine efficacy and coverage rates need to be investigated and the appropriate vaccine regimen for effective control requires further definition. newer vaccine approaches (e.g.., chimeric or virus protein subunit vaccines) are being investigated to potentially replace the current vaccine. elsewhere, a nearly identical strain to the kfdv was isolated from a patient suffering from acute febrile illness from yunnan province, china in . seroprevalence studies indicate that kfdv (or the nanjianyin virus or a related tickborne flavivirus) may be present in various parts of southwestern china. in a virus similar to kfdv called alkhurma hemorrhagic fever virus was isolated from patients with febrile illness in saudi arabia. overall, cases with two deaths occurred in sheep and camel handlers exposed to a tick ornithodoros savignyi. the disease has now been confirmed to be more widespread in the country than previously considered. as tickborne diseases are "diseases of place," kfd virus itself, if it spreads, is likely to disseminate locally. nevertheless, the discovery of antigenically related viruses elsewhere, such as alkhurma hemorrhagic fever virus, suggests a potential for more widespread use of kfd vaccine, depending on public health needs. hfrs, a widespread rodent-borne bunyaviral zoonosis in asia, is a pantropic infection with prominent capillary hemorrhages, interstitial nephritis, and a % to % case-fatality ratio that, until the last decade, caused more than annual cases in the republic of korea and more than , cases in china. although the disease had been well known in parts of russia and asia as a sporadic and occasionally epidemic disease among farmers, soldiers, and others exposed to campestral and sylvatic habitats, it was largely unknown in the west until thousands of military cases and deaths occurred during the korean war, when the disease was described as korean hemorrhagic fever. the etiologic agent eluded investigators until , when a novel bunyavirus, htn virus was isolated from the striped field mouse, apodemus agrarius, which proved to be the principal viral reservoir in most areas of asia. later, antigenically related seo virus was isolated from rattus rattus and rattus norvegicus, explaining the occurrence of sporadic hfrs cases and outbreaks in urban areas. subsequently, sin nombre and related hantaviruses were discovered in the western hemisphere, where rare encounters with infected rodents lead to small numbers of cases that feature prominent pulmonary involvement. a multitude of hantaviruses now have been described globally. the widespread impact of hfrs in china led public health authorities in the s and s to pronounce the disease second only to hepb as a public health menace, and, beginning in , several chinese vaccine manufacturers used smb, primary baby gerbil kidney cells (gkcs) or phk cells to produce inactivated, monovalent vaccines against htn or seo viruses. the gkc vaccine was inactivated by β-propiolactone and the other two by formalin. subsequently, vero cell linederived vaccines have been developed. these vaccines were evaluated in nine chinese provinces hyperendemic for hfrs during to . the gkc-derived vaccine against htn virus produced seroconversions to putatively protective titers of neutralizing antibody in . % of subjects after three primary doses at , , and days, the proportion rising to . % after a booster at year, and declining to . % at years and . % at years. similar immunogenicity results were reported for the phkderived vaccine and the purified smb vaccine. in a randomized, controlled, three-arm trial of gkc vaccine in which vaccinated subjects received three primary doses and a booster at year, hfrs cases were observed in the age-, sex-, and residence-matched controls, and cases in the , unvaccinated subjects of similar age ( to years), compared with none in vaccinees during months of follow-up, for a protective efficacy of % ( % lower confidence limit of . %, p = . , cumulative binomial probability). efficacy of the three primary doses alone was shown in the year between administration of the three primary dose series and the booster dose: with zero cases in the vaccinated, and nine and cases in the unvaccinated and control groups respectively. among cases in the control and unvaccinated groups, were caused by htn virus, were caused by seo virus, and four by a virus of indeterminate serotype. thus, the monovalent gkc-derived htn virus vaccine was protective not only against the homologous virus, but also cross-protective against seo virus. no vaccine-related serious adverse event was reported during the trial, and mild local and systematic reactions were reported in . % of vaccinees. the efficacies of the phk vaccine and the purified smb vaccine were similar: in nonrandomized trials, one hfrs case was found in , recipients of phk vaccine, compared with in , unvaccinated subjects, a reduction of . %; for the purified smb vaccine, the rates were . per , ( / , ) versus . per , ( / , ) for vaccinees and unvaccinated subjects, respectively, a reduction of . %. the observed reductions were maintained through years of follow-up. nonsevere reactions were found in . % of phk vaccine recipients and in . % of smb vaccine recipients. , bivalent htn and seo gkc-and phk-derived vaccines were developed and improved by purification procedures through gradient density ultracentrifugation or chromatography to be more immunogenic and less reactogenic. the purified bivalent gkc vaccine induced neutralizing antibody seroconversion against htn virus and seo viruses in . % ( / ) and . % ( / ) of volunteers, respectively, after two doses with an interval of days, and . % ( / ) and . % ( / ), respectively, after a booster dose at months. only mild reactions were observed; local reactions in . % ( / ) and systemic reactions in . % ( / ) of the vaccinees. the purified bivalent phk vaccine induced neutralizing antibody seroconversion against htn virus and seo virus in . % ( / ) and . % ( / ) of subjects, respectively, after two doses separated by days, and . % ( / ) and . % ( / ), respectively, after a booster dose at months. no systemic reaction was found among vaccinees and mild local reactions were observed in two ( . %). the purified, bivalent gkc vaccine was tested for protective efficacy in a nonrandomized trial among , subjects, to years of age; , persons received the two primary doses with an interval of days and a booster dose at months; , persons were unvaccinated. the two groups were similar in age distribution. during years of follow-up, hfrs cases were found in , person-years among the unvaccinated, a rate of . per , , compared with none in the vaccinated , person-years, a reduction of %. several manufacturers have adapted their processes from primary gerbil or hamster cells to continuous vero cells. the purified, bivalent vero cell-derived vaccine administered in two doses separated by days, induced neutralizing antibody against htn virus and seo viruses in . % ( / ) and . % ( / ) adult volunteers, respectively. mild systemic reactions were observed in . % ( / ) and mild local reactions in . % ( / ) of vaccine recipients. the immunogenicity and safety profiles of the vero cell-derived, purified bivalent vaccine were similar in children and older adults. based on the above data, a schedule of two primary doses with an interval of days, plus a booster at months, has been recommended for the purified bivalent gkc-, phk-, and vero-cell-derived vaccines. a postlicensure, retrospective study was conducted to measure the long-term effectiveness of the gkc vaccine among , adults to years of age, in villages located in a hyperendemic area of shaanxi province. hfrs incidence rates were compared between the vaccinated and the unvaccinated adults: . % ( / ) versus . % ( / ), respectively, for the first years after vaccination; . % ( / ) versus . % ( / ) in years to ; . % ( / ) versus . % ( / ) for years to ; and . % ( / ) versus . % ( / ) at to years. the vaccine's effectiveness was thus estimated at . %, . %, . %, and . %, respectively, for the four study periods. the effectiveness was underestimated because the year of onset of hfrs was unknown for cases, all of whom belonged to the unvaccinated group and were not included for analysis. the overall hfrs attack rate was . % ( / ) in the vaccinees and . % ( / ) in the unvaccinated subjects, a reduction of . %. a long-term study of the monovalent phk-derived seo virus vaccine also was conducted among adults to years old in a seo virus-predominating area, from through . only three primary doses were given at , , and days without a booster. seven hfrs cases were found in , , subjects in the vaccine group, a rate of . per , , and cases were found in , , controls, a rate of . per , , with an overall reduction of . % ( % ci, . % to . %) during the years of the study. the vaccine's effectiveness was estimated at % for the first year, . % for the second year, and . % for the th year. the rate reductions in other years were approximately %. a smb-derived htn virus vaccine also was developed in the republic of korea and is available for at-risk individuals. the incidence of hfrs in china and korea has declined in the last years with the introduction of vaccination and probably, more importantly, because of urbanization, rural economic development leading to improved (cement) houses, and grain harvesting and storage practices, resulting in reduced exposures to the rodent reservoir. this trend has been most evident in rapidly developing areas of southeastern china and likely will continue in other regions, leading to a diminution of disease incidence and, potentially, discontinuation of routine vaccination in endemic provinces. see table . . two similar live attenuated hepatitis a vaccines, based on the h and la- strains, and measles vaccines, based on the shanghai s- and changchun- strains, have been licensed in china and are used domestically and exported. the national institute of hygiene and epidemiology in vietnam developed an oral bivalent o -o killed whole-cell cholera vaccine that now is produced and distributed by vabiotech, company for vaccine and biological production no. , in hanoi; another oral bivalent o -o vaccine based on the vabiotec vaccine but with improved production design is produced in india by shantha (sanofi, france). both vaccines are used domestically and also exported. similarly, live rotavirus vaccines based on local strains have been developed in india and china for local use. ev-a and related enteroviruses have emerged in major seasonal epidemics in asia and australia, leading to millions of cases and extensive social disruption as daycares and schools are closed. the extent and impact of seasonal outbreaks stimulated vaccine development in china, taiwan, malaysia, singapore, and japan, with government prioritization and support in some countries, analogous to mechanisms that facilitated pandemic influenza vaccine development. an escherichia coli-expressed capsid peptide virus-like particle hepatitis e vaccine, approved by the china food and drug administration, is the first novel recombinant vaccine developed and licensed in asia. its potential use in africa, south asia and, possibly, even in developed countries in immunocompromised or other risk groups could be envisioned. implicit in the region's progress toward novel vaccine development is a maturing capacity to conduct clinical trials and improvements toward more robust regulatory processes and capacity, including pharmacovigilance systems. in addition, multinational companies increasingly have turned to countries in asia to conduct clinical trials because of lower costs and more streamlined regulatory approvals of clinical trial applications. international contract research organizations operate in many countries, and a growing local infrastructure to conduct clinical trials in compliance with the international conference on harmonization of technical requirements for registration of pharmaceuticals for human use and good clinical practices standards will improve clinical research conducted in the region. unlike europe, asian countries are not unified in a central regulatory approval process. nor is there a regional public health presence as in latin america, where the pan american health organization (paho) leads regional vaccination programs and also provides central purchasing of certain qualified vaccines. however, the -nation association of southeast asian nations (asean; includes brunei-darussalam, cambodia, indonesia, lao pdr, malaysia, myanmar, philippines, singapore, thailand, and vietnam) in initiated efforts for a subregional regulatory harmonization scheme to reduce differences in technical requirements and regulatory procedures for pharmaceuticals. a harmonization initiative, under auspices of a pharmaceutical product working group, aimed to remove barriers to regional commerce and to eliminate technical barriers to trade without compromising product quality, efficacy, and safety. eventually, a subregional central or mutual-recognition procedure similar to that of the european union could be envisioned. importantly, local clinical trials are not required for registration under abbreviated pathways specified by the asean common technical dossier if the vaccine was approved and licensed by a benchmark regulatory agency, resulting in a certificate of pharmaceutical product. by contrast, the national regulatory authorities of china, india, japan, korea, and taiwan have required local clinical trials before or after registration, and in other countries, while data in local populations may not be required for registration, those data are important in deliberations on a vaccine's inclusion in the national schedule. for dengue, a disease of special public health urgency regionally, the global debut of candidate vaccines in the region is being considered, with individual country vaccine registrations ahead of approval by a benchmark agency and provision of a certificate of pharmaceutical product. the text continued on p. various countries in the region have had the effect of delaying the registration of proven vaccines that otherwise could have prevented significant morbidity and mortality with more timely introductions. descriptions of individual regulatory requirements for clinical trial applications and new product approvals are beyond the scope of this chapter; see the previous edition for a more detailed introduction. governments have had a greater role in vaccine manufacturing in the region than elsewhere, although devolution toward privatized or state-owned enterprises (i.e., government-owned corporations) has occurred (e.g., commonwealth serum laboratories in australia was privatized, and the six major government vaccine institutes in china now operate as a state-owned enterprise, china national biotech group; see table . ). although a growing number of private manufacturers have emerged, especially in china and india, in other countries, national and local government manufacturers continue to be important sources of certain vaccines and biologicals for domestic needs (e.g., the government pharmaceutical office in thailand, research institute for tropical medicine in the philippines, biofarma in indonesia, the national institute of hygiene and epidemiology in vietnam, and the central research institute and local government institutes in india). these and other facilities also fill and distribute bulk vaccines supplied by international manufacturers. several private and state-owned enterprise manufacturers in the region are members of the dcvmn, a consortium that seeks to identify and develop solutions to common challenges faced by manufacturers in developing countries. , , , a number of manufacturers (including in five asia-pacific countries) operate under practices and procedures that have prequalified them to produce certain vaccines for unicef, paho, and gavi purchases (e.g., pentavalent dtp combinations, oral polio vaccine, inactivated polio vaccine, hepb, rabies, influenza, oral cholera, and measles-containing vaccines) or that allow them to export vaccine to other countries in the region. a reliable supply of inexpensive diphtheria and tetanus toxoids combined with whole-cell pertussis (dtwp)-hib-hepb combination vaccines, made possible largely by indian and korean manufacturers, has facilitated the introduction of hib antigen into schedules of economically disadvantaged countries that otherwise would not have adopted the monovalent vaccine. similarly, provision of measles and measles containing vaccine by indian manufacturers was key to the elimination of that disease in latin america and the current state of polio elimination could not have been achieved without supplies from asian regional manufacturers. the provision of oral cholera vaccine for outbreak control in haiti, pakistan and other countries is an important example of the increasing ability of and global dependence on these manufacturers. who prequalification requires that the manufacturers and plants not only must satisfy who good manufacturing practices inspections, but, in addition, that national notifications of adverse events following immunization are captured and analyzed satisfactorily. this last requirement has been the principal impediment to prequalification of products from some countries and prequalification aided by who blueprint and other vaccine safety-related guidelines have facilitated the improvement of vaccine-related pharmacovigilance in the region. in china, the state-owned china national biotec group is the dominant supplier of vaccines in the country, providing % of doses used in the public program and % taken up initiative is a collaboration among the nongovernmental organizations, the dengue vaccine initiative, and the world health organization (who) developing countries vaccine regulatory network (dcvrn). the who through the dcvrn has been actively working toward harmonizing procedures in affiliated countries, including china, india, and indonesia, to bring those regulators under the who prequalification umbrella and to facilitate approval and supply of their products for gavi and united nations children's fund (unicef). the requirement of some national regulatory authorities for clinical data in local populations is based on a concern that racial, ethnic, or environmental differences could affect responses of the local population, both immunologically and in their risk for adverse events. genetically based differences in drug pharmacokinetics and pharmacodynamics, as well as disease risk, increasingly have been recognized, including immune responses to vaccines. studies of antibody responses to pneumococcal conjugate vaccines in asia, for example, have found higher prevaccination and postvaccination antibody titers among philippine and taiwanese infants compared with european or historical control subjects, and in korea, a considerably higher proportion of subjects were seropositive to meningococcal serogroup w polysaccharide at baseline than in the united states. [ ] [ ] [ ] while the basis for these differences may be an earlier exposure in life to cognate or crossreacting antigens (e.g., because of regional differences in host microbiomes), genetically restricted responses, as have been observed with hepb, measles, vaccinia, rubella, hib, and other antigens, or, in the case of oral rotavirus vaccine, in genetically determined viral attachment or receptor binding molecules, have been described. [ ] [ ] [ ] [ ] from the perspective of adverse events following immunization, the example of narcolepsy occurring in some recipients of an adjuvanted pandemic h n vaccine illustrates the role of genetic background as a cofactor in risk. in many examples, regulatory systems and processes in the region have had the effect of markedly slowing or effectively blocking the introduction of novel vaccines developed externally. in china, the introduction of an internationally registered and otherwise widely used product nevertheless necessitates recapitulating the entire clinical development program in china, including phase i studies, despite an abundance of previously scrutinized evidence. this requirement introduces a delay of a decade or more for registration of internationally developed, as opposed to domestically developed, vaccines. specifications in national pharmacopeias that deviate from established compendia, for example, exclusion of well-accepted excipients or methods, also have seriously impeded or prevented registration of foreign products or, when imposed with a revision of the pharmacopeia, have led to withdrawal of a previously registered product. clinical trial processes also have hindered local introduction of established or novel products (e.g., a indian supreme court ordered suspension of ongoing clinical trials and reexamination of previously approved trials was followed by a wholesale revision of clinical trial guidelines, leading to a temporary cessation of all industry-sponsored clinical trial activity). the potential inclusion of video recording of the informed consent process, newer insurance requirements and further proposed but unclear amendments to the drug and cosmetics act that could impose criminal penalties against trial investigators for poorly defined violations may further limit trial activity. china and indonesia place severe restrictions on the exportation of clinical samples from study subjects, thereby requiring that validated laboratories and procedures are established locally, adding a barrier that has led to delays of or avoidance of clinical studies in those countries. whether resulting from inexperience, a dearth of trained personnel, trade protection, or other reasons, administrative mechanisms in in most countries in the region, public health authorities now draw on external advisors to help formulate national vaccine recommendations in national immunization technical advisory groups (nitag), resulting, in part, from activities of the supporting independent immunization and vaccine advisory committees initiative (at the agence de médecine préventive). [ ] [ ] [ ] [ ] the advisory committee on immunization practices (acip) in taiwan and korea, expert committee on immunization in singapore, chinese expert committee on epi, hong kong scientific committee on vaccine preventable diseases, immunization committee of the indonesian pediatric society, national technical advisory group for immunization in india, and the australian technical advisory group on immunization are examples of such medical advisory groups. in china, vaccine recommendations are made through the national centers for disease control based on recommendations of the chinese expert committee on epi under the ministry of health and family welfare; however, provincial or local centers for disease control may issue independent recommendations for specific vaccines or modify the national recommendation for routine vaccines (see tables . the issues considered by asian nitags in formulating vaccine recommendations parallel those of other nitags, focusing on medical need, vaccine safety and efficacy, national resources, as well as implementation issues, including supply, cold-chain, fit within the national schedule, vaccine presentation, etc. health economic analyses are considered in the deliberation of some committees or are provided by an independent body (e.g., the health intervention and technology assessment program in thailand); although, in general, the use of health technology assessments in the region lag behind the united states and united kingdom. in some cases, industry sponsors, in providing such analyses to nitags in their justifications to include new vaccines into national programs, have played a role in introducing cost-to-benefit analyses to the recommendation process. in indonesia and malaysia, the halal status of vaccines is an important factor in public acceptance of a product and also is a consideration in the vaccine recommendation process, although there is movement to remove this consideration from debate. in certain asian countries, as well as in latin america, the approval process to include a new vaccine into the national program is used to leverage multinational companies to foster local manufacturing expertise. in brazil, technology transfer of the vaccine production process is required in turn for the vaccine's inclusion into the national schedule while, in indonesia, all epi vaccines are locally produced by biofarma, and no new vaccine has been introduced into the national schedule unless it was produced locally. technology transfer of some element of the manufacturing process also is a factor in introduction of new vaccines to thailand and malaysia. such requirements may be tested as costly vaccines manufactured by more complex technologies are introduced to the region. the recommendation process in japan illustrates how, even after registration, organizational and administrative processes can result in a lengthy interval before a new vaccine is introduced to the national schedule. although, since , japan has recovered from a "vaccine gap"-the self-acknowledged interval during which antigens such as hib and pneumococcal conjugate, rotavirus, hpv, inactivated polio and various combination vaccines were not introduced into japan despite their widespread use in other developed countries-adoption of new vaccines into the national immunization program after their registration still lags several years. a number of sequential approvals lengthens the process: the immunization policy and vaccination committee provides an initial recommendation whether the newly registered vaccine should privately. the group comprises manufacturing sites, which produce some products, including the first who prequalified vaccine produced in china (sa - - je vaccine). other private companies compete principally to provide vaccines for out-of-pocket sales at local centers for disease control and prevention and hospitals. within the asean community, comprised principally of low-and middle-income countries, regional vaccine security has been a focus of discussion, reflected in the establishment of the asean-network for drug, diagnostics and vaccines innovation that focuses on a broad agenda of health technology development and collaborations on vaccine manufacturing and plans for regional vaccine purchasing-similar to paho's revolving fund. similarly, the eight-nation south asian association for regional cooperation includes biotechnology in its agenda for cooperative research. a goal to achieve self-reliance in vaccine supply also has been articulated in korea, in its horizon-setting. to a growing extent, multinational companies are acquiring or partnering with local companies in the region, with the result that manufacturing standards and their regulation should improve toward meeting international specifications. table . lists the region's principal vaccine manufacturers and their licensed products. the list is not intended to be comprehensive, as the sometimes rapid emergence or disappearance of pharmaceutical and vaccine companies in china and elsewhere is difficult to track. vaccines that are manufactured elsewhere and refilled and distributed by local manufacturers are not listed. countries in the region can be divided broadly into countries with a single national schedule and countries in which a basic schedule of free epi vaccines is supplemented by recommendations of a professional organization (such as the national pediatric society) for additional antigens that are paid for outof-pocket. countries in the first group include, on the one hand, mainly developing countries offering a basic epi schedule and, on the other, countries like australia, new zealand, and taiwan that provide a universal vaccination program that includes an array of antigens or combination vaccines paralleling those of european and u.s. schedules. the continued introduction of new and frequently expensive vaccines is an ongoing tension for vaccine recommending and funding entities that must weigh the relative value of such innovations against other preventive and therapeutic health expenditures. even for low-middle-income countries in the region, the total per capita expenditure for all healthcare may be less than the cost of a full course of a novel vaccine! on the other hand, national schedules in the region can be as comprehensive as to include the hpv vaccine (australia) and influenza and varicella vaccines (e.g., korea, taiwan). at the same time, hib vaccine still is not recommended in some jurisdictions with high per capita income (hong kong, singapore). to some degree, the seemingly paradoxical recommendations of relatively high-income countries in the region reflect different social expectations of personal responsibility in healthcare purchases (see subsequent text). as shown in table . , some national schedules provide optional recommendations for some antigens; in many countries where government tenders choose specific manufacturer products, specific combinations are recommended in the national schedule. in addition, for some antigens, provincial-specific recommendations address regional differences in risk (e.g., for routine group ac meningococcal vaccine in china; for je vaccine in sarawak, malaysia, and for the torres straits, australia; and for rabies vaccine [preexposure] in areas of the philippines). be classified as either "routine" or "voluntary," based on available data; the technical recommendation is considered by the tuberculosis & infectious diseases control division which makes the administrative decision for the vaccine's inclusion in the national schedule; however, that decision requires additional legislative approval whether the disease (category a or b) qualifies for full or partial vaccine funding (up to circa %), respectively. the recommendation process is even lengthier than appearances suggest, as the immunization policy and vaccination committee does not convene a deliberative vaccine working group until after the product is registered, unlike the parallel activities of the u.s. acip and food and drug administration. only then does the committee assemble a dossier (fact sheet) that establishes the epidemiology of the disease and its local burden; if insufficient data are available, de novo studies might be required to establish need. the overall interval between vaccine approval and issuance of a recommendation typically is years. other asian countries have similar or even lengthier intervals between vaccine registration and full epi implementation. in thailand, for example, after a preliminary nitag recommendation, a new vaccine is implemented in a pilot program to establish effectiveness and to collect additional safety experience. such a program may be gradually extended to other localities over a period of as long as a decade before the antigen is provided nationally. for diseases with regional differences in disease burden, high-risk provinces may be covered first (e.g., je vaccine initially was introduced in thailand to eight high-incidence provinces and progressively, from to , to all provinces, while local production was established and expanded). for new, often costly vaccines, phased introduction provides a mechanism to accommodate their full epi coverage costs over time. in the interim, local governments of wealthier provinces or municipalities have issued their own recommendations for vaccines to be reimbursed (e.g., shanghai provides pneumococcal polysaccharide vaccine free of cost to older adults and bangkok established a school-based hpv vaccination program, while neither vaccine is included in respective national schedules). innovative financing mechanisms have played an important role in the introduction of vaccines to low-income countries, and their extension to graduating gavi will enable more rapid adoption of new vaccines in those countries. at the same time, tiered pricing, negotiated between sponsors, local government and other entities will aid middle income countries to accelerate vaccine adoption, as exemplified by introductions of pcv and rotavirus vaccines. during the interval between a vaccine's registration and its inclusion in the national schedule, after which it is available without cost, out-of-pocket sales still may result in considerable uptake. while rotavirus vaccine is still considered a voluntary vaccine in japan, coverage among infants is estimated to be approximately %. in korea, although almost all pediatric vaccines are self-paid by parents, vaccine coverage for antigens such as hib and pneumococcal conjugate vaccine rapidly reached coverage rates of approximately % that, with herd effects, led to disappearance of the respective diseases as quickly as in other countries. although in japan, the "voluntary" vaccine recommendation emanates from a government committee, in other countries, academic societies play the principal role in recommending vaccines that are not included in the epi schedule. the malaysian pediatric association, the pediatric society of thailand, and the philippines foundation for vaccination not only advise their respective ministries and nitags in formulating national recommendations, but also promulgate recommended schedules of administration for other approved but not epi-covered antigens, emulating in large part or entirely from u.s., australian, or european schedules. vaccines are delivered in varying proportions through public or private channels, depending mainly on local income levels and accessibility to private practitioners. in general, vaccines on national schedules are available at no cost in primary health centers or their equivalent (e.g., puskesmas in indonesia; polyclinics or government hospital clinics in singapore, malaysia, and thailand; village and county level centers for disease control in china; village communes in vietnam; public health centers and clinics in india and japan; and at general practitioner offices in japan, and australia). as vaccines generally are available free in public clinics, even in affluent countries, families may obtain them in government clinics or hospitals (e.g., in singapore, ≈ % of families obtain vaccines through the government system of polyclinics and hospitals). however, to avoid long waiting times and rotating staff at public clinics, many families opt to obtain these otherwise free vaccines privately and to pay out-of-pocket at pediatric, general practitioner, or other private clinics. in addition, as newer vaccines may be delayed in their introduction to the national reimbursement scheme, it is common for parents to pay voluntarily for these vaccines (see earlier). as might be expected from the distribution of income, the proportion of children vaccinated in government primary health centers is higher in rural areas. overall, approximately % of children in thailand and % in malaysia are vaccinated through public channels. in china, all vaccinations are under control of centers for disease control and prevention; therefore, nearly all chinese children receive free epi vaccines, as well as payable optional vaccines (e.g., hib, pneumococcal conjugate vaccines, varicella, rotavirus, and others) at public clinics. fig. . summarizes the coverage for epi vaccines for selected countries. supplementary immunization activities have played a critical role in the elimination of polio from the who southeast asian region that was achieved in , and in ongoing efforts to eliminate measles and congenital rubella syndrome. routine and supplementary immunization activities tetanus vaccinations have eliminated maternal and neonatal tetanus in all but four countries in the region: cambodia, indonesia, papua new guinea, and pakistan. economic growth and development in asia and secular trends in population structure and the evolution of healthcare systems are forces that inevitably will change various aspects of immunization in the region, if in as-yet unforeseeable ways. , the population of asia, as in other regions, is aging and shifting toward a structure with a larger proportion of adults and elderly persons. between and , the birth cohort of asia will decrease slightly from . to . million, and the population of children to years old will hold nearly constant while the number and proportion of adults from to years will increase dramatically, and the number of people older than years of age will nearly double, from . to . million. a demographic crossover point with more adults + years of age than children younger than years of age was reached in europe in the s, and will occur within another generation in asia (fig. . ) . with the exception of almost universal epi programs of tetanus toxoid vaccination of pregnant women, adult vaccination has been viewed mainly in the context of travel, as in group a meningococcal vaccine for the hajj, and in tropical asia, influenza vaccine alliance for vaccines and immunization-eligible countries (shaded) have similar coverage rates of basic vaccines as countries at higher levels of economic development, illustrating the success of expanded programme on immunization. hepatitis a, interestingly, is now principally a risk in the cohort of young adults who were raised in an era of economic development and improved sanitation and who therefore lack natural immunity but were born before routine childhood vaccination was implemented. a catch-up program to address this epidemiological shift has been recognized by adult vaccination recommendations in some countries (see table . ). in china, adult measles vaccination is under discussion, as more than , cases have occurred annually in recent years, in equal proportion in adults older than years and in infants who had not received their first vaccine dose. growing awareness of adult vaccination is reflected in an increasing number of countries with adult vaccination recommendations (see table . ). two other population trends that will influence the demand for vaccines and channels for their delivery are urbanization and income disparity. the urban-dwelling population in asia is projected to increase by almost a billion persons between and , from . billion to . billion, while the rural population will decline only slightly. urban crowding is likely to affect the transmission patterns of certain person-to-person transmitted diseases and even of infections acquired from environmental sources. dengue, for example, is transmitted by mosquito vectors that are more prevalent in urban environments; the already great need for a dengue vaccine will almost certainly increase with the growth of urban centers. while the growing size and number of large cities may increase transmission of certain infections, delivery of vaccine and of healthcare in general is better organized in cities than in rural areas. specific interventions are needed to ensure that the existing disparity in access to healthcare between urban and rural dwellers does not widen. associated with urbanization is the increasing income gap in many countries that, in the health arena, has translated into a two-tiered system of healthcare, including preventive medicine. while vaccines are regarded by many as a public good to be provided as a government service, as mentioned, access to the increasing number of new vaccines is likely to be stratified by income level and ability to pay, as governments must choose among increasingly costly vaccines and other health interventions. as shown in table . , pediatric societies in a number of countries promulgate recommendations emulating those of the u.s. acip, and these schedules, aimed at practitioners serving private-paying families, may diverge increasingly from the national epi schedules benefiting the majority of children in those countries. how the public and governments will respond to an increasing disparity of what has been perceived as a basic medical service remains to be seen. in coming years, more novel vaccines are likely to be developed in asia or licensed first in asia for a regional, developing world, or international market. governments and asean have expressed increased interest in providing for national and regional vaccine security. the collaboration of industry sponsors with nongovernmental organizations and government in public private partnerships for new product development has been highlighted by the successful introduction of vaccines and drugs for several neglected diseases, for which the dcvmn view a responsibility. for example, the japan international cooperation agency and kitasato daiichi sankyo provided technical assistance to establish domestic measlesrubella vaccine production in vietnam's public corporation, center for research and production of vaccines and biologicals, polyvac. at the same time, the entry of nongovernmental organizations as actual sponsors of novel vaccine development for certain target diseases introduces competition with dcvmn manufacturers and multinational companies that might also consider similar development programs. asian academic institutions and companies possess elements the crossover point when the population of adults older than years of age exceeded the population of children younger than years of age was crossed in europe around ; that crossover is projected to occur in asia around , within a generation from now. for travelers to temperate locations. however, the severe acute respiratory syndrome and pandemic h n outbreaks and the regional threat of h n influenza have focused attention on routine seasonal influenza vaccination for the first time in many countries, beginning with elderly populations, and the role of children in influenza transmission is being recognized while it is rediscovered in japan. as a result of high pediatric vaccination coverage in developed countries in the region, je has become almost exclusively a disease of adults older than years of age, reflecting the intrinsic biological susceptibility of older adults to neurotropic flaviviruses and suggesting a of the scientific and technical expertise needed to develop vaccines for current and emergent needs and, seemingly, the will to establish themselves on the global stage and contribute to their development. regional institutions responded rapidly to threats of middle east respiratory syndrome virus and ebola virus with candidate vaccine development even when transmission was geographically remote. further participation of regional institutions in global responses in the future is likely. trends toward increasing local development and manufacturing in the region and the accompanying need to strengthen respective regulatory agencies have been recognized by the who and local national regulatory authorities. revising and harmonizing guidelines and procedures to international standards and enforcing procedures in a consistent and predictable manner will improve the timely regional introduction of vaccines developed internationally. as important, compliance with international standards will be required of regional manufacturers hoping to license locally developed vaccines more broadly. indian and chinese manufacturers currently export a limited number of vaccines, mainly regionally and to african and latin american countries, but their horizons undoubtedly will expand. in the six-component framework of product development capability-manufacturing; national and international distribution systems; private and public r&d capabilities; intellectual property system; and drug and vaccine regulation-regional manufacturers are at different stages of maturation. in its ascendance to an advanced country producing complex biologicals as well as other high technology products, korea followed a path that might be emulated by others in the region, highlighted by its arrival at a stage with a national system of innovation in science and technology, linking government, universities and industry, a strong regulatory system and observation of intellectual property rights, including adherence to trade-related aspects of intellectual property rights (trips agreement). a specific area of regulatory control needing particular attention is the strengthening of national control laboratories. many countries lack the laboratory capacity to test samples for lot release, and because manufacturing and testing technologies change rapidly, keeping up with new procedures and purchasing needed equipment are ongoing challenges. continuous support also is needed to produce working quantities of reference standards, validation of new assays, staff training, and proficiency testing. as resources are unavailable in many countries to establish and maintain a fully functioning national control laboratory, a regional network has been proposed as an approach to share expertise and to divide workload, while at the same time standardizing methods and criteria. field surveillance of adverse events following immunization is another area requiring strengthening. investigations of adjuvanted h n and h n pandemic and prepandemic vaccines administered in korea and taiwan, respectively, illustrated the interest in and epidemiological capacity of local investigators but also the limitations of existing systems and databases. japan is establishing a database of clinical encounters that if linked to immunization records could be used as a future adverse events surveillance system. regulatory oversight of clinical trials and human subjects protection are other areas that are under growing pressure for improvement. multinational companies have increased the number of clinical trials in asian countries to reduce costs and to obtain local registration of products. their activities serve an important role in strengthening local compliance with good clinical practices, as many groups conducting trials in the region have limited experience with these precepts and procedures. countries in the region have an interest to establish and enforce clear guidelines, not only as hosts to an increasing number of trials but also because their manufacturers, as future sponsors of new products, will be accountable internationally to uphold recognized standards. references for this chapter are available at expertconsult.com. immunization in the asia-pacific region .e references . country hub. gavi, the vaccine alliance role of vaccine manufacturers in developing countries towards global healthcare by providing quality vaccines at affordable prices asia's ascent-global trends in biomedical r&d expenditures emergence of biopharmaceutical innovators in china, india, brazil and south africa as global competitors and collaborators developing countries can contribute to global health innovation the indian and chinese health biotechnology industries: potential champions of global health? chinese health biotech and the biollion-patient market indian vaccine innovation: the case of shantha 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manner genetic polymorphisms of cxcr and cxcl are associated with non-responsiveness to the hepatitis b vaccine india's proposed amendments to the drug and cosmetics act: compensation for injuries to clinical trial participants and the criminalization of clinical research. life sciences law and industry report. lslr , / / bloomberg bna vaccines, our shared responsibility immunization policy development in thailand: the role of the advisory committee on immunization practice an overview of the national immunization policy making process: the role of the korea expert committee on immunization practices progress in the establishment and strengthening of national immunization technical advisory groups: analysis from the who/unicef joint reporting form, data for recent progress and concerns regarding the japanese immunization program: addressing the "vaccine gap who-unicef estimates of dtp coverage world health organization department of economic and social affairs population division vaccine preventable diseases surveillance program of japan. japanese encephalitis: surveillance and elimination effort in japan from to seroprevalence of hepatitis a and associated socioeconomic factors in young healthy korean adults urbanization and geographic expansion of zoonotic arboviral diseases: mechanisms and potential strategies for prevention development of health biotechnology in developing countries: can private-sector players be the prime movers? we are grateful for the help of john o'shea, jason humphries, takashi sugimoto, and hyun-ah chang. key: cord- - tpj vb authors: dass hazarika, rashna; deka, nayan mani; khyriem, a. b.; lyngdoh, w. v.; barman, himesh; duwarah, sourabh gohain; jain, pankaj; borthakur, dibakar title: invasive meningococcal infection: analysis of cases from a tertiary care centre in north east india date: - - journal: indian j pediatr doi: . /s - - - sha: doc_id: cord_uid: tpj vb objectives: to report an outbreak of invasive meningococcal disease from meghalaya, in the north east india, from january through june . methods: retrospective review of case sheets was done. one hundred ten patients with invasive meningococcal disease were included for the study. results: of the total patients, . % were boys and . % were girls (boy to girl ratio = . : ). the average age of presentation was . ± . y. meningococcal meningitis was seen in . % of cases, meningococcemia in % and . % had both. fever was the most common manifestation ( %) followed by meningeal signs ( . %), headache ( . %), vomiting ( . %), shock ( . %), low glasgow coma scale (gcs) ( . %), purpura and rashes ( . %), seizures ( . %), abdominal symptoms ( . %), irritability and excessive crying ( . %) and bulging anterior fontanalle ( %) in those below mo of age. raised intracranial pressure (icp) was the most common complication ( . %) followed by coagulopathy ( . %), hepatopathy ( %), herpes labialis ( . %), syndrome of inappropriate adh secretion (siadh) ( %), pneumonia ( %), arthritis ( %), purpura fulminans, respiratory failure, sixth nerve palsy and diabetes insipidus in . % each, subdural empyema, optic neuritis, ards and arf in . % each, cerebral salt wasting syndrome, third nerve palsy, cerebritis and hearing impairment in . % each. culture was positive in . %. patients were treated initially with ceftriaxone and dexamethasone but later on with chloramphenicol due to clinical drug resistance. mortality was . %. conclusions: this is the first epidemic report of invasive meningococcal disease from the north east india. chloramphenicol acts well in areas with penicillin or cephalosporin resistance. mortality reduces significantly with early diagnosis and prompt intervention. meningococcal disease is a global problem. it has a rapid onset with varied presentations and wide regional variation in disease pattern. the endemic disease is rare but epidemic form occurs commonly in many regions of the world especially described in the 'meningitis belt' in sub-saharan africa, parts of asia and also in india. meningococcal disease mostly affects children in the school going age and adults working in close contact such as in military barracks. the disease requires early and prompt antibiotic treatment and supportive therapy. the outcome of the disease depends on the time required to seek medical help i.e., the 'house to hospital time' and also on the rapidity of administration of the first antibiotic dose i.e., the 'door to needle time'. meghalaya situated at an altitude of , m above sea level has a predominantly rural tribal population. an epidemic of meningococcal disease occurred in this region during [ ] [ ] . the present study documents the occurrence of the disease in this part of the world, and also highlights the various clinical manifestations, laboratory findings and management outcome. this descriptive retrospective study over the period of the epidemic, january through june is being reported from the department of pediatric disciplines, nei-grihms, shillong. one hundred ten children diagnosed as either 'meningococcemia' or 'meningococcal meningitis' or 'meningococcemia with meningitis' during the study period were identified from discharge summaries and inpatient records. their charts were retrieved and reviewed thoroughly. at admission, blood and cerebrospinal fluid (csf) were sent to the laboratory immediately for culture and sensitivity testing, cytology and gram staining. complete blood count (cbc) and peripheral blood smear for malarial parasite, random blood sugar (rbs), liver function test (lft), coagulation profile, renal function test (rft), serum electrolytes and chest x-ray (cxr) were done on the day of admission in all patients and repeated periodically if necessary. mri brain was done when clinically indicated. the cases of meningococcal meningitis and meningococcemia in the present case series were labelled as probable meningococcal meningitis, confirmed meningococcal meningitis, probable meningococcaemia and confirmed meningococcaemia as per standard guidelines [ ] . patients were treated for the first mo with injection ceftriaxone but later with parenteral chloramphenicol due to observation of clinical drug resistance in the form of delayed or no response to ceftriaxone in - h. antibiotics were administered for a minimum of d in all patients along with supportive care and monitoring. injection dexamethasone was used in all cases with meningitis for d. shock was treated with normal saline and inotropes (dopamine and dobutamine), whenever indicated and hydrocortisone. a total of children were diagnosed as having either 'meningococcemia' or 'meningococcal meningitis' or 'meningococcemia with meningitis'. the demographic profile and clinical presentations are outlined in table . among these cases, . % were boys and . % were girls (boys:girls . : ). the mean age of presentation was . ± . y ( mo- y). fever was the most common symptom ( %) followed by headache ( . %), vomiting ( . %), altered sensorium ( . %), purpura and rashes ( . %), seizures ( . %), abdominal symptoms ( . %), irritability and excessive crying ( . %). meningeal signs were present in cases ( . %) and bulging anterior fontanalle in out of cases ( %) below the age of mo. shock was seen in cases ( . %) ( compensated and decompensated). the average number of isotonic saline boluses required was ml/kg (range: ml/kg to ml/kg). fifteen cases ( . %) required inotropic support and hydrocortisone singly or in combination. the average duration of inotropic support was - h. the laboratory investigations of all the cases are summarized in table . culture (either blood or csf) was positive in cases ( . %) (csf: , blood: ). in three cases ( . %), growth was seen both in the blood and csf. gram negative diplococci in csf was seen in cases; of which cases were culture negative. all cases were identified as serogroup a and were susceptible to ceftriaxone and chloramphenicol by in-vitro antimicrobial testing. the mean blood leukocyte count was , ± /cumm. the csf cell count ranged from to , /cu mm and hypoglycorrhacia were seen in . % of the cases. ten percent of the cases had deranged lft and . % had coagulopathy. majority of the cases were seen in the months of december and january to march (fig. ) . sixty nine percent of the cases were seen in children above y of age (fig. ) . meningococcal meningitis and meningococcemia were diagnosed in cases ( . %) and cases ( %) respectively with a corresponding mortality of . % ( / ) and . % ( / ). twenty children ( . %) presented with both meningococcemia and meningitis with death. there was no difference in mortality or morbidity between the culture positive or culture negative cases. of the children with meningococcal meningitis, had probable meningitis while were confirmed. of the children with meningococcemia, had probable meningococcemia while were confirmed. of the children with meningococcemia and meningitis, were probable while were confirmed (fig. ) . the important complications have been summarized in table . raised icp was the most common ( . %) and was diagnosed clinically by the presence of bulging anterior fontanelle, bradycardia/tachycardia, papilledema and hypertension. herpes labialis was observed in . % of cases. three important metabolic complications of meningococcal infection observed in the present case series were siadh ( cases, . %), diabetes insipidus ( cases, . %) and cerebral salt wasting syndrome ( case, . %). all the cases with diabetes insipidus and cerebral salt wasting syndrome expired. meningococcal purpura fulminans were seen in cases ( . %) whereas cases ( . %) developed arthritis, and cases each had subdural empyema and optic neuritis. mortality was . %. epidemic meningococcal disease was first described by vieusseaux in from switzerland [ ] . meningococcal infections are commonly found in developing countries such as in the african meningitis belt and occasionally in developed countries like the united states. serogroup a is more prevalent in developing countries whereas, in the developed countries the disease is mostly caused by serogroup b and c [ ] . in india, meningococcal disease is endemic in delhi with sporadic cases reported in the past [ ] . isolated cases of meningococcal meningitis were also reported from several states of india involving haryana, uttar pradesh, rajasthan, sikkim, gujarat, jammu & kashmir, west bengal, chandigarh, kerala and orissa in [ ] . most of these outbreaks have been caused by serogroup a [ ] . n. meningitidis was the dominant pathogen isolated in surat between and [ ] . in early , spurt of cases of neiserria meningococcemia and meningitis due to serogroup a have been reported from delhi and adjoining areas [ ] . no previous reports exist from north east india. approximately % were above y of age. maximum cases reported were below - y of age from usa for endemic disease [ ] . in epidemic outbreaks a shift to higher age occurs [ ] . in sudan, % were above y in a group a -n. meningitidis outbreak [ ] . in ghana however the peak incidence was found in - y old children [ ] . neonatal meningococcal meningitis is rare and there was no case of neonatal meningitis in the present study. meningococcal infection is characteristically fulminant presenting with fever, severe headache, vomiting, neck stiffness, positive meningeal signs, photophobia, drowsiness and confusion. deterioration and death can occur in hours. the disease spectrum usually ranges from meningococcal meningitis to meningococcemia. meningitis may or may not be present with rash. seizures occur in % of cases. meningococcemia is more abrupt presenting with chills, nausea, vomiting, myalgias and the classical purpuric or petechial rash with or without bullae formation. absence of meningitis is a poor prognostic factor. septicaemia was found in % cases. urmila et al. from delhi reported that % children had meningococcal meningitis, % had meningococcemia and % had both with mortality of . %, % and %, respectively [ ] . this is similar to findings in the present study. shock was the presenting symptom in % of the index cases. of these, % had compensated and % had decompensated shock compared to % in other reports [ ] . shock is endotoxin mediated and due to factors such as widespread capillary leak, loss of vasomotor tone and maldistribution of intravascular volume, impaired myocardial function and impaired cellular function. early recognition of shock is crucial for early intervention and improved outcome [ ] . tachycardia may be the only sign present in the early phase of the disease and is enough to mandate fluid resuscitation. circulatory management aims to maintain tissue perfusion and oxygenation. repeated fluid boluses with ml/kg of isotonic saline are to be given initially till shock resolves. in case shock persists after ml/kg of fluid, central venous pressure (cvp) line is inserted and fluid resuscitation continued with addition of dopamine and/or dobutamine. some children require as high as - ml/kg of fluid resuscitation but such patients also require mechanical ventilation. about . % of the index cases required inotropic support either alone or in combination for an average duration of - h. some studies have shown that . % albumin is more useful as a resuscitating fluid [ ] . albumin is routinely used in the uk with significant reduction in mortality in the last y (decrease up to %) in patients with meningococcal disease and albumin use may play a role along with other factors [ ] . the authors do not have any personal experience of using albumin. survival rate reaches % when shock is reversed within min of presentation [ ] . rash was observed in . %, while this sign ranged from . % to % in other studies [ , ] . meningococcal purpura fulminans is a hemorrhagic condition associated with meningococcal septicemia with features of hypotension, disseminated intravascular coagulation (dic), and purpura leading to tissue necrosis and small vessel thrombosis. in the present study, cases ( . %) presented with purpura fulminans and of them died. schaad ub [ ] has described arthritis in % of patients with meningococcal disease. in the present study, . % presented with arthritis involving big joints. arthritis may occur early in the disease due to direct bacterial seeding of the joints or in the sub-acute or convalescent phase of the illness secondary to immune-complex reactions. treatment of bacterial arthritis consists of analgesics, antibiotics and drainage of joint fluid if needed. immune complex reactions are usually treated with non-steroidal anti-inflammatory drugs or steroids. some may require intravenous immunoglobin [ ] . reactivation of latent herpes simplex virus infections (primarily herpes labialis) is common during meningococcal infection as observed in the present study with good response to local acyclovir. coagulopathy is frequent and multifactorial, and was seen in . % of the present cases. mild clotting abnormalities are well tolerated. in severe cases fresh frozen plasma (ffp) is recommended. the authors have used intravenous vitamin k and if required ffp with good results. currently the best treatment for meningococcal related coagulopathy is the optimal management of shock. dodge and swartz [ ] reported seizures in % in the acute stage of the disease, focal cerebral signs in %, and of patients had cranial nerve involvement early in the course of disease. in the present study, . % of the cases presented with seizures in the acute stage and cranial nerve involvement was present in . % cases. siadh was detected in of patients by dodge and swartz [ ] . in the present study, siadh was found in cases ( . %) and was managed with fluid restriction and low dose diuretic (furosemide) therapy. five cases ( . %) had diabetes insipidus (di), requiring aggressive management with hypotonic fluids, vasopressin and mechanical ventilation and one had cerebral salt wasting (csw). all the index patients with di and csw had % mortality. although pollard rb [ ] has reported that deafness has not been a common complication of meningococcal meningitis in the antibiotic era, there was one case with bilateral sensorineural hearing defect in the present study. pneumonia, epiglotitis and otitis media can occur. pneumonia is seen in to % of invasive meningococcal disease cases, particularly with serogroups y and w- [ ] . in the present study, pneumonia was present in . % cases. recovery may be complicated by ards, anuria and multi organ failure. in some cases ards develops within a few hours after admission and in the present study cases each developed ards and arf. in a study from punjab (ludhiana), . % were culture positive and all isolates were sensitive to most of the common antibiotics [ ] . urmila j et al reported positive cultures ( / blood cultures and / csf cultures) [ ] . low rate of culture positivity in the present study ( . %) may be due to prior use of antibiotics outside or delay in transporting the specimen. antibiotic therapy remains the cornerstone of therapy in meningococcal disease. three factors that influence the success of antibiotic therapy are timing of the antibiotic, tissue penetration and antibiotic resistance. broad spectrum antibiotics like penicillin g, ceftriaxone and cefotaxime remain widely used. increasing resistance to penicillin is being reported and ceftriaxone remains the recommended first line therapy in the present scenario. however in the authors' experience they had patients with good response to ceftriaxone in the beginning of the epidemic. after about mo of the epidemic, there was poor clinical response to ceftriaxone and the unit antibiotic policy was revised to intravenous chloramphenicol for d with good response. they now routinely use parenteral chloramphenicol as the first line therapy in meningococcal disease. there are other reports of ciprofloxacin as well as ceftriaxone resistance from india [ , ] . the second line therapy consists of vancomycin and azithromycin. the nice guidelines recommend dexamethasone therapy for suspected or confirmed bacterial meningitis above mo of age [ ] . the authors used injection dexamethasone in all meningococcal meningitis cases for d. steroids are not indicated in meningococcal shock unless there is suspicion of hypoadrenalism. overall fatality rate of invasive meningococcal infection is - %, although these rates are difficult to assess as some studies only take into account meningococcal meningitis, while others reflect overall fatality from meningococcal disease [ , ] . reported mortality from meningococcemia ranges from % to % [ ] . for overall invasive meningococcal infection, the fatality rate in the present study was low ( . %). for meningococcemia, fatality rate in the present study was . % which is similar to other studies [ ] . low mortality in the present study can be explained by the fact that patients reached the hospital fast due to good information, education and communication activities by the local health authorities, combined with a low threshold for diagnosis and aggressive management of shock, rapidity of administration of the first antibiotic dose (door to needle time) and continuous monitoring in a well equipped pediatric intensive care unit. this is the first epidemic report of invasive meningococcal disease from north east india. although the majority of patients had meningitis, the full range of manifestations were also seen. this study highlights that clinical resistance to commonly used antibiotics such as ceftriaxone can be seen where chloramphenicol is an alternative effective choice. mortality reduces significantly with early diagnosis and prompt interventions like early shock management, antibiotic therapy and frequent monitoring in an intensive care set up. although invasive meningococcal infection did not have much impact on the morbidity and mortality of children from this region compared to other parts of the world, it remains one of the major causes of life threatening infections requiring continuous vigilance. contributions rd conceived the idea of the study and approved the final manuscript and will act as guarantee of the paper; nmd, hb, sgd, pj and db were involved in data retrieval, analysis and writing of the paper; abk and wvl were involved in the laboratory diagnosis and analysis of the microbiological data. meningococcal disease, need to remain alert. cd alert mémoire sur la maladie qui a regné a genêve au printemps de meningococcal meningitis outbreak control strategies meningococcal meningitis in delhi and other areas group b meningococcal meningitis in india meningococcal meningitis in an industrial area adjoining surat citysome clinic-epidemiological aspects meningococcal disease: history, epidemiology, pathogenesis, clinical manifestations, diagnosis, antimicrobial susceptibility and prevention multicenter surveillance of invasive meningococcal infections in children update on meningococcal disease with emphasis on pathogenesis and clinical management clinical features and complications of epidemic group a meningococcal disease in sudanese children meningococcal meningitis in northern ghana: epidemiology and control measures clinical profile of group a meningococcal outbreak in delhi early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome albumin: saint or sinner treatment of meningococcal infection meningococcal disease among children who live in large metropolitan area review of management of purpura fulminans and two case reports arthritis in disease due to neisseria meningitides immune complex reaction after successful treatment of meningococcal disease: an excellent response to ivig bacterial meningitis-a review of selected aspects. ii. special neurologic problems, post meningitic complications and clinicopathological correlations early bilateral eight nerve involvement in meningoccal meningitis connecticut, and selected areas meningococcal meningitis in ludhiana emergence of non-ceftriaxonesusceptible neisseria meningitidis in india ciprofloxacin-resistant neisseria meningitidis management of bacterial meningitis and meningococcal septicaemia in children and young people: summary of nice guidance epidemiology of bacterial meningitis meningococcal infection in children: a review of cases prognostic factors in acute meningococcaemia role of funding source none. key: cord- -ww iq j authors: naithani, nardeep; datta, rakesh title: covid- : shades of grey date: - - journal: med j armed forces india doi: . /j.mjafi. . . sha: doc_id: cord_uid: ww iq j nan pandemics have shaped new world orders and history is full of examples of widespread death and destruction left by enemies we cannot even see. leo van bergen, a medical historian with special interest in world war i reported that the us lost , troops in the meuse-argonne offensive often regarded as 'america's deadliest' in . however, the toll exerted by the spanish flu pandemic on the us army far exceeded this, at , soldiers around the same time. swine flu, ebola and zika are only the latest in a long series of events that have ravaged the human species. covid- joined this 'elite' list on mar as who declared covid as a pandemic. the emergence of covid- raised many questions about the origin, spread, infectivity, risk factors, treatment and even handling of this pandemic. this is expected, considering the dynamic nature of scientific evidence. in the limited time since the first case of a novel coronavirus was known, a pubmed search query for covid- alone gives more than results. a similar search on google scholar gives more than , results. perhaps many more would be available in other libraries and preprint servers. while this might be encouraging, most questions still remain unanswered. it could be like a jigsaw puzzle with pieces yet to be found. to address this, gupta et al. from national centre for disease control, india, have very lucidly highlighted nine domains where healthcare workers need to find answers, in this issue of the journal. the editorial board of medical journal armed forces india (mjafi) could not agree more. every small bit of research counts. the overall understanding will be way more than a mere sum of parts. we have endeavoured to play our role as a peer reviewed medical journal while welcoming submissions on the entire spectrum of possible research on covid- from across the world. the journal has created a dedicated subsite (https://covid.mjafi.net) to highlight the same and accepted articles are being made open source by our publishing partners elsevier. the submissions and peer reviews are being fast tracked and accepted articles made available online ahead of print to enable the sharing of scientific thoughts at the earliest. the response has been heartening and we hope to fulfil our role in disseminating peer reviewed translational and clinical research to help fight sars-cov- . at the same time it is important for our readers to understand that what they see in one study is only a small part of the entire puzzle we are yet to see. as elegantly brought out by pai, we need to be wary of the inherent bias and confounders when drawing conclusions out of ecological studies in epidemiology. mathematical modelling has been one of the battlefronts to help plan and organise systems to prepare for the challenge of covid- . it uses data to make complex predictions. the results are usually dependent on the quality of inputs and assumptions made. chatterjee et al. have made predictions on the anticipated numbers of the pandemic in india with and without lockdown and social distancing. though it is only with time that we may know the accuracy of this prediction, many such models are being developed with increasing complexity and large number of parameters. it provides planners and policy makers a set of numbers to work with in the face of uncertainty. a word of caution is however necessary in all these models. as exit polls after a closely fought election may go horribly wrong and some turn out accurate, mathematical modelling is also not without its inaccuracies. the factors which determine the course of events are complex, and undoubtedly it is not possible to model real world complexities in any equation. regional diversities in countries like india are even more difficult to cater. nevertheless, to carry the exit poll analogy further, mathematical models are increasingly becoming a valuable tool to equip the public health response in covid- . as the understanding of the transmission of the disease changes, mathematical models need to be dynamic tools to help policy making bodies. to quote jewell et al., "models can be useful tools but should not be overinterpreted". hopefully, the benefits of mathematical models will trickle down to local city planners and public health experts to help them make short term specific predictions. another aspect which needs to be considered is the mental health aspect of this pandemic. it would not be wrong to say that each one of us has felt troubled with the exponential rising numbers, innumerable social media forwards of stories of struggle and sorrow and the 'clamp-down'. the name quarantine rings an alarm with reports of people escaping quarantine and stamping of covid- suspects by authorities. while another editorial highlights the psychological challenges of quarantine in the current issue, mental health of both, the population and the 'corona warriors' is a fertile field for research. healthcare personnel are frontline soldiers in this war. in the developing world, they are already a scarce resource, and for the less fortunate patients who need hospitalisation and critical care, the only ones around. they are as susceptible, if not three times more, to get infected as has often been quoted. they are exposed to multiple patients, multiple times for prolonged durations. and at many times with only a mutual lurking feeling of suspicion and fear between the patient and doctor about being infected by each other!! to add to the hostilities, they are also bearing the brunt of unfortunate incidents of violence as reported. guidelines, then are probably as helpful as a golf guidebook for a high handicapper trying to score a birdie ! the frequent changes in the guidelines do little to alleviate the confusions that might exist in the minds of the healthcare workers. udwadia, a pulmonologist who has been in the thick of things since covid- reached mumbai has penned a practical perspective of protecting the protectors in this issue and shared ten lessons for the medical community to learn. undoubtedly, healthcare workers are at risk. covid should probably be viewed as an occupational disorder for healthcare workers amongst others. covid- is the first new occupational disease to be described in this decade. the recent ordinance to amend the epidemic diseases act, by the govt of india will hopefully help to reduce the public brunt and help healthcare workers focus on sars-cov- . sars-cov- has changed our world. the fight against the virus will be prolonged with its share of ups and downs. we have barely begun to understand the disease and the way it brings us down. but there is nothing in black and white yet ! these are early days and we are seeing many shades of grey. the medical community has to rise, don their battle gear and get ready for world war iii. r e f e r e n c e s of the worst epidemics and pandemics in history death from pandemic influenza during the first world war: a perspective from personal and anecdotal evidence. influenza other respir viruses who director-general's opening remarks at the media briefing on covid- the missing pieces in the jigsaw and need for cohesive research amidst covid global response a skeptic's guide to ecologic studies during a pandemic data-based analysis, modelling and forecasting of the covid- outbreak healthcare impact of covid- epidemic in india: a stochastic mathematical model predictive mathematical models of the covid- pandemic: underlying principles and value of projections ist : . coronavirus in india: man stamped for quarantine in mumbai caught at secundarabad railway station epidemics, quarantine and mental health. med j armed forces india how to protect the protectors: lessons to learn for doctors fighting the covid- coronavirus occupational risks for covid- infection promulgation of an ordinance to amend the epidemic diseases act, in the light of the pandemic situation of covid- key: cord- - qld authors: agrawal, prashant; singh, anubhutie; raghavan, malavika; sharma, subodh; banerjee, subhashis title: an operational architecture for privacy-by-design in public service applications date: - - journal: nan doi: nan sha: doc_id: cord_uid: qld governments around the world are trying to build large data registries for effective delivery of a variety of public services. however, these efforts are often undermined due to serious concerns over privacy risks associated with collection and processing of personally identifiable information. while a rich set of special-purpose privacy-preserving techniques exist in computer science, they are unable to provide end-to-end protection in alignment with legal principles in the absence of an overarching operational architecture to ensure purpose limitation and protection against insider attacks. this either leads to weak privacy protection in large designs, or adoption of overly defensive strategies to protect privacy by compromising on utility. in this paper, we present an operational architecture for privacy-by-design based on independent regulatory oversight stipulated by most data protection regimes, regulated access control, purpose limitation and data minimisation. we briefly discuss the feasibility of implementing our architecture based on existing techniques. we also present some sample case studies of privacy-preserving design sketches of challenging public service applications. a welfare state may have legitimate interests in building large data registries with personally identifiable information (pii) for efficiency of service delivery. a state may also legitimately need to put its residents under purpose-specific surveillance. in fact, several commentators have alluded to the possibility of pervasive underthe-skin surveillance in a post-covid world [ ] . however, mandatory recordings of pii require enacting reasonable and fair laws to ensure that the processing of pii is proportionate to the stated objective, and safeguard the basic operative principles of privacy and fairness. citizens' basic rights need to be protected even when there is a legitimate state interest in digitisation with pii [ ] . the need to ensure that the information collected is not used adversely against citizens to harm them takes us into one of the hard problems of modern public policy: creating rules and technologies around information privacy to help strike this critical balance for online collection of pii at national scale. in this paper we address the problem of operationalising the broad privacy-by-design principles outlined in [ , ] , in the context of large public service databases. we present an architecture for implementing the data protection principles after the utility and proportionality of an application have been established through an appropriate regulatory analysis [ , , ] . the general principles of fair and reasonable processing, purpose, collection and storage limitation, notice and consent, data quality etc. have evolved since the s, both through sector specific standards in the us such as the social security number protection act [ ] and health insurance portability and accountability act (hipaa) [ ] , or through omnibus laws in general data protection standards such as the gdpr in the european union [ ] and the draft data protection bill of india [ ] . however, they have largely failed to prevent both direct harms that can occur as a result of data breaches or through unauthorised access of personal datasuch as identity thefts, unethical profiling and unlawful surveillance, or secondary harms that could arise due to the use of the data to adversely affect a person -such as through discrimination or exclusion, predatory targeting for unsuitable products, loss of employment, inaccurate credit rating etc. dictums such as personal data shall be processed in a fair and reasonable manner are non-specific, and they do not adequately define the contours of the required regulatory actions. as episodes like cambridge analytica [ ] demonstrate, harm is often not immediately obvious, and causal links of harm are not always easy to determine. this is compounded by the fact that data collection and use are becoming ubiquitous making it hard to trace misuse; the effects of misuse of personal data may not immediately manifest, and when they do they may not be easily quantifiable in monetary terms despite causing grave distress. hence, ex-post accountability and punitive measures are largely ineffective, and it is imperative to operationalise ex-ante preventive principles. as a consequence of the weak protection standards, most attempts at building large public services like national identity systems [ , ] , health registries [ , , ] , national population and voter registries [ , , ] , public credit registries [ , ] , income [ ] and tax registries [ ] etc. have often been questioned on privacy and fairness grounds and have been difficult to operationalise. the concerns have invariably been related to the need for protective safeguards when large national data integration projects are contemplated by governments and acknowledgment of the unprecedented surveillance power that this could create. in some situations they have even had to be abandoned altogether as they were unable to deal with these risks [ , , ] . in india too, the recent momentum and concerns around informational privacy guarantees have occurred in the context of the creation of new government databases and digital infrastructures for welfare delivery [ , ] . recording transactions with pii projects an individual into a data space, and any subsequent loss of privacy can happen only through the data pathway. hence data protection is central to privacy protection insofar as databases are concerned. the critical challenge in design of a data protection framework is that the main uses of digitisation -long term record keeping and data analysis -are seemingly contradictory to the privacy protection requirements. the legal principles around "fair information practice" attempt to reconcile these tensions, but there are four broad areas that require careful attention for effective data protection. first, a data protection framework is incomplete without an investigation of the nuances of digital identity, and guidelines for the various use cases of authentication, authorisation and accounting. it is also incomplete without an analysis of the extent to which personal information needs to be revealed for each use case, for example during know-your-citizen or -customer (kyc) processes. in addition, effective protection requires an understanding of the possible pathways of information leaks; of the limits of anonymisation with provable guarantees against re-identification attacks [ ] ; and of the various possibilities with virtual identities [ , ] . second, there have to be clear-cut guidelines for defining the requirements and standards of access control, and protection against both external and insider attacks in large data establishments, technically as well as legally. in particular, insider attacks are the biggest threat to privacy in public databases [ ] . these include possible unauthorised and surreptitious examination of data, transaction records, logs and audit trails by personnel with access, leading to profiling and surveillance of targeted groups and individuals, perhaps at the behest of interested and influential parties in the state machinery itself [ ] . thus, there must be guidelines on how the data may be accessed, under what authorisation and for what purpose. in addition, post data access purpose limitation -ensuring that there is no illegal use after the data crosses the access boundaries -is also crucial for privacy protection. third, a data protection framework is incomplete without guidelines for safe use of ai and data analytics. most theories for improving state efficiency in delivery of welfare and health services using personal data will have to consider improved data processing methods for targeting, epidemiology, econometrics, tax compliance, corruption control, analytics, topic discovery, etc. this, in turn, will require digitisation, surveillance and processing of large-scale personal transactional data. this requires detailed analyses of how purpose limitation of such surveillance -targeted towards improving efficiency of the state's service delivery -may be achieved without enabling undesirable mass surveillance that may threaten civil liberty and democracy. there must also be effective guidelines to prevent discriminatory and biased data processing [ ] . finally, it is well recognised in data protection frameworks [ , , ] that regulatory oversight is a necessary requirement for ensuring the above. while there is a rich set of tools and techniques in computer science arising out of decades of innovative privacy research, there is no overarching general framework for a privacy preserving architecture which, in particular, allows regulatory supervision and helps deal with the above issues in effective designs. in this paper we propose such an operational architecture for implementing the data protection principles. our immediate objective here is design space exploration and not specific implementations to evaluate performance and scalability. we illustrate the effectiveness of our proposal through design sketches of some challenging large public service applications. in particular, we illustrate through some real world case studies how some state-of-the-art designs either fail in their data protection goals, or tend to be overly defensive at the cost of utility in the absence of such an architecture. the rest of the paper is organized as follows. section briefly reviews the basic legal principles for data protection. section reviews concepts, tools and techniques from computer science for privacy protection. section presents our operational architecture. section discusses the feasibility and section discusses some illustrative case studies of large government applications. in what follows we briefly discuss the context of digitisation and privacy in india and the basic legal principles around privacy. we situate this analysis within the context of india's evolving regulatory and technical systems. however, many of these principles are relevant for any country seeking to align legal and technical guarantees of privacy for citizens. building public digital infrastructures has received an impetus in india in recent times [ ] and privacy has been an obvious concern. india has a long-standing legal discourse on privacy as a right rooted in the country's constitution. however, informational privacy and data protection issues have gained renewed visibility due to the recent national debate around the country's aadhaar system [ ] . aadhaar is a unique, biometric-based identity system launched in , with the ambitious aim of enrolling all indian residents, and recording their personal information, biometric fingerprints and iris scans against a unique identity number. aadhaar was designed as a solution for preventing leakages in government welfare delivery and targeting public services through this identity system. in addition, the "india stack" was envisioned as a set of apis that could be used -by public and private sector entities contract -to query the aadhaar database to provide a variety of services [ ] . however, as the project was unrolled across the country, its constitutionality was challenged in the courts on many grounds including the main substantive charge that it was violative of the citizens' right to privacy. over petitions challenging the system were eventually raised to the supreme court of india for its final determination. in the course of the matter, a more foundational question arose, i.e., whether the indian constitution contemplated a fundamental right of privacy? the question was referred to a separate -judge bench of the indian supreme court to conclusively determine the answer to this question. the answer to this question is important both for law and computer science, since the response creates deep implications for the design of technical systems in india. the supreme court's unanimous response to this question in justice k.s.puttaswamy (retd.) vs union of india (puttaswamy i) [ ] was to hold that privacy is a fundamental right in india guaranteed by part iii (fundamental rights) of the indian constitution. informational privacy was noted to be an important aspect of privacy for each individual, that required protection and security. in doing so, the court recognised the interest of an individual in controlling or limiting the access to their personal information, especially as ubiquitous data generation and collection, combined with data processing techniques, can derive information about individuals that we may not intend to disclose. in addition to cementing privacy as a constitutional right for indians, the supreme court in puttaswamy i [ ] also played an important role in clarifying certain definitional aspects of the concept. first, when defining privacy, the lead judgement noted that every person's reasonable expectation of privacy has both subjective and objective elements (see page of puttaswamy i), i.e., . the subjective element which is to the expectation and desire of an individual to be left alone, and . the objective element, which refers to objective criteria and rules (flowing from constitutional values) that create the widely agreed content of "the protected zone", where a person ought to be left alone in our society. second, informational privacy was also recognised (see page of puttaswamy i, from a seminal work which set out a typology of privacy) to be: ". . . an interest in preventing information about the self from being disseminated and controlling the extent of access to information." it would be the role of a future indian data protection law to create some objective standards for informational privacy to give all actors in society an understanding of the "ground rules" for accessing an individuals' personal information. these principles are already fairly well-developed through several decades of international experience. india is one of the few remaining countries in the world that is yet to adopt a comprehensive data protection framework. this section provides a brief overview of some of these established concepts. one of the early and most influential global frameworks on privacy protection are the oecd guidelines on the protection of privacy and transborder flows of personal data [ ] . these were formulated as a response to the advancements in technology that enabled faster processing of large amounts of data as well as their transmission across different countries. these guidelines were updated in , reflecting the multilateral consensus of the changes in the use and processing of personal data in that year period. therefore, it is a good starting point for the fundamental principles of privacy and data protection. the key principles of the oecd privacy framework are: collection limitation: personal data should be collected in a fair and lawful manner and there should be limits to its collection. use limitation: collected personal data be used or disclosed for any purposes other than those stated. if personal data must be used for purposes other that those stated, it should with the consent of the data subject or with the authority of the law. purpose specification: the purpose for collection of personal data should be stated no later than the point of collection. all subsequent uses of such data must be limited to the stated purposes. data quality: collected personal data should be relevant for the stated purposes and its accuracy for such a purpose must be maintained. security safeguards: reasonable safeguards must be adopted by the data controller to protect it from risks such as unauthorised access, destruction, use, modification or disclosure of the data. accountability: any entity processing personal data must be responsible and held accountable for giving effect to the principles of data protection and privacy. openness: any entity processing personal data must be transparent about the developments and practices with respect to the personal data collected. individual participation: individuals should have the rights to confirm from the data controller whether they have any personal data relating to them and be able to obtain the same within a reasonable time, at a reasonable charge and in a reasonable manner. if these requests are denied, individuals must be given the reasons for such denial and have the right to challenge such denials. individuals must also retain the right to be able to challenge personal data relating to them and able to erase, rectify, complete or amended. these principles, and many international instruments and national laws that draw from them, set some of the basic ground rules around the need for clear and legitimate purposes to be identified prior to accessing personal information. they also stress on the need for accountable data practices including strict access controls. many of these principles are reflected to varying degrees in india's personal data protection bill in [ ] which was introduced in the lower house of the indian parliament in december . the bill is currently under consideration by a joint select committee of parliamentarians following which it will enter parliament for final passage. the oecd privacy framework [ ] in article (g) also recognised the need for the promotion of technical measures to protect privacy in practice. there is also a growing recognition that if technical systems are not built with an appreciation of data protection and privacy principles, they can create deficits of trust and other dysfunctions. these are particularly problematic in government-led infrastructures. the failure of privacy self-management and the need for accountability-based data protection the need for data processing entities to adhere to objective and enforceable standards of data protection is heightened because of vulnerability of the individuals whose data they process. although research shows that individuals value their privacy and seek to control how information about them is shared, cognitive limitations operate at the level of the individuals' decision-making about their personal data [ ] . this "privacy paradox" signals the behavioural biases and information asymmetries that operate on people making decisions about sharing their personal information. especially in contexts where awareness that personal data is even being collected in digital interactions is low, such as with first-time users of digital services in india, it is often unfair and meaningless to delegate the self-management of privacy to users entirely through the ineffective mechanism of "consent". the inadequacy of consent alone as a privacy protection instrument has been well established, especially given that failing to consent to data collection could result in a denial of the service being sought by the user [ ] . in the context of these findings, it is crucial that digital ecosystems be designed in a manner that protects the privacy of individuals, does not erode their trust in the data collecting institution and does not make them vulnerable to different natures of harm. therefore, mere dependence on compliance with legal frameworks by data controllers is not sufficient. technical guarantees that the collected data will only be used for the stated purposes and in furtherance of data protection principles must become a reality, if these legal guarantees are to be meaningful. the need for early alignment of legal and technical design principles of data systems, such as access controls, purpose limitation and clear liability frameworks under appropriate regulatory jurisdictions are essential to create secure and trustworthy public data infrastructures [ , , ] . before we present our architectural framework, we briefly review some privacy preserving tools from computer science. cryptographic encryption [ ] , for protecting data either in storage or transit, have often been advocated for privacy protection. the following types are of particular importance: symmetric encryption symmetric encryption allows two parties to encrypt and decrypt messages using a shared secret key. diffie-hellman key exchange protocol [ ] is commonly used by the parties to jointly establish a shared key over an insecure channel. asymmetric encryption asymmetric or public key encryption [ ] allows two parties to communicate without the need to exchange any keys beforehand. each party holds a pair of public and private keys such that messages encrypted using the receiver's public key cannot be decrypted without the knowledge of the corresponding private key. id-based encryption id-based encryption [ ] allows the sender to encrypt the message against a textual id instead of a public key. a trusted third party provisions decryption keys corresponding to the ids of potential receivers after authenticating them through an out-of-band mechanism. id-based encryption considerably simplifies the public key infrastructure: a sender can encrypt messages using the semantic identifier of the intended recipient without explicitly knowing the public keys of the particular receivers. encryption with strong keys is a powerful method for privacy protection provided there are no unauthorised accesses to the keys. insider attacks, however, pose serious risks if the keys also reside with the same authority. even when the keys are stored securely, they have to be brought into the memory for decryption during run-time, and can be leaked by a compromised privileged software, for example an operating system or a hypervisor. digital signature a digital signature [ ] σ pk (m) on a message m allows a verifier to verify using the public key pk that m was indeed signed with the corresponding the private key. any alteration of m invalidates the signature. signatures also provide non-repudiation. blind signatures blind signatures [ ] are useful to obtain a signature on a message without exposing the contents of the message to the signer. a signature σ pk (b(m)) by a signer holding public key pk allows the signer to sign a blinded message b(m) that does not reveal anything about m. the author of the message can now use the σ pk (b(m)) to create an unblinded digital signature σ pk (m). chfs are functions that are a) 'one-way', i.e., given hash value h, it is difficult to find an x such that h = hash(x), and b) 'collision-resistant', i.e., finding any x and x such that hash(x ) = hash(x ) is difficult. chfs form the basis of many privacy preserving cryptographic primitives. there are several techniques from computer science that are particularly useful for data minimisation -at different levels of collection, authentication, kyc, storage and dissemination. some of these are: zkps [ ] are proofs that allow a party to prove to another that a statement is true, without leaking any information other than the statement itself. of particular relevance are zkps of knowledge [ ] , which convince a verifier that the prover knows a secret without revealing it. zkps also enable selective disclosure [ ] , i.e., individuals can prove only purpose-specific attributes about their identity without revealing additional details; for example, that one is of legal drinking age without revealing the age itself. "anonymity refers to the state of being not identifiable within a set of individuals, the anonymity set" [ ] . in the context of individuals making transactions with an organisation, the following notions of anonymity can be defined: unlinkable anonymity transactions provide unlinkable anonymity (or simply unlinkability) if a) they do not reveal the true identities of the individuals to organisations, and b) organisations cannot identify how different transactions map to the individuals. linkable anonymity transactions provide linkable anonymity if an organisation can identify whether or not two of its transactions involve the same individual, but individuals' true identities remain hidden. linkable anonymity is useful because it allows individuals to maintain their privacy while allowing the organisation to aggregate multiple transactions from the same individual. linkable anonymity is typically achieved by making individuals use pseudonyms. anonymous credentials authenticating individuals online may require them to provide credentials from a credential-granting organisation a to a credential-verifying organisation b. privacy protection using anonymous credentials [ , , ] can ensure that transactions with a are unlinkable to transactions with b. anonymous credentials allow an individual to obtain a credential from an organisation a against their pseudonym with a and transform it to an identical credential against their pseudonym with organisation b. an identity authority provisions a master identity to each individual from which all pseudonyms belonging to an individual, also known as virtual identities, are cryptographically derived. anonymous credentials are typically implemented by obtaining blind signatures (see section . . ) from the issuer and using zkps of knowledge (see section . . ) of these signatures to authenticate with the verifier. the credential mechanism guarantees: • unlinkable anonymity across organisations. this property ensures that a cannot track the uses of the issued credentials and b cannot obtain the individual's information shared only with a even when a and b collude. • unforgeability. a credential against an individual's pseudonym cannot be generated without obtaining an identical credential against another pseudonym belonging to the same individual. • linkable anonymity within an organisation. depending on the use case requirements, individuals may or may not use more than one pseudonym per organisation. in the latter case the transactions within an organisation also become unlinkable. if an organisation a requires to link multiple transactions from the same individual, it can indicate this requirement to the identity authority that checks if pseudonyms used by individuals with a are unique. if a does not require linking, the identity authority merely checks if the pseudonyms are correctly derived from the individual's master identity. if the checks pass, an anonymous credential certifying this fact is issued by the identity authority. all checks by the identity authority preserve individuals' anonymity. accountable anonymous credentials anonymity comes with a price in terms of accountability: individuals can misuse their credentials if they can never be identified and held responsible for their actions. trusted third parties can revoke the anonymity of misbehaving users to initiate punitive measures against them [ , , ] . one-time credentials and k-times anonymous authentication schemes [ , , ] also prevent overspending of limited-use credentials by revoking individuals' anonymity if they overspend. blacklisting misbehaving users for future access without revoking their anonymity is also feasible [ ] . linkability by a trusted authority linking across organisations may also be required for legitimate purposes, for example for legitimate data mining. also see examples in section . such linkability also seems to be an inevitable requirement to deter sharing of anonymous credentials among individuals [ ] . linkability by a trusted authority can be trivially achieved by individuals attaching a randomised encryption of a unique identifier against the trusted authority's public key for transactions requiring cross-linking. of course, appropriate mechanisms must exist to ensure that the trusted authority does not violate the legitimate purpose of linking. note that the anonymity of credentials is preserved only under the assumption that individuals interact with organisations through anonymous channels (e.g., in [ ] ). in particular, neither the communication network nor the data that individuals share with organisations should be usable to link their transactions (see section . . and . . ). anonymous networks, originally conceptualised as mix networks by chaum [ ] , are routing protocols that make messages hard-to-trace. mix networks consist of a series of proxy servers where each of them receives messages from multiple senders, shuffles them, and sends to the next proxy server. an onion-like encryption scheme allows each proxy server to only see an encrypted copy of the message (and the next hop in plaintext), thus providing untraceability to the sender even if only one proxy server honestly shuffles its incoming messages. anonymisation is the process of transforming a database such that individuals' data cannot be traced back to them. however, research in de-anonymisation has shown that anonymisation does not work in practice, as small number of data points about individuals coming from various sources, none uniquely identifying, can completely identify them when combined together [ ] . this is backed by theoretical results [ , ] which show that for high-dimensional data, anonymisation is not possible unless the amount of noise introduced is so large that it renders the database useless. there are several reports in literature of de-anonymisation attacks on anonymised social-network data [ , ] , location data [ ] , writing style [ ] , web browsing data [ ] , etc. in this setting, analysts interact with a remote server only through a restricted set of queries and the server responds with possibly noisy answers to them. dinur and nissim [ ] show that given a database with n rows, an adversary having no prior knowledge could make o(n polylog(n)) random subset-sum queries to reconstruct almost the entire database, unless the server perturbs its answers too much (by at least o( √ n)). this means that preventing inference attacks is impossible if the adversary is allowed to make arbitrary (small) number of queries. determining whether a given set of queries preserves privacy against such attacks is in general intractable (np-hard) [ ] . inferential privacy [ , ] is the notion that no information about an individual should be learnable with access to a database that could not be learnt without any such access. in a series of important results [ , , ] , it was established that such an absolute privacy goal is impossible to achieve if the adversary has access to arbitrary auxiliary information. more importantly, it was observed that individuals' inferential privacy is violated even when they do not participate in the database, because information about them could be leaked by correlated information of other participating individuals. in the wake of the above results, the notion of differential privacy was developed [ ] to allow analysts extract meaningful distributional information from statistical databases while minimising the additional privacy risk that each individual incurs by participating in the database. note that differential privacy is a considerably weaker notion than inferential privacy as reconstruction attacks described in section . . or other correlation attacks can infer a lot of non-identifying information from differentially private databases too. mechanisms for differential privacy add noise to the answers depending on the sensitivity of the query. in this sense, there is an inherent utility versus privacy tradeoff. differentially private mechanisms possess composability properties. thus, privacy degrades gracefully when multiple queries are made to differentially private databases. however, this alone may not protect against an attacker making an arbitrary number of queries. for example, the reconstruction attacks mentioned in section . . prevent many differentially private algorithms from answering a linear (in the number of rows) number of queries [ ] . for specific types of queries though, e.g., predicate queries, sophisticated noise-addition techniques [ ] can be used to maintain differential privacy while allowing for an exponential number of queries [ , ] . differentially private mechanisms also degrade gracefully with respect to group privacy as the group size increases. these guarantees may not be enough for policymakers who must protect the profile of specific communities constituting a sizable proportion of the population. the ability of an adversary to manipulate and influence a community even without explicitly identifying its members is deeply problematic, as demonstrated by episodes like cambridge analytica [ ] . therefore, the goal of modern private data analysis should not be limited to protecting only individual privacy, but also extend to protecting sensitive aggregate information. due to the inherently noisy nature of differentially private mechanisms, they are not suitable for any nonstatistical uses, e.g., financial transactions, electronic health records, and password management. privacy mechanisms for such use-cases must prevent misuse of data for malicious purposes such as illegal surveillance or manipulation, without hampering the legitimate workflows. the difficulties with differential privacy, and the impossibility of protection against inferential privacy violations, suggest that privacy protection demands that there should be no illegal access or processing in the first place. these check whether a given code-base uses personal data in accordance with a given privacy policy [ , , ] . privacy policies are expressed in known formal languages [ , ] . a compiler verifies, using standard information flow analysis [ ] and model-checking techniques [ ] , if a candidate program satisfies the intended privacy policy. in order to enforce various information flow constraints these techniques rely on manual and often tedious tagging of variables, functions and users with security classes and verify if information does not flow from items with high security classes to items with low security classes. these techniques define purpose hierarchies and specify purpose-based access-control mechanisms [ , , ] . however, they typically identify purpose with the role of the data requester and therefore offer weak protection from individuals claiming wrong purposes for their queries. jafari et al. [ ] formalise purpose as a relationship between actions in an action graph. hayati et al. [ ] express purpose as a security class (termed by them as a "principal") and verify that data collected for a given purpose does not flow to functions tagged with a different purpose. tschantz et al. [ ] state that purpose violation happens if an action is redundant in a plan that maximises the expected satisfaction of the allowed purpose. however, enforcement of these models still relies on fine-grained tagging of code blocks, making them tedious, and either a compiler-based verification or post-facto auditing, making them susceptible to insider attacks that bypass the checks. secure remote execution refers to the set of techniques wherein a client can outsource a computation to a remote party such that the remote party does not learn anything about the client's inputs or intermediate results. homomorphic encryption (he) schemes compute in the ciphertext space of encrypted data by relying on the additive or multiplicative homomorphism of the underlying encryption scheme [ , , ] . designing an encryption scheme that is both -which is required for universality -is challenging. gentry [ ] gave the first theoretical fully homomorphic encryption (fhe) scheme. even though state-of-the-art fhe schemes and implementations have considerably improved upon gentry's original scheme, the performance of these schemes is still far from any practical deployment [ ] . functional encryption (fe) [ ] schemes have similar objectives, with the crucial difference that fe schemes let the remote party learn the output of the computation, whereas fhe schemes compute encrypted output, which is decrypted by the client. secure multiparty computation (smc) -originally pioneered by yao through his garbled circuits technique [ ] -allows multiple parties to compute a function of their private inputs such that no party learns about others' private inputs, other than what the function's output reveals. smc requires clients to express the function to be computed as an encrypted circuit and send it to the server alongwith encrypted inputs; the server needs to evaluate the circuit by performing repeated decryptions of the encrypted gates. as a result, smc poses many challenges in its widespread adoption -ranging from the inefficiencies introduced by the circuit model itself to the decryption overhead for each gate evaluation, even as optimisations over the last two decades have considerably improved the performance and usability of smc [ ] . however, he, fe and smc based schemes involve significant application re-engineering and may offer reduced functionality in practice. in recent times, secure remote execution is increasingly being realised not through advances in cryptography but through advances in hardware-based security. this approach commoditises privacy-preserving computation, albeit at the expense of a weakened trust model, i.e., the increased trust on the hardware manufacturer. intel software guard extensions (sgx) [ ] implements access control in the cpu to provide confidentiality and integrity to the executing program. at the heart of the sgx architecture lies the notion of an isolated execution environment, called an enclave. an enclave resides in the memory space of an untrusted application process but access to the enclave memory and leakage from it are protected by the hardware. the following are the main properties of sgx: confidentiality information about an enclave execution can not leak outside the enclave memory except through explicit exit points. integrity information can not leak into the enclave to tamper with its execution except through explicit entry points. remote attestation for an enclave's execution to be trusted by a remote party, it needs to be convinced that a) the contents of the enclave memory at initialisation are as per its expectations, and b) that confidentiality and integrity guarantees will be enforced by the hardware throughout its execution. for this the hardware computes a measurement, essentially a hash of the contents of the enclave memory and possibly additional user data, signs it and sends it over to the remote party [ ] . the remote party verifies the signature and matches the enclave measurement with the measurement of a golden enclave it considers secure. if these checks pass, the remote party trusts the enclave and sends sensitive inputs to it. secure provisioning of keys and data sgx enclaves have secure access to hardware random number generators. therefore, they can generate a diffie-hellman public/private key pair and keep the private key secured within enclave memory. additionally, the generated public key can be included as part of additional user data in the hardware measurement sent to a remote verifier during remote attestation. these properties allow the remote verifier to establish a secure tls communication channel with the enclave over which any decryption keys or sensitive data can be sent. the receiving enclave can also seal the secrets once obtained for long-term use such that it can access them even across reboots, but other programs or enclaves cannot. sgx has been preceded by the trusted platform module (tpm) [ ] . tpm defines a hardware-based root of trust, which measures and attests the entire software stack, including the bios, the os and the applications, resulting in a huge trusted computing base (tcb) as compared to sgx whose tcb includes only the enclave code. arm trustzone [ ] partitions the system into a secure and an insecure world and controls interactions between the two. in this way, trustzone provides a single enclave, whereas sgx supports multiple enclaves. trustzone has penetrated the mobile world through arm-based android devices, whereas sgx is available for laptops, desktops and servers. sgx is known to be susceptible to serious side-channel attacks [ , , , ] . sanctum [ ] has been proposed as a simpler alternative that provides provable protection against memory access-pattern based software side-channel attacks. for a detailed review on hardware-based security, we refer the reader to [ ] . stateful secure remote execution requires a secure database and mechanisms that protect clients' privacy when they perform queries on them. the aim of these schemes is to let clients host their data encrypted in an untrusted server and still be able to execute queries on it with minimal privacy loss and maximal query expressiveness. one approach for enabling this is searchable encryption schemes, i.e., encryption schemes that allow searching over ciphertexts [ , ] . another approach is to add searchable indexes along with encrypted data, or to use special property-preserving encryptions to help with searching [ [ , ] is a useful primitive that provides read/write access to encrypted memory while hiding all access patterns, but these schemes require polylogarithmic number of rounds (in the size of the database) per read/write request. enclavedb [ ] has been recently proposed as a solution based on intel sgx. it hosts the entire database within secure enclave memory, with a secure checkpoint-based logging and recovery mechanism for durability, thus providing complete confidentiality and integrity from the untrusted server without any loss in query expressiveness. private information retrieval (pir) is concerned with hiding which database rows a given user query touches -thus protecting user intent -rather than encrypting the database itself. kushilevitz and ostrovsky [ ] demonstrated a pir scheme with communication complexity o(n ), for any > , using the hardness of the quadratic residuosity problem. since then, the field has grown considerably and modern pir schemes boast of o( ) communication complexity [ ] . symmetric pir (also known as oblivious transfer), i.e., the set of schemes where additionally users cannot learn anything beyond the row they requested, is also an active area of research. as is evident from the discussion in the previous section, none of the techniques by themselves are adequate for privacy protection. in particular, none are effective against determined insider attacks without regulatory oversight. hence we need an overarching architectural framework based on regulatory control over data minimisation, authorisation, access control and purpose limitation. in addition, since the privacy and fairness impacts of modern ai techniques [ ] are impossible to determine automatically, the regulatory scrutiny of data processing programs must have a best effort manual component. once approved, the architecture must prevent any alteration or purpose extension without regulatory checks. in what follows we present an operational architecture for privacy-by-design. we assume that all databases and the associated computing environments are under physical control of the data controllers, and the online regulator has no direct physical access to it. we also assume that the data controllers and the regulators do not collude. we illustrate our conceptual design through an example of a privacy-preserving electronic health record (ehr) system. ehrs can improve quality of healthcare significantly by providing improved access to patient records to doctors, epidemiologists and policymakers. however, the privacy concerns with them are many, ranging from the social and psychological harms caused by unwanted exposure of individuals' sensitive medical information, to direct and indirect economic harms caused by the linkage of their medical data with data figure : an illustration of the architecture of trusted executables using an example involving an ehr database, a patient, an mri imaging station, a doctor and a data analysis station. tes marked "approved by r" are preaudited and pre-approved by the regulator r. er(·) represents a regulator-controlled encryption function and acr represents online access control by regulator r. dti(x) represent various data types parametrised by the patient x (as explained in the right-hand side table). in particular, v irtualhospitalid(x) represents the hospital-specific virtual identity of the patient. the regulator checks the consents, approvals and other static rules regarding data transfer at each stage of online access control. presented to their employers, insurance companies or social security agencies. building effective ehrs while minimising privacy risks is a long standing design challenge. we propose trusted executables (te) as the fundamental building blocks for privacy-by-design. we introduce them in the abstract, and discuss some possibilities for their actual realisation in section . tes are dataprocessing programs, with explicit input and output channels, that are designed by the data controllers but are examined, audited, and approved by appropriate regulators. tes execute in controlled environments on predetermined data types with prior privacy risk assessment, under online regulatory access control. the environment ensures that only approved tes can operate on data items. in particular, all data accesses from the databases, and all data/digest outputs for human consumption, can only happen through the tes. we prescribe the following main properties of the tes: . runtime environment: tes are approved by regulators. they execute in the physical infrastructure of the data controllers but cannot be modified by them. . authentication: a regulator can authenticate related tes during runtime, and verify that indeed the approved versions are running. integrity: there is no way for a malicious human or machine agent, or even for the data controller, to tamper with the execution of a te other than by sending data through the te's explicit input channels. there is no way for any entity to learn anything about the execution of a te other than by reading data written at the te's explicit output channels. all data accesses and output can only happen through tes. besides, all tes should be publicly available for scrutiny. the above properties allow a regulator to ensure that a te is untampered and will conform to the limited purpose identified at the approval stage. as depicted in figure , a data agent -for example, a hospital -interacts with databases or users only through pre-approved tes, and direct accesses are prevented. all data stores and communication messages are encrypted using a regulator-controlled encryption scheme to prevent any information leakage in transit or storage. the data can be decrypted only inside the tes under regulated access control. the regulator provisions decryption keys securely to the te to enable decryption after access is granted. the regulator allows or denies of the patient and the doctor, respectively. σx (·) represents digital signature by patient x . autht e (·) represents authentication information of the te and authdt (·) represents authentication information of the supplied data's type. individuals are authenticated by verifying their virtual identities. access, online, based on the authentication of the te and the incoming data type, consent and approval checks as required, and the credential authentication of any human consumers of output data (e.g., the doctor(s) and data analysts). all sink tes -i.e., those that output data directly for consumption by a human agent -are pre-audited to employ appropriate data minimisation before sending data to their output channels. note that extending the te architecture to the doctors' terminals and the imaging stations ensures that the data never crosses the regulated boundary and thus enables purpose limitation. in the above example an independent identity authority issues credentials and engages in a three-way communication to authenticate individuals who present their virtual identities to the regulator. an individual can use a master health id to generate hospital-specific or doctor-specific unlinkable anonymous credentials. only a health authority may be allowed to link identities across hospitals and doctors in a purpose-limited way under regulated access control. we depict the regulatory architecture in figure . the first obligation of the regulator is to audit and approve the tes designed by the data controllers. during this process, the regulator must assess the legality of the data access and processing requirements of each te, along with the privacy risk assessment of its input and output data types. in case a te is an ai based data analytics program, it is also an obligation of the regulator to assess its fairness and the potential risks of discrimination [ ] . before approving a te, the regulator also needs to verify that the te invokes a callback to the regulator's online interface before accessing a data item and supplies appropriate authentication information, and that it employs appropriate encryption and data minimisation mechanisms at its output channels. finally, the regulator needs to put in place a mechanism to be able to authenticate the te in the data controller's runtime environment. the second obligation of the regulator is to play an online role in authorising data accesses by the tes. the authorisation architecture has both a static and a dynamic component. the static authorisation rules typically capture the relatively stable regulatory requirements, and the dynamic component typically captures the fast-changing online context, mainly due to consents and approvals. specifically, each static authorisation rule takes the form of a set of pre-conditions necessary to grant access to a te the data of a given type; and, in case of sink tes, to output it to a requester. the design of these rules is governed by regulatory requirements and the privacy risk assessment of tes and data types. the rules are typically parametric in nature, allowing specification of constraints that provide access to a requester only if the requester can demonstrate some specific relationship with the data individual (e.g., to express that only a doctor consulted by a patient can access her data). the pre-conditions of the authorisation rules may be based on consent of data individuals, approvals by authorities or even other dynamic constraints (e.g., time-bound permissions). the consent architecture must be responsible for verifying signatures on standardised consent apis from consent givers and recording them as logical consent predicates. the regulator, when designing its authorisation rules, may use a simple consentfor example, that a patient has wilfully consulted a doctor -to invoke a set of rules to protect the individual's privacy under a legal framework, rather than requiring individuals to self-manage their privacy. similar to the consent architecture, the approval architecture for data access must record standardised approvals from authorities as logical approval predicates. an approval from an authority may also be provided to an individual instead of directly to the regulator, as a blind signature against a virtual identity of the individual known to the approver, which should be transformed by the individual to a signature against the virtual identity known to the data controller and the regulator. this, for example, may enable a patient to present a self generated virtual identity to a doctor or a hospital instead of her universal health id. the regulator also requires an authentication architecture. first, it needs to authenticate individuals, i.e., consent givers, approvers and data requesters, by engaging in a three-way communication with an identity authority which may be external to both the data controller and the regulator. second, it needs to authenticate tes in order to be able identify the access requests as originating from one of the pre-approved tes. third, it needs to authenticate data types, i.e., identify the underlying type of the te's encrypted input data. the consent/approval predicates and the authentication information flow to the dynamic authorisation module, which can instantiate the static authorisation rules with the obtained contextual information to determine, in an online fashion, if access should be allowed to the requesting te. if yes, then it must also provision decryption keys to the te securely such that only the te can decrypt. the keys can be securely provisioned to the te because of the authentication, integrity and confidentiality properties, and by the fact that approved tes must never output the obtained decryption keys. an example control-flow diagram depicting the regulatory access control in a scenario where a doctor is trying to access the data of a patient who consulted them is shown in figure . several existing techniques can be useful for the proposed architecture, though some techniques may need strengthening. trusted executables can be implemented most directly on top of trusted hardware primitives such as intel sgx or arm trustzone where authentication of tes is carried out by remote attestation. secure provisioning of keys and data to tes can be done in case of intel sgx as per section . . . however, since sgx includes only the cpu in its tcb, it presents challenges in porting ai applications that run on gpus for efficiency. graviton [ ] has been recently proposed as an efficient hardware architecture for trusted execution environments on gpus. in our architecture, tes fetch or update information from encrypted databases. this may be implemented using special indexing data structures, or may involve search over encrypted data, where the tes act as clients and the database storage acts as the server. accordingly, techniques from section . can be used. since the tes never output data to agents unless deemed legitimate by the regulator, the inferential attacks identified with these schemes in section . have minimal impact. for added security, enclavedb [ ] , which keeps the entire database in secure enclave memory, can be used. enclavedb has been evaluated on standard database benchmarks tpc-c [ ] and tatp [ ] with promising results. for authentication of data types messages may be encrypted using an id-based encryption scheme, where the concrete runtime type of the message acts as the textual id and the regulator acts as the trusted third party (see section . . ). the receiver te can send the expected plaintext type to the regulator as part of its access request. the regulator should provision the decryption key for the id representing the requested type only if the receiver te is authorised to receive it as per the dynamic authorisation check. note that authentication of the received data type is implicit here, as a te sending a different data type in its access request can still not decrypt the incoming data. data minimisation for consents and approvals based on virtual identities is well-established from chaum's original works [ , ] . individuals should use their purpose-specific virtual identities with organisations, as opposed to a unique master identity. to prevent cross-linking of identities, anonymous credentials may be used. in some cases, individuals' different virtual identities may need to be linked by a central authority to facilitate data analytics or inter-organisation transactions. this should be done under strict regulatory access control and purpose limitation. modern type systems can conveniently express the complex parametric constraints in the rules in the authorisation architecture. efficient type-checkers and logic engines exist that could perform the dynamic authorisation checks. approval of tes needs to be largely manual as the regulator needs to evaluate the legitimacy and privacy risks associated with the proposed data collection and processing activity. however, techniques from program analysis may help with specific algorithmic tasks, such as checking if the submitted programs adhere to the structural requirement of encrypting data items with the right type at their outgoing channels. we require the regulatory boundary to be extended even to agent machines, which must also run tes so that data they obtain is not repurposed for something else. however, when a te at an authorised agent's machine outputs data, it could be intercepted by malicious programs on the agent's machine leading to purpose violation. solutions from the drm literature may be used to prevent this. in particular, approaches that directly encrypt data for display devices may be useful [ ] . we note that this still does not protect the receiving agent from using more sophisticated mechanisms to copy data (e.g., by recording the display using an external device). however, violations of this kind are largely manual in nature and ill-suited for large-scale automated attacks. finally, we need internal processes at the regulatory authority itself to ensure that its actual operational code protects the various decryption keys and provides access to tes as per the approved policies. to this end, the regulator code may itself be put under a te and authenticated by the regulatory authority using remote attestation. once authenticated, a master secret key may be provisioned to it using which the rest of the cryptosystem may bootstrap. in this section, we present two additional case studies to showcase the applicability of our architecture in diverse real-world scenarios. direct benefit transfer (dbt) [ ] is a government of india scheme to transfer subsidies to citizens' bank accounts under various welfare schemes. its primary objective is to bring transparency and reduce leakages in public fund disbursal. the scheme design is based on india's online national digital identity system aadhaar [ ] . all dbt recipients have their aadhaar ids linked to their bank accounts to receive benefits. figure shows a simplified schematic of the scheme that exists today [ ] . a ministry official initiates payment by generating a payment file detailing the aadhaar ids of the dbt recipients, the welfare schemes under which payments are being made and the amounts to be transferred. the payment file is then signed and sent to a centralised platform called the public financial management system (pfms). pfms hosts the details of various dbt schemes and is thus able to initiate an inter-bank fund transfer from the bank account of the sponsoring scheme to the bank account of the beneficiary, via the centralised payments facilitator npci (national payments corporation of india). npci maintains a mapping of citizen's aadhaar ids to the banks hosting their dbt accounts. this mapping allows npci to route the payment request for a given aadhaar id to the right beneficiary bank. the beneficiary bank internally maintains a mapping of its customers' aadhaar ids to their bank account details, and is thus able to transfer money to the right account. as dbt payments are primarily directed towards people who need benefits, precisely because they are structurally disadvantaged, their dbt status must be protected from future employers, law enforcement, financial providers etc., to mitigate discrimination and other socio-economic harms coming their way. further, since dbt relies on the recipients' national aadhaar ids, which are typically linked with various other databases, any leakage of this information makes them directly vulnerable. indeed, there are reports that bank and address details of millions of dbt recipients were leaked online [ ] ; in some cases this information was misused to even redirect dbt payments to unauthorised bank accounts [ ] . we illustrate our approach for a privacy-preserving dbt in figure . in our proposal, dbt recipients use a virtual identity for dbt that is completely unlinkable to the virtual identity they use for their bank account. they may generate these virtual identities -using suitably designed simple and intuitive interfaces -by an anonymous credential scheme where the credentials are issued by a centralised identity authority. additionally, they provide the mapping of the two virtual identities, along with the bank name, to the ncpi mapper. this information is provided encrypted under the control of the financial regulator r such that only the npci mapper te can access it under r 's online access control. this mechanism allows the npci mapper to convert payment requests against dbt-specific identities to the target bank-specific identities, while maintaining the mapping private from all agents. regulator-controlled encryption of data in transit and storage and the properties of tes allow for an overall privacy-preserving dbt pipeline. note that data flow is controlled by different regulators along the dbt pipeline, providing a distributed approach to privacy protection. pfms is controlled by a dbt regulator; npci mapper is controlled by a financial regulator, and the sponsor and beneficiary banks are controlled by their respective internal regulators. there have been a plethora of attempts recently from all over the world towards electronic app-based contact tracing for covid- using a combination of gps and bluetooth [ , , , , , , , , ] . (a) collecting spatiotemporal information. a and b come in contact via ble, as denoted by the dotted arrows. c does not come in contact with a or b via ble but is spatially close within a time window, as per gps data. vidx represents the virtual identity of agent x; locx i represents x's i-th recorded location; timex i represents its i-th recorded time. tx i represents i-th token generated by x; rx i represents i-th receipt obtained by x; σx () represents signing by x. dashed arrows represent one-time registration steps (illustrated only for c). (b) tracing the contacts of infected individuals. a gets infected, as certified by the doctor's signature σ doc on a's virtual identity vida and medical report reporta. ds and dt respectively represent chosen spatial and temporal distance functions and and δ the corresponding thresholds, as per the disease characteristics. ∆ represents the infection window, the time during which a might have remained infectious. timenow represents the time when the query was executed. even keeping aside the issue of their effectiveness, some serious privacy concerns have been raised about such apps. in most of these apps the smartphones exchange anonymous tokens when they are in proximity, and each phone keeps a record of the sent and received tokens. when an individual is infected -signalled either through a self declaration or a testing process -the tokens are uploaded to a central service. there are broadly two approaches to contact tracing: . those involving a trusted central authority that can decrypt the tokens and, in turn, alert individuals and other authorities about potential infection risks [ , , , ] . some of these apps take special care to not upload any information about individuals who are not infected. . those that assume that the central authority is untrusted and use privacy preserving computations on user phones to alert individuals about their potential risks of infection [ , , , , ] . the central service just facilitates access to anonymised sent tokens of infected individuals and cannot itself determine the infection status of anybody. the following are the main privacy attacks on contact tracing apps: ) individuals learning about other individuals as high-risk spreaders, ) insiders at the central service learning about individuals classified as high risk, ) exposure of social graphs of individuals, and ) malicious claims by individuals forcing quarantine on others. see [ ] for a vulnerability analysis of some popular approaches. the centralised approaches clearly suffer from many of the above privacy risks. while alerting local authorities about infection risks is clearly more effective from a public health perspective, to enable them to identify hotspots and make crucial policy decisions, it is mainly the privacy concerns that sometimes motivate the second approach. also, it is well known that location data of individuals can be used to orchestrate de-anonymisation attacks [ ] , and hence many of the above approaches adopt the policy of not using geolocation data for contact tracing despite their obvious usefulness at least in identifying hotspots. in addition, bluetooth based proximity sensing -which are isolated communication events over narrow temporal windows between two smartphonesis ineffective for risk assessment of indirect transmission through contaminated surfaces, where the virus can survive for long hours or even days. such risk assessment will require computation of intersection of space-time volumes of trajectories which will be difficult in a decentralised approach. it appears that the privacy considerations have forced many of these approaches to adopt overly defensive decentralised designs at the cost of effectiveness. in contrast, we propose an architecture where governments can collect fine-grained location and proximity data of citizens, but under regulated access control and purpose limitation. such a design can support both shortrange peer-to-peer communication technologies such as ble and gps based location tracking. additionally, centralised computing can support space-time intersections. in figure , we show the design of a state-mandated contact-tracing app that, in addition to protecting against the privacy attacks outlined earlier, can also protect against attacks by individuals who may maliciously try to pose as low-risk on the app, for example to get around restrictions (attack ). as before, we require all storage and transit data to be encrypted under a regulator-controlled encryption scheme, and that they be accessible only to pre-approved tes. we also require the app to be running as a te on the users' phones (e.g., within a trusted zone on the phone). we assume that everyone registers with the app using a phone number and a virtual identity unlinkable to their other identities. periodically, say after every few minutes, each device records its current gps location and time. the tuple made up of the registered virtual identity and the recorded location and time is signed by the device and encrypted controlled by the regulator, thus creating an ephemeral "token" to be shared with other nearby devices over ble. when a token is received from another device, a tuple containing the virtual identity of self and the incoming token is created, signed and stored in a regulator-controlled encrypted form, thus creating a "receipt". periodically, once every few hours, all locally stored tokens and receipts are uploaded to a centralised server te, which stores them under regulated access control as a mapping between registered virtual identities and all their spatiotemporal coordinates. for all the receipts, the centralised server te stores the same location and time for the receiving virtual identity as in the token it received, thus modelling the close proximity of ble contacts. when a person tests positive, they present their virtual identity to a medical personnel who uploads a signed report certifying the person's infection status to the centralised server te. this event allows the centralised server te to fetch all the virtual identities whose recorded spatiotemporal coordinates intersects within a certain threshold, as determined by the disease parameters, with the infected person's coordinates. as the recorded (location, time) tuples of any two individuals who come in contact via ble necessarily collide in our approach, the virtual identities of all ble contacts can be identified with high precision. moreover, virtual identities of individuals who did not come under contact via ble but were spatially nearby in a time window as per gps data are also identified. a notifier te securely obtains the registered phone numbers corresponding to these virtual identities from the centralised server te and sends suitably minimised notifications to them, and also perhaps to the local administration according to local regulations. the collected location data can also be used independently by epidemiologists and policy makers in aggregate form to help them understand the infection pathways and identify areas which need more resources. note that attack is protected by the encryption of all sent tokens; attacks and are protected by the properties of tes and regulatory access control; attack is protected by devices signing their correct spatiotemporal coordinates against their virtual identity before sending tokens or receipts. attack is mitigated by requiring the app to run within a trusted zone on users' devices, to prevent individuals from not sending tokens and receipts periodically or sending junk data. we have presented the design sketch of an operational architecture for privacy-by-design [ ] based on regulatory oversight, regulated access control, purpose limitation and data minimisation. we have established the need for such an architecture by highlighting limitations in existing approaches and some public service application designs. we have demonstrated its usefulness with some case studies. while we have explored the feasibility of our architecture based on existing techniques in computer science, some of them will definitely require further strengthening. there also needs to be detailed performance and usability evaluations, especially in the context of large-scale database and ai applications. techniques to help a regulator assess the privacy risks of tes also need to be investigated. these are interesting open problems that need to be solved to create practical systems for the future with built-in end-to-end 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operating procedure (sop) modules for direct benefit transfer (dbt) information security practices of aadhaar (or lack thereof): a documentation of public availability of aadhaar numbers with sensitive personal financial information aadhaar mess: how airtel pulled off its rs crore magic trick china's high-tech battle against covid- coronavirus: south koreas success in controlling disease is due to its acceptance of surveillance tracetogether app government of india apps gone rogue: maintaining personal privacy in an epidemic anonymous collocation discovery: harnessing privacy to tame the coronavirus epione: lightweight contact tracing with strong privacy privacy-preserving contact tracing the pact protocol specification key: cord- -hxxa y authors: nichols, carly e.; jalali, falak; ali, syed shoaib; gupta, divya; shrestha, suchita; fischer, harry title: the gendered impacts of covid- amid agrarian distress: opportunities for comprehensive policy response in agrarian south asia date: - - journal: nan doi: . /s x sha: doc_id: cord_uid: hxxa y covid- and its associated disease control measures have greatly altered everyday life. the burden of these challenges has fallen disproportionately on women. drawing on qualitative inquiry in agrarian north india and nepal, this research note analyzes how south asian covid- lockdowns have affected women's labor responsibilities in sometimes surprising ways. we find increased responsibilities for caregiving within the household, substantial stress in responding to food insecurity, and growing expectations to fulfill public roles in disease response measures. however, we also find that the return of male migrants and youth has, in some cases, reduced women's farming responsibilities and created opportunities for household togetherness at a time of great uncertainty. we conclude that more research is needed to examine the nuanced aspects of covid- 's gendered labor impacts to create comprehensive policy responses to address the multiple and sometimes conflicting effects the lockdown has had on agrarian women's informal labor and well-being. a s covid- and associated movement restrictions upend life around the world, it is well known that the responsibility for responding to these challenges has fallen disproportionately on women (kamdar ; wenham, smith, and morgan ) . globally, care work has long been highly feminized (rai and waylen ) , and the shutdowns of schools, businesses, and transport that occurred in response to covid- have intensified and shifted women's roles globally (wenham, smith, and morgan ) . in the mid-himalayan hills of rural india and nepal, women's unpaid labor has also acted as a shock absorber during the covid- lockdown, which was both strict and sudden. across south asia, women's unpaid labor burden is stark, with women averaging six hours per day compared with men's one hour (oecd ) . these disparities are attributable not only to strictly enforced patriarchal labor roles but also to the fact that large numbers of men and children work and study in cities, so women assume more responsibility for agriculture and livestock. while this is often referred to as the "feminization of agriculture," south asian scholars have argued compellingly that a more apt conceptual frame is the "feminization of agrarian distress," given the poorly remunerative state of agriculture in south asia along with poor village services and infrastructure (pattnaik et al. ) in this research note, we draw on qualitative data collected in nepal and the indian state of himachal pradesh (hp) to explore the complex impacts that covid- and lockdown policies are having on women's labor roles within the context of agrarian distress. our data suggest while the mass sheltering in place of families significantly expanded women's unpaid care work, the presence of returned family members also diminished women's agricultural labor burdens and created opportunities for familial togetherness. in highlighting these themes, our aim is to contribute to policy discussions on how looking at relief efforts in south asia through a feminist lens must entail a more nuanced examination of the ways lockdowns have impacted women within the ongoing crisis of feminized agrarian distress. our data are drawn from qualitative fieldwork conducted from march to june in villages in nepal and hp, india. our sites are socioeconomically diverse, including districts more integrated into urban centers with commercial agriculture (sirmaur, hp, and kavre, nepal), as well as remote areas with higher levels of subsistence agriculture (chamba, hp, and ramechhap, nepal). data were collected by trained field assistants from an existing research project that was disrupted by the pandemic. at the lockdown's onset, field staff returned to their homes with detailed instructions to document how the lockdown was affecting their own families, as well as their neighbors and individuals they could contact by phone. data collection was directed by a series of open-ended questions; assistants were instructed to keep extensive notes throughout the day and reflect on events in daily journals. participating researchers also conducted remote interviews with research subjects identified by field assistants. field assistants were evenly split between men and women, yet all were general category castes (i.e., not low castes) with relatively high education. since sampling relied on their social networks, privileged groups are more represented in our data. to help limit this bias, assistants were instructed to the gendered impacts of covid- amid agrarian distress make explicit efforts to get in touch with marginalized social groups. despite these limitations, we feel our data provide an invaluable view of the gendered impacts of covid- in mid-himalayan agricultural communities. given strong patriarchal gender roles across study sites, it was not surprising that women shouldered additional care work as family members stayed at home. while women had increased responsibilities for cleaning, laundry, and water and fuelwood hauling, the most dramatic impacts related to their role as food preparers. women were faced with a double burden of having to feed more people amid a period of unprecedented food scarcity. the lockdown began at the end of march, when monthly rations were almost depleted, and although all impoverished families in hp received two months of advance rations in april, the increased number of mouths to feed caused stress and rationing. in times of household food scarcity, it is typically the women who eat "last and least" (lentz, narayanan, and de ) , and we heard many reports of similar scenarios across field sites. one nepali woman stated she used to eat at a.m., but since her household had swelled to people, she was too busy cooking for others, so she now ate alone at noon (sunita, gokulganga, may , ). although the risk of contracting the coronavirus through food supplies is minimal, there were widespread perceptions in the villages that vegetables and rations that came from distant market towns could be holding virus particles. one woman in hp lamented, the vegetables come from the mandis [markets], which are very crowded. who knows how many hands it has passed through? if one person gets corona the whole village will get it. (santosh, india, june , ) these anxieties around virus contraction, some unfounded, meant that there were marked declines in dietary diversity, and women had to go to extra lengths to secure vegetables within the village. moreover, women sought to quell household anxiety through more arduous food preparations typically reserved for festivals. this was also something that family members demanded. this was especially true in nepal, which has higher rates of urban out-migration than india. in one nepal site, a . nepal does not have a national food subsidy program like india, so families there received no rations. . pseudonyms are used for all interviews to protect anonymity. woman reported feeling highly stressed because her children had returned from kathmandu and would "get irritated to eat maize every meal," instead requesting common street food snacks and fruit, which she could only sometimes provide (sunita, gokulganga, may , ). women derive much intra-household bargaining power through their roles as food provisioners, and their inability to meet family members demands in a time of scarcity and stress caused them great anxiety. it is critical to note that although most respondents we spoke to had some agricultural lands from which to procure foods, many spoke of marginalized landless households who were suffering because of the shutdown of their daily labor jobs (birbal, sirmour, june , ). alongside more food preparation, women also had to make more trips to haul water and collect fuelwood for their cookstoves. because of fears around both the virus and the police, women reported having to haul water from more distant, less utilized water springs or taking circuitous routes to the forest to avoid roadways where police were strictly enforcing lockdown. women were also responsible for enacting disease prevention measures and attending to the emotional needs of family members fearful about the pandemic. most villagers got information about covid- from television news and forwarded whatsapp messages. given the dearth of information from state or local officials, our respondents took conservative approaches to disease prevention. these included ensuring their children wore masks and practiced proper hand hygiene as well as preparing heated water throughout the day to ensure good immunity against the virus. as most women operated wood-burning cookstoves, this necessitated more frequent trips to forests for firewood. finally, with transport shutdown, there was little ability to go to the hospital or clinic so if householders got ill, the women were responsible for caring for them with traditional remedies. in hp, women also became schoolmasters for children, receiving daily homework assignments via whatsapp to distribute to their children, whom they also supervised. women largely reported that their children were unable to focus on or complete school work. this caused them stress as they mourned a lost year of their children's education. scholars have found that rural parents in india often sustain their own hope for the gendered impacts of covid- amid agrarian distress the future through investing in children's education (jakimow ) . perhaps a more enduring yet subtle impact will be on women's diminishing emotional resources to sustain hope through their children's education: one year of my son's life is lost and as per age he will be behind because in the future if he sits for tests for army, etc., then it will be problematic. . . . even if they pass the child but he does not know anything that a class student should know and it will cause problem later. half the year has passed now and doesn't look like the disease will get over anytime soon. (sunita, sirmour, may , ) moreover, the ability of children to complete schoolwork was dependent on having a working smartphone in the house, leading to further marginalization of the poor. while women faced significant expansions in the burden of care labor, our data also suggest a reduction in agricultural labor because of the presence of more people at home. for example, in hp, one woman explained there are more people at home so work was completed faster. she said, everyone helps in harvesting wheat in the farm. work that took two days now takes one day. now we have a lot more free time. now, we have - hours of rest [whereas] earlier [we had] had only hour of rest. (kiran, sirmour, may , ) experiences similar to kiran's were observed and reported in every field site. while in some households, girl children were tasked with greater work while boys focused on their studies, most respondents reported that boys would attend to fields and animals while girls assisted with cleaning and cooking. these findings highlight how agrarian distress has been shouldered by women as men increasingly seek labor work and children pursue studies in both nearby and distant towns. the data resonate with other scholars' assertion that the so-called feminization of agriculture seen across the global south might be more aptly called the feminization of agrarian distress as women's increased responsibility is not due to empowerment but to other family members' eagerness to escape the drudgery of smallholder farming. interestingly, some women also expressed happiness that their families were together, highlighting how the presence of additional household members not only reduced the agriculture work burden but also sometimes improved psychosocial well-being. while feminist scholarship has long highlighted the exploitation that occurs in the paid and unpaid care economy, there has been slow movement to structure a comprehensive policy approach to address this within south asia. however, as policies to mitigate covid- have been disproportionately subsidized by women's unpaid care labor, relief efforts offer an opportunity to begin to recognize and compensate women's substantial contributions to the economy. similarly, the impacts shed light on the ongoing phenomenon of rural distress being shouldered by women. a comprehensive policy solution would include social support (e.g., cash entitlements) to women as subsidies for unpaid labor but also create a broader investment portfolio into agrarian india to reduce the need for out-migration and reduce the drudgery of women's work. women's concerns around food, water, and fuel security alongside adequate transport for health service need to be addressed through provisions by state and local government councils. in the medium term, however, we concur with wenham, smith, and morgan ( ) that for any response to be effective, women's voices must be better represented within all relief policies. this resonates with policy recommendations put forth by feminist collectives both in india (dasgupta and mitra ) and globally (https://www.feministcovidresponse.com). while covid- and the lockdown have exacerbated gender inequities, they have also highlighted how during "normal" times rural women are individually responsible for an untenably broad range of activities in the home and agricultural fields. an effective feminist relief policy, therefore, should not only compensate and acknowledge the central role women are playing in the covid-response but should seek to learn from these . we do not wish to depict an overly sanguine picture, as there is substantive evidence of increased domestic violence across india and other countries throughout the lockdown. however, our data suggest a more complex picture in which many women also sincerely expressed improved well-being as their families were unexpectedly reunited. . wenham, smith, and morgan ( ) rightly caution that while women should have a larger say in policy and governance, this need not be another (unpaid) responsibility and proper compensation should be rendered. labor dynamics to produce policies that can shift gender inequities across the longer term. carly e. nichols is assistant professor in the department of geographical and sustainability sciences and global health studies at the university of iowa: carly-nichols@uiowa.edu; falak jalali is a phd student at the university of iowa: falak-jalali@uiowa.edu; syed shoaib ali is a phd candidate at ambedkar university: ssali. @stu.aud.ac.in; divya gupta is a senior research fellow at the indian school of business: divya_gupta@isb.edu; suchita shrestha is a researcher at the southasia institute of advanced studies: suchita@sias.-southasia.org; harry fischer is associate senior lecturer at the swedish university of agricultural sciences: harry.fischer@slu.edu a gender-responsive policy and fiscal response to the pandemic clinging to hope through education: the consequences of hope for rural laborers in telangana, india india's covid- gender blind spot last and least: findings on intrahousehold undernutrition from participatory research in south asia the feminization of agriculture or the feminization of agrarian distress? tracking the trajectory of women in agriculture in india feminist political economy: looking back, looking forward covid- : the gendered impacts of the outbreak this research would not have been possible without the untiring efforts of our field staff in india and nepal. we express our deep gratitude for their patience in helping us understand what their communities, families, and friends have experienced were going through in the midst of the global pandemic. this research was supported by the swedish research council (vetenskapsrådet) research project - . key: cord- -ibrzx c authors: aswal, d. k. title: quality infrastructure of india and its importance for inclusive national growth date: - - journal: mapan doi: . /s - - - sha: doc_id: cord_uid: ibrzx c in this feature article, the quality infrastructure (qi) of india is discussed. a national qi is comprised of internationally recognized metrology, standards and accreditation. the qi built on a technical hierarchy to ensure the accuracy and precision of measurements traceable to si units, is basic enabling system for providing the conformity assessment (calibration and testing, certification and inspection). the qi is an invisible force that binds the four helices, namely government, university, s&t institutions, civil society & media and enterprises, which are responsible for the growth of economy and quality of life. the existing apex capabilities of national physical laboratory, india—the national metrology institute of the country, national accreditation board for testing and calibration laboratories and the bureau of indian standards, are described. the mechanisms of enhancing the individual capabilities of these qi institutions and to boost synergy amongst them are presented. the need of a robust qi facility by various stakeholders in the areas of implementation of regulations, industrial growth, international trade, food safety, environmental monitoring, sustainable energy, affordable health, attraction of foreign investments, etc. is highlighted. for the year , the international monetary fund (imf) has listed india as the fifth largest economy of the world with gross domestic product (gdp) of $ . trillion. usa ($ . trillion), china ($ . trillion) japan ($ . trillion) and germany ($ . trillion) are ahead of india [ ] . india is aiming a goal of becoming a $ trillion economy by [ ] , which is a must to cater the livelihood of its large current population of . billion and that is expected to grow to . billion by [ ] . this implies an exponential-like growth is needed for all the sectors contributing to the gdp, i.e. agriculture, service and industry. in addition, the export growth rate should be significantly high. two recent books have aspiringly predicted that by harnessing technology and with a collaborative political, regulatory and business, the economy of india can surpass $ trillion by - [ , ] . it is well known that india is a country of magnificent paradoxes, and therefore, to enhance its economy and quality of life, a synergy between the government and business, demographics and democracy, culture and modernity, traditional knowledge and modern science & technology, etc. needs to be made stronger. unfortunately, the end of december witnessed the beginning of the new coronavirus (ncov ) pandemic that has infected more than four million people and killed [ , worldwide till date (may , ). it is good news that [ . million people have also recovered [ ] . the virus causing coronavirus-induced disease (covid- ) is transmitted through droplets released during the exhales, coughs or sneezes of an infected person. to avoid the spread of pandemic, most of the governments across the world imposed a complete lockdown for month together [ ] . this has resulted in halting all the economic activities worldwide, which has resulted in the loss of employment and prompted mass return of migrants to their native places [ ] . this will pose a great difficulty in reviving the economy, and therefore, a new thinking will need to be evolved to achieve the set targets of the economy. quadruple helix (qh) model of carayannis and campbell is widely used to understand how economies improve through the interactions amongst government, university/science & technology (s&t), industries and civil society & media [ ] . a schematic of qh model along with the responsibilities of each of the helices is depicted in fig. . qh model essentially is an extension of triple helix (th) model of etzkowitz and leydesdorff that deals with dynamics and evolution of university (s&t)-industrygovernment relations and their impact on global economy and other challenges, including unemployment, low economic growth, healthcare needs, environment and uncoordinated regulatory systems [ ] [ ] [ ] . the civil society and media were added in the qh model so that the innovation can effectively be communicated to the masses. in developed nations, the interactions amongst the four helices of qh are very strong and work in all directions, i.e. top down, bottom up, sideways and criss-cross. these strong interactions are facilitated through an invisible but robust quality infrastructure (qi), which ensures conformity assessment through well-established institutions of metrology, accreditation and standards. the qi in developed nations, e.g. usa, is well established and, therefore, has the strongest s&t and industrial policies resulting in their high gdp [ ] . united nations industrial development organization (unido) has extensively been working to strengthen the industrial growth of developing nations [ ] [ ] [ ] . unido defines the qi as: ''the system comprising the organizations (public and private) together with the policies, relevant legal and regulatory framework, and practices needed to support and enhance the quality, safety and environmental soundness of goods, services and processes. the quality infrastructure is required for the effective operation of domestic markets, and its international recognition is important to enable access to foreign markets. it is a critical element in promoting and sustaining economic development, as well as environmental and social wellbeing. it relies on metrology, standardization, accreditation, conformity assessment, and market surveillance''. in a country, as depicted in fig. . the quality infrastructure institutions, i.e. metrology, accreditation and standards, are usually formulated under national quality policy to ensure the qi services of conformity assessment through calibration, testing, certification and inspection. metrology is the science of measurement (physical, chemical and biological properties), embracing both experimental and theoretical determinations at any level of uncertainty in any field of science and technology [ ] . metrology is often classified into scientific metrology, industrial metrology and legal metrology. scientific metrology deals with research and development of new measurement standards as well as their maintenance and dissemination. this is performed by national metrology institutes (nmi) of the country. industrial metrology deals with the application of metrology to industrial processes and ensures the correctness of measurement instruments through their calibration. precise and accurate measurements improve the quality of the product and, therefore, their market. the strength of industrial metrology, therefore, governs the economic and industrial development of a country. legal metrology deals with the statutory requirements concerning measurements as well as the law enforcement on measurements. these statutory requirements arise from a need for the protection of public health and safety, consumers rights, enabling taxation, the environment, and fair trade are performed by competent bodies. accreditation is a process by which an authorized body officially recognizes (i.e. third-party attestation) that the person or organization is competent to carry out specific fig. well-functioned quadruple helix (qh) comprising governmentuniversity/s&t institutesindustry-civil society & media is needed to achieve a high economy and high quality of life. a robust quality infrastructure (qi) is essential for facilitating the strong interactions amongst the helices of qh tasks with a level of internationally accepted competence. standardization involves development of technical standards and their implementation to ensure the quality, compatibility, interoperability and safety. therefore, qi is the basic enabling system of a nation for providing the conformity assessment (compliance with standards and technical regulations) of products and processes with international acceptance through calibration and testing (the determination of the characteristics of a product), certification (a formal and written confirmation that a product, service, organization, system or individual complies with a given set of specifications and/or standards) and inspection (the determination whether products meet the requirements of a given standard) [ ] . qi in nutshell is a complete package for all-round growth of a nation as it: ( ) contributes to the formulation of government policies and regulations for s&t, industrial development and competitive international trade; ( ) supports enterprises for production of international competitive products and apprises them new trade standards; ( ) assists s&t institutions for scientific discoveries and innovation through accurate and precise measurements; and ( ) addresses the needs of the consumers in terms of quality products and services at par with international standards, food and health safety, environment and climate change, and efficient use of natural and human resources. the qi also acts a foundation for achieving the sustainable figure summarizes the international qi organizations along with the qi institutions of india and a comparison with that of usa-one of the best qi in the world. india has the desired qi system, and all of its three components, namely metrology, accreditation and standards, have wellestablished international affiliations. however, despite international affiliations, the qi strength of different countries can be widely dissimilar. the strength of qi system of a nation mainly depends upon ( ) overall measurable capabilities of international equivalence available with apex qi institutions and ( ) the dissemination mechanism of the available qi capabilities to all the stakeholders across the country. in usa, as shown in fig. , the national institute of standard and technology (nist) has multiple responsibilities, i.e. scientific metrology, legal metrology (ilmg/nist), accreditation (nvlap/nist) and standards [ ] . multiple roles of nist's for measurements, standards and legal metrology allow them to ensure measurement traceability for quality assurance as well as in harmonizing the documentary standards and regulatory notifications. for accreditation and standards, usa has multiple organizations (as listed in fig. [ , ] . as can be seen from the kcdb-bipm, npl, india has cmcs which is much lower as compared to cmcs of nist, usa. tables and summarize the cmcs and key/supplementary comparisons of npl-india that covers several metrology areas related to physico-mechanical, electrical and electronics, time and frequency, chemistry, etc. in addition, the barc has key/supplementary comparisons, as listed in table , in the area of ionization radiation. the interlaboratory comparisons are prerequisite for the declaration of cmcs. a large number of cmcs indicate that the nmi has participated in technologically complex interlaboratory comparisons and, therefore, has measurement capabilities in wide range of science and technology that facilitates their fundamental science and creates new technology and innovations, which in turn contributes to their economy and quality of life. therefore, there is a need for both npl and barc to enhance their cmcs at the kcdb. in , npli has launched certified reference materials under the trademarked as bhartiya nirdeshak dravya, bnd Ò [ ]. so far bnds have been launched related to high purity gold, coal, cement, water, hardness, petroleum products, etc. the indigenous development of bnds has greatly benefited the relevant indian industries in terms of ease of availability, low cost and savings of foreign exchange. npl is a member of comar (code d'indexation des matériaux de référence) database [ ] , and therefore, the information on bnds is also uploaded on comar database for the international community. as crms/bnds are the standards used to ensure quality and metrological traceability of products, to validate analytical measurement methods, or for the calibration of instruments, npl needs to develop bnds belonging to several fields, such as food, edible oils, minerals, heavy metals, pesticides, pharmaceuticals and textiles to ensure the quality and safety of the products. the benefits of the metrology need to be transferred to the common citizen of a country, and this is often done by legal metrology through appropriate law enforcement. the legal metrology ensures fair trade, specifically in the area of weights and measures, and has a main objective to assure citizens of correct measurements. the responsibilities of legal metrology system include ( ) type approval of measuring equipment, ( ) calibration and verification of measuring equipment, ( ) market surveillance of measuring equipment falling within the scope of regulation and ( ) controls of pre-packaged goods. therefore, legal metrology is an integral part of technical regulation regime and has to comply with the requirements of agreement on technical barriers to trade (tbt agreement) of world trade organization (wto). in addition, legal metrology is needed for technical regulations to protect the health and internationally, the standards are known to offer economic benefits to industries in the following ways: ( ) optimization of the internal operations of the industry that may result in reduction in operational time, increase in productivity, decrease in waste and reduction in procurement costs, ( ) innovation in new processes and products as well as scaling up operations/manufacturing, ( ) identification of new domestic and export markets. therefore, standards not only assist in improving the quality of products in the country but also help in exporting them. though bis is the standard body of india but several other ministries and departments develop standards for their area of specializations, usually referred as standard development organization (sdo), and few of these standards are adopted also by the bis. these sdo's are: [ ] . nabl does accreditation of conformity assessment bodies (cab) including calibration and testing laboratories (iso ), proficiency testing provider (ptp) using iso and reference material producers (rmp) using iso . the accreditation process has a responsibility to ensure that the cab meets metrological traceability to si units through the primary/national measurement standards of the nmi, as depicted in fig. . thus, nabl accreditation of testing laboratories produces test results of internationally acceptable level of competence. as shown in table , nabl so far has granted [ accreditations to calibration laboratories, testing laboratories, medical laboratories, proficiency testing provider and reference material producers. the scope of nabl accreditation is ( ) calibration laboratories: electrotechnical, mechanical, fluid flow, thermal, optical, radiological and medical devices; ( ) testing laboratories: biological, chemical, electrical, electronics, fluid flow, mechanical, non-destructive testing (ndt), photometry, radiological, forensic, diagnostic radiology qa testing and software & it system; ( ) medical laboratories: clinical biochemistry, clinical pathology, haematology & immunohematology, microbiology & infectious disease serology, histopathology, cytopathology, flow cytometry, genetics, nuclear medicine (in vitro tests only); ( ) reference material producers: chemical composition, biological & clinical properties, physical properties, engineering properties and miscellaneous properties. during the period of covid pandemic, nabl has accredited medical testing laboratories across the country for rt-pcr rna virus/ covid- , which has greatly benefited the country in terms of conducting these very important tests. nabl accreditation has advantage in terms of enhance business as major government ministries and regulators (e.g. bis, legal metrology, directorate general for foreign trade, ministry of drinking water and sanitation, ministry of health & family welfare, food safety and standards authority of india, etc.) have mandated nabl accreditation for all laboratories performing conformity assessment for their schemes. similarly, for rmps, the nabl accreditation has an advantage that they obtain metrological traceability from the npl and, therefore, can produce and market their certified reference materials under the bnd Ò , which are reached to international community through comar database. the accreditation of cabs not requiring the metrology traceability is conducted by other boards of qci, namely national accreditation board for certification bodies (nabcb) [ ] , national accreditation board for hospitals and healthcare providers (nabh) [ ] and national accreditation board for education & training (nabet) [ ] . the nabcb operates under the framework of iso and accredits cabs for inspection bodies (e.g. bis for product certification), management systems for food safety, medical devices, environmental monitoring, health safety, occupational hazards, information security, energy, etc. other boards, namely nabet for the management of education and training and nabh for the management of hospitals, function under self-regulation. figure shows the photograph of the ''graffiti wall'' at npl campus that was painted on may to mark the worldwide implementation of redefinition of si units based on the fundamental constants. it is evident that the accurate measurements that get implemented though rigorous conformity assessment contribute to the overall growth of the country through discoveries and innovations in the areas of science, development of high end technologies, sustainable green energy, environment free from pollution, affordable healthcare system, enhanced international trade, strong cybersecurity, and formulation regulation and policies that benefits the country. conformity assessment ensures manufacturers that their products and services are in accordance with the desired specifications of national/ international standards, ensuring quality, reliability, efficiency, safety, effectiveness, interoperability and environmental sustainability. a certification mark based on conformity assessment provides consumer a confidence that he/she has got the products or services of the desired specification. such products can be exported without facing any hurdle to technical barrier to trade. table summarizes a partial list of authorities of government of india related to regulators, policies, science and technology, forensic, strategic sectors, etc. all of them need conformity assessments to meet their targets. the regulators demand mandatory conformity assessment in the regulation that allows them to enforce legislation pertaining to national health, safety, food, radiation safety, finance, energy, environment, etc. the regulators, through appropriate legal and regulatory notifications in their domain, ensure that the interests of the public are protected. in order to implement and enforce their regulations, they require the conformity assessment of technical, safety and quality standards. for example, the central pollution control board (cpcb) has the major responsibility of prevention, control or abatement of water and air pollution across the country. to implement these, cpcb requires a robust quality infrastructure to ensure that the measured data on air and water pollutions are trustworthy. currently, the air quality and emission monitoring equipment in the country are calibrated and certified by foreign certifying agencies as the country did not have any certification agencies having the primary measurement standards. recently, the government of india has gazette notified the npl as the certifying agency for the air quality and industrial emission monitoring equipment in the country as per the indian standards, which not only will bring down the costs but also improve the measurement accuracies. it is very essential for the regulators to be aware of the all of them need conformity assessment to meet their targets quality infrastructure of india and its importance for inclusive national growth metrological capabilities of npl in their respective area of technical confirmatory assessments, otherwise the possibility of introducing unnecessary regulations or technical requirements may exist, which can become difficult to comply. in addition, if the regulations are substantially different to those of other countries, then they can lead to technical barriers to trade. therefore, robust conformity assessment services, harmonized internationally, are essential for facilitation of smooth import/export services. poor conformity assessment services can allow entry of the imports which are substandard and toxic in nature. one can find several news reports stating the import of poor quality [ ] [ ] [ ] [ ] [ ] [ ] , e.g. steel, toys, tyres, light emitting diodes (leds), electronic items, solar panels, food items, etc. similarly, inferior conformity assessments procedures can lead to technical barriers to trade, causing hurdles to the cross-border trade. the exporters are asked for multiple testing and/or certification of products, and in many cases, the products are rejected at the border causing them a huge monitory loss. there are several cases of the rejection of indian export at the border of foreign country due to not meeting the standards [ ] [ ] [ ] . in both the cases, i.e. import of poor-quality products and rejection of indian exports, the nation undergoes a huge economic loss. in the case of poor-quality imports having toxicity, not only their disposal becomes economic burden but also are the sources for health hazards. a strong quality infrastructure is also needed for the strengthening of micro, small and medium enterprises (msme) [ ] sector as well as the make in india programme initiated by department of industrial policy and promotion (dipp) [ ] . msmes are spread across the country and produce a range of products that cater the needs of local as well as global market. according to a report, msme contributed % of the gdp, created % of the manufacturing output and contributed to the % of the exports [ ] . in addition, msmes provide large employment opportunities (second after the agriculture sector) and act as the nucleation for entrepreneurship and innovation. however, it has been observed that contributions of msmes are declining gradually in gdp, manufacturing output and exports. the difficulties of msmes have further escalated by the outbreak of the covid- pandemic as the nation went for a complete lockdown for months together. after the relaxation in the lockdown, majority of the workers migrated to their native villages, and this would create acute manpower shortage to the msmes. therefore, to revive the msmes in coming days, new government policies should be formulated in which the concept of quality infrastructure must be built to ensure the production of internationally competitive products. moreover, the success of make in india, which is an excellent programme that encourages foreign companies to manufacture their products in india and aims at creating new job opportunities, requires an established quality infrastructure at par with international standard. a strong qi assists in the attraction of foreign investment as it allows innovation for the development products (e.g. analytical instruments, medical, defence, aerospace, etc.) compatible to indian environmental conditions as well as their conformity assessment as per the national/international standards. all the three pillars of quality infrastructure (i.e. metrology, standards and accreditation) are well placed in india. however, the strengthening of quality infrastructure would require ( ) enhancing the apex capabilities by npl/barc/ lm, all the boards under qci (including nabl) and bis, and ( ) a better synergy amongst these three pillars. the synergized qi should establish a collaboration with four helices (government, university/s&t institutions, civil society & media and enterprises), for enhancing the growth of economy and quality of life. to strengthen the quality infrastructure of the country, the following suggestions are made. of npl reported at kcdb of bipm need to be expanded for the areas belonging to energy, environment monitoring, biomedical, quantum standards, indian standard time (ist), etc. of course, the setting of new primary/national standards requires high capital investment, trained manpower and international intercomparison. npl has taken up setting up of primary standards in the areas of air quality and emission monitoring as well as in the solar cell efficiency. it is creditable that npl has trademarked the certified reference materials as bhartiya nirdeshak dravya (bnd Ò ) and has already developed a national mechanism for the production of bnds in collaboration with indian industries producing the reference materials in the fields of petroleum, cement, water, soil, metals and minerals, food, etc. these bnds are essential to support several thousands of laboratories across the country for generating the accurate and reliable test results. . nabl has accredited [ laboratories in different fields but has a long way to go as several thousands of the laboratories still need to be accredited. in order to ensure the metrological traceability to si units, the nabl should categorize calibration laboratories into two tiers. the tier calibration laboratories (equivalent to those of regional reference laboratories of legal metrology) get the measurement traceability directly from the npl and, therefore, will have lower measurement uncertainty. tier status can be assigned to laboratories under different ministries and/or private laboratories having the desired infrastructure and assessed by npl. the tier calibration laboratories would get the measurement traceability from tier and disseminate them to testing laboratories across the country. . bis should also develop new indian standards that benefit the msmes. moreover, testing laboratories used for conformity assessment should ensure the measurement traceability to the si units. to sum up, a strong qi is essential for the ''made in india'' programme that becomes almost essential for the nation in view of the covid pandemic, whereby the fundamental shifts in the national policies are expected. to revive the national economy and creation of employment, msmes need to be encouraged for the development of products as per the international standards by ensuring that they utilize the existing quality infrastructure of the country. from fifth-largest to $ -trillion economy navigating india: $ trillion opportunity india: a trillion economy by - ? rolling updates on coronavirus disease (covid- ), world health organization coronavirus india lockdown day live updates coronavirus: lockdown in india has affected million migrants, says world bank, business today mode and quadruple helix: toward a st century fractal innovation ecosystem the triple helix-university-industry-government relations: a laboratory for knowledge-based economic development the dynamics of innovation: from national systems and mode to a triple helix of university-industry-government relations the future of the university and the university of the future: evolution of ivory tower to entrepreneurial paradigm quality infrastructure: unido's unique approach quality infrastructure-building trust for trade, the united nations industrial development organization (unido) measurement of quality infrastructure what is metrology? bipm what is conformity assessment? international organization for standardization inetqi: international network on quality infrastructure department of consumers affairs international equivalence of measurements: the cipm mra calibration and measurement capabilities (cmcs), international bureau of weights and measures (bipm) the si redefinition to come into force from redefined si units and their implications the legal metrology act agricultural & processed food products export development authority (apeda) quality infrastructure of india and its importance for inclusive national growth directorate of marketing and inspection (dmi) the food safety and standards authority of india (fssai) ministry of ayush (ayurveda, yoga & naturopathy, unani, siddha and homoeopathy standardisation testing and quality certification (stqc) national accreditation board for testing and calibration laboratories (nabl international laboratory accreditation co-operation (ilac) national accreditation board for hospitals and healthcare providers (nabh) cheap imports and quality-killing cancer india's booming solar sector has one major flaw: poor quality, quartz india eight chinese pharma cos to be blacklisted for quality issues, may lead to shortage of medicines, firstpost low quality imports harm india's led market battery making firms wants government to prevent poor quality imports from china why so many indian food product exports get rejected, rediff.com 'made-in-india' items rejected by us-fda in yrs food industry must focus on quality to avoid rejection in export mkt: govt, india today make in india, department of industrial policy and promotion recommendations of the inter-ministerial committee for accelerating manufacturing in micro, small & medium enterprises sector about certified reference materials -about comar key: cord- -bhnv qbi authors: senapati, apurbalal; nag, amitava; mondal, arunendu; maji, soumen title: a novel framework for covid- case prediction through piecewise regression in india date: - - journal: int j inf technol doi: . /s - - - sha: doc_id: cord_uid: bhnv qbi outbreak of covid- , created a disastrous situation in more than countries around the world. thus the prediction of the future trend of the disease in different countries can be useful for managing the outbreak. several data driven works have been done for the prediction of covid- cases and these data uses features of past data for future prediction. in this study the machine learning (ml)-guided linear regression model has been used to address the different types of covid- related issues. the linear regression model has been fitted into the dataset to deal with the total number of positive cases, and the number of recoveries for different states in india such as maharashtra, west bengal, kerala, delhi and assam. from the current analysis of covid- data it has been observed that trend of per day number of infection follows linearly and then increases exponentially. this property has been incorporated into our prediction and the piecewise linear regression is the best suited model to adopt this property. the experimental results shows the superiority of the proposed scheme and to the best of our knowledge this is a new approach towards the prediction of covid- . the pandemic corona virus disease (covid- ) has spread all over the world and every country is trying their way to contain the disease. on march , , who declared the outbreak of covid- as a global pandemic. some countries like taiwan, south korea, vietnam, new zealand, germany, france etc. successfully control the disease but many countries including india, usa, and brazil is still struggling to suppress the pandemic. after lockdown up to st may , government of india started to unlock the country in a phased manner because it was not possible for a developing country like india to bear the financial losses of prolonged shut down of the entire country. from st june to th june has been declared as unlock- , st july to st july has been declared as unlock- and from st august to st august has been declared as unlock- . in all these unlock phases government of india have provided guidelines to general people as well as different organizations about how to operate/perform businesses, transportations, festivals and other social and commercial activities. a visual representation of the pandemic along with time frame and important decision of the indian government has been given in fig. . till today, indeed, no matter whatever actions/ precautions/ decisions government of india has taken, the spread of covid- across the different states of the country couldnt be stopped, which creates panic to millions of people all over the country. almost all the states across india, the new cases as well as deaths are increasing exponentially. because of the increase in the number of patients with limited healthcarerelated infrastructures, some states have started to impose lockdown either partially or fully from the middle of july during unlock phase- . due to this increased complexity in normal life, it has impacted the financial health of the different country and to anticipate additional resource requirements to combat covid- , the prediction of future development trend of the pandemic has become a very popular research topic in recent days. various mathematical and statistical forecasting tools [ ] [ ] [ ] [ ] [ ] were applied to generate short-term and long-term forecasts. multiple machine learning tools such as multiple regression analysis [ ] , progressive partial derivative linear regression model [ ] , and a hybrid approach of the auto regressive integrated moving average model and wavelet-based forecasting model [ ] have also been applied to make these predictions. different types of covid- related issues has been addressed in this study, with the help of the piecewise regression model, such as total number of positive cases, and the number of recoveries for different states in india such as maharashtra, west bengal, kerala, delhi and assam. our observation from the covid- data is that it follows the linear trend within a few days and after which pattern becomes non-linear. this property has been incorporated in piecewise linear regression, which is best suited model to adopt this linear property. moreover, the proposed scheme is also used to predict the number of total confirmed cases, active positive cases, and recoveries. we have chosen these five states because maharashtra is the most affected state where the number of positive cases is maximum while west bengal is within the top ten most affected states in india. the situation in delhi and kerala is a bit different from other states, while in delhi the number of cases is decreasing in recent days, but in kerala after controlling their daily infection rate, the number of positive cases per days increasing further. we have included assam also in our study because, in northeast india, assam is the state where the number of positive cases per day is increasing in alarming rate although initially, assam was very much successful to combat the spreading of the disease by taking corrective and preventive measures in advance. however, no states have yet become successful to cure covid- completely. therefore, it is important to detect the epidemic pattern for planning the early action to combating covid- . machine learning (ml) can help us to infer useful knowledge from past massive epidemic data. several researchers [ ] [ ] [ ] [ ] [ ] have adopted machine learning based approach to analyze covid- cases. ml is subdomain of artificial intelligence (ai) [ , ] . it can intelligently solve a variety of problems with the help of learning from the recorded information. generally, ml algorithms are classified into supervised learning and unsupervised learning [ ] . regression analysis, a part of supervised learning is a powerful statistical tool to utilizes previous experience or example data in making prediction through the learning strategy. based on the various learning strategies, there are many regression models such as linear regression, logistic regression, multiple regression, piecewise/ stepwise regression, etc. [ ] [ ] [ ] . in this paper, we use piecewise linear regression approach to predict and track the spreading of the virus. the proposed scheme can be a magnificent weapon for early alerts against battling covid- . the main contributions of this paper are given below: the rest of the paper is organized as follows. an overview of doubling exponential model and piecewise regression approach is presented in section . section provides the experimental results and discusses in detail the trend of covid- cases. finally in sect. , conclusions and future work are depicted. in this section, we have discussed in details of our proposed scheme based linear regression model for prediction of the number of total confirmed cases, active positive cases, and recoveries. firstly, infection spreading has been discussed, followed by the linear regression model used in the proposed work. in the proposed scheme, different types of data of various states such as data for confirmed cases, active positive cases, and recoveries have been collected. we have defined the infection spreading from the concept of exponential growth function or in particularly from the doubling exponential. first we describe the double exponent in brief and then it shows how the infection spreading is adopted from the doubling exponential. so far, many mathematical models characterized the early epidemic growth feature follow an exponential curve. some of them characterized the exponential growth by the doubling time. the doubling time implies the time taken for the number of infections to double from a given day. we have also adopted the doubling concept with the different interpretation. hence, for our model we consider the exponential function as. here, instead of finding the number of infections at time t, we find the doubling time from the given y(t) i.e. the number of positive cases. in our experiment, define the doubling time as the number of days taken to become the double of the current count. mathematically it can be defined as, if n is the positive case count at time t then ð  nÞ is the positive case count at time at a time ðt þ t d Þ, fig. . figure clearly shows that initially it is a highly spreading situation. but, practically that was not happened; the graph shows it because of the initial low value. the positive case starts with one, then it became double ð Â Þ as two, ð Â Þ four, and so on but it does not mean high infection but is the boundary value problem. next, it shows the infection spreading reaches the highest level i.e. the peak and gradually spreading became low and again it is gradually high. it indicates in the state kerala there is a second phase infection spreading is going on. the most notable case for delhi, it shows that it is gradually diminishing the spreading curve. on the other hand, for the state west bengal the spreading is tends to high. in our prediction model the piecewise linear regression have been used, it is a special case of the linear regression. sometimes data do not follow the linear pattern as shown in fig. a . however, if it still tries to model them using the linear regression then it will not be properly correlated. when such a model uses to predict, then it results high error value. in that situation, one line simply is not enough to fit the data, then the concept of piecewise linear regression comes to overcome such limitation as depicted in fig. b . when the data set follows different linear trends over the different partitions of data, then we should model the regression function in several pieces. each linear regression is corresponding to a partition is the pieces and the pieces are connected or not connected depends on the data and the problem. in case of connections, the connecting points are known as the break points, i.e. the points where the slope changes. the point at x ¼ p is the joining point of two lines, i.e., a breakpoint. our assumption is that the regression function to be continuous at the breakpoint, the two values for y need to be equal at the breakpoint (when x = p), i.e., we have the relation the same concept can be extended for more than two breakpoints, and it depends on the data. to implement this model from a given data set, the main challenge is to partition the data set for the piecewise regression. in other words, the problems are to find out the breakpoints from the data set. in our experiment, we have done by finding the slope of the consecutive pairwise points, i.e., if there are n points, then there will be ðn À Þ such slopes. from these slopes, whenever there is an abrupt change, then we consider that point is the breakpoint. this is done by the heuristic approach by the observation of the slopes. this section presents the experimental results in detail and discusses trend possibilities in the future. in our prediction, we have considered the training data up to th september . the prediction results of confirm and cure cases of covid- upto - - are listed in tables and respectively. the source of the dataset used in this paper for the covid- outbreak of india is kaggle [ ] . the cumulative confirm cases and daily confirm cases of covid- for selected states in india are shown in fig. . cumulative confirmed and daily confirmed covid- cases has increased exponentially in maharashtra, whereas also would be increased further in near future as per our predicted model. however, it has been spotted that daily confirmed cases in delhi is decreasing in nature and following the same trend in upcoming days. also, from our study, it is inferred that in the case of kerala, west bengal and assam follows the same current trend in the upcoming month. figure shows cumulative confirm cases and daily confirm cases of covid- for five states separately. figure provide the cumulative recovery cases and daily recovery cases respectively of covid- for selected states in india. the predicted results for cumulative confirm cases are also shown in table . in the earlier section, we have seen that the maximum cumulative and daily basis positive active cases have been found in the state of maharashtra. and the same trend has been observed in maharashtra for the current and predicted recovery cases from covid- . sometimes, delhi has also reported maximum daily recovery cases. also, from our study, it is perceived that in the case of kerala, west bengal and assam follows the same current trend in the upcoming month. a comparison is carried out with an existing other system on the regression model of a sixth-degree polynomial [ ] . for the compatibility, we have considered the same training data as of that system and predicted the dated as they predicted. the training data is used in [ ] from st march to th april and predicted for the next seven days i.e. from th april to th april . on the other hand, our proposed approach uses the training data from st march, to th september and predicts confirm and cure cases till th october, . moreover, the proposed model also addresses the cure cases which is missing in [ ] . table and fig. gives the details of the comparison. the magnitude of relative error (mre) and mean absolute percentage error (mape) are mostly used to measure the accuracy of regression based prediction model [ , ] . the performance of the proposed scheme is evaluated using the magnitude of relative error (mre) and mean absolute percentage error (mape). the magnitude of relative error (mre) is defined as and the mean absolute percentage error (mape) is where x i is actual value, y i is the predicted value and n is total number of observations. table presents the values of mre and mape for both of the positive covid- cases and recovery covid- cases. a lower mre value indicates that data are scattered close to the regression line. correspondingly small value of mape denotes that the differences between the actual and predicted values are small. therefore, it can be concluded from table that the actual and predicted values are much closed. the covid- outbreaks have become a disaster for several nations. however, the recovery rate of covid- in india is more than %. in this study, we have proposed the piecewise linear regression based machine learning approach for the prediction of actual positive cases and recovery cases of five different states in india. the main novelty of the proposed scheme is that we have applied piecewise linear regression method instead of simple linear regression. as a result, the proposed scheme produces an accurately predicted result for both cases. henceforth, it may be concluded that our model could be applicable for other parameters of covid- also in any state or country as well.in the future, we will focus on developing various ml-and dl-based model to enhance the performance to combat covid- as well as other pandemic may be. the main challenge to implement the piecewise linear regression is to find the point of partition of data .in this paper, the partition has been done by observing the slope of the point heuristically and we have considered the past days data to predict the next day. in future, our aim is to solve the problem to find an optimal partitioning point such that the error becomes minimum. xing x ( ) early transmission dynamics in wuhan, china, of novel corona virus infected pneumonia now casting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study analysis and forecast of covid- spreading in china, italy and france early dynamics of transmission and control of covid- : a mathematical modelling study preliminary estimation of the novel coronavirus disease (covid- ) cases in iran: a modelling analysis based on overseas cases and air travel data prediction of the number of deaths in india due to sars-cov- at weeks partial derivative nonlinear global pandemic machine learning prediction of covid data analysis of covid- epidemic using machine learning methods: a case study of india nemati nazafarin ( ) machine-learning approaches in covid- survival analysis and discharge-time likelihood prediction using clinical data covid- epidemic analysis using machine learning and deep learning algorithms din ud et al ( ) machine learning based approaches for detecting covid- using clinical text data real-time forecasts and risk assessment of novel coronavirus (covid- ) cases: a data-driven analysis a machine learning based method to detect epilepsy deep learning: evolution and expansion a review of supervised and unsupervised machine learning techniques for suspicious behavior recognition in intelligent surveillance system piecewise linear regression based on plane clustering regression based fpga power estimation tool ( fpetool ) for embedded multiplier block comparison and analysis of logistic regression, nave bayes and knn machine learning algorithms for credit card fraud detection covid- in india, dataset on novel corona virus disease in india alternatives to accuracy and bias metrics based on percentage errors for radiation belt modeling applications. no. la-ur- - an iot-based system to evaluate indoor air pollutants using grey relational analysis key: cord- -gahlq uh authors: chundakkadan, radeef; ravindran, rekha title: information flow and covid- recovery date: - - journal: world dev doi: . /j.worlddev. . sha: doc_id: cord_uid: gahlq uh this study examines whether the flow of information pertaining to covid- helps to contain the pandemic. we capture the information flow of the pandemic using the google search volume index for the keyword coronavirus+covid in states and union territories in india. we find that the information flow is inversely related to positive cases reported in these regions. this result suggests that internet inclusion is a relevant factor in the fight against the pandemic. pandemic. we capture the information flow of the pandemic using the google search volume index for the keyword coronavirus+covid in states and union territories in india. we find that the information flow is inversely related to positive cases reported in these regions. this result suggests that internet inclusion is a relevant factor in the fight against the pandemic. keywords: covid- ; google search volume index; pandemic recovery; india the novel coronavirus outbreak in china at the end of has spread widely across the world and infected more than . million people by th july . as a response, several governments have declared lockdowns and adopted strict social distancing and quarantine measures. on the one hand, these measures are crucial for slowing transmission of the pandemic; on the other hand, these measures have had severe economic consequences (see, for instance, imf, ; mckibbin and fernando, ; sumner et al., ) . the economic loss due to the pandemic is a function of how quickly the economy recovers and restarts its productive activities. since the covid- vaccine is not yet developed, the ideal strategy to contain the pandemic is through the proliferation of information pertaining to the coronavirus among the public and make them aware of the precautionary measures. as a result, governments all over the world and other institutions released online information to cope with the crisis. india is not an exception. since the first case reported in january, both state and central governments initiated various measures to tackle the spread of covid- . on th march , the government declared a nationwide lockdown for days; later, it was extended till may end. despite these efforts, india is still fighting to contain its spread as the number of affected cases continues to rise. as of th july , india registers , confirmed covid- cases, out of which there are , active cases, , deaths, , cured cases, and migrated case. the states which report the highest number of active cases are maharashtra, tamil nadu, delhi and karnataka while the north-eastern states are least affected. to contain the pandemic, various initiatives have been undertaken by the government through online platforms to make people aware of the symptoms and preventive measures. for instance, the government introduced a covid- tracking mobile application (known as 'arogya setu') which has over million installs. visit https://www.mohfw.gov.in/#state-data for current covid- status in india. in this article, we examine whether the information flow through online platforms helps in containing the spread by raising public awareness. for this purpose, we examine the relationship between the number of new cases reported and the information flow on covid- . to capture the information flow, we rely on the google search volume index (gsvi) for the keyword coronavirus+covid in each state of india. gsvi contains useful information about individuals' interest and attention, considering the growing access to the internet through mobile devices (narita and yin, ) . the google trend data has also been used in previous studies for the surveillance of disease outbreaks (carneiro and mylonakis, ). we use the data of units ( states and union territories) for the period ranging from st april to th july . the choice of the study period is based on the availability of data. we gather information on the number of confirmed cases, the number of tests conducted, and the population from https://api.covid india.org/; and gsvi from https://trends.google.com/. rather than using raw gsvi, we employ its moving average of days. therefore, it captures the average information flow of the pandemic for the last weeks. we present our estimation results in table . we regress the number of new cases on the information flow along with control variables. the control variables include the previous day's confirmed case, the total number of covid- tests and the population (in log). in addition, to capture the state-specific effects, we also include state dummies in our model. the estimation results posit that coefficient of lagged gsvi is negative and statistically significant at percent level. this result indicates that if the information is penetrating more, then it may help people to undertake necessary safety measures and can prevent the spread of the novel coronavirus. this finding suggests that the flow of covid- related information through the internet might be an effective containment strategy against the pandemic. we employ the -days moving average of gvsi in the analysis. the (log of) population projection of the national commission on population is used. robust standard errors in parentheses. *** p< . , ** p< . . despite the nation-wide lockdown and lockdowns based on containment zones, the number of covid- cases is still rising in india. in such a situation, using digital platforms to spread awareness about covid- is one of the appropriate strategies that will complement the other containment measures of government. a corollary, internet inclusion is a relevant factor in the fight against the pandemic. we recommend the government to design policies to improve internet access among people. google trends: a web-based tool for real-time surveillance of disease outbreaks world economic outlook cama working paper no. / . centre for applied macroeconomic analysis in search of information: use of google trends' data to narrow information gaps for low-income developing countries. imf working paper no. / . international monetary fund united nations university-world institute for development economics research examine whether the information flow through online platforms helps in containing covid- google search volume index is used to capture the information flow we find information penetration is inversely related to the number of new cases reported internet inclusion is a significant element to contain the pandemic date: -jul- the authors declare no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within three years of beginning the submitted work that could inappropriately influence, or be perceived to influence, our work.authors: dr. radeef chundakkadan : ms. rekha ravindran key: cord- -zb wxt authors: hardiman, david title: the influenza epidemic of and the adivasis of western india date: - - journal: soc hist med doi: . /shm/hks sha: doc_id: cord_uid: zb wxt the influenza epidemic of was the single worst outbreak of this disease known in history. this article examines an area of western india that was affected very badly—that of a tract inhabited by impoverished indigenous peoples, who are known in india as adivasis. the reasons for this are discussed. some oral accounts help to bring out the enduring memory of that terrible time. the general health of the adivasis and the existing medical facilities in this area are examined. attempts to check and treat the disease by the colonial government and its doctors, as well as missionary doctors and other non-governmental agencies, are considered to see why they had so little overall impact. some comparisons are made with the fate of indigenous people in other parts of the world during the epidemic, in particular with the inuits of alaska. in the usa, for example, african americans had lower mortality rates during the pandemic than whites, even though they generally suffered much higher death rates from respiratory and other such diseases. native americans, however, suffered worst of all. the reasons for these mortality patterns are still not well understood, though various propositions have been put forward. although there is considerable contemporary documentation of the epidemic, for many years afterwards it was not studied in any depth by historians. compared to other great epidemics, such as the black death, and to events that were contemporary with it, such as the mass slaughter and traumas of the first world war and the revolutions and displacements that followed in its wake, the influenza epidemic received little attention. this began to change in the wake of new epidemiological discoveries from the s onwards. in particular, robert webster and graeme laver's discovery of the way in which the influenza virus migrated from birds, mutating into a human form, transformed understanding of the epidemiology of the disease. they argued that this process was an ongoing one, producing new strains of the virus through 'antigenetic drift'. although most such mutations proved relatively mild, virologists warned that this was not always going to be the case. a future epidemic on a par with that of -or perhaps worse-was predicted to be almost certain at some time or other. these findings provided a wake-up call for historians. the first of a new wave of studies appeared in , with richard collier's the plague of the spanish lady. this was based mainly on interviews with survivors from different countries, and although anecdotal, brought out how people experienced the epidemic. it failed, however, to analyse the dissonance between such graphic memories and the official and academic silence on the pandemic. a more scholarly study followed in by alfred w. crosby, epidemic and peace. it was republished in as america's forgotten pandemic: the influenza of . in his preface to this new edition, crosby noted how the hubris surrounding the supposed triumphs of medical science had ensured that until the s the epidemic of was regarded-when it was at all-as an aberration that was largely irrelevant to our present condition. this had all changed as people began to understand how 'pathogens .ˆ.ˆ. seem to the general public to have become nastier faster than scientists have become smarter'. now, it seemed a harbinger of a dark future rather than an oddity from the past. by the s, the trickle of studies on the epidemic became a firm flow, with the current becoming ever stronger in the subsequent decade. despite this, the area that suffered the highest mortality of all in -india-has hardly been examined at all. indeed, there are only a couple of articles, by i. d. mills little or nothing about the epidemic. both mills and ramanna focus on bombay presidency, making widespread use of an excellent source for the epidemic in this regionthe annual report of the sanitary commissioner for the government of bombay for the year . this contained a detailed survey of the outbreak, along with extensive statistics on mortality. together, this report and the two articles show that the disease appears to have entered india through bombay port at the end of may , becoming epidemic in bombay presidency in june. at this juncture-as elsewhere-it was relatively mild, with most victims recovering. it spread to other parts of india by august . the second, and much more virulent wave, began again in bombay presidency, and was well established by september. official figures at that time put the death rate at . per cent of the population of the presidency, although mills estimated that about half the twenty million people of the presidency were infected, and that , , , or . per cent of the population died. he based this estimate not on recorded deaths (which were usually much under-reported in india) but on his own projections relating to population growths based on the census reports of and . mortality rates were particularly high in certain pockets of the interior of the presidency. the coastal districts were in general less hard-hit. urban areas were badly affected; in bombay presidency the urban death rate for was . per cent of the population, as compared to the rural death rate of . per cent. in normal years, there was no great difference between urban and rural death rates. as elsewhere, a feature of this phase of the epidemic was the high incidence of death among those aged to . unlike in the west, however, women in india suffered more. in bombay presidency, for example, . per cent of all women in the - age range died, compared to . per cent of all men. also, in contrast to the west, the poor suffered disproportionately. in bombay city, for example, low caste hindus had a death rate of . per cent in , in contrast to death rates of . per cent for europeans, . per cent for parsis, . per cent for anglo-indians, . per cent for indian christians, . per cent for high caste hindus, and . per cent for muslims. the millworkers, who were mostly low caste hindus, were badly affectedand this was said to be because they tended to be poorly-fed, and lived in badly-ventilated rooms with a smoky atmosphere filled with coal and dust. disproportionately-between and their population in india as a whole fell from , , to , , , or by . per cent-while the overall population of india increased during the same period by . per cent. the decline in the adivasi population was caused chiefly by the influenza epidemic of . in her study of the epidemic in bombay presidency, ramanna describes the way that the disease spread rapidly through western india in , and the measures adopted by colonial medical officials to try to contain it-largely without success. she points out that good nursing provided the best hope for a cure, but that there was a paucity of trained nurses in bombay presidency. she examines the response by voluntary groups, arguing that such public relief work was confined mainly to the larger cities. she states there was an 'absolute lack of any public health organisation in rural areas', so that the rural population was left helpless in the face of the epidemic. she does not, however, provide much detail on exactly how the rural population fared, or explain why some rural areas were harder-hit than others. my own experience from research in the mountain tracts that run between southern gujarat and maharashtra suggest that there are many histories yet to be written of the epidemic in india. when conducting interviews in villages in the early s, some older adivasis had told me about a fearsome epidemic that devastated their society when they were young. it was known as 'mā nmodi'. large numbers, i was told, had died suddenly. never before or since then had so many died in such a short space of time. in some households, everyone was wiped out. the bhagats (diviners, exorcists and herbalists) had tried to counter it by bringing out the spirit that was causing the sickness. for the most part they failed in this, and many lost their confidence in the bhagats at that time. i was told that 'mā nmodi' had occurred not long before the coming of the goddess, or devi, known as salabai. this was the topic that i was researching at the time, and later wrote about in a book. the coming of the devi is dated in the colonial and other records as occurring in - . this convinced me that 'mā nmodi'-which according to the adivasis occurred just a few years earlier-was the great influenza epidemic of . navsubahi patel of chankal village in the dangs said that people would be sitting, and they would start shaking all over and die. some went mad, and fell into water and died. some jumped up and down on the ground very vigorously. some died of fever. he, a youth of about fifteen at that time, helped to dispose of the dead. at first they had buried them, but soon were overwhelmed, and began throwing the bodies over cliffs. he had helped dispose of bodies in these ways. no home escaped. this was the case all over the dangs. govinda karbhari of saputara in the dangs said that of the inhabitants of his villages, had died in mā nmodi. in some villages, half the population had died, in others three-quarters. the bhagat was helpless, and they were so scared that they had fled the place. this went on for about one-and-a-half to two months. memories of the epidemic remained alive in these villages even in the twenty-first century. when my colleague gauri raje carried out research in some adivasi villages in eastern surat district in , she was told of an epidemic that they knew as 'dhani pani'. as with 'mā nmodi', it was said to have occurred just before the coming of the devi. they considered it a landmark in their history as so many had died. their parents had told them about it, as family members had succumbed. the symptoms were head thrown back, rigid limbs, high fever and delusions, and death came in a day or two. people who recovered were immune to any disease thereafter. large numbers died in each village, and whole villages were evacuated. it affected the entire region. oral histories such as these, collected many years after the event are valuable for the way they bring to life the intense emotions stirred at such a time, such as the sensation of dread and social threat, helplessness in the face of the unknown, and the desperate means employed to try to deal with the danger, such as fleeing a village. they provide what joann mcgregor and terence ranger have called an 'alternative narrative' that enriches the existing medical history and which also can be set against and contrasted with the official and other narratives that come down to us through the archives. as lucy taksa has shown in her admirable oral history of the epidemic in sydney, australia, such accounts bring out the multiple ways in which the epidemic was experienced, described and understood. they reveal the partiality of the official historical account, allowing us to reach toward different interpretations of the event. no such oral histories have, however, been attempted for india-a lacuna that the present article will attempt to rectify for one region at least. my aim is to focus on the epidemic of in the areas of southern gujarat and the immediately adjoining parts of maharashtra that have large adivasi populations. as i have indicated already, the topic first came to my attention through the interviews that i conducted there in the early s. at the time, i knew very little about the epidemic, and as it was not a part of my wider research agenda, i put it aside as a subject that i could return to at a later date. once i did this many years later, i began to discover that the adivasis appeared to have suffered particularly badly in comparison with other peoples of the plains of southern gujarat. i wondered why this was the case. what made the difference at such a time of extreme medical crisis? what was the state of medical facilities in these tracts, and could better facilities have saved lives? starting from the oral histories, i sought to answer these questions by examining the written evidence from that time-as produced by both official and non-officials agencies (notably missionaries). who were the 'adivasis' of india? they tended to inhabit the hilly and forested regions of the subcontinent. many lived from hunting and gathering combined with shifting agriculture. some were found in adjoining plains regions, where they practised a more settled peasant agriculture-sometimes independently, sometimes as tenants or labourers for non-adivasi landlords and usurers. such peoples were described by the british as 'aboriginals' or 'early tribes', being characterised, so it was said, by their 'clan'-based systems of kinship and their 'animistic' religious beliefs. sometimes, they were defined in terms of their habitat, as 'jungle tribes'. by classifying them in these ways, the british created a conceptual unity that such peoples had not hitherto possessed. from the s onwards they claimed, assertively, to be the 'original inhabitants' of their tracts, calling themselves by the hindi term that expresses such an idea-that of adivasi. i have used this term in this paper for the sake of convenience, even though it was not yet in currency during the epidemic of . in india, the largest concentrations of such people were in the northeast. elsewhere, many were found in the central-eastern region, in what is now the state of jharkhand and areas adjoining to it in bengal, orissa and bastar, and in a section of western india that spans the border regions between the four modern indian states of rajasthan, gujarat, madhya pradesh and maharashtra. the adivasis that form the subject of this article inhabited a belt that stretches nearly as far as the city of bombay in the south, to the narmada river in the north, to the districts of west khandesh (now dhule) and nasik in the east, and to the arabian sea in the west (see map). in terms of terrain, they inhabited the hills and forests of the sahyadri and satpuda mountain ranges and the immediately adjoining plains areas. in the past, they were classed by non-adivasi indians as belonging to two main groups-the 'kaliparaj' ('black people') and the bhils. the former were generally considered to be less aggressive than the latter. the 'kaliparaj' were divided in turn into a number of separate communities, such as the chaudhrys, dhodiyas, gamits, konkanas and varlis. before examining the epidemic in this adivasi region, i shall say something about the nature of the epidemic, how it was understood and treated at the time, and look briefly at a well-documented case in which indigenous people were severely hit by the pandemic-that of the inuit in alaska-to help to draw out some lessons about the response to the crisis more widely. although the symptoms of influenza in differed throughout the world, its most frequently reported indicators were severe headaches, body pains and fever; with coughing of blood and bleeding from the nose. death was often caused when the disease affected the lungs, causing massive pulmonary oedema or haemorrhage, turning the lungs into sacks of fluid and thus effectively drowning the sufferer. a particular feature of the malady was the 'heliotrope cyanosis' (a term coined at the time), in which the face of victims turned blue as they in effect drowned in the fluids that accumulated in their lungs. an attack normally lasted - days. however, death could be sudden, even within a few hours. in , the epidemiology of influenza was poorly understood. since the s, it had been held that influenza was caused by a bacillus, identified as pfeiffer's bacillus. little was then known about viruses, and much of the research into the disease in was focused in the wrong direction. the influenza virus was in fact only identified in , and it was found that its surface antigens change from epidemic to epidemic. this made it hard to classify the virus retrospectively. later research on the corpses of victims frozen in the arctic tundra suggest that it was most likely a particularly lethal form of the h n -subtype influenza a virus that had mutated from an aggressive bird flu. it is not yet known precisely why it caused such high mortality among those in the prime of their life. in bombay, the medical establishment tried to establish that pfeiffer's influenza bacillus was the cause of the disease. investigators at the bombay bacterial laboratory had difficulty in isolating the bacillus, but they believed that it was 'one of the most constant elements in the bacteriology of the disease and it appears to thrive best in symbiosis with other organisms such as the pneumococcus and streptococcus.' a combination of the three was held to account for the particular virulence of the outbreak in september-october . in particular, the pneumonia that generally occurred on the second or third day of the illness frequently proved life-threatening, and it was believed that it was likely to be especially fatal in the case in patients who failed to take proper rest as soon as they fell ill. despite the epidemiological uncertainty, it was felt that a vaccine was needed, and one was prepared and used for the military for preventive purposes only. the constitution of the vaccine was only decided on at a conference in delhi in december , and it was then manufactured and provided free of charge-after the most lethal phase of the epidemic had passed. although many medics knew at the time that there was no effective drug-remedy for influenza, others were not short of recommendations-often conflicting. thus, while many indian doctors advised daily doses of the wonder-drug of the day, quinine, the surgeon-general of bombay warned against it. particular doctors advocated a wide range of remedies, such as belladonna, laudanum, camphor, creosote, a mixture of iodine and chloroform and the like. many indian medics, as well as ayurvedic practitioners, dispensed indigenous medication, such as powdered long pepper, mixed with ginger juice and honey. to prevent congestion and bronchitis, they prescribed tulsi and turmeric in milk. the bombay government itself disparaged the use of such indigenous remedies. people were also advised to take preventive measures, particularly the wearing of face masks, irrigating their noses with warm salt water, disinfecting their houses, avoiding congregation in crowds, and refraining from smoking tobacco and consuming alcohol. in practice, many resorted to prayer and patent medicines. in fact, probably the most effective treatment for sufferers at that time was the prescription of aspirin to lower the body temperature, complete bed-rest and good nursing care. the sanitary commissioner's report for bombay noted that a previous bout of influenza did not appear to confer immunity in . it was argued that certain individuals were by their nature more susceptible to the infection, but that this was aggravated by 'overwork, lack of food, bad housing and overcrowding'. the poor monsoon of that year had also meant that people were malnourished and had less resistance. the report also noted the fact that in general, regions lying close to the arabian sea had lower mortality than those inland. the reason for this was not however clear. the report also mentioned that female mortality was in general considerably higher than male mortality. this gender difference was not found to be the case in all age categories, as more male babies under one year and more males in the - age group had died. the report argued that women who had domestic responsibilities had been unable to take the necessary rest when ill, having to cook and tend to other members of the family who were ill. this was compounded by 'their continued indoor existence in the average ill-ventilated house', which made them more vulnerable to the pneumonia that was such a killer. the reports did not take note of the fact that women from poor families tended to be malnourished-more so in a year of crop failure-and also more likely to suffer from anaemia and other debilitating conditions. a different report of noted that pregnant women were particularly at risk, and that in almost all cases those who contracted influenza aborted and died of post-partum haemorrhage. the high female mortality was a feature of the epidemic in india-elsewhere, male mortality tended to be strikingly higher. the particularly high mortality rates from influenza suffered by indigenous and aboriginal peoples throughout the world in has been brought out in a number of studies. this was the case of native americans and the inuits of northern canada and alaska, and in new zealand the epidemic killed more maoris than people of european origin. it had a devastating effect in many pacific islands; in fiji about per cent of the population died, in tonga per cent and in western samoa per cent. in alaska, some isolated inuit villages had death rates of up to per cent of the adult population. in some cases, the relative isolation of indigenous people made them more vulnerable to such infection; this was not however the case with most, as there had been widespread contact with outsiders for many years. crosby's study of the alaskan case brings out just how important the reaction to the crisis by the authorities and concerned and well-informed citizens could be. the epidemic began in alaska in october, just before the winter freeze cut off the interior, so that it spread rapidly from seaports up the rivers that provided the main means of access to the interior. the us authorities put a lot of resources into providing health care, establishing emergency hospitals and hiring extra physicians and nurses, who were sent to places where they were needed most. in the more remote areas that lacked such care, death rates proved to be much higher. the epidemic arrived in many interior settlements just as winter was closing in, isolating them almost completely as it raged. cases were reported of people panicking and wandering about spreading the disease. there was nobody to perform the life-saving tasks, such as cutting firewood, and providing food (the people were too weak to hunt the moose). cabins became dirty, and vermin increased. people became demoralised and merely sat in their cabins waiting for death. they no longer lit fires, and many froze to death. when a number were rounded up and placed in a single large, heated building where they could be cared for better, several responded to what they saw as incarceration in a deathhouse by hanging themselves. crosby notes that where there was strong leadership in an inuit village by people such as schoolteachers, survival rates were much better. meetings were held to explain what was happening and ways in which people might avoid infection, and arrangements were made to provide food and firewood for infected families. the lesson here was that although the cause of the pandemic was not understood, and although there was no wonder-cure, infection-rates could be kept down through quarantine, and there was a better chance of survival if the sufferer had complete bed-rest and good-quality nursing. as i shall argue, these conditions were lacking for the most part in the more remote adivasi tracts of western india. if we compare mortality rates for districts, as given in the annual report of the sanitary commissioner for bombay presidency, , there does not appear to be any obvious statistical correlation between high mortality and the districts with larger numbers of adivasis. sholapur district was recorded as having the highest mortality rate of all districts in the presidency- . per cent of the population. nasik followed, with . per cent, then west khandesh with . per cent. other districts had mortality rates under per cent. while nasik and west khandesh had sizeable adivasi populations in their western regions, sholapur-with the highest of all mortality rates-did not. also, some districts with large adivasi populations had below average figures-such as the districts of thana ( . per cent), panchmahals ( . per cent), and surat ( . per cent). such averages concealed, however, variations within each part of a district. the annual report of the sanitary commissioner for also provides breakdowns for sub-districts (talukas), and these can be used to pinpoint the areas with highest mortality with greater precision. the highest mortality rates of all were found in sakri and baglan talukas, where respectively . per cent and . per cent of the populations died; per cent of the population of sakri were adivasis, while the figure for baglan was per cent. these two talukas were in the sahyadri mountains adjoining the dangs-the area where i had first encountered a strong and abiding popular memory of the epidemic of . kalwan, which bordered both the dangs and surgana state had a mortality rate of . per cent, and peint, which adjoined dharampur state, had a mortality rate of . per cent. in the report, there are no mortality figures for the princely states, but in the dangs the population dropped by . per cent and in dharampur by . per cent between and , and in both cases the main cause was said to be the epidemic of . mortality rates in the british-ruled talukas of surat district were lower, with an average rate of . per cent for its rural areas and . per cent for its three largest towns. the highest rates were found in the talukas that adjoined the forests and hills of dharampur, namely chikhli ( . per cent mortality and per cent of the population adivasi), valsad ( . per cent mortality and per cent adivasi), and pardi ( . per cent mortality and per cent adivasi). besides chikhli and pardi, the only other talukas of surat district with adivasi populations over per cent were mandvi and valod, and they had mortality rates that were in line with the district rural average. significantly, i did not come if we accept mills' argument, we may double this and the other mortality figures that follow in this section to give more likely realistic mortality rates. it is beyond the scope of this article to try to explain the reasons for the large differences in mortality rates within bombay presidency as a whole. the worst-affected areas were all in the interior plateau regions of maharashtra-the deccan and khandesh-while the coastal regions of the konkan and the gujarat plains had considerably lower mortality rates. there may have been a mutation that appeared first in the area around pune in september and caused particularly high mortality in the adjoining areas of the deccan and khandesh in october, thereafter subsiding in virulence. this is merely a conjecture that requires further investigation, as no convincing explanation has been provided either in the official reports or by subsequent historians, such as mills. my general argument in this paper is, nonetheless, that varying degrees of virulence could be compounded-sometimes dramatically-by the underlying health profile of different social groups and their access to medical knowledge and care. i have been unable to find mortality rates during the epidemic for the talukas of navsari district of baroda state. all we have are the census figures. if we examine the baroda state census report for , we find that the population of songadh taluka had declined by . per cent since , mangrol and vajpur (the two were counted together) by . per cent, while vyara recorded a small increase of . per cent. mahuva, another largely adivasi taluka recorded a decline of . per cent. in the other four talukas of navsari district, which had a far lower concentration of adivasi in their population, the population increased by . per cent between and . this points to relatively high mortality in the adivasi areas of navsari district-and, significantly, these lay for the most part close to the foothills of the sahyadri mountains. the taluka figures for navsari are however significantly lower than the rates found in the more mountainous adivasi regions to the east. continuing in a southerly direction, we find that in thane district there were two talukas with high adivasi populations-umargam ( . per cent mortality rate and per cent adivasis) and dahanu ( . per cent mortality rate and per cent adivasis). in addition there was jawhar, a princely state in the mountainous interior of the region that was largely surrounded by dahanu taluka, in which per cent of the population was adivasi and the mortality rate was a higher . per cent. these statistics, taken together, suggest that mortality rates were generally lower in the adivasi areas of south gujarat and thane district that lay in the coastal plains. pardi taluka was an exception to this rule, although it had a considerable amount of its territory in the interior on the borders with dharampur, and this region may have accounted for the higher mortality rate of this taluka as a whole. to the immediate south of pardi, umargam taluka, which lay mostly in the coastal plain, had a relatively low mortality rate ( . per cent) that was comparable to the adivasi-dominated talukas of the plains of surat district. the general finding is thus that the worst-affected adivasi areas were located in a broad line that stretched from northeast to southwest along the spine of the sahyadri range and its adjoining foothills in gujarat and maharashtra. in this area the particularly virulent strain of the disease that swept inland maharashtra affected the adivasis of the mountain villages worst of all. i shall now go on to say something about the social, economic and medical history of the adivasis of this region in order to try to understand why some of them suffered so badly in . using census data to suggest mortality rates is open to the problem that it might show out-migration from the region-caused perhaps by an agricultural crisis such as rain failure-rather than mortality from influenza as such. the census reports do not put forward any such suggestion. discussing the period - , the baroda census commissioner, s. v. mukerjea, argued that although the rains had failed in , there was little distress or human starvation due to the implementation of more effective famine relief measures than in earlier years. in the past, the adivasis of southern gujarat were known as the 'kaliparaj', or 'black people'. this was a disparaging term given to them by the high castes, who were known locally by contrast as the 'ujliparaj', or 'white people'. the kaliparaj were for the most part poor subsistence farmers. in the more fertile plains regions of southern gujarat they lived in settled villages and cultivated fixed plots of land, while in the forested and hilly tracts in the east crops were grown both in fields in the valleys and through shifting slash-and-burn cultivation on the hilly slopes. the adivasis of the hilly tracts tended to move their places of settlement in periodic cycles, finding fresh land to cultivate. they had in general suffered badly from colonial rule. the british had appropriated large tracts of the forests that the adivasis had previously controlled so that state foresters and timber merchants could exploit the natural wealth of the woodlands. those so displaced were encouraged to settle down as full-time farmers. the commodification of farmland by the colonial state had in turn allowed landlords, usurers and liquor dealers to move in and expropriate large areas of their land, leaving them as tenants or agricultural labourers. their hard conditions of life reflected on their health. this was remarked on by colonial officials, missionaries and indian outsiders alike. writing in , e. maconochie of the indian civil service noted that the health of the 'kaliparaj' was in general poor as compared to the high caste people who lived in the same area. this was due to their 'coarse and scanty food, bad water and insufficient clothing'. they were 'generally of inferior physique' to members of the higher castes, probably because of the malaria that they more than others suffered from. the focus on malaria-or 'fever'-was a longstanding trope in colonial commentary on the health of the kaliparaj. in the nineteenth century, this was believed to be caused by what a colonial official described in as 'the pestilential vapours of this unsettled land'. a british official, writing in , noted the 'inferior and wretched' sanitary condition of the villages of mandvi taluka, stating that: 'the inhabitants are generally dull looking with their pale faces, enlarged abdomen and emaciated limbs and their health on the whole giving proof of it being below par.' women, he said, were generally in worse health than men. the connection between malaria, an enlarged spleen and anaemia was pointed out by missionary doctors working in the tract in . they called this 'malarial anaemia', but more recent investigations in this area have discovered that there is widespread sickle cell anaemia amongst the adivasis. while providing some protection against malaria, it is also very debilitating. there is also a close connection between female nutritional anaemia and maternal and fetal morbidity and mortality. an indian anthropologist who carried out research in the area in the late s remarked on the very high infant mortality rate in the adivasi village that he studied-with . per cent of all deaths there being of children under five. . per cent of all children failed to survive to their fifth birthday. in all this, there was a clear link between the material poverty of the adivasis and their poor health. this was a fate suffered by such people elsewhere in india. p. o. bodding, a missionary ethnographer whose wife was a doctor carried out a detailed study of the health and therapeutic practices of the santal adivasis of eastern india in the early twentieth century. he noted that they suffered from most diseases found in india at that time. he was told by his santal informants that they had not suffered from syphilis, tuberculosis or leprosy before the middle of the nineteenth century. although he felt that this was perhaps an exaggeration, he suggested that their former isolation may have protected them from many infections. by the twentieth century, however, all of the three abovementioned diseases had become widespread in the community. the most prevalent maladies of all were malaria, then skin diseases, bowel complaints such as dysentery, eye diseases, pneumonia, and rheumatism. they also suffered badly in epidemics, fearing cholera and smallpox in particular. government officials commonly argued that this could all be remedied through forest clearance and agricultural development in adivasi villages. a senior tax officer employed by the baroda state government (which ruled a large tract of territory in this region, often interspersed with the british-held areas) stated in that the poor social and economic conditions of the adivasi tracts was caused by poor health, and particularly malaria, as mosquitoes thrived in the dense vegetation. he held that if the jungle and scrub was cleared, their health would improve dramatically. the unhealthy nature of this area was also said to deter non-adivasi settlers who might have developed the land more productively. the drawback with this argument was that even in the supposedly 'healthy' tracts of the areas of south gujarat that adjoined the arabian sea and had no forestswhich was an area in which high caste landowners carried on commercial agriculture with adivasis making up most of the agricultural labour force (working either as bonded labourers or indebted tenants)-the health of the adivasis was not noticeably better than that of their counterparts in the forest zones. poverty, rather than terrain, ) . it may be noted that modern irrigation projects have in the past four decades allowed intensive cultivation of sugarcane in large swathes of the plains regions of south gujarat. the cane is cut largely by adivasi migrant labourers, who live in appears to have been the more likely cause of their ill health. non-official high caste commentators, on the other hand, tended to blame the generally poor health of the adivasis throughout south gujarat on their high consumption of alcohol, contrasting this with the more 'healthy' high castes-who were said to generally abstain from taking liquor. because their health was generally poor, the south gujarat adivasis suffered particularly badly in epidemics. reports from the dangs speak of whole villages becoming deserted after outbreaks of cholera. there was a particularly deadly cholera epidemic during the time of the great famine of - in which large numbers of adivasis died. there was an influenza pandemic in that affected the whole region, but while in general in india it was relatively mild compared to the later epidemic of - , it killed about , out of a total population in the dangs of , -that is per cent of the population. all of this suggests that the adivasis of the region were particularly vulnerable in epidemics, and this was certainly the case in . indeed, the effects of poor general health and malnourishment were compounded in that year by a severe economic crisis and rain-failure. there was soaring inflation during the first world war, making the cost of imported essential commodities extremely high. there was only about one-third the normal rainfall in the region that we are focusing on here during the monsoon of , with widespread crop failure just at the time that the particularly lethal form of influenza swept the area in september-october. due to illness, many were unable to harvest the little crop that remained. despite all this, it was widely observed in - that good medical information and care could make a big difference. biomedical facilities were not, however, available for a large majority of the adivasis. during the nineteenth century, the british colonial and princely state governments provided minimal health care for these people, with small town dispensaries mainly serving local officials and high caste people. this situation began to change in the first decade of the twentieth century as government establishments expanded and missionaries started to provide care for the rural poor. the missionary organisation that worked in the interior of south gujarat was that of the church of the brethren mission, based in illinois, usa. its first missionaries arrived in the area in , established a base at valsad-which was on the main railway from bombay to delhi, and on the border with the adivasi tracts-with new mission stations being opened as and when fresh mission workers arrived from america. however, only a small number of qualified doctors were employed by the mission, as at valsad, where they ran a mission hospital. in most of the mission stations, missionaries without medical temporary camps next to irrigation canals. they suffer very badly from malaria. the prediction that agricultural development would protect all of the people from malaria has not therefore been fulfilled. qualifications provided basic health care. for example, in the dangs in the year ending march , the medically-unqualified missionaries treated , cases in a population of about , . on top of this, medically unqualified teachers in the five mission schools situated in different parts of the dangs gave out basic remedies to local people. there was also a government-run dispensary at ahwa in the dangs, where, in , , patients were treated. in general therefore, only a fairly small minority of the adivasis of the area were able to avail themselves of either government or mission medical facilities. as already pointed out, the chance of survival from an attack of this strain of influenza depended significantly on whether or not the patient obtained plenty of rest, light but nourishing food-preferably in liquid form-and good nursing. as medical facilities were so inadequate, few were able to benefit from such care in a hospital. at that time, the training of nurses was in its infancy, and there was no nucleus of trained nurses outside the city of bombay. the hospitals and health workers of the church of the brethren mission provided this to some extent in the adivasi tracts, but in they were quickly overwhelmed by the disease. their reports stated that the epidemic started in their area in september , and that by october many people in both towns and rural areas were falling ill and dying. both dr laura cottrell and her husband dr a. raymond cottrell, the mission doctors at valsad, went down with the disease at the moment that they were most needed, and the hospital had to be closed for a time. fortunately for them and the mission, both survived. dr barbara nickey, who ran the clinic at dahanu, was also kept very busy there treating cases of influenza. after the cottrells fell ill, nickey went to valsad and reopened the hospital there. others of the american missionaries also fell ill. the missionaries who were not affected did their best to alleviate the suffering. this was the case in the dangs, where the medically unqualified missionaries worked in very difficult circumstances. they reported that the epidemic was at its worst there in october, with a mortality in some villages, they reported, of from - per cent. of the twelve teachers employed in the mission schools of the dangs, two died. adam ebey reported that although there was a government dispensary at ahwa, the sick preferred to come to the missionaries for treatment. he said: 'people have more faith in an un-medical missionary than in a non-missionary medical man.' nonetheless, however hard the missionaries tried, there was little they could do to prevent the high mortality. in particular, those who developed pneumonia had little chance of survival. when all the members of a family had died, the ebeys had to bury their bodies. other christians helped them in this sombre task. they wore masks over their faces, kept damp with eucalyptus oil, to ward off possible infection. the missionaries thus tried to provide medical aid and well-informed leadership during the pandemic, but they were in general overwhelmed, and were only able to have a minimal impact. was there any comparable effort from philanthropically minded indians at that time? a notable feature of the epidemic that was observed in the major cities of bombay presidency was the mobilisation of voluntary organisations to provide relief. they raised funds, distributed medicines, set up temporary hospitals and propagated the vaccine when it was available. according to ramanna, such 'relief was not extended to the villages, because there was neither the infrastructure nor the resources.' this was not, however, the case in south gujarat, where a caste association called the patidar yuvak mandal (patidar youth association) formed a 'mitra mandal' (association of friends) to fight the epidemic. volunteers, who were largely young patidars who were studying in surat city, travelled around the rural areas distributing ayurvedic medicine free of charge. the patidar yuvak mandal was a very dynamic organisation with strong links with the nationalist movement, and the young men were both idealistic and energetic in their work. they opened over distribution centres in thirteen talukas of the region, including ones under baroda rule, and medicine was provided for over , people. there were such centres in bardoli taluka, and in mandvi taluka-a predominantly adivasi area. this provided the first occasion on which these young nationalists made contact with the adivasis of the interior-and they gained an experience that they were able to turn to political advantage in later years. nonetheless, on this occasion they found that the adivasis were suspicious of them as outsiders from a caste that they had hitherto considered their exploiters. many adivasis rejected their medicines, telling them that it was of no use and that all they could do was to propitiate their deities. only a few were persuaded to take the ayurvedic remedies. although these young nationalists were, during the s, able to gradually win the confidence of the adivasis, with gandhian projects being established in their villages, in there was no time during the brief span of the epidemic to build such contacts and trust. later, in the s, gandhian workers were able to provide extremely effective leadership in areas in which they had influence during a recurrence of plague. in , this sort of civil society response was still embryonic in the rural areas, and could not be expected to have a significant impact. in most cases, the adivasi were left to their own resources in the face of the pandemic. this can be brought out through the use of oral evidence, as collected in interviews. such testimonies are, in the case of memories of epidemics, valuable mainly for the way they bring to life the intense emotions stirred at such a time, such as the sensation of dread and social threat, helplessness in the face of the unknown, and the desperate means employed to try to deal with the danger, such as fleeing a village. they cannot be expected to provide a clear description of the symptoms, causes or extent of a disease that would stand up to the scrutiny of medical science. indeed, the statements are by such standards often confusing, and all we can do is record them without necessarily trying to explain them in unconvincing ways. dhuliya powar, who lived in what was then surgana state, said that older people were particularly hard hit, though in some households all had died. this contradicts the wider picture of mortality-by-age, although it might have been a peculiarity of this particular locality. others gave the symptoms, variously, as diarrhoea and vomiting, high fever and delusions, violent shakes and fits, and the throwing back of the head. the latter was seen to be so characteristic that the disease itself was called 'mā nmodi', or 'the breaking of the neck' ailment. the term 'mā nmodi' does not appear in any of the records on the influenza epidemic of . it is a marathi word, and all of the references to it in interviews were either from villages that are now situated in the state of maharashtra, or the dangs, where the local dialect is heavily influenced by the marathi language. there is in fact a village called mā nmodi in the dangs-and there is a local legend that the village was so called after a man had his neck (mā n) severed after he had angered the god baramdev. the man's head was replaced after a sacrifice to the deity. d. d. kosambi has also mentioned a 'unique and primitive goddess mā nmodi' who is worshipped in a cave in the mā nmodi hills near junnar, in pune district of maharashtra, which is nearly kilometres from the dangs. he says that the literal meaning of the word is 'neck-breaker', and in this is reminiscent of the goddess kavada-dara ('skull-splitter') that is worshipped in an adjoining valley kilometres away. he says that the goddess mā nmodi 'is not found elsewhere, in any context'. the caves at junnar were nonetheless located at a place where several ancient trade routes met, and the caves became a location for a buddhist monastery called manamakuda. after the decline of buddhism, they were used for local forms of worship, and he believes that the earlier name evolved in time into mā nmodi. traces of the buddhist origin, he believes, have continued in the custom that no blood sacrifice is ever offered to the goddess, which is most unusual for such a deity. the fact that the cave was on a trade route, and that the dangi village of mā nmodi lies close to the old route from maharashtra to gujarat via saputara (the one that shivaji is said to have used in his raid on surat in -in which he assembled his force first at junnar ) suggests that the term might have travelled. why the term is used for what clearly was influenza is not so obvious, as influenza does not, as such, 'break the neck'. the villagers of vansda state who knew the epidemic by a different name, that of 'dhani pani', spoke of the head being thrown back, as well as high fever, rigid limbs, and 'delusions'-and the 'neck-breaking' might have referred to the way that people threw their heads back while in a very high fever and suffering the resulting hallucinations. it could be the case that the disease was considered to be a visitation of a goddess who was either called 'mā nmodi', or linked in some way to the word. it was commonly believed that epidemic disease was caused by such visitations; sitala, the smallpox goddess, was the best known, and cholera was known in those parts as 'marakhi', after a goddess of cholera called mari mata. in the interviews, nonetheless, informants referred to the 'neck-breaking' qualities of the disease, and did not link the use of the term 'mā nmodi' to the goddess of that name. there are, however, some references from outside the dangs to a belief that the disease was caused by the visitation of a goddess, as we shall see below. the way in which the popular name for the epidemic differed from area-to-area is also significant. lucy taksa, in her oral history of the epidemic in sydney, recounts how most people there remembered it as 'the plague'. for them, the seriousness of the crisis required it to be described in terms of what was popularly believed to be the most fearsome epidemic disease, that of bubonic plague. even those who accepted that it was in fact influenza still talked of the great 'plague' of that year. she also notes how the epidemic was known by many different names throughout the world, whether the 'spanish influenza', 'the pneumonic flu', 'bronchial pneumonia', 'singapore fever', and even the 'bolshevik disease'. in iran, it was known as 'the disease of the wind'. in the dangs, where there were no local words for 'influenza', 'plague', and the like, 'mā nmodi'-the neck-breakerappears to have provided an appropriate metaphor for this fearsome, seemingly supernatural force that spread through the villages with such terrifying speed. as for 'dhani pani'; no explication of the term was provided for raje when she conducted her interviews, and although the meaning of 'pani' ('water') is quite clear, 'dhani' has more than one meaning in gujarati, and so it is not possible to hazard any guesses in this case. in some of the interviews, old adivasis recounted how they and their families had fled their villages to escape the epidemic. whole villages became deserted at this time. this is borne out by the mission evidence. adam ebey of the church of the brethren mission, who was based at ahwa in the dangs, reported that many people of the tract had fled from their villages to ahwa during the epidemic, trying desperately to escape the disease, generally to no avail. indeed, in that forest region where people lived in huts in small settlements, it was very common for them to desert a locality whenever an epidemic struck, as it was believed that the place was then haunted by the spirits of the dead. the downside to this practice was that it ensured that the infection was disseminated quickly through the area. this was almost certainly a contributing element to the exceptional severity of the epidemic in this hilly region. the adivasis of the south gujarat plains generally lived in villages in more substantial houses on fixed sites, and were less likely to flee their villages at such a time. this would in part explain the lower mortality rates there. from interviews, it appears that the adivasis resorted to remedies that they knew. in the villages of eastern vansda state, the bhagats had sought to treat the disease by catching a particular type of crab from the rivers and streams, roasting it on a fire with some grain, and then making the patient inhale the smoke. no spices or oils were to be consumed. this latter prescription is found also with measles, chickenpox and other diseases believed to be caused by the visitation of a goddess. more commonly, however, they sought to exorcise and drive away the spirit or deity that was causing the outbreak. in unbarthan in surgana, as we have seen, the diviners and exorcists-the bhagats-made a figure of a man from a mixture of ground flour and water. they passed the figure over those who were ill, exhorting the spirit to pass from the sick person into the figurine. a few of those so treated were said to have survived, but most did not, and the people lost their confidence in the bhagats at that time. vedu powar of chankapur in kalvan takuka said that nine or ten had died there in the mā nmodi epidemic, and the bhagat of the village could save only one or two. the failure of the bhagats at that time is brought out also in accounts collected by a. n. solanki, an anthropologist who carried out a study of the dhodiya adivasi community in the s. he was based at khergam, a village in the interior of chikhli takula. he found that there were still many vivid memories of that time. his informants believed that the epidemic was caused by a goddess. a ceremony was performed to entice the goddess into a pot called a khapru, which was then placed on a small cart-a rath-and drawn beyond the boundaries of the village. this did not, he was told, stop the disease, and people died in great numbers, including the bhagats whom they had looked to save them. the failure of the bhagats appears to have caused some loss of confidence in them at this time. this was compounded by the devi movement of - , when many new-style reformed bhagats emerged who denounced the older bhagats, whose demands were often extravagant, and instead asked for offerings in coconuts rather than live animals, liquor or sexual favours. another feature that comes out from the mission record was that was that the epidemic broke out once more in a virulent form in the interior villages of this region in the early months of . in the dangs, the ebeys took over the mission from the bloughs at the end of january . soon after they arrived, in early february, influenza struck again. though they, like the bloughs, lacked medical training, they dealt with this as best they could. they reported that the new cases were mainly in villages that had not been affected in october and november. in chankal, for example, where the headman, his family, and six other families had been converted to christianity, the headman died, along with nineteen other of the christians. when i visited chankal in , i was told that the influenza lingered on in the village for five years. in homes in which no one had died in the first year, people often died in the second. no home escaped altogether in those years. the sanitary commissioner's report for bombay described only the second phase of the epidemic that peaked in october, and provided mortality statistics only up to the end of december . it acknowledged that deaths from the disease continued into january , but says that this was mainly the case in sindh, where the course of the epidemic ran a month later than in the rest of the presidency. examining wider mortality rates for bombay presidency, mills notes that the death rate remained elevated up until march . by april it was back to normal. he also notes that the epidemic had a profound influence on fertility, as many survivors lost their partners, and even if they remarried, women took time to conceive. the ongoing dearth and, in some areas, famine of - , would have contributed to this effect. studies of the effects of the epidemic in other parts of the world have brought out a common 'post-flu fatigue characterised by mental apathy, depression, subnormal body temperatures and low blood pressure, which could last for weeks or months'. the lack of proper funerals for the dead was also considered highly inauspicious, causing widespread demoralisation. recent studies have also suggested that those who survive severe bouts of influenza are prone subsequently to diseases of the central nervous system, and it has been suggested that there was a close connection between the epidemic of and the widespread incidence of the sleepy sickness encephalitis lethargic (el) that killed around five million globally during the s. the statement by navsubahi patel of chankal village that people in his village continued to suffer for five years afterwards appears to conform to these recent findings. in the adivasi villages, the bhagats provided the main leadership in times of epidemiological crisis. faith in their remedies soon failed as their remedies proved of no avail. an educated middle-class leadership of the sort found quite widely in alaska was not available for the vast majority of the adivasis. there were few schoolteachers, and officials tended to be aloof and uninterested in the so-called 'primitive' classes whose destiny-so they saw itwas to either acculturate to high caste values or perish. although some idealistic young nationalists tried to provide ayurvedic remedies for the adivasis of south gujarat, they had no previous connection with the villages, and they were unable to have much impact at the time. other nationalists adopted a moralistic stance, holding that the adivasis suffered disproportionately because of their moral deficiencies and in particular their alleged drunkenness. in the words of the congress leader of surat, haribhai desai: 'those addicted to drink paid a frightful toll to the epidemic of influenza in . whole villages were devastated in forest areas and those parts of the district inhabited by kaliparaj.' in this region, christian missionaries provided almost the only wellinformed and sympathetic leadership, as well as biomedical health care, but taken as a whole, they were few and far between, so that their overall impact was fairly minimal. this all left the adivasis of this region particularly vulnerable to epidemic disease. their poverty, poor sanitation, diet and water supply, and the chronic malaria that sapped their energy and undermined their immune system, along with-at that time-an undiagnosed sickle-cell anaemia, all made them particularly susceptible when influenza swept their villages in . to compound this, the colonial state failed to provide any welfare for these people, and in particular any meaningful health care or guidance and leadership, and aid and help from civil society organisations was poorly developed and only able to have a small impact. the adivasis were largely left alone to suffer, and so traumatic was their experience that to this day they still, in those hill and forest villages, remember that terrible time of mā nmodi. sanitary commissioner for government of bombay to secretary to government one year's visiting with our missionaries in india: a story thirty-fifth annual report of the church of the brethren mission for year ending the aborigines of south gujarat myth and reality: studies in the formation of indian culture the masked disease shuttleworth to bombay government the dhodias: a tribe of south gujarat area on this, see hardiman, the coming of the devi thirty-fifth annual report of the church of the brethren mission for year ending the - influenza pandemic death in india a fierce hunger": tracing impacts of the - influenza epidemic in southwest tanzania the spanish influenza pandemic of - , xvii-xix report of the excise committee appointed by the government of bombay key: cord- -oip m br authors: kumar, s. udhaya; kumar, d. thirumal; christopher, b. prabhu; doss, c. george priya title: the rise and impact of covid- in india date: - - journal: front med (lausanne) doi: . /fmed. . sha: doc_id: cord_uid: oip m br the coronavirus disease (covid- ) pandemic, which originated in the city of wuhan, china, has quickly spread to various countries, with many cases having been reported worldwide. as of may th, , in india, , positive cases have been reported. india, with a population of more than . billion—the second largest population in the world—will have difficulty in controlling the transmission of severe acute respiratory syndrome coronavirus among its population. multiple strategies would be highly necessary to handle the current outbreak; these include computational modeling, statistical tools, and quantitative analyses to control the spread as well as the rapid development of a new treatment. the ministry of health and family welfare of india has raised awareness about the recent outbreak and has taken necessary actions to control the spread of covid- . the central and state governments are taking several measures and formulating several wartime protocols to achieve this goal. moreover, the indian government implemented a -days lockdown throughout the country that started on march th, , to reduce the transmission of the virus. this outbreak is inextricably linked to the economy of the nation, as it has dramatically impeded industrial sectors because people worldwide are currently cautious about engaging in business in the affected regions. as of may th, , maharashtra, delhi, and gujarat states were reported to be hotspots for covid- with , , , , and , confirmed cases, respectively. to date, , patients have recovered, and , deaths have been reported in india ( ) . to impose social distancing, the "janata curfew" ( - h lockdown) was ordered on march nd, . a further lockdown was initiated for days, starting on march th, , and the same was extended until may rd, , but, owing to an increasing number of positive cases, the lockdown has been extended for the third time until may th, ( ) . currently, out of states and eight union territories in india, states and six union territories have reported covid- cases. additionally, the health ministry has identified districts as hotspot zones or red zones, as orange zones (with few sars-cov- infections), and as green zones (no sars-cov- infection) as of may th, . these hotspot districts have been identified to report more than % of the cases across the nation. nineteen districts in uttar pradesh are identified as hotspot districts, and this was followed by and districts in maharashtra and tamil nadu, respectively ( ) . the complete lockdown was implemented in these containment zones to stop/limit community transmission ( ) . as of may th, , government laboratories and private laboratories across the country were involved in sars-cov- testing. as per icmr report, , , samples were tested till date, which is . per thousand people ( ). the recent outbreak of covid- in several countries is similar to the previous outbreaks of sars and middle east respiratory syndrome (mers) that emerged in and in china and saudi arabia, respectively ( ) ( ) ( ) . coronavirus is responsible for both sars and covid- diseases; they affect the respiratory tract and cause major disease outbreaks worldwide. sars is caused by sars-cov, whereas sars-cov- causes covid- . so far, there is no particular treatment available to treat sars or covid- . in the current search for a covid- cure, there is some evidence that point to sars-cov- being similar to human coronavirus hku and e strains ( , ) even though they are new coronavirus family members. these reports suggest that humans do not have immunity to this virus, allowing its easy and rapid spread among human populations through contact with an infected person. sars-cov- is more transmissible than sars-cov. the two possible reasons could be (i) the viral load (quantity of virus) tends to be relatively higher in covid- -positive patients, especially in the nose and throat immediately after they develop symptoms, and (ii) the binding affinity of sars-cov- to host cell receptors is higher than that of sars-cov ( , ) . the other comparisons between sars and covid- are tabulated in table , and references for the same are provided here ( , , ) . as per the official government guidelines, india is making preparations against the covid- outbreak, and avoiding specific crisis actions or not understating its importance will have extremely severe implications. all the neighboring countries of india have reported positive covid- cases. to protect against the deadly virus, the indian government have taken ( , ( ) ( ) ( ) . the outbreak of sars in china was catastrophic and has led to changes in health care and medical systems ( , ) . compared with china, the ability of india to counter a pandemic seems to be much lower. a recent study reported that affected family members had not visit the wuhan market in china, suggesting that sars-cov- may spread without manifesting symptoms ( ) . researchers believe that this phenomenon is normal for many viruses. india, with a population of more than . billionthe second largest population in the world-will have difficulty treating severe covid- cases because the country has only , ventilators, which is a minimal amount. if the number of covid- cases increases in the nation, it would be a catastrophe for india ( ) . ( ) . economists assume that the impact of covid- on the economy will be high and negative when compared with the sars impact during . for instance, it has been estimated that the number of tourists arriving in china was much higher than that of tourists who traveled during the season when sars emerged in . this shows that covid- has an effect on the tourism industry. it has been estimated that, for sars, there was a and % decline in yearly rail passenger and road passenger traffic, respectively ( ) . moreover, when compared with the world economy years ago, world economies are currently much more inter-related. it has been estimated that covid- will hurt emerging market currencies and also impact oil prices ( ) ( ) ( ) . from the retail industry's perspective, consumer savings seem to be high. this might have an adverse effect on consumption rates, as all supply chains are likely to be affected, which in turn would have its impact on supply when compared with the demand of various necessary product items ( ) . this clearly proves that, based on the estimated losses due to the effect of sars on tourism (retail sales lost around usd - billion and usd - billion was lost at a global macroeconomic level), we cannot estimate the impact of covid- at this point. this will be possible only when the spread of covid- is fully controlled. until that time, any estimates will be rather ambiguous and imprecise ( ) . the oecd interim economic assessment has provided briefing reports highlighting the role of china in the global supply chain and commodity markets. japan, south korea, and australia are the countries that are most susceptible to adverse effects, as they have close ties with china. it has been estimated that there has been a % decline in car sales, which was % of the monthly decline in china during january . this shows that even industrial production has been affected by covid- . so far, several factors have thus been identified as having a major economic impact: labor mobility, lack of working hours, interruptions in the global supply chain, less consumption, and tourism, and less demand in the commodity market at a global level ( ) , which in turn need to be adequately analyzed by industry type. corporate leaders need to prioritize the supply chain and product line economy trends via demand from the consumer end. amidst several debates on sustainable economy before the covid- impact, it has now been estimated that india's gdp by the international monetary fund has been cut down to . % from . % for the fy . the financial crisis that has emerged owing to the worldwide lockdown reflects its adverse effect on several industries and the global supply chain, which has resulted in the gdp dropping to . % for fy , which was previously estimated at . %. nevertheless, it has been roughly estimated that india and china will be experiencing considerable positive growth among other major economies ( ) . an easy way to decrease sars-cov- infection rates is to avoid virus exposure. people from india should avoid traveling to countries highly affected with the virus, practice proper hygiene, and avoid consuming food that is not home cooked. necessary preventive measures, such as wearing a mask, regular hand washing, and avoiding direct contact with infected persons, should also be practiced. the ministry of health and family welfare (mohfw), india, has raised awareness about the recent outbreak and taken necessary action to control covid- . besides, the mohfw has created a h/ days-a-week disease alert helpline (+ - - and - - ) and policy guidelines on surveillance, clinical management, infection prevention and control, sample collection, transportation, and discharging suspected or confirmed cases ( , ) . those who traveled from china, or other countries, and exhibited symptoms, including fever, difficulty in breathing, sore throat, cough, and breathlessness, were asked to visit the nearest hospital for a health check-up. officials from seven different airports, including chennai, cochin, new delhi, kolkata, hyderabad, and bengaluru, have been ordered to screen and monitor indian travelers from china and other affected countries. in addition, a travel advisory was released to request the cessation of travel to affected countries, and anyone with a travel history that has included china since january th, , would be quarantined. a centralized control room has been set up by the delhi government at the directorate general of health services, and other districts have done the same. india has implemented covid- travel advisory for intra-and inter-passenger aircraft restrictions. more information on additional travel advisory can be accessed with the provided link (https://www.mohfw.gov.in/ pdf/traveladvisory.pdf). india is known for its traditional medicines in the form of ayush (ayurvedic, yoga and naturopathy, unani, siddha, and homeopathy). the polyherbal powder nilavembukudineer showed promising effects against dengue and chikungunya fevers in the past ( ) . with the outbreak of covid- , the ministry of ayush has released a press note "advisory for coronavirus, " mentioning useful medications to improve the immunity of the individuals ( ) . currently, according to the icmr guidelines, doctors prescribe a combination of lopinavir and ritonavir for severe covid- cases and hydroxychloroquine for prophylaxis of sars-cov- infection ( , ) . in collaboration with the who, icmr will conduct a therapeutic trial for covid- in india ( ). the icmr recommends using the us-fda-approved closed real-time rt-pcr systems, such as genexpert and roche cobas- / , which are used to diagnose chronic myeloid leukemia and melanoma, respectively ( ) . in addition, the truenattm beta cov test on the truelabtm workstation validated by the icmr is recommended as a screening test. all positive results obtained on this platform need to be confirmed by confirmatory assays for sars-cov- . all negative results do not require further testing. antibody-based rapid tests were validated at niv, pune, and found to be satisfactory; the rapid test kits are as follows: infections caused by these viruses are an enormous global health threat. they are a major cause of death and have adverse socio-economic effects that are continually exacerbated. therefore, potential treatment initiatives and approaches need to be developed. first, india is taking necessary preventive measures to reduce viral transmission. second, icmr and the ministry of ayush provided guidelines to use conventional preventive and treatment strategies to increase immunity against covid- ( , ) . these guidelines could help reduce the severity of the viral infection in elderly patients and increase life expectancy ( ) . the recent report from the director of icmr mentioned that india would undergo randomized controlled trials using convalescent plasma of completely recovered covid- patients. convalescent plasma therapy is highly recommended, as it has provided moderate success with sars and mers ( ) ; this has been rolled out in health centers and will be increased this month (may ) ( ) . india has expertise in specialized medical/pharmaceutical industries with production facilities, and the government has established fast-tracking research to develop rapid diagnostic test kits and vaccines at low cost ( ) . in addition, the serum institute of india started developing a vaccine against sars-cov- infection ( ) . until we obtain an appropriate vaccine, it is highly recommended that we screen the red zoned areas to stop further transmission of the virus. medical college doctors in kerala, india, implemented the low-cost wisk (walk-in sample kiosk) to collect samples without direct exposure or contact ( , ) . after kerala, the defense research and development organization (drdo) developed walk-in kiosks to collect covid- samples and named these as covid- sample collection kiosk (covsack) ( ) . after the swab collection, the testing of sars-cov- can be achieved with the existing diagnostic facility in india. this facility can be used for massive screening or at least in the red zoned areas without the need for personal protective equipment kits ( , ) . india has attempted to broaden its research facilities and shift toward testing the mass population, as recommended by medical experts in india and worldwide ( ) . publicly available datasets were analyzed in this study. this data can be found here: https://www.mohfw.gov.in/ and https://www. icmr.gov.in/. sk, dk, and cd were involved in the design of the study and the acquisition, analysis, interpretation of the data, and drafting the manuscript. bc was involved in the interpretation of the data. cd supervised the entire study. the manuscript was reviewed and approved by all the authors. available online at declares global emergency as wuhan coronavirus spreads. the new york times ( ) indian council of medical research. government of india. icmr ( ) covid- update. covid- india. ministry of health and family welfare. mohfw ( ) ministry of health and family welfare. goi ( ) available online at all metro cities marked red zones responding to global infectious disease outbreaks: lessons from sars on the role of risk perception, communication and management mers coronavirus: diagnostics, epidemiology and transmission the sars, mers and novel coronavirus (covid- ) epidemics, the newest and biggest global health threats: what lessons have we learned? rates of respiratory virus-associated hospitalization in children aged < years in rural northern india respiratory pathogens in infants diagnosed with acute lower respiratory tract infection in a tertiary care hospital of western india using multiplex real time pcr characterization of the receptor-binding domain (rbd) of novel coronavirus: implication for development of rbd protein as a viral attachment inhibitor and vaccine sars-cov- viral load in upper respiratory specimens of infected patients emergencies preparedness, response. who | severe acute respiratory syndrome (sars)-multi-country outbreak -update cdc. coronavirus disease (covid- ) -symptoms coronavirus scare in east up due to cases in nepal. the siasat daily ( ) the sars epidemic and its aftermath in china: a political perspective the impacts on health, society, and economy of sars and h n outbreaks in china: a case comparison study sars to novel coronavirus-old lessons and new lessons a familial cluster of pneumonia associated with the novel coronavirus indicating person-to-person transmission: a study of a family cluster nations within a nation: variations in epidemiological transition across the states of india, - in the global burden of disease study coronavirus may hit sitharaman's % growth target; second case surfaces in india. the financial express ( ) coronavirus cases in china overtake sars -and the economic impact could be "more severe winning the $ trillion decathlon: going for gold in emerging markets research opportunities in emerging markets: an interdisciplinary perspective from marketing, economics, and psychology coronavirus and oil price crash what coronavirus could mean for the global economy oecd economic outlook chapter -policies to support people during the covid- pandemic antiviral activity of ethanolic extract of nilavembu kudineer against dengue and chikungunya virus through in vitro evaluation advisory for corona virus, homoeopathy for prevention of corona virus infections, unani medicines useful in symptomatic management of corona virus infection lopinavir/ritonavir combination therapy amongst symptomatic coronavirus disease patients in india: protocol for restricted public health emergency use available online at med council backs modern drugs. the economic times ( ) anti-hcv, nucleotide inhibitors, repurposing against covid- convalescent plasma: a possible treatment of covid- in india covid- : vaccine development and therapeutic strategies. indiabioscience ( ) how india must prepare for a second wave of covid- inspired by south korea, walk-in covid- test kiosks built in kerala covid- : kerala hospital installs south korea-like kiosks to collect samples. livemint ( ) available online at: https:// drdo.gov.in/covid- -sample-collection-kiosk-covsack people power: how india is attempting to slow the coronavirus we acknowledge the ministry of health and family welfare (mohfw) and indian council of medical research (icmr) for publicly providing the details of covid- . the authors would like to use this opportunity to thank the management of vit for providing the necessary facilities and encouragement to carry out this work. key: cord- -wjpi uvz authors: pandey, abhishek; nuti, sudhakar v.; sah, pratha; wells, chad r.; galvani, alison p.; townsend, jeffrey p. title: the effect of extended closure of red-light areas on covid- transmission in india date: - - journal: nan doi: nan sha: doc_id: cord_uid: wjpi uvz the novel coronavirus disease (covid- ) pandemic has resulted in over , cases in india. thus far, india has implemented lockdown measures to curb disease transmission. however, commercial sex work in red-light areas (rlas) has potential to lead to covid- resurgence after lockdown. we developed a model of covid- transmission in rlas, evaluating the impact of extended rla closure compared with rla reopening on cases, hospitalizations, and mortality rates within the rlas of five major indian cities, within the cities, and across india. closure lowered transmission at all scales. more than % of cumulative cases and deaths among rla residents of kolkata, pune, and nagpur could be averted by the time the epidemic would peak under a re-opening scenario. across india, extended closure of rlas would benefit the population at large, delaying the peak of covid- cases by to days, and avert % to . % of cumulative cases and % to . % of cumulative deaths at the peak of the epidemic. extended closure of rlas until better prevention and treatment strategies are developed would benefit public health in india. the novel coronavirus disease pandemic, caused by the severe acute respiratory syndrome-coronavirus (sars-cov- ) virus, has resulted in millions of cases, hundreds of thousands of deaths, and a negative economic impact worldwide. india, a country with over . billion people across metropolitan areas and rural villages and an underdeveloped medical infrastructure , could be particularly hard hit with the unmitigated spread of covid- . to address this challenge, india has implemented widespread lockdown measures, including social distancing and travel restrictions , . on march , india first announced nationwide lockdown for three weeks, effectively home quarantining everyone in the country to curb the pandemic growth. the lockdown in india was subsequently extended three times, first to may , then to may , and currently to may . evidence from both india and abroad demonstrates that social distancing is essential to prevent the spread of covid- and reduce mortality , - , especially until a vaccine is developed. nevertheless, several countries, including india, are now cautiously beginning to lift some restrictions in hopes of restarting the economy and preventing economic distress. the government of india has categorized districts of india into three zones based on the covid- risks. the hotspots of transmission, categorized as "red zones," are identified based on total active cases, doubling rate of confirmed cases, extent of testing, and district feedback. areas with declining or stable numbers of cases are classified as "orange zones" and areas with no reported cases for a significant number of days are classified as "green zones" , . while nationwide lockdown continues until may , considerable relaxations for economic and public service activities are now being allowed in lower-risk districts marked as green and orange zones. during the first phase of reopening of the country-starting june -intra-state and inter-state travel will gradually be allowed without need of prior permission from the government. similarly, places of worship, hotels, restaurants, malls and other hospitality services would resume operation from june . as restrictions are eased within specific zones, attention should be directed to geographic hot spots that may disproportionately exacerbate the spread of covid- . red light areas (rlas), where thousands of sex workers typically live and work , are one area of concern for rapid transmission of covid- . by design, these areas have high contact rates between sex workers and clients, and sex acts are not amenable to social distancing. sex workers are vulnerable to high rates of infectious diseases , , experiencing particularly high rates of asymptomatic transmission of infections-a notable component of covid- epidemiology. moreover, visitors to rlas include many truck drivers and migrant workers , who not only live locally but travel long-distances and can potentially spread the virus more broadly, including to green and orange zones. the combined features of a high volume of visitors, high contact rates, potential higher infectivity of sex workers, and long-distance travel of clients across india may make the reopening of rlas a risk to increasing covid- transmission, health care utilization, and death. therefore, the impact of covid- within rlas, on the cities in which they reside, and on the indian populace requires critical evaluation. an analysis in japan has demonstrated a surge of covid- cases transmitted in rlas-cases that have overwhelmed local hospitals . considering the high risk of covid- transmission, other countries, such as the netherlands , germany , and australia , have identified brothels as the last enterprises to reopen. in australia, brothels and strip clubs are the only businesses to be designated as indefinitely closed. prior studies have evaluated the benefits of lockdown in india for slowing covid- transmission , , . however, no previous analysis has examined the effect that the reopening of rlas would have on the spread of covid- in india, or whether keeping them closed would lead to a reduction of cases, reduced health care utilization, and improved mortality rates. such an analysis would be helpful to the national and local governments to make targeted decisions about when, where, and how to ease lockdown measures in the best interest of public health, the health care system, and the economy. to understand the potential impact of extended closure of rlas on covid- in india, we developed a model that quantifies the effects of re-opening rlas after the end of the lockdown. we estimated the change in the time to reach peak covid- cases: the change in cases, hospitalization rates, and mortality rates; and the spread of covid- within rlas at both the national level and among some of the largest cities in india that have been designated within the red zones . data collected on rlas ( table ) facilitated model parameterization. closure of rlas after lockdown significantly delayed the spread of covid- in all cities and nationally, including reduced numbers of cases and deaths ( fig. - ). the magnitude of these effects varied with greater infectiousness (increasing r ; appendix tables - ) and increased with a greater resident population of rlas relative to the general population of the city and with a greater contact rate between the general population of the city and residents of the rla ( fig. ; table ). the initial nationwide lockdown is projected to substantially delay the peak of the epidemic for each city considered and india ( fig. , appendix table ). extended closure of rla after the lockdown is lifted can further delay the epidemic peak further by at least days and up to days with an r of . - . in india ( appendix table ) . there was variation between peak delays among cities. the smallest delay in the peak of cases with an extended closure of the rla in mumbai was a -day delay using r = . (a -day delay to a -day delay; appendix table ). the largest delay in the peak of cases with an extended closure of the rla in kolkata was days-close to the delay that was produced by lockdown alone-using r = . (a -day delay to a -day delay; appendix table ). we found that an extended closure of rlas after the initial lockdown period would avert % to . % of cumulative cases and % to . % of cumulative deaths across india when compared at the date of the peak of epidemic under re-opening of rlas ( fig. , appendix table ). among cities, these reductions of covid- cases and deaths were at least . % and . % respectively for r = ( fig. ). in kolkata, pune, and nagpur, reductions in cumulative cases and deaths at the date of this peak were more than % for all r considered ( appendix table ). extended closure of rlas after the initial lockdown reduced cases, hospitalizations, and mortality within rlas in accordance with potential r values for covid- . with re-opening of the rlas, . % ( , ) to . % ( , ) of all rla residents were projected to be infected by covid- by the peak of the epidemic in india ( appendix table ). by the same date under a scenario of extended closure of the rla, the proportion of rla residents infected would be between . % to . %. for r = , the maximum reduction in cumulative cases at the peak of epidemic occurs within the rla of kolkata (from , cases to cases; appendix table ) and the minimum reduction occurs within rla of mumbai (from cases to cases; appendix table ). india has approximately . million hospital beds, thousand icu beds, and thousand ventilators. most of the beds and ventilators in india are concentrated in seven states-uttar pradesh ( . %), karnataka ( . %), maharashtra ( . %), tamil nadu ( . %), west bengal ( . %), telangana ( . %), and kerala ( . %) . as a result of extended closure of rlas after the initial lockdown, current hospital capacity would be reached on october rather than october (fig. ) . moreover, at the projected november peak of cases, india would need times more hospital capacity than current capacity, while under extended closure of rlas, required hospital capacity would be . times higher ( fig. ) . indian central and state governments are adding additional beds on a daily basis to ramp-up the healthcare capacity. under the scenario in which closure of rlas is not extended, the high number of imminent cases and consequent demand for hospitalization/icu admission and ventilator use rates will likely surpass india's peak medical resource capacity, especially in the vulnerable zones-leading to a higher mortality rate (fig. ). our study demonstrates a beneficial impact of extended closure of rlas in india compared with their re-opening on covid- cases, hospitalization and mortality. extended closure would delay the peak number of cases by - days and result in a . - . % reduction in the cumulative number of covid- cases nationally, when compared at the date of the epidemic peak under a scenario of re-opening the rlas. there would also be a - . % reduction in the cumulative number of covid- -related deaths nationally. these benefits of extended closure of rlas, including a delayed peak in cases, a reduced increase in cases, and a reduction in deaths were demonstrated in mumbai, new delhi, pune, nagpur, and kolkata, as well as across india. mumbai and kolkata (at the two extremes of r considered) produced the most disparate results across cities-a difference that can be attributed to the size of the resident populations of the rlas relative to the general population of the city and to the contact rates between the general population of the city and residents of the rla. the lockdown, contact tracing, and other post-lockdown government interventions , can continue to suppress transmission and flatten the curve, but it is unlikely for the pandemic to be resolved until there is a vaccine for the population . vaccine development and widespread distribution throughout india may take at least more months . in the absence of efficacious treatments or vaccines for covid- , there are limited public health interventions that can substantially reduce covid- cases and deaths when re-opening a country as large and diverse as india , . extended closure of rlas in india may be one of these interventions-and it is feasible. given the disproportionate impact of rlas on covid- transmission and the increase of mortality associated with its spread, extension of closure is essential to the protection of sex workers; their clients; the people who interact closely with sex workers and those close to rlas, including local businesses, police personnel, ngo workers, and the local community; and the population of india at large. in addition to the lower immediate cases, hospitalizations, and deaths, extended closure confers additional time for the nation to plan and execute measures to protect public health and the economy, and to exchange public health and medical advances with the rest of the world. similar to decisions to close cinema halls, gyms, and large public gatherings, rlas should be critically evaluated for their ongoing potential to accelerate covid- transmission and spread. the outcomes of our model are supported by the experiences of other countries with covid- and rlas. in japan, for example, medical facilities were overwhelmed by a surge of cases linked to an rla , , . the sharp increase in cases manifested among sex workers and their clients, and was largely contained within that sector only because of targeted and robust public health interventions. japanese medical institutes have placed sex workers in the highest risk category for contracting the virus-the only profession in that classification not related to the medical field . in germany and australia, brothels remain indefinitely closed, with some politicians calling for their permanent closure in germany . due to concern regarding covid- transmission, sole-operator sex workers and strip clubs have also been banned in australia , . the diversity of businesses that function to enable commercial sex work or other activities involving close physical proximity as part of the nature of service share many of the same risk factors as the sex workers. these other businesses include strip clubs, ladies' bars, hotels that also commerce in sexual services, private sex-work establishments, spas, and massage parlors. there are many social, economic, and health challenges, alongside the spread of covid- , that sex workers and their families will face under extended closure. residents of rlas typically live in confined, communal living spaces. without sex work, they have very limited access to food and other vital living supplies. furthermore, many sex workers lack government-approved documentation and thus are unable to benefit from the government's financial relief packages , table ). individuals table ). the probability of infection given a contact between a client from the general population and a resident of an rla was assumed to be one, if the resident was a sex-worker, and , if the resident was a non-sex worker. as non-sex workers account for five times more interactions with clients than sex-workers, we calculated the probability of infection given a contact between a client from the general population and any resident of the red-light area as the weighted average of these two probabilities, the interactions between the general population and the rla occurring via clients were defined by the connectivity matrix where is the contact rate between the two communities. this contact rate was calculated as the per-capita daily clients from the general population who visit the red-light area. we used social contact matrices estimated for india overall and within specific locations such as households to construct contact patterns between age-groups based on whether individuals are quarantined in their home or not. the contact patterns between age-groups were captured by two matrices: ( table ) to the average number of interactions in the contact matrix . we specified that individuals with asymptomatic and mild infections are only % infectious compared to severe infections ( appendix table ). to generate epidemic projections, we first estimated the initial prevalence of covid- at table ) using the least-squares method. using our calibrated model, we generated results under scenarios of no initial lockdown, initial lockdown followed by return to status quo, and initial lockdown followed by extended closure of the rla. to implement the -day national lockdown in our model, we specified that everyone remained at home, and their contact patterns were informed by the household matrix for the duration of lockdown. moreover, we set the interaction rate between the general population and the rla at zero during this period. after the initial lockdown period, contact patterns were informed by the overall contact matrix , and it was assumed that as a result of improved contact-tracing capacity achieved during lockdown, % of symptomatic cases were isolated after the lockdown period . for the scenario of extended closure of the rla after lockdown, we maintained the contact rate ; with no extended closure, it returned to its original value. the basic reproduction number, r , is the expected number of cases directly generated by an infected person in a completely susceptible population early in an epidemic, without public health intervention. for example, if early in an outbreak, a single individual typically develops the infection and passes it to people, the r is . if r > , there will be an exponential spread of the infection. if r < , the rate of infection spread will be lower and eventually stop. epidemics grow faster with higher r . in this study, we show a range of results based on r values of . to . calculated in recent research on the covid- pandemic , , . to obtain current estimates of city-level population data, we applied population growth rate for national-level data, the number of sex workers, brothels, and client visits was determined from secondary sources , . exhaustive face validation with subject experts was conducted for the dynamic data sets pertaining to the movement of sex / non-sex workers, clients, and their interaction within the brothels due to the high volatility of movement patterns of primary respondents at any given time-space in rlas. where more general secondary sources exhibited discrepancies with the specific rla surveys, the more specific estimates from the five rla surveys were used to compose final data at the national level. references for all the data used in the analysis are provided in the article and supplementary material. all data generated from this study is shared publicly at the github repository https://github.com/abhiganit/redllightareas-covid the mathematical model used to generate results for this study were developed and implemented in matlab. all code used for this study are publicly available at the github repository https://github.com/abhiganit/redllightareas-covid table : delay (in days) in the peak of outbreak for each location and . healthcare impact of covid- epidemic in india: a stochastic mathematical model can india contain the pandemic? covid- : india imposes lockdown for days and cases rise the lancet. india under covid- lockdown wikipedia contributors. covid- pandemic lockdown in india. wikipedia, the free encyclopedia the effect of human mobility and control measures on the covid- epidemic in china the effect of travel restrictions on the spread of the novel coronavirus (covid- ) outbreak substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (sars-cov- ) interventions to mitigate early spread of sars-cov- in singapore: a modelling study prudent public health intervention strategies to control the coronavirus disease transmission in india: a mathematical model-based approach coronavirus lockdown . : will your area fall in 'red zone' post may ? check out district-wise full list india's districts divided into red, orange and green zones; here's what it means -republic world unlock . : what's open & from when in mha's phase-wise reopening plan effect of weather on covid- spread in the us: a prediction model for india in country report on human rights practices. u.s. department of state evidence for high prevalence & rapid transmission of hiv among individuals attending std clinics in pune prevalence of sexually transmitted infections and performance of sti syndromes against aetiological diagnosis, in female sex workers of red light area in surat a study on sexual risk behaviors of long-distance truck drivers in central india sex workers feared to be spreading coronavirus in tokyo's red-light district sex work banned in netherlands until september german sex workers struggle amid covid- lockdown strip clubs and brothels claim 'moral discrimination' over indefinite covid bans mathematical modelling to assess the impact of lockdown on covid- transmission in india: model development and validation prediction for the spread of covid- in india and effectiveness of preventive measures covid- in india: state-wise estimates of current hospital beds, icu beds, and ventilators -center for disease dynamics view of covid- : the end of lockdown what next? emerging from the other end: key measures for a successful covid- lockdown exit strategy and the potential contribution of pharmacists public statement for collaboration on covid- vaccine development how long will a vaccine really take? covid- : extending or relaxing distancing control measures the novel coronavirus disease (covid- ) pandemic: a review of the current evidence many people infected with kabuki-cho customs such as cabaret clubs and hosts dozen-plus infected in kabukicho, tokyo's leading entertainment district surprising list of ' occupations' with high corona risk german lawmakers call for buying sex to be made permanently illegal | dw they are starving': women in india's sex industry struggle for survival. the guardian india's sex workers fight for survival amid coronavirus lockdown census of india website: office of the registrar general & census commissioner temporal dynamics in viral shedding and transmissibility of covid- projecting social contact matrices in countries using contact surveys and demographic data coronavirus in india: latest map and case count public health measures and the reproduction number of sars-cov- age-structured impact of social distancing on the covid- epidemic in india un population division's methodology in preparing base population for projections: case study for india trafficking in women and children in india: nature, dimensions and strategies for prevention the palgrave international handbook of human trafficking trafficking in women and children in india ministry of home affairs. crime in india global march against child labour. economics behind forced labour trafficking appendix: the effect of extended closure of red-light areas on covid- transmission in india pratha sah , chad wells , alison p. galvani , jeffrey p. townsend³ ¹center for infectious disease modeling & analysis mumbai and reopening of red-light areas age-structured impact of social distancing on the covid- epidemic in india regression model based covid- outbreak predictions in india substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (sars-cov ) the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application temporal dynamics in viral shedding and transmissibility of covid- clinical and epidemiological features of children with coronavirus disease (covid- ) in zhejiang, china: an observational cohort study projecting hospital utilization during the covid- outbreaks in the united states covid- . (github) clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study table : cumulative hospitalizations in the red-light area projected at the time the epidemic would peak under the scenario of rla re-opening.cumulative hospitalization a initial lockdown in india from march to may and reopening of red-light areas. b extended closure of red-light areas after the initial lockdown. table : cumulative icu admissions in the red-light area projected at the time key: cord- -t s emf authors: tandon, hiteshi; ranjan, prabhat; chakraborty, tanmoy; suhag, vandana title: coronavirus (covid- ): arima based time-series analysis to forecast near future date: - - journal: nan doi: nan sha: doc_id: cord_uid: t s emf covid- , a novel coronavirus, is currently a major worldwide threat. it has infected more than a million people globally leading to hundred-thousands of deaths. in such grave circumstances, it is very important to predict the future infected cases to support prevention of the disease and aid in the healthcare service preparation. following that notion, we have developed a model and then employed it for forecasting future covid- cases in india. the study indicates an ascending trend for the cases in the coming days. a time series analysis also presents an exponential increase in the number of cases. it is supposed that the present prediction models will assist the government and medical personnel to be prepared for the upcoming conditions and have more readiness in healthcare systems. the pandemic of -ncov commenced from december in wuhan, china and has caused extreme havoc in almost the whole world. , -ncov or covid- , commonly known as coronavirus, is a novel highly contagious virus belonging to coronaviridae family that has been suspected to be transmitted to humans from animals. this virus causes mild to severe respiratory illness and death. this pandemic has engulfed countries/regions in merely four months infecting , , people and taking the death toll to , . , however, the premature cases show the infection is less severe as compared to other coronaviruses such as syndrome corona virus), the cases of rapid human-to-human transmission signify that -ncov is highly infectious than others. although a local seafood market in wuhan is believed to be the source of exposure, the scope of occurrence of this disease is not clear since its occurrence at present is so dynamic. an apparent variation is present in epidemiological examinations and detection abilities performed by different countries for detecting infected cases. presently, the highest cases of -ncov infections have been reported in us, however, the cases are abruptly rising in spain, italy, france and germany daily. china, the place of origin of the disease, is now receiving a very few cases. the first case of coronavirus infection in india was reported on january in kerela, which was an imported case from wuhan city of china. in the initial phase the spread was extremely slow and only people were positive for more than a month. however, the numbers started rising exponentially after one month and continue to do so. the numbers in india have reached up to , for confirmed covid- infected cases with deaths and recoveries as reported on april . at present, there is neither a treatment nor a vaccination for the covid- infection. currently, it is a major health crisis around the world and it would not be wrong to say that it is 'an enemy to humanity'. in this circumstance, the only option is preventing the occurrence of infection and preparing our healthcare system for the probable up-comings. in that reference, it is extremely crucial to construct models that are computationally competent as well as realistic so that they can help policy makers, medical personals and also general public. modeling the disease and providing future forecast of possible number of daily cases can assist the medical system in getting prepared for the new patients. the statistical prediction models are useful in forecasting as well as controlling the global epidemic threat. in the present effort, we have employed auto-regressive integrated moving average (arima) model for predicting the incidence of -ncov disease. as compared to other prediction models, for instance support vector machine (svm) and wavelet neural network (wnn), arima model is more capable in the prediction of natural adversities. for our study, we have identified the best arima model and then predicted the number the cases for the next days. the main objective of the study is to find the best predictive model and apply it to forecast future incidence of covid- cases in india. this data is used to build predictive models. for forecasting a time series, arima modeling is one of the best modeling techniques. arima models are always represented with the help of some parameters and the model is expressed as arima (p, d, q). here, p stands for the order of auto-regression, d signifies the degree of trend difference while q is the order of moving average. we have applied an arima model to the time series data of confirmed covid- cases in india. autocorrelation function (acf) graph and partial autocorrelation (pacf) graph is used to find the initial number of arima models. these arima models are then tested for variance in normality and stationary. next, they are checked for accuracy by observing their mape, mad and msd values to determine the finest model to forecast. in addition, the best fit arima model is compared with linear trend, quadratic trend, s-curve trend, moving average, single exponential as well as double exponential models using an output of measure of accuracy, viz. mape, mad, msd, so as to select the finest model to forecast. the finest model is the one which has the lowest value for all the measures. after fitting the model, its parameters are estimated followed by verification of the model. the built model is employed to forecast confirmed covid- cases for the next days, i.e. april to may . the model for forecasting future confirmed covid- cases is represented as, here, xt is the predicted number of confirmed covid- cases at t th day, α , α , β and β are parameters whereas zt is the residual term for t th day. the trend of forthcoming incidences can be estimated from the previous cases and a time series analysis is performed for this purpose. time series forecasting refers to the employment of a model to forecast future data based on previously observed data. in the present study, time series analysis is used to recognize the trends in confirmed covid- cases in india over the period of january to april and to predict future cases from april till may . the level of statistical significance is set at . . a graph is plotted for actual confirmed cases and predicted confirmed cases with respect to time to verify the efficiency of the model. to get an idea of the recovery and death trends in india, a graph is plotted with respect to time. a comparative study is also performed to examine the status of confirmed covid- cases of india with respect to those of highly infected countries. a similar comparison is made with the countries of south-east asia region as well. all the model developments, computations and comparisons have been performed using minitab software (version ). the present work encompasses development of a model to forecast covid- incidences in the coming days. the results for measure of model accuracy for arima, linear trend, quadratic linear, s-curve trend, moving average, single exponential as well as double exponential model are presented in table arima ( , , ) model (eq. ( )) is used to forecast confirmed covid- cases in india for the next days, i.e. april to may . the forecast for cases is presented in table with % confidence interval by china, that is, severe control and quarantine, it can be expected that india will also recover soon because of its similar preventive measures. time series analysis presents the meaningful statistics for confirmed covid- data. figure for comparing the actual and forecasted confirmed covid- cases, a time series graph is plotted starting from january till april . the plot is represented by figure . the similarity of forecasted data with actual data is clear from these plots. this comparison reveals the precision of the model in forecasting. january to april . trend for the number of recovery and death cases with respect to time due to covid- infections in india depicted in figure . it is observed that the number of recoveries as well as deaths increase with time, however the rate of recovery is higher than the death rate. thus, a low mortality rate could be expected from the disease. figure shows a comparative study of confirmed covid- infection cases of india with respect to those of highly infected countries. according to the plot, us is the most infected while india the least infected of the selected countries, viz. us, spain, italy, france, germany, china and iran. it is very obvious as india was the last amongst these countries to get infected. however, the plot also reflects that china has been able to control the pandemic and is now presenting very few new cases. thus, it follows that if strict prevention measures such as quarantine and sanitization are continued for some days, the situation could be controlled in the coming days. in the remaining countries, infected cases are growing exponentially and severe spread of infection is seen. a similar comparison is performed for the countries of south-east asia region as well as shown in figure . a look at the figure suggests india to be the most infected amongst the south-east asian countries followed by indonesia and thailand. all the three countries are presenting continuous rise in confirmed covid- infections. the remaining countries of the region have a very low infection rate, lowest being in timor-leste. it is clear that measures like quarantine and sanitization can decrease human exposure and control this pandemic. thus, these measures should be stringently imposed in india and strict actions must be taken against those people who violate the rules and don't consider the severity of the situation. although a large amount of data helps in providing a more exhaustive prediction and explanation, in the present circumstance, these models could be valuable in anticipating future cases of infection if the pattern of virus spread didn't change abnormally. it is obvious that this virus is new and has the capability to be transmitted intensely. hence, it may have an influence on the predictions, however as per our knowledge, in the present situation this model is the finest. the novel coronavirus disease (covid- ) has been declared as pandemic by who and is currently a major global threat. in order to support the prevention of the disease and aid in the healthcare service preparation, we have conducted this study to examine the finest model for the prediction of confirmed covid- infection cases and to employ that model for forecasting future covid- infection cases in india. as per the model forecast, the confirmed cases are expected to greatly rise in the coming days. the time series analysis shows an exponential enhancement in the infected cases. however, it is also anticipated that the efforts such as lockdown may affect this prediction and cases may start to decline after a month approximately. a comparative study with some of the highly infected countries and countries in south-east asia region indicates that india can still control the situation if the prevention measures such as quarantine and city sanitization are strictly followed. the prediction models will help the government and medical workforce to be prepared for the upcoming situations and have more readiness in healthcare systems. a novel coronavirus from patients with pneumonia in china coronavirus infections-more than just the common cold coronavirus (covid- ) cases - coronavirus outbreak the epidemiological characteristics of an outbreak of novel coronavirus diseases (covid- ) in china quantifying bias of covid- prevalence and severity estimates in wuhan, china that depend on reported cases in international travellers kerela confirmed first novel coronavirus case in india comparison of the ability of arima, wnn and svm models for drought forecasting in the sanjiang plain time series analysis. basic statistics and data analysis minitab statistical software both the corresponding authors are thankful to presidency university, bengaluru and manipal university jaipur, jaipur for providing research facility. h.t. and t.c. conceptualized the project. h.t. designed the study, performed the computations and investigations, contributed to data analysis and wrote the manuscript. p.r. provided the resources. t.c. and v.s. supervised the study and reviewed the manuscript. the authors declare no competing interests. this research did not receive any specific grant from funding agencies in the public, commercial, or not-forprofit sectors. key: cord- -dvbua pf authors: nepal, binod title: aids denial in asia: dimensions and roots date: - - journal: health policy doi: . /j.healthpol. . . sha: doc_id: cord_uid: dvbua pf abstract aids denial has long been viewed as the obstacle to forging effective response in many asian countries. this article examines the dimensions and roots of this phenomenon. it identifies seven types of views, attitudes, or tendencies that can be described as denial, dissent, disagreements, or doubts. three major factors underlying the aids denial are discussed. these are ( ) historical impressions that stds are western diseases, ( ) desire of some asian leaders to forge eastern points of view, and ( ) long-held negative image towards the peoples or groups who happened to be at the front-line of the population groups exposed to the epidemic. the third factor is the most important source of denial. aids denial is not a new and isolated phenomenon but the one shaped by the global and historical institutions. asian aids denial reflects the authoritarian and moralist grievances arising from the perceived deterioration of traditional moral order. since the late s, well within a decade of the identification of the disease, asia has been warned to be heading towards a devastating aids epidemic. the epidemic has been described as the 'gathering storm' [ ] which could create a 'next wave' [ ] of infections and deaths in asia pushing the 'continent in peril' [ ] and putting the 'economic and social progress in jeopardy' [ ] . though the prevalence of the disease in asian regions such as south and southeast asia ( . %) and east asia ( . %) is much lower than that in sub-saharan africa ( . %), almost all the countries have detected the virus in their nationals [ ] . yet people who take drugs intravenously and those who sell sex are at the front-line of the population groups hit by the 'storm'. the virus has been detected in the majority of injecting drug users in one or more sites of china, india, indonesia, myanmar, nepal, thailand, and vietnam, and among one-tenth or more sex workers in some sites of cambodia, india, myanmar, nepal, thailand, and vietnam [ , ] . the incidence of hiv is rising among low-risk female populations in many countries [ ] . however, responses to this ongoing crisis have often remained scanty even in the countries which have been speculated to be at the risk of larger epidemics. dwyer et al. observed that although information about devastating impacts of hiv/aids in africa was widely circulated in the region, most countries in asia took no initiative to adopt the measures proven to be effective in controlling the epidemic [ ] . there are notable disagreements about the extent, prospect, and prevention of the disease. at the first hand, the control of aids epidemics looks simple, as thailand has shown that the disease can be contained provided that the leaders are committed and focused interventions are put in place [ ] . but many other countries have done little to reach the people who are the first to face the 'storm'. a review showed that only a small fraction of at-risk populations such as injecting drug users, sex workers, and migrants had been reached with the basic prevention services [ ] . not much was changed by [ ] . even thailand was no exception given that only a few drug injectors and homosexuals were receiving some outreach services [ ] . so, why are the responses to the prospective 'storm' low, slow, and fragmented? why is there little appre-ciation among the leaders that the disease might take a heavy toll if left unchecked? the phenomenon of low, slow, and fragmented responses has been described as the outcome of aids denial. time and again, aids denial has been mentioned as the serious obstacle to controlling aids in asia. the generic label, however, obscures many important dimensions of this challenge. the paper attempts to explore the dimension and roots of the aids denial in asia. the analysis is guided by the social constructionist approach which assumes that the diseases are biological phenomena but they carry socially constructed meaning. widespread stigma and discrimination against people with hiv/aids arise partly from the existing negative public attitude towards these people [ ] . the negative public image of hiv/aids and people carrying the virus is not only associated with the nature of the disease but also with the socially constructed meaning or understanding about the risk factors. the extent of stigma varies according to modes of transmission or behaviours perceived to be responsible for the infection and the pre-existing characteristics of the at-risk groups. many different social institutions contribute to the construction of specific public images of the target populations. the people and places at risk of contracting a disease are identified by the epidemiological studies but they do not necessarily become comprehensible to the masses. the public, the media, and the policy-makers begin to develop certain images about the disease and the at-risk people. according to schneider and ingram [ ] , 'officials develop maps of target populations based on both the stereotypes they themselves hold and those they believe to prevail among the segments of the public likely to become important to them.' formulation and shifts in policy for a particular group, subpopulation, or community depend on how they are viewed by policy-makers. gauri and liberman contend that where social institutions divide the population groups deeply, elites and common people perceive aids to be a disease of other people outside their community and who are unlikely to mingle with them [ ] . when responsible authorities take 'us' and 'they' approach by prejudicially linking the disease with specific sections of the populations, aids policies remain misguided and fragmented. to illustrate, despite very similar socio-demographic setups, response to aids were very different in brazil and south africa; unlike brazil where aids was considered a general threat for the entire population, aids was linked in south africa with the racial issues and aids policy was marred with racial divisions [ ] . like aids, the aids denialism is a global phenomenon. this has even tied the hands of the united nations (un) agencies which are looked for leading the global efforts to fight this pandemic. the political declaration adopted on june by the un general assembly mentioned the term 'vulnerable groups' five times but nowhere specified what they include [ ] . this was aimed at avoiding the acknowledgment of the existence of vulnerable groups such as injecting drug users and sex workers. yet much of the international comments on aids denial refer to south africa where the president thabo mbeki questioned the prevailing mainstream views on hiv/aids, and set up the presidential aids advisory panel [ ] [ ] [ ] . inclusion of the so-called dissident scientists in the panel was the most controversial aspect of his initiative and the major cause for severe criticism against him. refuting the established biomedical explanations, mbeki raised doubts about the role of sexual behaviours in driving the epidemic, attributed poverty as a cause for widespread aids deaths in africa, and expressed skepticism to the relevance of antiretroviral therapy. he was, therefore, branded as a 'denialist' and was even considered responsible for 'genocide' for the deaths due to aids in his country [ ] . no leader in asia has done anything as controversial as it was done by mbeki. yet asia is not free from denial if the term is understood as encompassing the range of dissenting voices and disagreements. schneider and fassin [ ] refer to denial as the 'individual or collective inability to face an intolerable reality by pretending that it does not exist'. there is, however, little clarity as to what the aids denial means in the asian contexts. mention of this term in one or the other context or to accuse governments [cf. , ] is not helpful to understand the full picture of the denial in this region. aids denial is a complex phenomenon manifested in various forms, ways, and contexts. seven major dimensions of denials, doubts, or disagreements about hiv/aids in asian societies are briefly discussed below. for sim-plicity, the term denial has been used here to represent the range of disagreements, controversies, doubts, or dissents. first, a small group of scientists and other professionals have doubted or even denied whether hiv has really been identified or whether it really causes aids. they are mostly from the us or europe but includes a few from asia. a group of the dissidents -leading among them is peter duesberg -argued that hiv is a harmless virus, and that aids is caused by drug abuse, anti-aids drugs, or malnutrition [ , ] . the other group of dissidents, primarily the perth group, questioned whether hiv was actually identified as a unique retrovirus [ ] . in , more than scientists and professionals signed a statement known as 'the durban declaration' dismissing those dissenting arguments [ ] . some of the signatories were from asia. nevertheless, the voices of aids dissidents appear to have no significant influence upon aids policies, as no countries have publicly subscribed to these views. second, aids has long been seen as foreigners' disease. a widely held view in asia in the pastand to a little extent so far -is that aids is a westerner's disease. initial cases of aids identified in some countries of asia belonged to the tourists or citizens returning from the west or the patients receiving the blood imported from the west. the first aids case in indonesia was found in a dutch tourist in bali, a tourist island, in . in china, the first aids case was identified in an argentina-born us citizen and the first four chinese identified with hiv were the haemophiliac patients who received blood imported from the united states (us) [ ] . the first aids patient documented in thailand was a thai male returned from the us [ ] . these incidents created an illusion about the source and prospect of the disease. third, many asian leaders were apparently confident about the persistence of moral order in their countries. many of them believed that deviant behaviours were absent or rare, and therefore the disease was unlikely to spread to the masses. moralistic and ideological roots of aids denialism in asia will be discussed in next section. to illustrate the illusion of moral order, it is sufficient to quote the then indian health minister: 'ours is a moral society. while tackling aids you [cannot] say you lead licentious lives because [you can use] condoms. i don't think that should be the message. ' [ ] fourth, aids has been considered a disease of deviants or isolated groups. when the disease began to appear among the local populations of asia, the virus was initially identified among people who were traditionally considered deviants or immoral. in india, a female sex worker from chennai was the first local person identified with hiv. initial outbreaks of hiv in this country occurred among injecting drug users in manipur, a northeastern state bordering on myanmar [ ] and female sex workers in mumbai [ ] . likewise, in indonesia, initial cases of hiv infections were found in costal areas frequented by thai fishermen [ ] . the first major outbreaks of hiv in china were limited to the injecting drug users mostly from the ethnic minorities in yunnan province [ , ] . this might have created a false hope that the mainstreams of the society would be insulated from the epidemic. fifth, denial of services to the people exposed to the disease was an inevitable outcome of the perception that individuals contracted the disease owing to their own sinful, deviant, or immoral behaviours. statistics reported by the government agencies showed that until recently only a small fraction of vulnerable groups such as injecting drug users, sex workers, and men who have sex with men were reached with outreach services [ ] . even in thailand which has one of a few model programs successful to control the epidemic at the national scale, the interventions have not covered all identified at-risk groups [ ] . some critical groups such as injecting drug users, prisoners, men who have sex with men (msm), and immigrants have been deprived of basic prevention and treatment services. therefore, despite growing evidence about the effectiveness, such programs as harm reductions and condom use remain controversial in the region [ ] . sixth, statistics on hiv/aids or at-risk groups are considered sensitive items deserving to be hidden. thailand, which developed a model condompromotion program later on, initially suppressed the results of hiv testing among sex workers for the fear that the news of hiv outbreaks would harm the tourism industry. though the country soon took bold steps to publicise the statistics and to insti-tute the much-admired condom-promotion campaign [ ] , many other countries in the region continued to show high sensitivity towards the statistics on hiv/aids and the most-at-risk groups. this is one of the reasons behind limited availability and quality of the statistics on the at-risk groups such as injecting drug users, sex workers and their clients, and men who have sex with men in the region [ ] [ ] [ ] . attitude of authorities in several countries of this region is probably reflected in the un theme group's observation about the local governments in china: many local governments do not want to know, or let others know about hiv/aids in their area for fear that it will reflect poorly on the locality and its officials. local governments sometimes suppress information and sometimes even actively oppose research on hiv/aids. [ ] finally, sensitivity about the disease is translated into denial of, or disagreement over, the scale of the epidemics. on several occasions, internal and external agencies have seriously doubted one another's estimates. generally, india and china kept questioning the validity of the hiv/aids estimates and relevance of the prevention programs prescribed by the international institutions and western health experts. in , indian officials disagreed with the un estimate of million people living with hiv/aids in the country, and the media even suspected that the 'figures were being inflated by the west to pressure india into accepting vaccine trial and other research on hiv infected people' [ ] . a doctor familiar with the aids situation in india, however, warned that 'denial, complacency, and blaming others for the epidemic are the main reasons why hiv has spread so successfully' in the country [ ] . similar disagreements erupted in when richard feachman, the executive director of the global fund to fight aids, tuberculosis, and malaria warned that india had the largest number of people living with hiv/aids in the world, surpassing south africa. he remarked, 'i don't believe in official statistics. india is already in [the] first place' [ ] . his arguments were refuted by several senior government officials of india citing that these two countries were not comparable and the gap in hiv prevalence levels were large [ ] . likewise, on september , the lancet published a news report entitled 'human rights organization blasts china over hiv/aids cover-up.' human rights watch accused chinese government of being 'in denial' over scale of hiv/aids epidemic. in this report, asian division director of human rights watch, a new york based organization, was quoted as commenting: 'the chinese government has been in denial about the problem for many years', and 'beijing's failure to act decisively in the aids epidemic continues to cost lives and cause incalculable suffering to those living with the virus' [ ] . though the aids denial is not so unique to asia, there are certain features specifically conducive for this phenomenon. this section discusses three salient factors: ( ) historical impressions that some sexually transmitted diseases (stds) are western diseases, ( ) desire of some asian leaders to forge eastern points of view, and ( ) long-held negative image towards the peoples or groups who happened to be at the highest risk of contracting the disease. these three factors are, however, interrelated. historically, the well known stds such as syphilis were understood by asians as the westerners' disease. european colonizers were seen as the sources of syphilis into asia. mukherji and chakravarti [ ] observed that syphilis, which is believed to have brought to europe by columbian voyagers, was unknown in ancient india until the arrival of portuguese, although gonorrhoea and soft chancre existed since ancient time. they maintained that the absence of any comment about syphilis in sanskrit works would illustrate the absence of this disease in this region. they noted: 'the disease is first mentioned in bhabaprakasa under the name of feringhi roga (portuguese disease) and mercurial preparations are recommended its treatment' [ ] . the term feringhi was used in many countries of asia not only to refer to portuguese but any european. in nepal, for example, local name of syphilis is viringi and it seems probable that the name was coined to identify the disease with the feringhi. medical history also indicates that incidence of venereal diseases was probably higher among europeans than asians. according to the annual report of the public health commissioner with the government of india, rates of hospital admissions for treatment of venereal diseases of british troops ( . per ) was four times higher than that of indian troops ( . per ) [ ] . an important ideological background to the aids denial stems from the desire of asian leaders to forge an independent view reflecting on the culture, traditions, and philosophies of the east. the thought exaggerates morality, hierarchical relations among the member of the society, community cohesiveness, and extended family systems as unique characteristics of the asian societies. this pattern of thought is sometimes referred, particularly in the east or southeast asia, as the asian values. though the concept of asian values has been criticised as having no factual base [ ] , it cannot be denied as having served the authoritarian officials to interpret the aids as a disease of deviants or bad people. this idea imagines asia as unique and denies or denounces behaviours that are considered to be inspired by the western thoughts and promotes oppressive or eliminative approach towards the people who are engaged in those behaviours. the concept of asian value -or exaggeration of morality in particular -is not the only background for aids denial. on several issues, asians have developed opinions different from that of the western scholars, governments, and institutions. the aids denial, which is considered the single most threat to effective aids policy in asia, parallels, to a limited extent, the previous debates on emerging issues of global concern. a relevant example is the great population debate -evolved in the s -about the role of aggressive family planning programs versus role of development for population control in the developing countries [ , ] . in the s, developing countries questioned the western policy of the uni-focal family planning programs to control population in the third world countries. on some occasions, development was argued as the best contraceptive. for aids, moral order has been seen as the best protection. this paves way for painting negative image of the people who rather need support. the construction of public impression about aids and the at-risk groups began with its initial epidemiological mystery. the disease remained mysterious for some years and societies developed various metaphors reflecting fear, stigma and moralistic misapprehensions [ ] . various perceptions about aids and at-risk groups evolved in the west permeated asia well before the disease arrived. in the us, aids was initially found among gays and hence characterized as a 'gay plague' [ ] . this prompted the asian policy-makers to dismiss the potential challenge of this epidemic assuming that homosexuality was absent in asia. in the s, aids cases detected in asia were mostly among foreigners, overseas returnees, and female sex workers. until the early s, aids in asia was generally interpreted as the foreigner's disease, particularly westerner's disease, associated with homosexuality and prostitution. for example, in , a journalist observed that the 'indian government's perception that "foreigners" are the principal carriers of hiv does not seem to have changed in recent years' [ ] . he added, 'most laws proposed to check the spread of aids are aimed at non-nationals' [ ] . similar was the situation in thailand where aids was initially perceived as 'a foreign disease, carried by foreigners and brought from foreign lands', and later as 'a disease of homosexuals' and then as 'a disease of intravenous drug users' [ ] . in the philippines, aids was mainly identified with the prostitutes and lower class gays who had contact with foreigners. even the upper class gays were arguing that 'low class gay people should be rounded up for aids testing since they're the only ones now who go around with the foreigners' [ ] . in some instances, people from high prevalence neighbouring regions were also blamed and cautioned. for example, when taiwan started to recruit foreign labourers in to make up its labour shortage, the labourers from south and southeast asia were characterized as the highest risk category who would pass hiv to innocent locals [ ] . it has been taking a long time to overcome the misinterpretation that aids is simply a disease of bad people. the groups identified as the high-risk are powerless, unorganized, often from disadvantaged backgrounds, and negatively viewed. so, these groups have been blamed for spreading the disease and considered to be personally accountable for the infections. major messages directed to the negatively viewed powerless groups are that 'they are bad people whose behaviour constitute a problem for others,' and that 'they can expect to be punished unless they change their behaviour or avoid contact with the government' [ ] . the negatively viewed powerless at-risk groups mostly included injecting drug users, female sex workers, men who have sex with men, and immigrants. in japan, as the official medical care system excludes undocumented foreign nationals, the immigrants are reluctant to take hiv test and to seek medical care for the fear of deportation [ ] . burmese migrants in thailand, especially those who lack work permit, also avoid visiting health facilities because of the fear of deportation [ ] . on may , a thai daily, the nation, reported that hiv prevalence among migrants was twice the prevalence in pregnant women, and hence the local public health experts were pointing out migrants as emerging vectors of hiv. marginal population groups such as idus, sex workers, and msms who are the most vulnerable to aids were stigmatized even without aids; the disease has added another burden upon them creating the phenomenon of double stigma [ , ] . in yunnan, china, for example, drug users carry stigma and are denied participation in the community activities and state sponsored services irrespective of their hiv status [ ] . a study from six asian countries identified that the tendency to blame, stigmatize, and discriminate the people vulnerable to, or living with, hiv is realised more clearly in interpersonal contexts such as health facilities but this is grounded in cultural, religious, institutional, and structural frameworks [ ] . in some instances, governments use strong negative terms such as social evils to described these people and emphasize punishment rather than support and care [ , ] . comparatively, aids carries more stigma than do other killer diseases such as severe acute respiratory syndrome and tuberculosis because aids is still seen as the consequence of one's own carelessness [ ] . aids denial has many dimensions but the most important one arise from the long-held negative attitude towards the vulnerable populations. there are some variations in the images of aids and at-risk groups across the regions but they are not merely local products; rather they have been shaped by the global and historical institutions as well. the echo has been felt up to the un general assemblies at the international level and down to the individuals at the micro-level. interestingly, no one in asia has taken views as extreme as the south african president mbeki, but there are many instances of disagreements, doubts, and denials that have been affecting the people directly exposed to the pandemic. while indifference, doubts, and blame underpin inaction or slow action in some instances, they have led to adopt negative policies in the other instances. overcoming denials is an important step towards instituting positive and comprehensive responses to aids. strategies can vary among the nations depending on their socio-cultural context and economic and technical ability. a general approach is to tackle pre-existing background stigma towards these vulnerable groups by promoting solidarity and intensifying advocacy. this helps reduce the long-held tendency to see aids as a disease of some careless people. the efforts of local and international networks of people with hiv have been showing some impacts but these institutions should have more than ceremonial recognition. further work is required to improve surveillance, research, and analysis and to better understand the extent and prospect of the epidemics and to show the implications to the society of the continued inactions. such work should be supplemented by conceptual debate on how broader social contexts, not only individual desires, underpin the risk behaviours. in sum, asian aids denial is a reflection of lamentation about the perceived deterioration of traditional moral orders and weakening hold on new generations, rather than the aids per se. when the authorities realise that they need to adapt their views and policies to suit the rapidly changing societies, the phenomenon of aids denial begins to fade. concerted advocacy spearheaded by organized members of the most vulnerable groups can speed up this process. aids in asia: the gathering storm the next wave of hiv/ aids: nigeria aids in asia: a continent in peril economic and social progress in jeopardy: hiv/aids in the asian and pacific region: integrating economic and social concerns, especially hiv/aids, in meeting the needs of the region report on the global aids epidemic hiv/aids surveillance database. us census bureau monitoring the aids pandemic network (map network) report on the global hiv/aids epidemic: th global report challenge and response: hiv in asia and the pacific breaking the silence: setting realistic priorities for aids control in less-developed countries unaids, world health organization (who), centers for disease control and prevention (cdc), policy project. coverage of selected services for hiv/aids prevention, care and support in low and middle-income countries in interventions to reduce hiv/aids stigma: what have we learned? social construction of target populations: implications for politics and policy boundary institutions and hiv/aids policy in brazil and south africa political declaration on hiv/aids denial defiance: a socio-political analysis of aids in south africa a synthesis report of the deliberations by the panel of experts invited by the president of the republic of south africa, the honourable mr the embodiment of inequality: aids as a social condition and the historical experience in south africa the aids scare in india could be aid-induced. editorial comments human rights organisation blasts china over hiv/aids cover-up: human rights watch accuses chinese government of being "in denial" over scale of hiv/aids epidemic hiv does not cause aids the aids dilemma: drug diseases blamed on a passenger virus a critique of the montagnier evidence for the hiv/aids hypothesis the durban declaration hiv infection and aids in china through acquired immune deficiency syndrome in thailand. a report of two cases india minister vows to beat aids rapid spread of hiv among injecting drug users in north-eastern states of india the current situation of the hiv/aids epidemic in indonesia current status of hiv infection in yunnan province of china hiv infection and aids in china thailand's response to aids: building on success, confronting the future aids and public policy: the lessons and challenges of 'success' in thailand estimates of the number of female sex workers in different regions of the world estimating the number of men who have sex with men in low and middle income countries estimates of injecting drug users at the national and local level in developing and transitional countries, and gender and age distribution un theme group on hiv/aids in china. hiv/aids: china's titanic peril the aids scare in india could be aid-induced india surpasses south africa in aids cases india's response to the hiv epidemic prostitution in india. calcutta: das gupta and company development as freedom famplan: the great debate abates. international family planning perspectives the politics of family planning: issues for the future aids and its metaphors understanding aids: historical interpretations and the limits of biomedical individualism india: less complacency now thailand: the 'foreign' disease philippines: focusing on the hospitality women sexual cultures in east asia: the social construction of sexuality and sexual risk in a time of aids japanese foundation for aids prevention. hiv/aids update sexuality, reproductive health and violence: experiences of migrants from burma in the third phase of hiv pandemic: social consequences of hiv/aids stigma and descrimination and future needs using case vignettes to measure hiv-related stigma among health professionals in china drug abuse, hiv/aids and stigmatisation in a daicommnity in yunnan hiv discrimination: integrating the results from a six-country situational analysis in the asia pacific sex in the city: sexual behaviour, societal change, and stds in saigon uncharted waters: the impact of u.s. policies in vietnam comparative stigma of hiv/aids, sars, and tuberculosis in hong kong this article draws on the research conducted by the author as a phd scholar at the demography and sociology program, the australian national university. the author would like to thank prof. terry hull and dr. zhongwei zhao for their insightful comments on an earlier version of this article. key: cord- -d l sbeb authors: oberoi, sumit; kansra, pooja title: economic menace of diabetes in india: a systematic review date: - - journal: int j diabetes dev ctries doi: . /s - - -z sha: doc_id: cord_uid: d l sbeb aim: diabetes mellitus is recognised as a major chronic pandemic disease that does not consider any ethnic and monetary background. there is a dearth of literature on the cost of diabetes in the indian context. therefore, the present study aims to capture the evidence from the literature on the cost of diabetes mellitus in india. methods: an extensive literature was reviewed from academia, ncbi, pubmed, proquest, ebsco, springer, jstor, scopus and google scholar. the eligibility criterion is based on ‘picos’ procedure, and only those studies which are available in the english language, published between and february , indexed in abdc, ebsco, proquest, scopus and peer-reviewed journals are included. results: a total of thirty-two studies were included in the present study. the result indicates that the median direct cost of diabetes was estimated to be ₹ , /- p.a. for the north zone, ₹ , /- p.a. for the south zone, ₹ , /- p.a. for the north-east zone and ₹ /- p.a. for the west zone. similarly, the median indirect cost of diabetes was ₹ , /- p.a. for the north zone, ₹ /- p.a. for the south zone, ₹ , /- p.a. for the north-east and ₹ /- p.a. for the west zone. conclusion: the present study highlighted that diabetes poses a high economic burden on individuals/households. the study directed the need to arrange awareness campaign regarding diabetes and associated risk factors in order to minimise the burden of diabetes. electronic supplementary material: the online version of this article ( . /s - - -z) contains supplementary material, which is available to authorized users. 'diabetes is a metabolic disease characterised by hyperglycemia resulting from defects in insulin secretion, insulin action or both' [ ] . with rising pervasiveness globally, diabetes is conceded as a major chronic pandemic disease which does not consider any ethnic background and monetary levels both in developing and developed economies and has also been designated with the status of 'public health priority' in the majority of the countries [ , ] . individuals with diabetes are more susceptible to develop any of the associated complications, viz. macrovascular or microvascular. as a consequence, people experience frequent and exhaustive confrontation with the health care systems [ ] . the treatment cost for diabetes and its associated complications exert an enormous economic burden both at the household and national levels [ ] [ ] [ ] [ ] [ ] . in a developing nation like india, the majority of diabetes patients experience a substantial cost burden from out-ofpocket (oop). also, the dearth of insurance schemes and policies escalate the cost of diabetes care [ ] . instantaneous urbanisation and socio-economic transitions, viz. rural to urban migration, low exercise regimen, lifestyle disorder, etc., have resulted in an escalation of diabetes prevalence in india over the last couple of decades [ ] [ ] [ ] [ ] [ ] . according to the international diabetes federation [ ] , 'india is the epicentre of diabetes mellitus and it was found that in india had the second-largest populace of million diabetic patients, after china. and the figure is expected to be just double million by '. considering that fact, the epidemiologic transition of diabetes has a colossal economic burden [ ] . the estimated country-level health care expenditure on diabetes mellitus in india after amending purchasing power difference was billion us dollars in , pushing india in fourth place globally after the usa, china and germany. looking at the economic burden, in india, diabetes alone exhausts to % share of an average indian household earning [ ] [ ] [ ] . chronic nature and the rising epidemic of diabetes have everlasting consequences on the nation's economy and health status [ ] . therefore, managing diabetes and its comorbidities is a massive challenge in india due to several issues and stumbling blocks, viz. dearth of awareness regarding diabetes, its risk factors, prevention strategies, health care systems, poverty-stricken economy, non-adherence to medicines, etc. altogether, these issues and problems remarkably contribute to the economic menace of diabetes in india [ ] [ ] [ ] [ ] [ ] . after a perspicuous representation of the economic menace of diabetes in india, policymakers and health experts should provide healthier prospects to enhance the quality of life of millions [ ] . thus, the present study aims at capturing the evidence from the literature on the cost of diabetes mellitus in india, reviewing the materials and methods used to estimate the costs and, lastly, exploring future research area. for the accomplishment of the objective, the paper has been divided into five sections. the 'introduction' section of the study discusses diabetes and its economic burden. the 'materials and methods' section deals with materials and methods applied for data extraction and quality assessment. the 'results' section of the present study reports the results of the study. the 'discussion' section concludes the discussion along with policy implications and limitations. a comprehensive literature review was carried out by following the 'preferred reporting items for systematic reviews and meta-analysis (prisma) guidelines' [ ] . the article suggests a minimum set of guidelines and procedures of writing items to enhance the quality of the systematic review. a search was performed between february and march for the accumulation and review of studies published up to january . [ ] . later, articles were identified to be duplicate and removed immediately. of the total articles, limited studies managed to clear the eligibility criterion based upon the significant elements of the 'patient intervention comparison outcome study (picos)' procedure [ ] . title, abstract and keywords of the remaining studies were assessed to determine their relevance. those articles which have been included (a) were available in english language; (b) were published between and february ; (c) were indexed under abdc, ebsco, proquest and scopus; (d) were under journals that are to be peer-reviewed in nature; (e) highlighted unprecedented research outcomes on costs; and (f) were comprising at least one or more demographic zones. thus, the screening procedure facilitated the selection of articles. majority of research publications were excluded on the grounds if they (a) did not provide the detailed analysis of how costs were estimated; (b) were conference articles or posters; (c) only presented the costs of diabetes prevention; and (d) were published in non-peer-reviewed journals. the exploration includes those articles which highlight the cost burden of diabetes in india. whilst performing the analysis, two interdependent excel spreadsheets were developed for data to be summarised. in the very first spreadsheet, a predefined category was used, viz. publication title/year, study type, location, diabetes type, methodology and findings. relevant information is drawn out and presented in table , highlighting the study characteristics of the included articles. the second excel spreadsheet focuses its attention on the list of technical criteria applied to assess the quality of the articles incorporated in the review process. copious checklist has been put forward for the quality assessment of the included studies and majority of them emphasise on the economic assessment, viz. cost analysis, cost-benefit analysis (cba), health care utility analysis, etc. [ , ] . therefore, the quality indicators developed for the present study were grounded on the criterions suggested by prior literature [ ] [ ] [ ] [ ] . a symbol of (√) yes, (×) no and (±) moderately available was assigned to individual quality indicator. each symbol was allocated with a score of , which leads to a maximum attainable score of for each study reviewed. hence, a complete detailed analysis of the parameters utilised is presented in table . the characteristics of the included thirty-two studies are presented in table were included. the cost of diabetes was estimated from various locations such as the south zone (n = ), followed by the north zone (n = ), the north-east zone (n = ) and the west zone (n = ). a large proportion of studies ( %) were defined under india as a whole. whilst conducting review studies, it is imperative to initially define the type, study interest, sample size, data source and outlook of the study. the included studies majorly focus on type diabetes (n = ), followed by both type and type studies (n = ), studies were identified under type diabetes and only study was acknowledged under gestational/foot ulcer category, whilst the remaining studies did not define any diabetes type (table ). of the total studies, % of studies focus on general costs and the remaining studies emphasise on foot ulcers and others. whilst discussing the cost interests, the complications associated with diabetes were estimated by merely studies and the remaining studies ( %) estimated the diabetes cost without any complications. defining sample size is the utmost priority of the study, studies ( %) of the total studies have properly identified the sample size to be ≤ respondents, only studies specified the population size to be > respondents and studies ( %) did not define or provide the sample size. under the source of the cost data section, studies ( %) retrieved data on cost from the patients themselves; for studies ( %), source of cost data was obtained from medical institutes; and the remaining studies ( %) acquired the data on cost from publications. studies on the economic burden of illness could be done through several perspectives, viz. household, patient, societal and governmental. in the particular study, the patient's perspective was most commonly the research question of the study was mentioned? epidemiological definition such as type of diabetes ( and ) studied was provided? complications associated with diabetes were clearly stated? the location of the study respondent was clearly defined? the sample size of the study was adequate? acknowledged by studies ( %), studies considered societal perspective, followed by government perspective for studies and lastly, household perspective was adopted by studies as highlighted in table . the quality of the included studies is broadly presented in table . for all studies, research questions and findings were discussed and explained in a very well-defined manner. the presentation of the results was completely in synchronisation with the aim and conclusions derived from the reviewed articles. it was found that % ( ) of the studies have comprehensively defined the epidemiological definition such as type of diabetes (type and type ). limitations experienced by the majority of studies that hampered the quality of the reviewed articles were the absence of a broad definition of diabetes and a lack of adequate sample size. a major proportion of studies ( %) did not extensively define diabetes and studies ( %) moderately considered the sample size. for most of the reviewed articles, the sampling technique for data collection was addressed and only study did not define the sampling technique. however, % ( ) of studies lucidly defined the tools and technique employed in the reviewed articles and the remaining studies moderately describe the tools and technique. a majority of studies ( %) have properly classified the cost of diabetes and the remaining studies defined moderately. hence, based on quality index scores, the majority of the studies (n = ) scored ' yes' on a -point scale. interestingly, studies attained a marginally higher score of ' yes' of the total studies as presented in table . the economic burden of diabetes mellitus has led to numerous studies on the cost of illness. the cost exerted by diabetes can be categorised into three groups: direct cost, indirect cost and intangible cost [ , ] . direct cost includes both direct health care costs (diagnosis, treatment, care and prevention) and direct non-health care costs (transport, housekeeping, social service and legal cost) [ , ] . indirect cost includes cost for absenteeism, loss of productivity and disability [ , ] . lastly, intangible costs embrace cost for social isolation and dependence, low socio-economic status, mental health and behavioral disorder and loss of quality of life [ , , ] . all twenty-one reviewed studies put forward data and statistics to evaluate per capita cost of individual/household at zone level and the remaining eleven studies highlighted the cost of diabetes at the national level (table ) . to have a clear insight on cost, the reviewed articles have been categorised into four different zones, viz. north zone, west zone, south zone and north-east zone. were lucidly defined? . cost of diabetes was properly classified? the estimated annual direct cost was ₹ /individual and indirect cost was ₹ , including productivity and income loss through illness. ---- the mean total cost of diabetes in india accounts to ₹ /p.a. the mean direct cost of diabetes was ₹ /-and indirect cost, viz. hospitalisation, was /-p.a. (some regional differences in patterns of expenditure exist, with patients in the west of india likely to spend % more on laboratory fees, check-ups and medicines than any other region.) ---- the mean annual direct cost of treatment was ₹ /and % of amount is spent on drugs and medicines. the mean annual indirect cost of treatment was ₹ /of which . % was wage loss. ---- the total cost for diabetes management was ₹ /p.a. of which ₹ /was direct cost for the treatment of diabetes and ₹ /was spent on indirect cost. the total cost for treatment of diabetes with comorbidities was ₹ /p.a. the direct cost with complications was ₹ /p.a. and indirect cost amounts to be ₹ /p.a. ---- the mean direct cost of diabetes for consultation, lab investigation, medicines etc. was ₹ /monthly, whereas indirect cost for outpatient care was ₹ /monthly and indirect cost for inpatient care was ₹ per month. ---- the total average yearly direct cost was observed to be ₹ /-. however, the mean direct cost for all patients with diabetes was ₹ /p.a. individuals with three or more comorbidities encountered % more cost of care, amounting to ₹ , /annually. [ ] katam et al. the average total direct cost per patient annually was amounted to be ₹ , /-. the highest portion of direct cost was spent on insulin and glucose test strips ( %). ---- [ ] khongrangjem et al. the total median cost of illness per month was ₹ /-. total cost was made up of ₹ /direct cost and ₹ /indirect cost. ---- [ ] kumar et al. the total mean evaluation of annual direct spending on ambulatory diabetes care was ₹ /-. ---- [ ] kumar and mukherjee the total direct expenditure incurred on diabetes was ₹ , /p.a. and total indirect expenditure was ₹ , /p.a. ---- kumpatla et al. the total direct cost estimates without any complication were observed to be ₹ /-. the total cost of expenditure with complication was ₹ , /-. (cost for patients with foot complication was ₹ , /-, also average cost for renal patients under the north zone, studies were included to calculate both direct and indirect costs of diabetes at the individual/household level (fig. ) . the median direct cost of diabetes is estimated to be ₹ , /per annum, ranging from ₹ /to ₹ , , /- [ , , , , , [ ] [ ] [ ] . the most commonly measured costing items under direct cost were expenditure on medicines ( studies), diagnostic expenses ( studies), transportation cost ( study), hospitalisation ( studies) and consultation fee ( studies). the median indirect cost of diabetes for the north zone was evaluated to be ₹ , /per annum, ranging from ₹ / -to ₹ , /- [ , , , ] . for all indirect cost studies, costing items, viz. wage loss and leisure time forgone, were used majorly. south zone includes studies, majorly from karnataka state ( studies), followed by tamil nadu ( studies) and andhra pradesh ( study). the median direct cost was assessed to be ₹ , /per annum (fig. ) , ranging from ₹ /to ₹ , /per annum [ , - , , , , , , ] . direct costing items, viz. medicine cost ( studies), consultation fees ( studies) and hospitalisation ( studies), were used in the reviewed article. the median indirect cost of diabetes was ₹ /per annum, ranging from ₹ /to ₹ /per annum with major cost items such as monitoring cost ( study), absenteeism ( studies) and impairment ( study) [ - , , ] . under the north-east and west zone, only one-one study was observed, to evaluate the direct and indirect cost of author publication year was ₹ , /followed by , /-for cardiovascular disease.) [ ] ramachandran the average inpatient and outpatient cost of diabetes is ₹ /p.a. and ₹ /p.a. ---- [ ] ramachandran et al. the total median direct expenditure on health care was ₹ /p.a. ---- the mean cost per hospitalizations was ₹ /p.a. for diabetes. ---- rayappa et al. the direct annual cost (incl. hospital, test, monitoring etc.) was ₹ , /and indirect annual cost was ₹ /-. the total direct cost (incl. drugs, tests, consultation, hospital, surgery, transport) was ₹ /half yearly. the total direct cost (drugs and medicine) for diabetes patients was ₹ p.m. ---- [ ] thakur et al. the mean annual direct expenditure for diabetes care was ₹ and indirect cost was ₹ . ---- [ ] tharkar et al. the total direct cost for hospitalisation was ₹ , p.a. the total direct cost for hospitalisation with comorbidities was ₹ , /p.a. [ ] tharkar et al. the median annual direct cost associated with diabetes care was ₹ , and indirect cost was ₹ , respectively. ---- diabetes at the individual/household level [ , ] . the median direct cost of diabetes for north-east was evaluated to be ₹ , /per annum and ₹ /per annum was observed for the west zone (fig. ) . commonly estimated costing items were surgical procedures, expenditure on drugs/medicines, clinical fees, etc. the median indirect cost estimated for the north-east zone was ₹ , /per annum and ₹ /per annum was analysed for the west zone. indirect costing items identified for both reviewed studies were loss of wage, spendings on health class, travelling expenditure and spendings on diet control. lastly, studies were incorporated to estimate the cost of diabetes for india as a whole at the individual/ household level [ , , - , , , , - ] . the median direct cost of diabetes for india as a whole was ₹ /per annum, ranging from ₹ /to ₹ , /per annum. also, the median indirect cost of diabetes at the individual/ household level was estimated to be ₹ /per annum, ranging from ₹ /to ₹ , /annually ( figs. and ). diabetes mellitus is associated with a large number of serious and chronic complications, which act as a major cause of hospitalisation, morbidity and premature mortality in diabetic patients [ , , , ] . diabetes mellitus is commonly associated with chronic complications both macrovascular and microvascular origin [ , ] . microvascular complications of diabetes mellitus include retinopathy, autonomic neuropathy, peripheral neuropathy and nephropathy [ , ] . the macrovascular complication of diabetes mellitus broadly includes coronary and peripheral arterial disease [ , ] . of the total reviewed studies, only studies estimated the cost of complications associated with diabetes (table ) . a couple of studies on diabetes assessed the cost of illness to be . times higher for individuals with complications as exhibited in table [ , ] . a similar study by sachidananda et al. [ ] concluded that the cost of diabetes is . times higher for complicated non-hospitalised patients and . times higher for complicated hospitalised patients. kapur [ ] inferred that individuals with three or more comorbidities encounter % more cost of care, amounting to ₹ , /annually. according to cavanagh et al. [ ] , india is the most expensive country for a patient with a complex diabetic foot ulcer, where . months of income was required to pay for treatment. three reviewed studies incorporated in the study estimated the cost of individual/household with both macrovascular and microvascular complications [ , , ] kansra [ ] , as suggested by moher et al. [ ] the cost of illness prompted by renal (kidney) complication [ , ] . lastly, eshwari et al. [ ] estimated the total cost for the treatment of diabetes with comorbidities was ₹ /annually. direct cost with complications was ₹ /per annum and indirect cost amounts to be ₹ /annually. rising menace of diabetes has been a major concern for india. with a frightening increase in population with diabetes, india is soon going to be crowned as 'diabetes capital' of the world. a swift cultural and social alteration, viz. rising age, diet modification, rapid urbanisation, lack of regular exercise regimen, obesity and a sedentary lifestyle, will result in the continuous incidence of diabetes in india. the primary objective of this article is to detect and capture the evidence from published literature on the per capita cost at the individual/household level for both direct and indirect costs of diabetes in india which are available and published since . of the total records, studies were identified to meet the inclusion criterion. therefore, the findings of the present study suggest that per annum median direct and indirect cost of diabetes at the individual/household level is very colossal in india. a large proportion of health care cost is confronted by the patients themselves, which affects the fulfilment of health care because of financial restraints [ ] . the proportion of public health expenditure by the indian government is the lowest in the world. as a consequence, out-of-pocket (oop) spending constitutes to be % of the total health expenditure. hence, financing and delivering health care facilities in india is majorly catered by the private sector for more than % of diseases in both rural and urban areas [ ] . direct cost items (expenditure on medicines, diagnostic expenses, transportation cost, hospitalisation and consultation fee) and indirect cost items (loss of wage, spendings on health class and travelling expenditure) were most commonly reported costing items in the present study [ , , , , , ] . most of the reviewed studies on the cost of diabetes highlighted expenditure on drugs/medicine as the foremost costing item which accounts for a significant share of all direct costs. the finding of the present study is consistent with yesudian et al. [ ] , 'cost on drugs constitutes % of the total direct costs'. the majority of the reviewed articles included in the study justify that the primary cause for such abnormal costs of medicines is the common practice adopted by physicians to prescribe brandnamed medicines, rather than generic medicines. in context to the quality of tools and techniques incorporated by the included studies, a large number of articles ( %) witnessed to acknowledge the standards of tools and techniques. similarly, the classification of the cost of diabetes was also determined by the majority of reviewed articles ( articles) . but the absence of a comprehensive definition of diabetes and a small size of individuals/ households produce dubiousness about the standards or quality of the study. hence, the limitations experienced by the majority of reviewed articles hampered the quality of the present study. thus, it is beneficial to develop and suggest standard procedures and framework to conduct a comprehensive and exhaustive study on the cost of diabetes. the present study holds few limitations. primarily the exclusion of the relevant articles presented as conference papers and those studies published under nonpeer-reviewed journals. with the omission of the above literature, some biasness might have been introduced into the review process. furthermore, the major limitation of the present study is the non-availability of published articles under the central and east zone of india. also, the studies published under the north-east zone and west zone were only one. lastly, the heterogeneity in material and methodology used in cost estimation are not analogous. as a consequence, conducting a metaanalysis is not feasible. the above discussion highlighted a huge economic burden of diabetes in india and variations were recorded in the different zones. it was observed that the cost of drugs/medicines accounts for a major burden of the cost of diabetes. the study suggested few policy interventions to cope with the high economic burden of diabetes. there is a dire need in the country to arrange awareness programmes on diabetes and associated risk factors. the menace of diabetes can be controlled by devising new health care policies, introducing new generic medicines and taxing alcohol/tobacco. diabetes is a lifestyle disease so along with the above measures, a change in dietary habits, physical activity, beliefs and behavior can reduce its economic burden. conflict of interest the authors declare that they have no conflict of interest. ethical approval the study is a review-based study, so it does not contain any studies with animals. the present study only reviews those studies which contain individual's performance. informed consent for the present study, it is not necessary to obtain any consent. diagnosis and classification of diabetes mellitus the costs of treating long term diabetic complications in a developing country: a study from india diabetes mellitus and its 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published maps and institutional affiliations key: cord- - be yda authors: asawa, parth; gaur, manas; roy, kaushik; sheth, amit title: covid- in spain and india: comparing policy implications by analyzing epidemiological and social media data date: - - journal: nan doi: nan sha: doc_id: cord_uid: be yda the covid- pandemic has forced public health experts to develop contingent policies to stem the spread of infection, including measures such as partial/complete lockdowns. the effectiveness of these policies has varied with geography, population distribution, and effectiveness in implementation. consequently, some nations (e.g., taiwan, haiti) have been more successful than others (e.g., united states) in curbing the outbreak. a data-driven investigation into effective public health policies of a country would allow public health experts in other nations to decide future courses of action to control the outbreaks of disease and epidemics. we chose spain and india to present our analysis on regions that were similar in terms of certain factors: ( ) population density, ( ) unemployment rate, ( ) tourism, and ( ) quality of living. we posit that citizen ideology obtainable from twitter conversations can provide insights into conformity to policy and suitably reflect on future case predictions. a milestone when the curves show the number of new cases diverging from each other is used to define a time period to extract policy-related tweets while the concepts from a causality network of policy-dependent sub-events are used to generate concept clouds. the number of new cases is predicted using sentiment scores in a regression model. we see that the new case predictions reflects twitter sentiment, meaningfully tied to a trigger sub-event that enables policy-related findings for spain and india to be effectively compared. the covid- pandemic has seen several countries become epicenters for spread. spain was one such country; however, their policies were effective in curbing the initial outbreak of aaai fall symposium on ai for social good. copyright © for this paper by its authors. use permitted under creative commons license attribution . international (cc by . ). in march-may of . this is arguably due to people and governments taking precautions to limit the population of people susceptible to the virus -masks, social distancing, lockdowns, business closures, etc from an early stage . accordingly, the effectiveness of individual countries' policy responses to an epidemic or pandemic can be determined by how well citizens respond to those policies . a person's conformity to a policy may be inferred from their ideologies mined through social media, such as twitter [van holm et al., ] . as shown in figure , over three months, spain recorded a decline of % in the number of new cases, whereas india has shown a % influx in new patients. is it possible to explore policy transfer from spain to india to curb the alarming covid- cases? could the number of infections be modeled using the twitter concepts about causal trigger sub-events in a causality network [helbing, ammoser, and kühnert, ] ? the reason we are conducting this study is there is limited prior research relating policy and changes in case counts, through social media analysis, for covid- . we use twitter as the active platform for live information on the spread of covid- . government policies, especially in developing nations, based on the epidemiological data, ignore the population-specific behaviors of culture, ideology, and politics that hinder these policies' implementation. for example, a large number of people in the us are opposed to wearing masks. to this end, we juxtapose spain and india's epidemiological data to identify a date when the curves show the number of new cases diverging from each other, and india started showing worsening conditions.although it could be argued that the differences we see in cases were due to travel from hotspots, it's important to note that india closed its borders by suspending all international flights starting march nd, in addition to taking steps to suspend inter-state travel by suspending domestic flights and domestic trains throughout the time frame of our analysis . we recognized some critical policy-related concepts which are causally related in the covid- context. for instance, "settlement areas", "confinement to barracks", "mistrust of people", "loss of government authority" where x% refers to the share of covid- tests that came back as positive in a -day rolling average. bottom row: june th, spain . % and india . %, where x% refers to the share of covid- tests that came back as positive in a -day rolling average. causally follow announcement of "public policy". hence, we used the causality network of policy-related concepts identified by experts during severe acute respiratory syndrome (sars) to perform a knowledge-guided search on twitter [helbing, ammoser, and kühnert, ] (see figure ) . we show kerala and mumbai's policy-related concept clouds. then we investigate the applicability of interventional policies in madrid and barcelona to kerala and mumbai. likewise, we observed a policy-level association between the canary islands and andhra pradesh as both regions have strong healthcare infrastructure. the main contributions of this work are thus investigating twitter conversations corresponding to explanatory causal trigger events, to form an ideological map of the population that provides insights into response to government policy (see methods). in turn, this is validated through the prediction of new cases using the sentiment scores of the twitter conversation (see regression analysis and explanatory events). finally, a comparison of policy and responses across similar regions in spain and india is discussed (see discussion and findings). [cowling et al., ] statistically analyzed the impact of policy on reducing the transmissibility rate of covid- . the study was conducted on the epidemiological data of hong kong, and inferences were made using confidence intervals. our research aims to investigate the applicability of policies created by developed nations onto developing nations. such an exploration is not possible in cowling et al.'s study. further, cowling et al. provide statistical explanations on government policies' potency in hong kong rather than conceptual explanations, which is required to decide the "what next." while probing government policies' relevance from one nation to another, population-specific behaviors negatively affect cross-nation policy transfer. for instance, figure : causality network of sub-events during sars pandemic by helbing et al.. we utilized this graph to represent sub-events within the covid- pandemic during extraction of the word cloud a likely source of infection in india was the tablighi jamaat movement, a religious gathering , which became a coronavirus vector and was not taken into account in government policy or enforcement [sivaraman et al., ] . likewise, the return of migrant laborers to their home states in india and long weekend celebrations and parties in the united states led to an increase in covid- cases. as a result, policies such as reopening, contact tracing, and ensuring public compliance, which was effective in europe, are not directly applicable to india and the united states [hellewell et al., ] . it is essential to relate patterns in epidemiological data with evolving policy-related concepts and sentiment on social media to better study the likelihood of policy effectiveness [kalteh and rajabi, ] . other regression models that predict new cases do not consider social media information, which we posit is a significant predictor [shayak, sharma, and gaur, ] [prem et al., ] . in this research problem, we use multiple publicly available datasets and government resources, specific to spain and india (e.g., news reports, insights on epidemiological data). the first country dataset is a covid- dataset for spain data. the dataset is available here: link. it contains attributes including but not limited to: total # of cases, total # of hospitalizations, total # of patients in the icu, total # of recovered patients, and total # of new cases. the dataset was derived entirely from spain's ministry of health website and transformed into csv files. all of the data is available by province (the equivalent to states in the united states). the second dataset we use is a covid- dataset for india, available here . this dataset contains attributes including but not limited to: # of confirmed cases per day, # of recovered per day, # of deaths per day, # of people in the icu, # of people on ventilators. the dataset was sourced from several sources, a list of which can be found here . all of the data is available on a state-by-state level within india. after having the two datasets for identifying divergence points and initial identification of a problem, the final dataset we use is a dataset of twitter-ids, for our twitter social media analysis available here . as stated in the dataset, "the repository contains an ongoing collection of tweets ids associated with the novel coronavirus covid- (sars-cov- ), which commenced on january , . we used twitter's search api to gather historical tweets from the preceding seven days, leading to the first tweets in our dataset dating back to january , ." this dataset gives us access to the tweet id's pre-filtered concerning the coronavirus with keywords accessible here . from this dataset, we hydrated , , tweets from april to may , of which were geotagged from the state of kerala, and , the state of mumbai. we want to analyze the differences between the spread of the virus in spain and india; however, the countries are too diverse to compare in their entirety. thus, we instead propose comparing the two countries on more granular scales, specifically by identifying pairs of states/regions (india/spain) that are similar on the following grounds: ( ) population density, ( ) unemployment rate, ( ) tourism, and ( ) quality of living, and examining the results. for this study, we restrict to the following two pairs of states/regions: ( ) kerala and madrid, and ( ) maharastra (mumbai city) and cataluña (barcelona region). on the data from these states/regions, we did visualizations of counts of new cases during april and may. this period was essential to assess the effectiveness of government policies in controlling the covid- pandemic. by creating pairs of states/regions from india and spain, we identified divergence points where india started showing worsening public health. figure shows may st, , as the divergence point for kerala and madrid. likewise, april nd, , is the divergence point for mumbai and barcelona ( figure ). once the relevant timeframe is defined, we extract tweets geotagged to the local indian regions, such as kerala and mumbai. it allows us to explore the people's responses towards government policies, which helps assess the rise in covid- cases. semantically understanding people's reactions from their twitter conversations is a challenging task for statistical natural language processing. hence, we utilize a hypothesized causal graph of policy-dependent subevents in helbing et al., which describes a series of activities occurring during a pandemic. some of the concepts described by helbing et al. are mistrust, church hospitals, mask distribution, mental health. we identify a set of relevant concepts that describe kerala and mumbai's tweets using a pre-trained multilingual conceptnet model from a sem-eval task [speer and lowry-duda, ] . we use the spacy parser to generate phrase embeddings of concepts and nouns extracted from tweets . next, we perform a cosine similarity between the tweet vector and concept vector, with an empirically determined threshold of . . the frequency of concept phrases was recorded and presented as people's responses in the given region during the given time frame. we begin by performing a preliminary visualization of the dataset. in figure , we observe the new case counts in kerala scaled up by a factor of (for trend visibility) compared to madrid's region. it seems that the data points remained reasonably close from the period of march th to may st, after which there is a second wave of covid- spread in kerala. in contrast, madrid remained relatively close to for the rest of the period. this divergence from its previous relative similarity to madrid is a key feature we intend to explore using real-time conversations on twitter. through semantic analysis of kerala's tweets around the point of inflection, we recorded mentions of gatherings such as marriages and poor capacity of the health system, which are potential causes of the rise in new cases (see figure ) . furthermore, people mentioned information on ways of transmission with no known source of origin, prompting the government to reinstate lockdown procedures. overextension of lockdown by the government developed a panic reaction among the individuals in kerala. the state also saw a lack of cooperation among authorities in affected regions, which contributed to a surge in cases. rumors circulated through misleading campaigns that developed uncertainty and fear upsetting people's livelihood in kerala, making them restless in critical containment zones. from april to may, people's responses to government policies showed expressions of social instability, unemployment, uncontrolled infection transmission, and circulation of rumors. in figure , we observe the plots of daily new cases in maharashtra, whose case counts were almost all from mumbai and cataluña (spain, barcelona). first, it seems that the data points remained fairly close from march th to april nd, at which point the new cases in cataluña remained fairly close to for the rest of the period. though the population density and social composition of mumbai are different from kerala, we recorded the use of similar concept phrases reflecting similar consequences of government policies. for instance, social instability, reaching out to catholic hospitals (or church hospitals), seeking military aid during lockdown , mental health, panic reaction, and people seeking therapy. compared to kerala, mumbai showed a significant rise in unemployment, which is relatively similar to the trend in unemployment in barcelona, and madrid . the figure : workflow detailing the approach described in this study to analyze citizen response to policies and generate explainable inferences on the epidemiological data, in addition to predicting future changes in the spread of an epidemic. situation of unemployment remained constant from april to may in kerala and mumbai. further, the concept of "general population behavior" describes the migrant population, which constituted % workforce in india, contributed to the rise in the covid- cases as people travelled back to and-barcelona-both-rank-in-the-bottom- -of-best-cities-forjobs-following-coronavirus-crisis/ their homes for security. these external factors, which aren't recorded in epidemiological data but explain epidemiology patterns, should be incorporated in models like sir to better estimate the future patterns in the spread of disease [sivaraman et al., ]. as we can see, within both states, the topical content being discussed is relatively the same. in the time series curve, including april, we saw that the coronavirus cases had a steadily increasing number of new cases per day with a slight curvature. this indicates that the simi- figure : after the first wave of covid- spread in the month of march, the government of india instituted various policies, such as school closings, business closings, travel bans, over-extensions, which impacted public life, especially for daily wage families. hence, we see rise in the frequency of tweets concerning mental health, medical care, and unemployment. as a consequence of the policies, we observe emerging events such as rumors, churches becoming hospitals due to overloaded healthcare facilities, social instability, and mistrust (in rectangle black box). through citizen sensing around the point of inflection (figure ) , we noticed a constant frequency of concepts such as poor public life and bad condition of the state, which reflected on the imperfection in policy implementation. larity in thinking over time compounded, possibly resulting in the eventual seemingly exponential growth in the spread of covid- . we will next validate if these thinking patterns captured in twitter sentiments are a good predictor of new cases. we use multivariate linear regression (mvr) with tweet sentiment to predict future cases in kerala and mumbai's regions from mid-april to mid-may, over a month across different periods. to determine each tweet's sentiment, we use the flairnlp python library . we combine sentiments of concepts (figure and ) identified from each tweet into daily sentiment values -from the period of april th to may th/ th. we then perform mvr using the features is described in materials sections and another with tweet sentiment. the first mvr model uses the past days of new cases and recovered cases to predict the next , and the second mvr model also uses tweet sentiment to predict the next days. we use a cumulative function on both new cases and recovered cases to better reflect the upward trend. we find that the regression error does indeed decrease when using the tweet sentiments. we specifically look at the differences in the rmse values and the adjusted r for quantitative performance gains. further, we use periods of , , and days from may th for the two mvr models, as these have been shown in [pavlicek, rehak, and kral, ] to be the periods of days with which covid- https://github.com/flairnlp/flair figure : as we can see, within both states, the topical content being discussed is relatively the same. throughout the frame of the time series, including april, we saw that the trend in coronavirus cases had a steadily increasing number of new cases per day, or a positive second derivative. this indicates that the similarity in thinking over time compounded, possibly resulting in the eventual seemingly exponential growth in the spread of covid- that we witness. deaths show regularities (see table and ). previous literature suggests that the rmse uncertainty for this number of data points would be approximately . % [faber, ] . a model's explainability is vital in such a high stakes application for humans to trust and understand its predictions. while the weights of a linear model lend themselves nicely to interpretation, they alone do not provide any insight into the type of events that may have triggered such conversation on twitter. for tweets with concepts of high sentiment score weight in the model, we use the causal graph [helbing, ammoser, and kühnert, ] built for the sars epidemic to provide explanatory sub-event triggers for those concepts. an example is shown in figure , where the causal structure of sub-events that guided the extraction of twitter conversation is marked. the government can use this graphical explanation to shape its policy going forward. note that the dataset of mumbai tweets was times more extensive than kerala, resulting in high rmse. we see a more noticeable difference in adjr and rmse values for mumbai further in time from may th, than we do for kerala except for the days. thus, we believe that this research can be explored further with potentially more statistically significant findings through access to larger datasets in this paper, we presented a methodology to determine crowd responses to governmental policies that can impact health and new case predictions in real-time, and evaluate those responses to provide direction for new public health policy. in broad terms, the method presented is the first visualization of the data to identify the features of interest, elicit time-frames of events upon which to focus analysis, and explain the pattern in epidemiological data with social network sentiment analysis. for our comparison of the effectiveness of policies in spain and india, we were able to identify a critical time-frame across multiple state/province pairs that proved to be a divergence point in the spread of the virus where spain appeared to be succeeding in containing the virus. in contrast, india seemed to be experiencing exponential growth. looking at the timelines of government lockdowns: after the th case, india took action on day and spain on day . after the st death, india took action on day and spain on day . finally, after the th case, india took action on day and spain on day . we see that arguably, the nations took action on a similar timescale concerning the beginning of the spread. we posit, therefore, that the differences in responses to policies can be found in crowd ideology via twitter. looking at a few of the previously identified key phrases, we can see some examples of selected tweets that display concepts previously identified in the concept clouds, along with a timely response from authorities in spain: . medical care tweet (mumbai): "when the richest country has zero public health care in place and they need to hire in the middle of a pandemic" --spain used a royal decree to declare a -day national emergency back on march th [legido-quigley et al., ] . it dedicated significant investments to its healthcare system, quoted "it had allocated c . billion to all regions for health services and created a new fund with c billion for priority health interventions." . social instability tweets (kerala and mumbai): (a) "if you get into a cyclical lockdown it will be devastating for economic activity because that would destroy trust."(b) "people will lose trust if the lockdown continues indefinitely. need to work out a way.#rahulshowstheway" --spain's civil guard dedicated time to compiling a report and evaluating possible scenarios of growing social unrest in conjunction with law enforcement agencies, coming up with different responses to rising crime rates or civil unrest. the report specifically noted that the spanish population has accepted the lockdown, "which started out as one of the strictest in europe" . this is where real-time nlp analysis plays an instrumental role. identifying topical categories and sentiments associated with them through social network analyses like twitter provides an avenue to quantitatively and qualitatively evaluate and rank responses to different policies. for quantitative assessment, we considered intuitive model performance metrics, such as rmse and adjr . qualitative inspection was performed by mapping the people's response to sub-events in sars's causality network. we project the identified causally triggered sub-events onto a concept cloud and analyze over two critical months post-initiation policies. even though a linear model is already interpretable in terms of weights, this type of explainability is of paramount importance to understand and trust the model predictions in such a high stakes application. this can give governments insight into whether they must make policies stricter, add more policies, or enforce policies differently than they are at the moment. real-time analysis of the social network and virus data can significantly change the course of health events and are a promising yet relatively unexplored tool for governments and policymakers to use. we have presented in this work a case study with two (state, region) pairs, specifically (mumbai, barcelona) and (kerala, madrid). we posit that this work can be extended to other (state, county) pairs. considering one pair such as andhra pradesh and the canary islands (see figure )both of which are known to have strong healthcare systems relative to the rest of their countries -we can plot the time series visualization and analyze the divergence point. it's important to note that there other uncontrolled variables that make it hard to draw affirmative causal conclusions, and this is an important aspect we hope to consider in future work. the results from this preliminary work could be used to explain epidemiological models, specifically, the exo-sir (exogenous -susceptible, infected, recovered) model. exo-sir is built to model the disease's spread while taking into account exogenous factors (e.g., gathering, compliance to public policy). since our study identified concepts such as social instability, mistrust, and poor medicare as responses of the population against the instated policies, it could be considered potential exogenous factors influencing sir models. our future research may entail including government policies themselves as the exogenous impact on a sir population, and more accurately identifying and explaining the spread of a disease in a community by considering citizen response to policies. all the code and datasets for this study are available for the reproducibility of our results here. impact assessment of non-pharmaceutical interventions against coronavirus disease and influenza in hong kong: an observational study estimating the uncertainty in estimates of root mean square error of prediction: application to determining the size of an adequate test set in multivariate calibration disasters as extreme events and the importance of network interactions for disaster response management feasibility of controlling covid- outbreaks by isolation of cases and contacts. the lancet global health covid- and digital epidemiology the resilience of the spanish health system against the covid- pandemic. the lancet public health oscillatory dynamics in infectivity and death rates of covid- the effect of control strategies to reduce social mixing on outcomes of the covid- epidemic in wuhan, china: a modelling study a new delay differential equation model for covid- conceptnet at semeval- task : extending word embeddings with multilingual relational knowledge the impact of political ideology on concern and behavior during covid- we would like to acknowledge dr. victor vicente palacios for his support in the spain data collection and its interpretation. also we would like to acknowledge mr. nirmal sivaraman and dr. sakthi balan of lnmiit-jaipur for their brain-storming and input into the direction of this research. we acknowledge partial support from the national science foundation (nsf) award : "spokes: medium: mid-west: collaborative: community-driven data engineering for substance abuse prevention in the rural midwest". any opinions, conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the nsf. key: cord- - xvj zey authors: chakrabarti, sankha shubhra; kaur, upinder; banerjee, anindita; ganguly, upasana; banerjee, tuhina; saha, sarama; parashar, gaurav; prasad, suvarna; chakrabarti, suddhachitta; mittal, amit; agrawal, bimal kumar; rawal, ravindra kumar; zhao, robert chunhua; gambhir, indrajeet singh; khanna, rahul; shetty, ashok k; jin, kunlin; chakrabarti, sasanka title: covid- in india: are biological and environmental factors helping to stem the incidence and severity? date: - - journal: aging dis doi: . /ad. . sha: doc_id: cord_uid: xvj zey the ongoing corona virus (covid- ) pandemic has witnessed global political responses of unimaginable proportions. many nations have implemented lockdowns that involve mandating citizens not to leave their residences for non-essential work. the indian government has taken appropriate and commendable steps to curtail the community spread of covid- . while this may be extremely beneficial, this perspective discusses the other reasons why covid- may have a lesser impact on india. we analyze the current pattern of sars-cov- transmission, testing, and mortality in india with an emphasis on the importance of mortality as a marker of the clinical relevance of covid- disease. we also analyze the environmental and biological factors which may lessen the impact of covid- in india. the importance of cross-immunity, innate immune responses, ace polymorphism, and viral genetic mutations are discussed. could also be infected by sars-cov- . older individuals with pre-existing chronic health condition shave a higher risk of developing severe complications after sars-cov- infection. covid- has emerged as a pandemic of respiratory illness ever since the first cases appeared in wuhan, china, in december [ ] . currently, it has spread to countries/territories worldwide, with > , infected cases and > , casualties (www.worldometers.info/coronavirus/). this ongoing pandemic has witnessed global political responses of unimaginable proportions. many nations have implemented lockdowns that involve mandating citizens not to leave their residences for nonessential work. the rules of lockdown vary from country to country. the indian prime minister announced a nation-wide lockdown from the midnight of th march . only essential services would be functioning and government services apart from health, law and order, banking, power and a few others have been suspended altogether. while the response by the indian government both at the central and state levels has been commendable and timely given the global covid- crisis, we deliberate some of the other reasons why the authors believe covid- may have a lesser impact on india. the world's second-most populous country lies around the th rank among nations for the number of diagnosed covid- cases (www.worldometers.info/coronavirus/). the first case of covid- was detected in india in the southern state of kerala on th january and was a medical student who had returned from wuhan. two other cases, also medical students back from wuhan soon surfaced from kerala (https://weather.com/en-in/india/news/news/ - - -kerala-defeats-corona virus-indias-three-covid- -patients-successfully). the indian government implemented thermal screening of inbound international air-travelers. such measures were implemented for china around th january and then, in a stepwise fashion, expanded to include all international passengers (https://pib.gov.in/pressreleaseiframepage. aspx?prid= ). interestingly, thermal screening is far from a fool-proof way to detect sars-cov- carriers, many of whom may be in the middle of the incubation period or mild cases and hence asymptomatic. further, the quarantine of international travelers on arrival was initiated only for those from china and its immediate neighbors at the beginning and then expanded for travelers from other countries, that too in a phased manner, while observing global trends of covid- spread. domestic travel in india continued unabated without incorporating any screening. further, the initial testing criteria with confirmatory qrt-pcr (quantitative reverse transcription polymerase chain reaction)-based tests for suspected patients, released by the indian council of medical research (icmr), emphasized testing only those with laboratory-proven contacts or recent foreign travel (www.icmr.nic.in/content/covid - ) . with such restrictions, the movement of several sars-cov- positive patients, whether asymptomatic or symptomatic, must have occurred all over india. however, weeks after the first case was diagnosed, india has a covid- count of (www.mohfw.gov.in/). in contrast, the first two italian cases were chinese tourists who arrived in milan on rd january, and tested positive on th january, the same time when the first indian case was recorded [ ] . the case positivity in italy exploded after the fourth week since march st when daily more than new cases (more than new cases daily since th march) were diagnosed (https://ourworldindata.org/coronavirus). it is curious that among the two countries which reported their first case at almost the same time, the progression has been so disparate. one may argue that testing in india has been sluggish in contrast to aggressive testing by some developed nations. however, india had tested samples (nasal/throat swabs for qrt-pcr) from patients suspected to have covid- , as of th march which still gave a testing positivity rate of . %, a figure which has not increased significantly over time or with changes in testing criteria (https://icmr.nic.in/sites/default/files/ whats_new/icmr_website_update_ march_ am_ist .pdf). a further update by the icmr pegged the figure at samples by th march ( . % test positivity). in comparison, italy at the top of the spectrum had carried out nearly tests as of th march with positives, which translates into a positivity rate of tested individuals of . %. south korea, on the other hand, adopted a comprehensive strategy of community testing. such an approach translated into positives in tests ( . %) (www.statista.com/statistics/ / covid -tests-select-countries-worldwide/). a few other countries at different ends of the spectrum are represented in the graph in figure . one instantly notices the surprisingly low rates of covid- positivity in india, and the south korean example implies that higher testing may not necessarily alter the incidence rates of covid- . this low rate of covid- positivity remaining constant over a couple of weeks has led most experts to believe that community spread of the disease has not taken place in india as yet. such inference is, however, intriguing and needs careful analysis. the reports of hospitalization of covid- patients appeared in china from mid-december and given the average incubation period of days for the manifestation of the disease, the viral spread likely started in china in early december [ ] . the geographical proximity of india to china and the regular unrestricted movement of people between two countries through multiple daily direct and indirect flights throughout december until mid-january should have made a densely populated nation like india rapidly invaded by covid- . considering these, we propose several possibilities for the low incidence of covid- in india, which include both environmental and biological factors. the population density of india is persons/km , which is higher than the six countries with maximum covid- cases. such a finding is a paradox as countries with higher densities and people staying closer to each other are theoretically at a higher risk of contracting communicable diseases transmitted by fomites or aerosols. similarly, the examples of south korea ( persons/km ) and japan ( persons/km ), which have a relatively lower incidence of covid- and a higher population density, support this curious case. trying to explain this paradox would require further research. in the köppen classification of climatic zones of the world, both wuhan, the apparent epicenter of the pandemic and most of italy are categorized as type c (mild temperate) whereas much of india has either a dry (type b) or tropical climate (type a). however, this again raises queries on why iran having a dry desert climate (type b) bore the brunt of covid- cases [ ] . it has been suggested that high temperatures and high relative humidity levels significantly reduce sars-cov- transmission [ ] . it may be fortuitous for india that as it enters the weeks deemed to mark its entry into phase of the epidemic, the climate over large portions of the country is taking a turn for this same high temperature, high humidity state. like other animal and human corona viruses, sars-cov- is also a positive-strand rna (approximately kilobases) virus which codes for a replicase enzyme associated with other enzymatic activities and several structural proteins of which the spike protein (s) is essential for viral entry into host cells [ ] . sars-cov, hcov-nl and sars-cov- enter the host cells through the protein angiotensin converting enzyme (ace ) on the cell membrane and the viral entry requires the cleavage of s protein by a serine protease (tmprss ) [ , ] . ace protein is expressed in many different types of cells, and the virus can invade multiple organs [ ] . since pulmonary alveolar cells and mucosa of the gastrointestinal tract have high expressions of ace , sars-cov- can easily invade these organs [ , ] . the invasion of lungs leads to the most critical pathology of pneumonia with severe respiratory distress and hypoxemia that accounts for the significant mortality in this disorder. enhanced production of pro-inflammatory cytokines and chemokines by immune effector cells leading to a cytokine storm is thought to be the cause of multiple systemic and respiratory symptoms. the genomic sequences of sars-cov- from multiple isolates show more than % identity which is sufficiently different from other human corona viruses and its origin has been traced to a bat corona virus [ ] . apart from sars-cov and mers-cov which caused severe respiratory diseases following outbreaks in and , there are four endemic human corona viruses, hcov- e, hcov nl- , hcov-oc , hcov-hku in populations that are responsible for various types of respiratory illness which are generally self-limiting in young and immunecompetent persons [ ] . the defense against any viral infection involves both innate immunity and adaptive immunity. while adaptive immunity relies on antibodies and t-cells which can recognize viral antigens with high degrees of specificity, the innate immunity utilizes receptors (pattern recognition receptors of several types) which recognize broad structural motifs present in bacteria or viruses but generally absent in host cells. there are currently no established data on the specific role of either humoral or cellular immunity or innate immunity in patients recovering from covid- , but immune response associated with sars-cov and mers-cov has been studied in some detail [ ] . it can be assumed that some degrees of sequence homology or conformational similarities among the structural proteins, especially the s protein, of sars-cov- and the endemic corona viruses (hcov- e, hcov nl- , hcov-oc , hcov-hku ) may result in cross-reactive immunity (circulating antibodies or primed t-cells) in persons with prior exposure to the latter viruses, and this may modulate the course and outcome of covid- . this kind of crossreactive immunity modulating the host-response to viral infection is well-known and widely studied in infections with flaviviruses (between different subtypes of dengue viruses or between the dengue virus and zika virus) [ , ] . although the cross-reactive immunity may be protective in some cases, it may lead to augmented harmful reactions in other cases which has been termed antibody-dependent enhancement (ade), and these processes have been established from epidemiological studies as well as in animal models [ , ] . thus, the possibility of a protective cross-immunity in the indian population against covid- cannot be ignored in explaining a rather mild effect of the current coronavirus pandemic in india in comparison to that in europe and the usa. it is important to note that the presence of crossreactive antibodies in the sera of patients infected with different types of human corona viruses have not been studied extensively. however, one study reported that sera of subjects who had sars-cov infection developed cross-reactive antibodies to hcov- e and hcov-oc [ ] . similarly, sera of convalescent patients of sars-cov have been shown to contain neutralizing antibodies against mers-cov [ ] . likewise, sera of convalescent patients of sars-cov contain neutralizing antibodies that inhibit the entry of sars-cov- in vero cells [ ] . therefore, cross-reactive antibodies generated as a result of infections from other human corona viruses may have a protective role in a population affected by covid- . of note, antibodies against mers-cov have been detected in a significant fraction of persons exposed to camels and dromedaries without any clinical evidence of prior mers suggesting that mers-cov can infect individuals without any symptoms, and yet induce signs of protective immune response [ ] . it is noteworthy that many corona viruses are widely present in cattle, pigs and chickens producing a variety of diseases affecting the respiratory and gastro-intestinal systems in these species [ ] . the animal corona viruses do not infect human beings unless a mutation breaks the species-barrier. nonetheless, a large number of people working in dairy farms and livestock sectors come in close contact with animals and extensively handle the raw meat of these species in markets and houses with bare hands, which may expose the circulating immune cells to viral proteins through minor injuries in the skin. such exposures may result in the development of crossimmunity because of possible antigenic similarities among human and animal corona viruses. another interesting observation is the apparent exclusion of malaria-endemic zones by the covid- epidemic. india, large parts of africa, and parts of south america that report ongoing malaria transmission have had a low incidence of covid- . the reasons are not known, but an explanation may lie in the ensuing cytokine storm, that may be involved in the severe respiratory manifestations of covid- [ ] . it is now widely accepted that not only malaria but many other acute infective conditions such as sepsis have deleterious effects mediated through the human body's response to the infective agent, in the form of a cytokine storm [ ] . it is plausible that persons in malaria-endemic zones, which may also be endemic for several tropical pathogens including viruses, have recurrent cytokine fluctuations in response to minor and subclinical infections. these recurrent fluctuations may have a de-sensitizing effect on the body's immune system, which prevents an uncontrolled and detrimental immune response and thus severe clinical disease in sars-cov- infection. hence, many infected patients, may not manifest any symptoms and, as a corollary, may not meet testing criteria, resulting in a low positivity rate. it may be mentioned here that a novel therapeutic approach has been tried recently in covid- utilizing the immunomodulatory role of mesenchymal stem cells to attenuate the cytokine storm [ ] . apart from cross-immunity, an essential mechanism of the variable outcome of covid- may lie in the polymorphism of ace protein, which is coded by a gene on the x-chromosome. several single nucleotide polymorphisms of this protein have been described which may have implications in altered expression levels of ace or its interaction with s protein of sars-cov- . however, a detailed analysis of such polymorphisms in different populations vis-à-vis the outcome of covid- will require more time [ ] . further, in viral infections, host antiviral mirnas play a crucial role in the regulation of immune response, depending upon the viral agent. many known human mirnas appear to be able to target viral genes and their functions by interfering with replication, translation, and expression. in this context, an interesting, but yet to be peer-reviewed research article, performing a sequence-based analysis has reported a unique mutation in the indian sars-cov- strain affecting the s protein of the virus that allows it to be a target for a mirna (hsa-mir- b) [ ] . while not directly relevant to issues discussed in this article, a possibility also exists that many cases may be missed due to the sensitivity of the tests being performed. mostly pharyngeal and nasal swabs are used for qrt-pcr based diagnostics. a recent article mentions these samples as having only % and % positivity while testing for covid- [ ] . another vital aspect of covid- is mortality in diagnosed cases. mortality is the statistic that is most relevant for developing nations such as india. acute viral illnesses as well as acute infections due to any pathogenic agent, are prevalent in india, owing to dismal standards of hygiene, especially among a large section of its population which lives below the poverty line. an exact number cannot be ascribed to the incidence of viral infections, because of the sheer diversity of such infections ranging from respiratory viral infections (influenza, rhinovirus, adenovirus, coronavirus, etc.) to several arthropod-borne viral fever syndromes. the diagnostic facilities are nonexistent in the periphery, and the majority of these infections may be subclinical or may present with atypical manifestations [ ] . an idea can be obtained from the data of the integrated disease surveillance programme (idsp) of the ministry of health and family welfare (mohfw) of the government of india. during , the idsp reported disease outbreaks in india, of which % were due to viral pathogens [ ] . the authors, in their clinical practice, also treat patients regularly who present with classic symptoms of viral respiratory disease. sometimes, the same patient with comorbidities such as copd visiting multiple times in a year. whereas such patients in affluent nations would be subjected to additional testing and probably annual influenza vaccination, such measures are mostly non-existent in the indian scenario, apart from a few of the apex centers. the majority of such patients with fever, upper and lower respiratory tract symptoms, bodyache and headache may either not turn up at clinics, dismissing their symptoms as another bout of viral fever and resorting to home remedies, or even in case they present to a trained practitioner, supportive management is at best done. even drugs such as oseltamivir are scarcely used in routine practice. even with community transmission of the virus (phase of the epidemic), most cases may turn out to be subclinical and mild. in the end, mortality and not morbidity is the statistic that matters. such a scenario brings us to the critical question; what is the actual attributable mortality of covid- ? a peek into the italian scenario may be helpful. nearly % of covid- -related deaths in italy have been individuals in the + years age group. among the deceased patients, chart details were available for . out of these only patients did not have any comorbidities. among the patients of age < years who died (m= , f= ), clinical information was available for , and each had pre-existing serious comorbidity(www.epicentro.iss.it/coronavirus/bollettino /report-covid- _ _marzo_eng.pdf). even in india, more than half of the deaths that have ensued have affected patients more than years of age, the accepted geriatric age cutoff in the country. although the chart details of the indian patients are unavailable, the available data collected from reputed news sources is presented in table . most cases with fatality, whether young or old evidently had comorbidities. it is common sense that in a patient with a fatality, in the presence of severe renal or pulmonary or cardiac disease, the mere presence of covid- positivity does not confirm the role of coronavirus in causing death. detailed case histories may be revealed in the coming days, which may further clarify the matters. there may be a faulty statistical angle to covid- mortality in india too. italy ( %) stands second in the world after japan ( %) in having a population of > years age (www.worldatlas.com/articles/countries-withthe-largest-aging-population-in-the-world.html). in lifeexpectancy it also ranks second after japan among all countries with a population more than million. italian healthcare provides for universal coverage and is largely free. what this means is a sizeable section of the population in italy has survived to an age that would be impossible for them to do up to, in other countries. contrast this to the situation in india where healthcare services do not have this much peripheral penetration. further, transport and awareness issues as well as societal preferences for the younger earning population, results in neglect of the elderly and failure of free healthcare to translate into health gains for the older population. india's life expectancy stands at years, interestingly less than the mean age of covid- fatalities in italy. so, india may not have the most vulnerable age group for covid- to exert its effect to the fullest. overall, if one analyzes the mortality statistics of india in comparison to other countries (fig. ) , it is clear that the curve has been flat for quite long. a plot between total confirmed cases and total confirmed deaths clarifies the situation in india further in comparison to other major countries (fig. ). the different restrictive measures adopted by the central and the state governments in india like visa and travel restrictions, home isolation and quarantine, and finally nation-wide lockdown are classical methods of prevention of the community spread of sars-cov- . these methods must have played a role in limiting the effect of this pandemic on the indian population. however, we strongly feel that various biological and environmental factors have also contributed significantly to this process, which may result in covid- in india behaving more mildly in contrast to its global effects. the careful analysis of such biological factors will certainly open new avenues to combat outbreaks of novel viruses, through research on cross-immunity, immuno-modulation and perhaps lifestyle management and dietary manipulations. the epidemiology and pathogenesis of coronavirus disease (covid- ) outbreak the first two cases of -ncov in italy: where they come from present and future köppen-geiger climate classification maps at -km resolution high temperature and high humidity reduce the transmission of covid- coronaviruses: an overview of their replication and pathogenesis sars-cov- cell entry depends on ace and tmprss and is blocked by a 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the role of inflammatory cytokines in malaria and related diseases transplantation of ace -mesenchymal stem cells improves the outcome of patients with covid- pneumonia comparative genetic analysis of the novel coronavirus ( -ncov/sars-cov- ) receptor ace in different populations comparative analyses of sar-cov genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis detection of sars-cov- in different types of clinical specimens morvan's syndrome-is a pathogen behind the curtain? emerging/reemerging viral diseases & new viruses on the indian horizon prof chakrabarti thanks the maharishi markandeshwar (deemed to be) university, mullana for research support. key: cord- - jtfnuf authors: sawadkar, mrudula m.; nayak, varun r. title: respiratory therapists: the unnoticed warriors during covid- pandemic in india date: - - journal: can j respir ther doi: . /cjrt- - sha: doc_id: cord_uid: jtfnuf nan the novel coronavirus (covid- ) pandemic has emerged as the biggest health care crisis, affecting more than countries worldwide. as per the world health organization (who), more than million cases had been reported globally by mid-september [ ] . india is one of the highly affected countries, and the number of cases is still rising drastically, with current active cases reaching million. as a health care crisis, this pandemic requires support from all health care workers. along with the known health care communities like doctors and nurses, respiratory therapists (rts) are working selflessly in tackling this situation. in india, the rt profession has been recognized for years and is still an emerging allied health profession [ ] . based on the estimation of the human resource development survey, around universities offer rt programs and more than rts have been trained since [ ] . according to shevade et al. [ ] , rts are working in different locations throughout india, predominantly in south india. we work alongside doctors in areas like intensive care units (icu), emergency departments, out-patient departments, and home care settings providing essential respiratory care services tailored for a vivid group of patients. during the covid- pandemic, approximately %- % of the total diagnosed cases require icu admission, and around %- % of them require airway management and mechanical ventilation [ ] . trained staff called "frontline warriors," such as doctors, nurses, and rts are required to perform these skills. we have observed that on average a working rt spends around - h per day treating covid- patients. according to the opinion of the working rts in india, even if the working hours are not extended, wearing personal protective equipment and performing intense skills makes it exhaustive. it is also proven that the burnout levels are significantly higher among these frontline warriors in india [ ] . the most stressful environment is in the icu and high-dependency units of the hospital where the rt's work is vital. globally, the rt profession is not only well established but also is well recognized. the american association of respiratory care (aarc) and canadian society of respiratory therapists (csrt) are the two major bodies working for the benefits and expansion of this community. "respiratory therapists sacrifice and dedicate themselves to helping their patients and their communities during this time of covid- ," said tom kallstrom, aarc executive director [ ] . he also added by saying, "now, more than ever before, the role of the respiratory therapist is vital to the health of our nation." these encouraging words motivate rts working to fight against covid- . the indian association of respiratory care (iarc) is striving hard to portray the hard work done by rts throughout india and on international grounds. even after working selflessly, the rt profession remains unrecognized in various aspects like individual safety, work profile, and even as a part of the health care team. with this short article, we appeal to be noticed by all the major health care communities and given opportunities to prove our knowledge and skills. with this appeal, as an rt community, we promise to do our level best as frontline warriors in this time of crisis. twenty-five years of excellence; respiratory therapy in india -past, present, and future ministry of human resource development, department of higher education. all india survey on higher education a cross-sectional survey of practice patterns and selected demographics of respiratory therapists in india. respiratory care critical care for covid- affected patients: position statement of the indian society of critical care medicine burnout among healthcare workers during covid- pandemic in india: results of a questionnaire-based survey department of respiratory therapy, manipal college of health professions, manipal academy of higher education key: cord- -zpyms b authors: joshi, madhuri s.; ganorkar, nital n.; ranshing, sujata s.; basu, atanu; chavan, nutan a.; gopalkrishna, varanasi title: identification of group b rotavirus as an etiological agent in the gastroenteritis outbreak in maharashtra, india date: - - journal: j med virol doi: . /jmv. sha: doc_id: cord_uid: zpyms b acute gastroenteritis outbreak occurred at pargaon, maharashtra, india in cases with an attack rate of . % between november to december . the stool specimens (n = ) were investigated for different enteric viral agents using conventional methods. transmission electron microscopy and rna polyacrylamide gel electrophoresis respectively identified morphologically distinct rotavirus particles in % and rna migration pattern of group b rotavirus (gbr) in % of the specimens. reverse transcription polymerase chain reaction and nucleotide sequencing confirmed presence of gbr in % of the samples analyzed. the predominance of gbr infections and absence or insignificant presence of other agents confirmed gbr as an etiological agent of the gastroenteritis outbreak occurred in maharashtra, india. gar is the leading cause of gastroenteritis in children and has been linked to diarrheal outbreaks among hospitalized infants, young children attending day care centers, and old age individuals. gbr and gcr infections have been reported more frequently in adult cases of gastroenteritis outbreak. , globally, outbreaks due to norovirus, adenovirus, and astrovirus have also been reported. [ ] [ ] [ ] an outbreak of acute gastroenteritis started on th november, with epicenter around the bhimashankar sugar factory, a total of stool samples were collected from patients (n = ) within h of hospitalization. in the present study, a case of acute gastroenteritis was defined as the passage of ≥ watery stools in a day with or without associated symptoms such as vomiting, fever, and abdominal pain. all patients were examined for fever, number of episodes, and duration of vomiting and diarrhea, extent of dehydration, and treatment for the assessment of disease severity score (dss). according to the scores obtained, the disease condition of each of the patients was categorized as mild (scores - ), moderate (scores - ), severe (scores [ ] [ ] [ ] [ ] [ ] , and very severe (scores [ ] [ ] [ ] [ ] [ ] . the mean vesikary score between the two groups was compared using t-test. all specimens were examined for virus like particles by electron microscopy (em) using clarified % stool supernatant by negative staining as described earlier. the electropherotyping of viral rna was carried out in % page at v using tris-glycine buffer. the gel was stained with silver nitrate as described earlier. . | rna extraction, pcr/rt-pcr, and nucleotide sequencing gbr positive stool specimens were genotyped using primers published earlier for vp gene. rna was denatured at °c for min and was rapidly chilled on ice for min. briefly, the rt-pcr reaction was carried out with an initial reverse transcription step at °c for min followed by pcr activation at °c for min followed by cycles of amplification ( s at °c, s at °c, and s at °c) with final extension at °c for min in a thermal cycler. the superscript ® iii one-step rt-pcr system with platinum ® taq dna polymerase kit (invitrogen) was used for both cdna synthesis and pcr amplification in a single tube for detection of rna viruses. all the pcr products were electrophoresed in % agarose gel containing ethidium bromide ( . %) and visualized under uv transiluminator. pcr amplicons were excised from the gel for purification (qiaquick, qiagen, hilden germany) and cycle sequencing was carried out using big dye terminator v . cycle sequencing kit (applied biosystems, foster city, ca) and abi xl genetic analyzer (applied biosystems). nucleotide sequence identity was determined through blast (www.ncbi.nlm.nih.gov/blast). the phylogenetic tree was generated with maxiumum likelihood method using mega software. the nucleotide sequences of the strains of gbr infections observed in adults (median age years) was in concordance with earlier reports. , the low prevalence in children compared to adults has been suggested to be either due to low exposure of children to gbr or faecal shedding below the detection limit of the assay employed in the study. in china, a series of widespread gastroenteritis epidemics affecting millions of people were reported to be caused by gbr. over the period, epidemics settled to sporadic focal outbreaks and after , no such reports were available from china. in india, circulation of gbr in sporadic cases of gastroenteritis was revealed from the retrospective analysis of stool samples collected in . rna page analysis has been reported to be times less sensitive as compared to rt-pcr assay the correlation between viral load and severity of the disease has been shown earlier among gastroenteritis patients infected with gar using quantitative real time pcr assay. in view of this, gbr rna page positive and negative faecal specimens need to be tested by quantitative real time pcr assay. the study strains were closer to indian bangladeshi strains of gbr and highly conserved in nature as has been demonstrated previously. however, further studies are necessary to ascertain the role of subtle genetic substitutions observed in the study strains coupled with nucleotide analysis of remaining genes to understand the genetic evolution of the virus over the period, its role in pathogenicity and epidemiology of the disease. the state/sub divisional health laboratory declared that the piped well water with a high coli form count was the common source of infection and that the leakage in the pipeline and irregularity in chlorination of water led to gastroenteritis outbreak. even though, the analysis of piped and well water samples for viral agents was not conducted in the present study, the predominance of gbr infections among outbreak cases and the common source of water with high coli form count indicate spread of gbr through fecal contaminated water. the use of well water was completely stopped and the alternative arrangement was made to supply the drinking water. to prevent the gbr spread, regular chlorination of well water was performed. training was also provided to the family member of every house for hygienic practices and decontamination of water. a waterborne outbreak of epidemic diarrhea due to group a rotavirus in malatya,turkey occurrence of group b rotavirus infections in the outbreaks of acute gastroenteritis from western india group c rotavirus infections in patients with acute gastroenteritis in outbreaks in western india between analysis of integrated virological and epidemiological reports of norovirus outbreaks collected within the foodborne viruses in europe network from an outbreak of adenovirus serotype infection in infants and children with acute gastroenteritis in maizuru city astrovirus-associated epidemic gastroenteritis in japan rotavirus disease in finnish children: use of numerical scores for clinical severity of diarrhoeal episodes virus morphology chapter: a question of size rapid diagnosis of rotavirus infection by direct detection of viral nucleic acid in silver-stained polyacrylamide gels molecular characterization of vp genes of human rotavirus isolates: correlation of genogroups with subgroups and evidence of independent segregation foodborne outbreak caused by a norwalk-like virus in india detection and differentiation of antigenically distinct small round structured viruses (norwalk-like viruses) by reverse transcription pcr and southern hybridization polymerase chain reaction for detection of adenoviruses in stool samples enteroviruses in patients with acute encephalitis diversity in the enteric viruses detected in outbreaks of gastroenteritis from mumbai, western india identification of the gene encoding the major outer capsid protein of adrv: primary characterisation of rna segment mega : molecular evolutionary genetics analysis version . waterborne outbreak of rotavirus diarrhoea in adults in china caused by a novel rotavirus outbreak of diarrhoea in daman and detection of group b rotavirus from three adult cases group b rotavirus infection in patients with acute gastroenteritis from india group b rotaviruses similar to strain cal- , have been circulating in western india since the application of polymerase chain reaction to the detection of rotaviruses in faeces quantitation of group a rotavirus by real-time reversetranscription-polymerase chain reaction: correlation with clinical severity in children in south india full genome analysis of group b rotaviruses from western india: genetic relatedness and evolution the evolution of human group b rotaviruses identification of group b rotavirus as an etiological agent in the gastroenteritis outbreak in maharashtra, india the authors declared that there is no conflict of interest. http://orcid.org/ - - - key: cord- -f v cih authors: paul, aneesh mathews; susanthomas, sinnu title: multifaceted covid- outbreak date: - - journal: nan doi: nan sha: doc_id: cord_uid: f v cih the time when everyone is struggling in the cruel hands of covid , we present the holistic view on the effects of this pandemic in certain aspects of life. a lot of literature exists in covid- , but most of them talk about the social and psychological side of the covid problems. covid- has affected our day-to-day life and its effects are extensive. most of the literature presents the adverse effect of the pandemic, but there are very few state-of-the-art approaches that discuss its beneficial effects. we see the multiple faces of the pandemic in this paper. to the best of our knowledge, this is the first review that presents the pros and cons of the pandemic. we present a survey that surrounds over effects on education, environment, and religion. the positive side of covid- raises an alarm for us to wake up and work in that direction. digital transformation in the marketplace. devaux et al. [ ] investigated the effects of hydroxychloroquine against sars-cov- virus. faridi [ ] has studied the effect of middle east respiratory syndrome coronavirus (mers-cov) that has caused havoc in saudi arabia in . the author has seen the effect of mers-cov on male and female in riyadh. the authors in [ ] , [ ] , [ ] , [ ] assessed the psy-chological stress of covid- on health workers. xiang et al. [ ] reported an overview of infected healthcare workers in china and italy during the early periods of the covid- . the authors in [ ] , [ ] , [ ] studied some social impacts of covid- . chakraborty and maity [ ] studied the covid- effect on the economy and global environment. ivanov [ ] predicted the impact of covid- on global supply chains. xu et al. [ ] studied the air quality index to see the effects of covid- on the environment. chinazzi et al. [ ] studied the effect of travel and quarantine influence on the dynamics of the spread of covid- . braun [ ] narrated examples of the situations of the poor during covid- . ahmed et al. [ ] highlighted the precarious position of postdoctoral fellows in academic positions due to covid- . staniscuaski et al. [ ] projected out the problems faced by academic mothers having many difficulties working at home during covid- . bouillon et al. [ ] discussed the positive side effect of coronavirus on air pollution. suicide rate has increased during the pandemic time [ ] , [ ] .the situation of covid- has diverse effects in india [ ] . in this paper, we study the multi-faceted effects of covid- on our planet. our contribution in this paper is threefold. ) the pandemic has affected the entire education sys-tem and a new era of distance learning has emerged. a review on various education systems during the pandemic is looked out. ) covid- has benefits in certain areas such as the environment. the environmental effects are discussed. ) overall change in religious practices has changed and we review these aspects in this paper. the remainder of this paper is organized as follows. section ii highlights the overall change in the education system during the covid- season, and discusses the social and psychological impacts of the pandemic. section iii presents the religious and environmental effects of coronavirus. section iv presents the conclusions of this paper. education system is one of the prime pillars in developing a nation. it constitutes an important ingredient in deter-mining the growth of a country. human development is an important determinant in a person's health and trade. the education system is severely interrupted in most of the countries since the outbreak of this pandemic across the globe. the schools, colleges, and universities are in the total closure mode. billions of academic learners became devoid of their knowledge acquisition during this pandemic. the teachers, students, schools, and families -all became a victim of this bitter truth. the world has gone under complete reorganization during this period be it any sector, the education sector is not left apart. the speed of the pandemic and the closure of schools was so fast that it was difficult to come up with a solution with all facilities. the closure of educational institutes will not only have short term impact, but leave a footprint on economic and societal components. there are number of areas in education that is affected by the pandemic: the landscape of higher education across the world is defined by the cross border movements of the students. globally every year there is an increase of % in the number of students studying abroad as shown in fig. . as per the unesco [ ] , the students enrolled for higher education for a period of typically a year to seven years. according to the statistics given by organization for economic cooperation and development (oecd), the in-ternational student population with demographic changes is likely to reach million by [ ] . most of the international students prefer either the united states, the united kingdom, germany, france, or australia for their higher education [ ] as shown in fig. . as per the statistics in , the top host countries involved in sending students to other countries include china, india, south korea, and france [ ] as shown in fig. . the pandemic has brought a sluggish impact on the movement of students across the border. the travel restrictions during lockdown and the fear of pandemic will affect the cash flow at the universities. parents are afraid to send their ward across any border in this situation. the universities in these countries are undergoing extreme pressure on student admission. if this problem persists, there is a possibility of decline in international higher education in the com-ing years. the pandemic has brought a devastating effect on the global education system. the pandemic has shrinked the world under their own home and hometown and cross border movements seem to be a threat to the life of an individual. ) online learning active learning is not only a source of fun but also a source of formation of cognitive social skills. carlsson et al. [ ] emphasized on the increase in cognitive skills with the total number of school days attended. the study carried out in sweden showed that crystallized intelligence can be aug-mented significantly by % of a standard devia-tion while attending ten days of extra schooling. the closure of schools for almost a month at the beginning of this pandemic can cause a trivial loss of % of the standard deviation. the pandemic has left the learning systems with no options other than embracing a distant or online learning. as per the statistics released by unesco [ ] , the pandemic has affected nearly . billion learners around the world. the recovery of the disruption of the learning process is essential to facilitate the continuity of the education system. when physical presence is a risky situation, an alternative has to be taken at various levels of learning. online learning is a new strategy embraced by the education system in this time of pandemic. the transition from active learning to passive learning was very rapid during this pandemic. the curriculum was not designed for passive learning, so the viewers are losing their interest in the content. the shift in developed countries to the online learning system does not pose any problem, but for developing and under-developed countries -it is a challenging situation. the rural areas of these countries do not have the basic infrastructure to facilitate the online learning. the pandemic has posed a threat to the overall development of the underprivileged in these countries resulting in shattering their economies. the video telephony softwares is being used for distant learning. the concept of keeping the electronic gadgets far from the children has been loosened even for a primary school going child during this pandemic. the online learning has removed the commuting time for the learners but on the other hand, made them addicted to electronics devices leading to many social, psychological, and physical disabilities. online learning brought a paradigm shift in one's own comfort zone. the hassle of traffic jams, pollution, queues, health problems, allergies is halted in this course of time. most of the learners are happy with the online learning system since environmental problems do not leave them void of attending classes. online learning has brought an end to the centuries old practice of chalk and talk. due to the sudden change to the online learning in the education system, the preparedness of the tutors was a concern. an inhibition of this sudden change was found in the tutors during the beginning phase. the course curriculum was not made for passive learning. the sudden shift in the teaching system with inadequate preparation from the learner side was also noticeable. teaching is a knack that everybody is not gifted with, so many tutors are not so effective in an online mode. in countries like india, where there is a huge shortage of technology savvy tutors, this model of learning would not work out. lack of infrastructure and resources in the rural parts of these countries is an obstacle for teachers for a complete preparation of imparting the knowledge. an unavailability of dedicated online platforms is posing a threat for outcome based education. the tutors are adjusting the platforms with the video telephony platforms. if the problem of pandemic persists, there is a need for creating dedicated learn-ing platforms. most of the schools and universities undergo the ad-mission process during the month of may-june for fall semester. due to the severity of the pandemic in many parts of the world, the admission process is hindered. the situation in the admission process is becoming alarming in the foreseeable future with the pandemic situation. traditional admission procedures would not take place in this season. new procedural strategies for admissions should be considered in order to fill the gap in this pandemic. some universities are not con-sidering taking any students the current academic year, while some are luring people with discounts. it is a crucial task for the students to decide which school they would like to attend without visiting respective campuses. the pandemic has forced people to create a virtual world of working at home. the virtual world cre-ates effortless paths to collaborate across the globe. the conferences, academic meetings, classes, and seminars have gone online leaving a space for academic collaborations. we see a lot of unprecedented collaborative work globally among the educators [ ] during this pandemic leading to a loss in the travel economy. the cancellation of universityfunded international travel for conferences, blanket bans on any international travel for spring break, canceling study-abroad programs [ ] made different academicians closer virtually. collaborations serve a larger purpose as an individual and also as an organization [ ] . there are lots of scope for online conferencing platform business. the concept of education will be reformed envisaging the global collaboration. globally, the collaboration has brought a new direction to certification courses and degrees. these collaborations fulfills the need of each other while dividing the work in chunks. the pandemic has brought a halt to the organizational structure making a scarcity in the manpower. the universities are facing challenges to recruit new students, and faculty during this pandemic. the retention is also questionable. the recruitment for the faculty is a worrisome issue for the administration when the risk of losing students is hovering around them. when survival of many institutes is a burden for them, the recruitment of new faculty members increases their load. due to the recession in the corporate sector, the recruitment process for the students is a great disaster. the job offers have been withdrawn creating a havoc in the student community. the global outlook of the pandemic would massively devastate the livelihoods in the entire world. fig. the consequences of a sudden shift in the learning system brought a slowdown to the world economy. the international students from china and india constitute . % and . % of the total international students in the usa higher education sector. the travel restrictions during the pandemic would cut down the admission process leading to an economic burstdown. the conveyance to the institutes are at a halt causing recession in the travel sector. all the learners cannot afford to stay near their institutes, so they stay far and face a time-consuming and costly commute [ ] . students spend approximately £ a month for commutation to their academic institutes. pandemic has saved the pocket of students in higher education. in countries like india, private schools and private vehicles charge a heavy conveyance fare for the commutation. the pandemic has given relief to the parents. same time, the train services and the road services are hit badly. cashflow in these services reduced leading to an economic crunch in these sectors. the students use to take long commutes to the institutes taking away their well-being [ ] . they are deprived of their sleep and exercises. to commute long distances, students get up early and the daily routine is hampered. lack of daily exercises make them obese which is a major cause of concern among the youngsters. students carry a heavy load of bags on their backs to the school in countries like india. carrying school bags are back breaking work to the students. heavy loads of school bags have deleterious effects on the spine of children [ ] . many measures are taken to reduce the amount of school baggage, but it was all at a minuscule level. the online learning during the pandemic season turned out to be a heavy relief to the students carrying heavy school bags. being in a well-being state is an important aspect of human being. we tend to give rest to the body if it is not in a position to commute. the learners refrain from going to class if they are not well. the pandemic situation takes off all the health issues and helps in smooth learning of classes. the students are free to learn from their home in any physical condition. the structure of the learning system is based on various assessment procedures. the students are assessed based on the merit system. the pandemic hit the world during the key assessment period cancelling many exams. the cancellation of exams would have a long-term consequence on the ca-reer of the student. first, the internal assessment and then the public examinations were cancelled. the grades at the end of the academic year were predicted according to some undefined rules influ-encing the privileged students. education system is shifting to an online assessment system that can cre-ate measurement errors. these errors in an abrupt assessment would increase the differences between the privileged and under-privileged students in the future. the labour market would face the dire consequences of inefficient assessment scores. the entrance exam in higher education is a worst hit in assessment procedures. the entrance exams to top universities are either postponed or cancelled. the exam agencies are coming up with alternative solutions in consultation with the international in-stitutes. ) strike free education education system is at stake be it teachers strike or any other political strike. these strikes prevent students from attending classes. according to the study at argentina [ ], days of teachers strike there is a decline of years of education by : % in an academic year. the teacher strike has a negative effect on student learning and their overall achievement [ ]. frequent political strikes or hartals impact the overall education system. according to the statistics in kerala, india [ ], there would be one hartal in every four days leading to disruption in the holistic coverage of prescribed syllabus. the online education system is not affected by any sort of socio-political disruptions. education system in the virtual platform eased out the disturbances due to the strike. the education aspects during the pandemic impacted the family in many ways. a) the education system comes with mid day meals for the underprivileged in countries like india and the pandemic situation has taken the bread out of the mouth of some children. children from poor families would come to school with the greed for getting a one time meal. if the pandemic persists, then there is a high chance of drop-outs from the school. moreover, it would be a tremendous challenge to keep up the motivation of the underprivileged children after the pandemic. b) most of the parents in the pandemic era are working from home. it is difficult for most of the parents to handle domestic pressure and work pressure at home. working parents are juggling with children and working at home. global home schooling would pro-duce disparities depending on the ability of the family members to help their children learn. the inequality in each student skill set would overall affect human capital growth. c) the unprecedented learning system needs assistance of basic infrastructure for its smooth conduct. power supply and internet connectivity are the essentials needed without disruption. to avail these resources at home and keep the student without stress is a burdensome work for the parents. in developing countries, it is a difficult situation to maintain the resources around the clock. d) women take care of the children and rela-tives at home when compared to men. they are more insecure in their jobs. women are struggling with their household obligations and work during the pandemic. the juggling between children at home and work would reduce their opportunities and earnings at the workplace. women have to work harder in order to compensate for the workload and at an increased stress during this period. the study says that many women have left their job during the pandemic due to the imbal-ance in the worklife. covid is a disaster that would widen the gender inequalities. studies reveal that there is an increase of % in usage of electronic gadgets by the impressionable minds. gadget addiction is one of the major drawbacks of the online learning system. irritational behavioural patterns are observed in the students during this pandemic. the long time exposure to electronic gadgets are making them obese. an attachment towards gadgets creates a space for emo-tional imbalances in their personality. students have confined themselves into their own territory keeping them away from the societal component of life. studying and living together with their companions under one roof increases their social abilities but lockdown has created a void space for problem solving and decision making skills. social unawareness and lack of cognitive skills would be more visible. these skills improve their employability, productivity, health, and well-being in the future, and ensure the overall progress of the nation. people around the world are worried about the undergoing changes in the climate. the global temperature is a major concern for many environmen-tal changes. the last five years ( - ) were recorded as the hottest years. globally °c temperature has increased since the last century. an increase in per capita gross domestic product (gdp) is proportional to global warming. a study conducted by [ ] shows the environmental degradation and co emission has increased with the economic growth and more production [ ] . according to the census in , the countries with the highest co emis-sion in the world is shown in fig. . we see that the environmental degradation increases with the increase in production for economic growth. a lot of measures were taken to reduce the hazardous emis-sion, but a substantial decrement was not possible. the co or greenhouse gas disturbs the natural regulation of temperature in the atmosphere and leads to global warming and climate change. humans manipulated nature according to his whims and fancies that resulted in paradoxical im-reduced by % or . gigatonnes (gt) which is equivalent to a decade earlier data. there was an average decline of % energy demand per week during full lockdown and an average of % decline in partial lockdown countries. an unprecedented decline in demand for various fuels is seen during the pandemic as shown in fig. . the crisis of pandemic is paving a way for clean energy transitions. this decline in co emission is unprecedented and would be temporary, unless there is a resilient effort to change the structure. balances. humans are responsible for the emission of the greenhouse gas in the atmosphere over the last years. covid is the only disaster that has come as a boom to the environment. the major sources of co emission are energy, agricultural processing, land use changes, industrial processing, and other waste. electricity and heat is generated by burning fossil fuel, coal, and natural gas. a total of . % greenhouse gases are emitted while burning these fuels and are the leading cause for tempera-ture regulation. industries emit . %, transporta-tion - . %, agriculture processing - . %, land use change - . %, and industrial processes- . %. distribution of different sources of greenhouse gas are shown in fig. . before the arrival of pandemic, it was difficult to control the industrial and transportation emission. an impossible action of putting a halt on these hazardous sources was done overnight. accord-ing to estimates published by international energy ) vibration in the earth crust high frequency seismic waves are propagated into the earth mainly due to the activities of the human. the seismic noise renders the real time estimate of population dynamics. the covid pandemic period is the longest seismic noise quiet period ever recorded. according to the royal observatory of belgium [ ], the seismic noise of the earth during the pandemic is not prevalent, reducing the vibration of the earth by %. the vibrations are reduced by one-third of the normal activity during the lockdown. it becomes easy for seismologists to detect the movement in the earth crust without much of an expedition. the construction projects in some countries were at complete hold during the initial stages of the lockdown. the availability of the workforce and the site constraints halted some of the projects. construction activities create an adverse impact on the environment. the burning of fossil fuel, noise, and the waste of the construction contribute to the regulation of the temperature in the environment. the halt in construction reduced the amount of pm by three times in the month of april . air pollution is recorded highest in many cities of india. the annual average pm . concentration during the lockdown was much better than the safer limit [ ], [ ], [ ] , [ ] as shown in fig. . under the banner of economic growth, entire industrial and other waste is dumped into the rivers making it difficult to breathe. the aquatic species are becoming extinct due to the pollutants in the river. india is at the top of river pollution. ganges river is the most populated river in the world. the present pandemic has come as a blessing in disguise for rivers. the water pollution has decreased con-siderably during covid period. the waters from the rivers in india are tested during covid and the results provoke us to take measures to clean the rivers. the ph levels, the conductivity level, dissolved oxygen (do), and the biological oxygen demand (bod) of the water is reduced during the lockdown period [ ] . a betterment in standards of drinking water was seen during the lockdown period as shown in fig. . pandemic season was a lockdown for mankind, but on the contrary animals were liberalized. humans were away but animals took over the deserted cities and towns. animals took the advantage of the drop in human activity and came out to explore and play in the public places. scavengers are not around to shoo them away giving a space for wildlife to thrive. mallard ducks, wild deers, herd of goats, troop of monkeys, kangaroos, gangs of turkeys, and many others are taking human spaces. road mortality was a threat to the wildlife population [ ] . the mortality has reduced to % due to less traffic on roads in the usa. less roadkill reduces the ecological imbalances. some animals have successfully adapted to live alongside humans and their survival is dependent on them. an absence of human activity endangers some wildlife species. some governments mobilize funds to feed and preserve these animals, and the lockdown hindered their progress. according to the livestock census of , there are around million stray dogs in india. these dogs are fed by ngos or leftovers from restaurants. the closed restaurants and the restrictions in the movement made these stray dogs starve. the sustenance of the people in rural places of poor countries became difficult during the pandemic. people are driven to take extreme steps for their livelihood through poaching. the illegal hunting of endangered species in african continent is a threat for the wildlife society. according to study conducted by traffic, the wildlife poaching in india has increased twice during the pandemic pe-riod. it has increased from % to % during the lockdown period. it may turn disastrous and pave a way for another pandemic. humans struggled from recent pandemics such as aids, ebola, mers, and sars that came as an effect of consumption of animal meat [ ] , [ ] . it becomes the responsibility of the wildlife conservation society to prevent any pandemic in the future. due to the clean air and lockdown, non-covid diseases are at steep decline in countries prone to all pollution. the behavioural changes during the lockdown has brought a decline in insurance claims by % in india. waterborne infectious diseases and respiratory related diseases are being recorded as lowest during the pandemic time. the claims on deadly diseases such as cancer has turned down by % as per the statistics of the insurance companies in india [ ] . due to decrease in vaccination [ ] and disruption in the hospital services, there is a possibility of an outbreak of other diseases. religion makes people follow different practices and form socio-cultural groups. each culture recorded in human his- ) wildlife effects tory practised some organized system of beliefs and prac-tices. we tend to see very few people practicing faith in normal life. for some it seems absolutely mandatory but for some these are obnoxious practices. religion and faith is an integral part of people's lives worldwide, even though it is increasing. religious practices were hampered during lockdown. various aspects of religion during lockdown are discussed in detail: religion is a predominant factor for satisfaction in life, on the contrary the religious tensions can be annoying [ ] and affect the economic growth of the country. religious fervency is vigorous in most secularized countries [ ] . the polarization towards targeted groups increased in many countries during the earlier stage of the pandemic [ ] . since the cases of the virus were aggravated by the religious gathering in some countries, we could see religious bigotries coupled with the pandemic. the virus has morphed itself into an anti-community virus [ ] , [ ] . the bigotries and xenophobia towards different sects of people can be seen in different countries as shown in fig. . prayer meeting in france, and many more [ ] , [ ] , [ ] . the pandemic spread in various countries was sparked by religious gatherings as shown in fig. religion and politics are a crucial part of life and covid- has acquainted the human life without these jargon words. the places that culminated religious polarization at the earlier stages of the pandemic were felt at peace in the later stages of the pandemic. everybody came out in unison to curb this pandemic through their services. charity works and social commitment was seen at large during the pandemic. the role of religious practices in spreading covid- was predominant [ ] , [ ] . the religious lead-ers surpassing the mass gathering orders became a source of virus carriers in the entire nation. some of the early covid outbreaks were traced back to religious gatherings such as daegu church in south korea, bnei-brak in israel, oom in iran, tablighi-jamaat in india, tabligh-e-jamaat in malaysia, many people are fervent in religious practices such as visiting places of worship, mass gatherings, religious celebrations, and many more. all these practices are hindered during the pandemic. entire paradigm shift was seen in the religious fraternity. the religious holidays and celebrations were practiced at home. the key moments of rituals were experienced in their own home. religious leaders were bound to ask their followers to stay at home during pandemics. they started releasing double the amount of messages for the community to cope up with the stress during the pandemic. the religious organizations started doing more charita-ble services. people started living with faith rather than religious places. social distancing would be the most tricky in places of worship. the survey concludes that the public has become comfortable staying at home and practising their faith till the resumption of the normal situation [ ] . religious leaders are challenged to foster and to bring their services and communities together in these trying times from a distance. the online platforms were used to connect to the community during religious ceremonies. during the pandemic time, the searches for prayer have skyrocketed in google search engines. many spiritual and therapeutic activities, such as yoga, meditation, martial arts, and conscious dance classes have gone online during this pandemic. these temporary solutions are not sustainable solutions as they need physical relationships with people. the places of worship is a source of income for many religious leaders and the common man. these sources of income are hindered by the pandemic. life without religious practices also hit livelihoods of businesses around the places of worship. a loneliness during the pandemic times created furore among the individuals. people were compla-cent in their comfort zone but they were kicked out of that with hopelessness and despair. adapting to a new environment with a u-turn in an individual's life was a difficult task. life is fragile during pan-demic time but increase in spirituality and faith be-came a vital part of their life. religion is considered as a source of solace in terms of pain and scepticism. the role of prayer in the current pandemic situation among the general public is noteworthy [ ] . there was an increased interest ever recorded in search of prayer as per the daily data recorded from google for countries. according to tearfund covid prayer public omnibus research [ ] conducted in the uk during the lockdown period gauged the responses to spiritual practices. the statistics was conducted on , uk adults aged + and shows that nearly half ( %) of uk adults pray regularly and a quarter ( %) of uk adults attended online religious service during lockdown. one in twenty uk adults ( %) who attended religious service have never gone to church and twothirds ( %) of uk adults agree that prayer changes the world. generally, religion is more appealing to the older generation, but during the lockdown period the reli-gious revival was seen in younger ones. the highest number of quran apps from google playstore was downloaded during pandemic [ ] . irrespective of any religion, everybody started seeking hope in their faith and started praying for various topics as shown in fig. . we humans have gone through multiple virus pandemics in different times. pandemic came with human devastation but with times we came over it. covid- is a disaster in many aspects of life, but in some it has proved a blessing. this paper describes the multiple faces of virus outbreak. we have looked upon a few possible areas of life which have been affected by covid- such as the educational sector, environmental sector, and religious sector. the areas where it is a boom leaves a space to ponder on the living standard of human beings. lot of effort was taken with respect to some serious problems on the earth, but everything was in vain and it was noticed that there was a sudden break in these problems during a pandemic. once the pandemic is over, there is a call by the earth to make it a better healthy living place. comparative pathogenesis of covid- , mers, and sars in a nonhuman primate model effects of covid pandemic in daily life rolling updates on coronavirus disease (covid- ) predicting covid- in china using hybrid ai model a weakly-supervised framework for covid- classification and lesion localization from chest ct deep learning covid- features on cxr using limited training data sets accurate screening of covid- using attention based deep d multiple instance learning dual-sampling attention network for diagnosis of covid- from community acquired pneumonia diagnosis of coronavirus disease (covid- ) with structured latent multi-view representa-tion learning wearable sensing and telehealth technology with potential applications in the coronavirus pandemic easyband: a wearable for safety-aware mobility during pandemic outbreak the impact of covid- on consumers: preparing for digital sales a comprehensive review of the covid- pandemic and the role of iot, drones, ai, blockchain, and g in managing its impact new insights on the antiviral effects of chloroquine against coronavirus: what to expect for covid- ? middle east respiratory syndrome coronavirus (mers-cov): impact on saudi arabia the psychological im-pact of covid- pandemic on health care workers in a mers-cov endemic country occurrence, prevention, and management of the psychological effects of emerging virus outbreaks on healthcare workers: rapid review and meta-analysis epidemic on medical staff in china: a cross-sectional study mental health impact of covid- pandemic on spanish healthcare workers the impact of novel coronavirus sars-cov- among healthcare workers in hospitals: an aerial overview covid- : disease, management, treatment, and social impact mitigating the psychological effects of social isolation during the covid- pandemic loneliness and social isolation during the covid- pandemic covid- outbreak: migration, effects on society, global environment and prevention predicting the impacts of epidemic outbreaks on global supply chains: a simulation-based analysis on the coronavirus outbreak possible environmental effects on the spread of covid- in china the effect of travel restrictions on the spread of the novel coronavirus (covid- ) outbreak the moment to see the poor the precarious position of postdocs during covid- impact of covid- on academic mothers coronavirus and exceptional health situations: the first disaster with benefits on air pollution can we expect an increased suicide rate due to covid- ? uncomfortably numb: suicide and the psychological undercurrent of covid- covid- pandemic: mental health and beyond -the indian perspective facts and figures: mobility in higher education study abroad statistics: convincing facts and figures online learning during the covid- pandemic centre for monitoring indian economy long school commutes are terrible for kids the effects of teacher strike activity on student learning in south african primary schools kerala suffers hartal every each one burns rs -crore hole in state's economy economic growth and carbon dioxide emissions? quieting of high-frequency seismic noise due to covid- pandemic lockdown measures air pollution dropped % in bengaluru during lockdown air quality in chennai during lockdown -do we have clues to mitigate air pollution reduction in water pollution in yamuna river due to lockdown under covid- pandemic impact of covid- mitigation on wildlife-vehicle conflict prioritizing zoonoses for global health capacity building-themes from one health zoonotic disease workshops in countries anthropogenic drivers of emerging infectious diseases insurers see up to % fall in non-covid medical claims who and unicef warn of a decline in vaccinations during covid- religious polarization, religious conflicts and individual financial satisfaction: evidence from india religious polarization: contesting religion in secularized western european countries india: infections, islamophobia, and intensifying societal polarization new center for public integrity/ipsos poll finds most americans say the coronavirus pandemic is a natural disaster statca of increase in anti-asian sentiment, attacks covid- and religious congregations: implications for spread of novel pathogens religion and the covid- pandemic god and covid- public health response to the initiation and spread of pandemic covid- in the united states high covid- attack rate among attendees at events at a church-arkansas have prayers changed in lockdown? people of faith answer in crisis, we pray: religiosity and the covid- pandemic tearfund covid prayer public omnibus research how coronavirus is leading to a religious revival key: cord- -f mzwhrt authors: aggrawal, anil title: agrochemical poisoning date: journal: forensic pathology reviews doi: . / - - - - _ sha: doc_id: cord_uid: f mzwhrt a general increase in the use of chemicals in agriculture has brought about a concomitant increase in the incidence of agrochemical poisoning. organophosphates are the most common agrochemical poisons followed closely by herbicides. many agricultural poisons, such as parathion and paraquat are now mixed with a coloring agent such as indigocarmine to prevent their use criminally. in addition, paraquat is fortified with a “stenching” agent. organo-chlorines have an entirely different mechanism of action. whereas organophosphates have an anticholinesterase activity, organochlorines act on nerve cells interfering with the transmission of impulses through them. a kerosene-like smell also emanates from death due to organochlorines. the diagnosis lies in the chemical identification of organochlorines in the stomach contents or viscera. organochlorines also resist putrefaction and can be detected long after death. paraquat has been involved in suicidal, accidental, and homicidal poisonings. it is mildly corrosive and ulceration around lips and mouth is common in this poisoning. however, the hallmark of paraquat poisoning, especially when the victim has survived a few days, are the profound changes in lungs. other agrochemicals such as algicides, aphicides, herbicide safeneres, fertilizers, and so on, are less commonly encountered. governments in most countries have passed legislations to prevent accidental poisonings with these agents. the us government passed the federal insecticide, fungicide and rodenticide act (fifra) in and the indian government passed the insecticides act in . among other things, these acts require manufacturers to use signal words on the labels of insecticides, so the public is warned of their toxicity and accompanying danger. a general increase in the use of chemicals in agriculture has brought about a concomitant increase in the incidence of agrochemical poisoning. organophosphates are the most common agrochemical poisons followed closely by herbicides. many agricultural poisons, such as parathion and paraquat are now mixed with a coloring agent such as indigocarmine to prevent their use criminally. in addition, paraquat is fortified with a "stenching" agent. organochlorines have an entirely different mechanism of action. whereas organophosphates have an anticholinesterase activity, organochlorines act on nerve cells interfering with the transmission of impulses through them. a early humans are believed to have started agriculture around bce. as the knowledge of chemistry grew, so did the use of chemicals in agriculture. today, chemicals are used in agriculture for three main purposes: to increase farm production (fertilizers and related chemicals), to kill pests (pesticides), and to preserve farm products (preservatives). unfortunately, all three classes of chemicals can cause serious poisoning in humans, mainly through improper labeling, storage, or use. most poisonings with agrochemicals occur in predominantly agricultural economies where a lack of hygiene, information, or adequate control creates unsafe and dangerous working conditions. cases of such poisonings also occur in small factories where pesticides are manufactured or formulated with little respect for safety requirements. accidental poisonings may also take place at home when pesticides are mistaken for soft drinks or food products, and often the victims are curious children who can easily reach pesticides if they are not kept safely away from them. then, there are the intentional poisonings, where compounds, such as phosphorus, arsenic, paraquat, organophosphates, and strychnine, are used as agents for suicidal or even homicidal purposes. this may happen because these chemicals are easily available, relatively cheap, and almost certainly cause death. poisoning occurring as a result of improper use of chemicals used in agriculture has been termed "agrochemical poisoning." agrochemical poisoning can be classified as shown in table . agrochemical poisoning remains one of the major causes of morbidity and mortality around the world today ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) , and a review of this relatively untouched subject seems to be justified. experience has shown that above the wide range of chemicals a vast majority of poisonings occur because of pesticides only. the annual report of the american association of poison control center's (aapcc) toxic exposure surveillance system listed a total of , , human exposures to poisons occurring in the united states during the year alone ( ) . out of these, there were , exposures to pesticides ( % of all exposures) and , exposures to fertilizers ( . % of all exposures); a total of fatalities caused by pesticides and one caused by fertilizers were reported. the break-up for pesticide exposure is shown in table , and the fatalities caused by pesticides are given in table . two categories in which deaths were not reported at all were fungicides and repellants. most deaths (n = ) were to the result of insecticides. herbicides and rodenticides accounted for five deaths each, and one death was caused by fumigants. a comparison of poisoning data for the years to ( ) ( ) ( ) ( ) indicates that, although the absolute number of pesticide exposure has been increasing, it is more or less stable at around % of all exposures to poisons; fatalities owing to pesticide poisoning amount to . to % of all fatalities resulting from poisons (table ). in the following sections, those agrochemical poisons that are important from a medicolegal and pathological point of view will be discussed. organophosphorus insecticides are derivatives of phosphoric acid (h po ) or phosphonic acid (h po ) in which all h atoms have been replaced by organic moieties (figs. - ) . l represents the so-called "leaving moiety" and is the most reactive and most variable substituent. it is called so because this moiety "leaves" the organophosphate molecule after it is attached to the esteratic site of the acetylcholinesterase (ache, also known as true cholinesterase type che). r and r are less reactive moieties. most commonly they are poisonous plants (used as green manure, e.g., ricinus communis). . chemicals used to kill pests (pesticides) (i) acaricides (used to kills mites and ticks, also known as miticides, e.g., avermectins, azobenzene, benzoximate, bromopropylate, dofenapyn, nikkomycins, tetranactin). (ii) algicides used to control growth of algae in lakes, canals, and water stored for agricultural purposes (e.g., cybutryne, hydrated lime [component of bordeaux mixture]). (iii) aphicides (used to kill aphids, e.g., triazamate, dimethoate, and mevinphos). (iv) avicides (used to kill birds harmful to agriculture, e.g., -aminopyridine, -chloro-p-toluidine hydrochloride). bactericides (e.g., bronopol, nitrapyrin, oxolinic acid, oxytetracycline). (vi) fumigants (gas or vapor intended to destroy insects, fungi, bacteria, or rodents, used to disinfect interiors of buildings, as well as soil, before planting, e.g., carbon disulfide, sulfuryl fluoride, methyl bromide). (vii) fungicides (e.g., sodium azide, various compounds of copper and mercury, thiocarbamates, captan, captafol). (viii) herbicide safeners (e.g., benoxacor, cloquintocet, cyometrinil, dichlormid, dicyclonon). these compounds basically protect crops from herbicide injury by increasing the activity of herbicide detoxification enzymes, such as glutathione-s-transferases and cytochrome p- . (ix) herbicides/weed killers (e.g, paraquat, diquat, - dichlorophenoxyacetic acid, mecoprop). (x) insecticides (e.g., organophosphorus compounds, organochlorine compounds, carbamates). (xi) microbial pesticides (those pesticides whose active ingredient is a bacterium, virus, fungus, or some other microorganism or product of such an organism, e.g., bti which is made from the bacterium bacillus thuringiensis var. israelensis and used to control mosquito and black fly larvae, bacillus sphaericus and laegenidium giganteum, a fungal parasite of mosquitoes). (xii) molluscicides (used to kill molluscs, such as snails and slugs, e.g., metaldehyde). (xiii) nematicides (used to kill nematodes that feed on plant roots, e.g., , dichloropropene, , -dibromoethane, ethylene dibromide, diamidafos, fosthiazate, isamidofos). (xiv) ovicides (used to kill eggs of insects and mites). (xv) pesticide synergists (e.g., piperonyl butoxide, n-octyl bicycloheptene dicarbozimide, piprotal, propyl isome, sesamex, sesamolin). (xvi) rodenticides (used to kill rodent pests, e.g., strychnine, vacor, antu, cholecalciferol, anticoagulants and red squill). (xvii) virucides (e.g., ribavirin, imanin). (xviii) miscellaneous chemical classes including contaminants and adjuvants of some pesticides which are toxic on their own (e.g., dioxins, present as contaminants of some herbicides produce toxicity of their own). . chemicals used to disturb the feeding/growth/mating behavior etc. of pests, or used for other miscellaneous agricultural purposes (i) bird repellents (e.g., anthraquinone, chloralose, copper oxychloride). (ii) chemosterilants (e.g., , -dibromo- -chloropropane, apholate, bisazir, busulfan, dimatif, tepa). (iii) desiccants (chemicals which promote drying of living tissues such as unwanted plant tops or insects). (iv) defoliants (chemicals which cause leaves or foliage to drop from a plant, usually to facilitate harvest). feeding deterrents or antifeedants (chemicals having tastes and odors that inhibit feeding behavior, e.g., pymetrozine, azadirachtin a). (vi) insect attractants (substances that attract or lure an insect to a trap, e.g. brevicomin, codlelure, cue-lure, dominicalure, siglure). (vii) insect growth regulators (chemicals which disrupt the action of insect hormones controlling molting, maturity from pupal stage to adult, or other life processes, e.g., hexaflumuron, teflubenzuron and pyriproxyfen). (viii) insect repellents (e.g., butopyronoxyl, dibutyl phthalate, diethyltoluamide). (ix) mammal repellents (e.g., copper naphthenate, trimethacarb, zinc naphthenate, ziram). mating disrupters (e.g., disparlure, gossyplure, grandlure). (xi) plant activators (a new class of compounds that protect plants by activating their defense mechanisms, e.g., acibenzolar, probenazole). (xii) plant growth regulators (substances [excluding fertilizers or other plant nutrients] that alter the expected growth, flowering, or reproduction rate of plants through hormonal rather than physical action). . chemicals used for preservation of grains (i) aluminum phosphide. (ii) nitric oxide. available as dusts, granules, or liquids, organophosphorus insecticides are among the most popular and widely used insecticides throughout the world. they began to be synthesized first around with the esterification of alcohols to phosphoric acid. the earliest synthesis of an organophosphate, tetraethyl pyrophosphate, was reported by phillipe de clermont at a meeting of the french academy of sciences in ( ) . many different organophosphorus compounds were synthesized in the early s, but their toxicity was first recognized by lange in . lange stated that inhalation of the vapor of dimethyl or diethyl phosphofluoridate produced a choking sensation and dimness of vision. as nations started looking for lethal gases with the start of world war ii in , interest in these compounds was rekindled. by , schrader in germany and saunders in england and their study groups had synthesized a number of highly toxic organophosphates for possible use in warfare. most notable among these were soman, sarin, and tabun. currently, about organophosphorus compounds are in use as insecticides worldwide. of these, parathion is the most effective for insecticidal use. tetraethyl pyrophosphate enjoys two distinctions among organophosphates: it was the first organophosphate to be synthesized in and is the organophosphorus insecticides are basically ache inhibitors allowing the accumulation of excess acetylcholine at various nicotinic and muscarinic receptors throughout the body including the central nervous system (cns). this essentially results in acetylcholine toxicity. the main symptoms can be remembered by either of the two acronyms sludge (salivation, lacrimation, urination, defecation, gastrointestinal distress, emesis) or dumbels (diarrhea, urination, miosis, bronchospasm and bradycardia, emesis, lacrimation, salivation). rarely, there is chromolachryorrhoea (shedding of red or bloody tears) ( ) because of a disturbance in porphyrin metabolism and its accumulation in lacrimal glands. ld (lethal dose; the amount of a material, given all at once, which causes the death of % of a group of test animals) of these compounds varies from to mg/kg (extreme toxicity) to more than mg/kg (slight toxicity). compounds that are extremely toxic are chlorfenvinphos, diazinon, and methyl parathion, whereas those that are slightly toxic are malathion, acephate, and trichlorphon ( ) . most patients who have ingested a fatal dose will die within hours of ingestion. organophosphorus toxicity has recently been reviewed extensively by rousseau and co-workers ( ). signs of asphyxia are commonly found in fatal intoxications with organophosphorus insecticides. there is congestion of the face and cyanosis of the lips, nose, fingers, and acral parts of the extremities. one of the most remarkable findings is the characteristic odor emanating from the corpse: it has been described as garlic-or kerosene-like and is due to the fact that organophosphates are dissolved on a kerosene base. there is often frothy, bloody staining at the mouth and nostrils, and the pupils may be constricted. a coloring agent, indigocarmine, is added to parathion (e ® ) to prevent its accidental ingestion or criminal use as a poison. this gives rise to a bluishgreenish discoloration of the lips and oral mucosa. the addition of indigocarmine, however, is not a general practice worldwide. for instance, in india and several other asian countries, this practice is not followed. an interesting sign to be observed (albeit only in somewhat less modern mortuaries) is the death of bluebottles and others insects and flies dying immediately after they alight on an opened cadaver at autopsy ( ). the gastric mucosa is congested and may appear hemorrhagic (fig. ) and the stomach contents often contain an oily, greenish scum. the mucosa of the respiratory tract is congested and the airway passages contain frothy hemorrhagic exudate. the lungs show congestion, hemorrhagic pulmonary edema, and subpleural petechiae. the brain is swollen and there is generalized visceral congestion. parathion (e ) has been studied most extensively for histopathological lesions and these are considered to be representative of other organophosphorus insecticides, too ( ) . in the kidneys, there is epithelial necrosis in the straight sections of the renal tubules. in the epithelia of the remaining renal cortical sections, there is pronounced plasma granulation, nuclear wall hyperchromatosis, and clumping and reduction in the chromatin and marginal nucleoli. epithelia in loops of henle and collecting tubules appear swollen. the liver is more resistant to the effects of organophosphates, partly because of its ability to manufacture serum cholinesterase on its own. hepa- tocytes show opaque swelling and glycogen depletion; there are destructive changes in the liver cell strands, detached hepatocytes, and perivascular edema. myocardium, medulla oblongata, and vagal nuclei of the brain show fine, maculate perivascular hemorrhages. limaye has described a type of toxic myocarditis that he had observed in autopsy cases ( ) . kiss and fazekas described focal myocardial damage with pericapillary hemorrhage, micronecrosis, and patchy fibrosis in victims of organophophorus poisoning ( ) . pimentel and da costa ( ) have described the following myocardial ultrastructural changes in fatal poisonings with organophosphorus: multiple circumscribed necroses are found in the skeletal musculature. the oolemma is damaged and sometimes even necrotic. the glomus caroticum shows an increase in the number of dark-cell nuclei, perhaps as a consequence of increased nuclear metabolism owing to augmented demand. ache and butyrylcholinesterase (bche, also known as pseudocholinesterase or type che) levels are depressed in deaths owing to organophosphorus insecticides. the measurement of their levels can assist in the determination of the cause of death ( ) . ache is found mostly in red blood cells, motor endplates, and gray matter, whereas bche is found mostly in plasma, white matter, liver, heart, and pancreas. the physiological function of bche is unknown ( ) , but it is established that bche hydrolyzes suxamethonium (succinylcholine), and for this reason it is of interest to anesthesiologists as well. postulated functions of bche include its role in transmission of slow nerve impulses, lipid metabolism, choline homeostasis, permeability of membranes, protection of the fetus from toxic compounds, and degradation of acetylcholine and in tumorneogenesis ( ) . the plasma cholinesterase (pseudocholinesterase) is more sensitive and levels fall more rapidly than those of the red blood-cell cholinesterase. red blood-cell cholinesterase levels are more satisfactory for the diagnosis of organophosphorus poisoning because they represent the true cholinesterase levels. sample collection and storage (time and temperature) are critical to the catalytic stability of che and thus influence the quality and interpretation of results of the toxicological analysis. fluids and tissues that should be collected at autopsy are blood, cerebrospinal fluid (csf), semen, muscle, brain, liver, heart, and pancreas. the recommended procedures for collection and storage of biological fluids are as follows: . blood must be collected in heparinized tubes. . the samples must be collected and stored in glass rather than plastic containers to avoid contamination by leachates from plastic. . sample contamination with acid or alkali must be avoided. . samples must be immediately refrigerated because che catalytic activity is temperature dependent. . fluid and cellular components of blood, csf, and semen have to be separated. . determine enzyme activity as soon as possible. if enzyme activity is not determined immediately, samples can be stored for several days at °c. if tissues are intended to be stored for longer periods, the storage temperature should be - °c or below. . tissue should be homogenized at ph . to . using a sonicator or nonmetallic homogenizer and then should be stored as indicated above. che activity in blood, serum, and tissues can be measured by a number of methods. one of the most popular is the ph method by michael ( ), whereby a change in ph is measured when che acts on acetylcholine. the principle is that cholinesterase hydrolyzes acetylcholine, thus producing acetic acid, which in turn decreases the ph of the reaction mixture. electrometric determination of the change in ph from . for a definite period of time (e.g., hour) at a specific temperature (e.g., °c) represents the enzyme activity. normal values of che activity as measured by this method (in Δph/hour/ . ml red blood cells or plasma at °c, mean ± standard deviation) are given in table ( ) . in deaths owing to organophosphorus insecticides, the values will be much lower. a % or greater depression of the red blood-cell che level is a true indicator of poisoning. death occurs when levels have decreased by more than %. blood and urine should be preserved for toxicological analysis of che levels. samples from lung, liver, kidney, skeletal muscle, brain, and spinal cord, as well as gastric contents, must similarly be preserved for toxicological analysis of cholinesterase levels ( ) according to the precautions detailed in steps - in section . . . . paranitrophenol is a metabolite of many organophosphates. it is excreted in urine and its presence in urine is characteristic of organophosphorus poisoning. organophosphates usually resist putrefaction and can be detected in the viscera for quite some time after death. wehr ( ) studied five exhumations where the decedents were suspected having been poisoned with parathion. he could detect the degradation products of parathion (aminoparathion and p-nitrophenol) up to years after burial, but after years, neither parathion nor any of its degradation products were detectable. pohlmann and schwerd found evidence of parathion in a corpse exhumed after months ( ) . more recently, karger and co-workers ( ) described a case where they detected paraoxon, the main conversion product of parathion, from the abdominal cavity of a -month-old boy, months after his death. his mother had poisoned him with parathion; her deed was detected when, several months later, her second child-a -year-old girl-also suffered the same fate and parathion was detected in her blood. carbamates (fig. ) are derivatives of carbamic acid. their structure is similar to that of organophosphates (fig. ) . the first recognized anti-che was in fact a carbamate, physostigmine (also called eserine), obtained in pure form in by jobst and hesse from the calabar bean ( ) . some common carbamates used as insecticides today are aldicarb, carbaryl, γ-benzene hexachloride, triallate, propoxur, methomyl, carbofuran, and carbendazim. like organophosphates, carbamates are inhibitors of ache, but instead of phosphorylating, they carbamoylate the serine moiety at the active site. this is a reversible type of binding, and therefore, their toxicity is less severe and of lesser duration ( ) . because they do not penetrate the cns to any great extent, the cns toxicity of carbamates is relatively low. signs and symptoms are the same as those seen in poisoning with organophosphates/organophosphorus insecticides but they are milder in nature. convulsions are not seen in carbamate poisoning. postmortem findings in carbamate poisonings are mostly similar to those found in organophosphates. a bluish discoloration of the mucosa of the mouth and stomach is not seen because the blue green dye indigocarmine is usually not mixed with carbamates. determination of cholinesterase levels is not of much help because these are restored very rapidly in carbamate poisoning. organochlorine pesticides are nonselective insecticides. they are cyclic in nature, have molecular weights between and d, are cns stimulants, and have limited volatility. they are poorly soluble in water but readily soluble in organic solvents and fats, which is the way how they accumulate in the human body. they are very stable, both in the environment and in the body tissues, and can be demonstrated in the bodies of most people born since . based on their chemical structures, organochlorines can be divided into four categories ( fig. ) ( ): (a) dichlorodiphenyltrichloroethane (ddt) and related analogs, such as methoxychlor, (b) hexachlorocyclohexane or lindane, (c) cyclodienes and related compounds (e.g., aldrin, dieldrin, endrin, endosulfan, chlordane, chlordecone, heptachlor, mirex, isobenzan), and (d) toxaphene and related compounds. the best known organochlorine, ddt, was synthesized by the german chemist othmar zeidler in , but he failed to realize its value as an insecticide. it was the swiss paul hermann müller ( - ) who recognized its potential as an effective insecticide. in , ddt was tested successfully against the colorado potato-beetle by the swiss government. the united states department of agriculture used it successfully in . in january , ddt was used to quash an outbreak of typhus carried by lice in naples, italy; this was the first time a winter typhus epidemic could be stopped. so revolutionary was his work that müller was awarded with the nobel prize in medicine in . it is ironic that just years later, in , ddt was banned in the united states. it is perhaps a unique example in the history of science that a nobel prize-winning work was banned within such a short period of time. the main driving force behind this ban was the ecologists' concerns about the persistence of ddt in the environment and its resulting harm to the habitat-humans are equally affected by persistent ddt in the environment. it was rachel carson's book silent spring, published in , which brought the problem to everyone's notice. endrin, one of the cyclodienes, is chiefly used against insect pests of cotton, paddy, sugarcane, and tobacco. it is active against a wide variety of insect pests, and hence is commonly known as plant penicillin. it has been banned in most western countries, but unfortunately continues to be used in several agrarian economies. the mechanism of action of organochlorines is entirely different from that of organophosphates and carbamates. organochlorines act on axonal membranes affecting the sodium channels and sodium conductance across the neuronal membranes. organochlorines also alter the metabolism of acetylcholine, noradrenaline, and serotonin. lindane and cyclodienes appear to inhibit the γaminobutyric acid-mediated chloride channels in the cns. therefore, not very surprisingly, the main symptoms induced by poisoning with organochlorines are cns-related and include vertigo, confusion, weakness, agitation, hyperesthesia or paresthesia of the mouth and face, myoclonus, rapid and dysrhythmic eye movements, and mydriasis (in contrast to organophosphates and carbamates, where miosis is found). other symptoms include nausea, vomiting, fever, aspiration pneumonitis, and renal failure. the fatal dose of ddt and lindane is to g, whereas that of aldrin, dieldrin, and endrin is to g ( ). the conjunctivae are congested and the pupils are dilated. there may be a kerosene-like smell emanating from the mouth and nostrils. this is because most organochlorines are poorly soluble in water and are dispensed as solutions in organic solvents that may have a kerosene-like smell. fine white froth, which may or may not appear hemorrhagic, can be seen around the mouth and nostrils; this is a general effect of pulmonary edema coupled with respiratory distress and therefore, signs of cyanosis are seen on the face, ears, nail beds, etc. the mucosa of the respiratory tract appears congested and the respiratory passages contain frothy mucus which may or may not be tinged with blood. subpleural and subpericardial petechial hemorrhages are common. the lungs appear large and bulky, showing pulmonary edema. the mucosa of the esophagus, stomach, and bowel is congested owing to the irritating effect of organochlorines on the gastrointestinal tract. the stomach contents smell kerosene-like. the visceral organs are congested. hepatic necrosis may be found on cut sections of the liver. in animals killed by ddt, vacuolization around large nerve cells of the cns, fatty change of the myocardium, and renal tubular degeneration can be detected histologically ( ). feces, urine, and subcuatenous adipose tissue (placed in a glass-stoppered vial or a vial with a teflon-lined cap [ ] ) should be collected for toxicological analysis. samples must be frozen before onward transmission to the toxicology laboratoy. nicotine salts, such as nicotine sulfate, were very popular pesticides in the s and s. these compounds generally contained % nicotine (fig. ). now, because most countries have banned nicotine-based insecticides, less than % of home garden insecticides are nicotine-based. these are usually available in powder form. main among these is black leaf- (manufactured by black leaf products company, elgin, il). when nicotine-based insecticides come in contact with moist skin, fatal doses of nicotine may be absorbed through the skin ( ) . apart from occupational exposure to nicotine spray, other methods of fatal exposure include careless storage and inadvertent mixing with foodstuffs, fruits, and vegetables. these insecticides have also been used successfully with suicidal or homicidal intention. brownish froth around the mouth and nostrils is a frequent finding in nicotine poisoning. there is a characteristic odor of stale tobacco emanating from the gastric contents. the esophageal and gastric mucosa is intensely congested, showing a brownish discoloration. liver and kidneys show considerable acute congestion ( ). the liver shows plaque-like granulations in the cytoplasm of centrilobular and intermediary hepatocytes. intrapulmonary hemorrhages and pulmonary edema are typical and there often is detachment of the alveolar epithelium. in the kidneys, there is necrosis and detachment of the epithelia in the straight and convoluted renal tubules. a variety of arterial wall lesions, including lacerations of the elastic interna, are seen that have been connected with extreme fluctuations in blood pressure from the effects of nicotine ( ). an estimated % of all plant species are weeds, with a total of some , species. chemicals, such as common salt, have been used for centuries for weed control. the era of chemical weed control is generally recognized as starting in . bonnet in france found that the bordeaux mixture, already being used on vines to control powdery mildew, also provided control of specific weeds. by the s, farmers were still using simple chemicals for this purpose; for example, copper sulfate (blue vitriol), which was first used for weed control in , was still in use at this time. in the early th century, scientists in europe started using the salts of heavy metals to control weeds but when this was attempted in the united states, the low humidity in the western states prevented these chemicals from being absorbed by the weeds. other chemicals were tried, but most of them had drawbacks. for instance, carbon bisulfide used to control thistles and bindweeds smelled like rotten eggs and was, therefore, quite understandably unpopular. most chemical weed killers of those times (such as sodium arsenate, arsenic trioxide, and sulfuric acid) were highly toxic to humans and had to be used in large quantities (several kilograms per hectare), which was another serious drawback. the first synthetic organic chemical for selective weed control was introduced in . its chemical name was -methyl- , -dinitrophenol, and it could control some broadleaf weeds and grasses in large seeded crops, such as beans. more modern herbicides are now available. these have to be sprinkled in very low doses (grams per hectare) in order to kill weeds and the crop is spared. herbicides are categorized as selective when they are used to kill weeds without harming the crop and as nonselective when the purpose is to kill all vegetation. killing of all vegetation is generally not intended in an agricultural setting. it is required more often in places such as recreational areas, railroad embankments, irrigation canals, fence lines, industrial sites, roadsides, and ditches. both selective and nonselective herbicides can be applied to weed foliage or to soil containing weed seeds and seedlings depending on the mode of action. the term true selectivity refers to the capacity of an herbicide, when applied at the proper dosage and time, to be active only against certain species of plants but not against others. selectivity can also be achieved by placement, such as when a nonselective herbicide is applied in such a way that it reaches only the weeds but not the crop. herbicides can also be classified as contact or translocated. contact herbicides kill the plant parts to which the chemical is applied. translocated herbicides are absorbed either by the roots or the above-ground parts of plants and are then circulated within the plant system to distant parts. timing of herbicide application regarding the stage of crop or weed development forms another basis of classification. a preplanting herbicide is sprinkled on the farm before the planting of the crop. a preemergence herbicide is sprinkled after planting but before emergence of the crop or weeds. finally, a postemergence herbicide is used after the emergence of the crop or weed. herbicides can be applied to weeds in a number of ways. a band application treats a continuous strip, such as along or in a crop row. broadcast application covers the entire area, including the crop. spot treatments are confined to small areas of weeds. directed sprays are applied to selected weeds or to the soil to avoid contact with the crop. in the more recent overthe-top-application, herbicides are applied "over the top" of the crop and weeds shortly after germination. the crops in these instances are naturally tolerant to the specific herbicide or have been genetically engineered to be tolerant to the herbicide used. from a toxicological point of view, the following herbicides are the most important. dipyridyl weed killers include paraquat, piquat, and morfamquat ( fig. ). paraquat is the most important of these three. paraquat ( , ′dimethyl- - ′bipyridylium dichloride) is an important agricultural chemical from a toxicological viewpoint. out of the deaths caused by pesticides reported by the aapcc annual report ( ) , two were the result of paraquat poisoning. paraquat was first synthesized in , but its herbicide activity was discovered very late. its use as an herbicide was first reported in , and paraquat was introduced commercially as a nonselective herbicide in . the introduction of paraquat caused an agricultural revolution because it has some unique properties. it can be sprayed from the ground level or the air and is totally denatured when it comes in contact with the earth. thus, it cannot harm the seeds or young plants that will be placed in the same ground a short time later. indeed, the crop can be planted within days, if not hours, after herbicidal treatment with paraquat. an additional advantage is that plowing is unnecessary aggrawal in many cases with much less soil erosion. paraquat is therefore of immense value in an economic sense ( ) . in countries like sri lanka, its use has resulted in three crops, instead of two, per year being taken off the same field ( ) . paraquat is highly soluble in water and is marketed most commonly as a concentrate containing g paraquat dichloride per liter ( % wt/vol); this is an odorless brown liquid. a "stenching" agent (a pyridine derivative) is added to prevent accidental or criminal poisoning; a bluish-greenish dye is also added for the same reason, and an emetic may be added as well. paraquat is sometimes sold in combination as a mixture with diquat and other herbicides. the liquid concentrate is known as gramoxone (not to be confused with gammexane, which is the trade name for lindane); a weaker, granulated preparation for horticultural use, known as weedol, is also available ( % wt/vol). the solution may be decanted in soda bottles and left unlabelled. because it looks like a cola drink, accidental ingestion may occur. it may be mistaken for vinegar as well; one patient is reported to have sprinkled it on his french fries. wesseling and co-workers ( ) reported that paraquat is the pesticide most frequently associated with injuries among banana workers in costa rica; the injuries involve mostly the skin and eyes. although most fatalities caused by paraquat occur from ingestion, absorption through the skin can also cause fatalities. wohlfahrt ( ) reviewed paraquat poisoning in papua new guinea from to and found that out of fatalities caused by paraquat, six were the result of transdermal absorption. diquat ( , ′-ethylene- , ′-dipyridylium dibromide) is less commonly used than paraquat. it has the same indications and mode of action as paraquat. diquat is, however, used additionally for the control of aquatic weeds. jones and vale ( ) compiled all cases of diquat poisoning published between the years and and found that only cases were reported in detail in the literature, of which ( %) were fatal. conning et al. showed that out of the three dipyridyl weed killers, it was only diquat that produced bilateral cataracts ( ) . diquat was introduced in as a fast-knockdown, contact herbicide and plant desiccant. diquat-only formulations manufactured by syngenta (formerly imperial chemical industries) or its subsidiaries do not contain the dye, "stenching" agent, or emetic added to paraquat ( ). the symptoms include intense pain in the mouth and pharynx, with inflammation and even ulceration of the oral mucosa. esophageal ulceration may lead to perforation with all its attendant risks. renal and hepatic failure develop within to days. the most important effect is on the lungs (pneumotropism), where massive, irreversible pulmonary fibrosis is seen. pulmonary fibrosis is thought to be the result of an increase in the pulmonary concentrations of prolyl hydroxylase, an enzyme which promotes collagen formation. paraquat is one of the few poisons that may produce necrosis of the adrenal glands, possibly leading to hypotension. the fatal dose is to g (about a mouthful of gramoxone). subcutaneous injection of just ml of gramoxone has shown to be fatal ( ) , with death occuring after to weeks as a result of respiratory failure caused by pulmonary fibrosis; greater doses can kill a human within hours. why does paraquat show such remarkable pneumotropism? it has been postulated that inside the pneumocytes, the paraquat dication pq + accepts one electron from reduced nicotinamide adenine dinucleotide and becomes the monocation pq + . (pyridinyl-free radical) (fig. ). the monocation pq + . is unable to cause any injury on its own, but in the presence of molecular oxygen (o ) in the lungs, it is oxidized once again to its dication form (pq + ). in this process, it passes on its electron to the molecular oxygen (o ), which, in turn, becomes the superoxide anion radical (o -. ). this process, known as redox cycling, is sustained by oxygen in the lungs. the superoxide anion radical o -. (reactive oxygen species) generated as a result of this cycle is responsible for cell death. this also explains why oxygen enhances the toxicity of paraquat and should never be administered during paraquat intoxication; by administering oxygen, one is supplying the "raw material" for the formation of the damaging superoxide radical. formation of free radicals is implicated in injuries caused by at least two other poisons-myocardial injury caused by doxorubicin and liver injury by carbon tetrachloride. the related bipyridylium compounds, such as diquat and morfamquat, do not affect the lung as seriously, but rather cause liver damage ( ). there is ulceration around lips and mouth, although it is not as bad as is seen after ingestion of inorganic acids, such as nitric or sulfuric acids. the oral and esophageal mucosa is reddened and desquamated. a unique feature of paraquat ingestion is the formation of pseudomembranes in the pharynx resembling to that seen in diphtheria ( ). patchy hemorrhages in the stomach mucosa are a frequent finding. the liver is pale, showing fatty changes. the kidneys may exhibit pallor of the cortex. the most striking findings are found in the lungs. both type and type alveolar epithelial cells accumulate paraquat and are thereby destroyed. this destruction is followed by inflammatory cell infiltration and hemorrhages; fibroblast proliferation then leads to fibrosis and impaired gas exchange. the lungs are congested, appear stiffened, and retain their shape during evisceration. each lung is typically approx g or more in weight. teare ( ) reported a case of paraquat poisoning (a -year-old man dying of suicidal ingestion of paraquat after days of illness), with the left lung weighing g and the right lung weighing g. blood-stained pleural effusions and fibrinous pleurisy are other typical autopsy findings. cut surfaces of the lungs reveal edema and fibrosis. subendocardial hemorrhages may accompany the aforementioned pathological findings. the pathological features of paraquat poisoning have been reviewed in detail by vadnay and haraszti ( ) . at the beginning of the toxic process, severe degenerative changes appear in the pneumonocytes with fatty infiltration, desquamation, necrosis, and detachment ( ) . later, there is splintering of the basement membranes, fragmentation, aneurysma formation, and multiple ruptures. fibrinous edematous fluid is seen in the interstitium and within alveoli and hyaline membranes can be observed. there is a large-scale dissolution of the pulmonary structure. there may be active proliferation of the bronchial epithelium, forming small adenomata within the pulmonary parenchyma. marked proliferation of fibroblasts with an increase in macrophages in the alveoli (these two mechanisms obliterate the alveolar spaces) can be seen. acute tubular necrosis is a frequent finding in the kidneys. extensive renal cortical necrosis is also seen at times. in the liver, centrilobular hepatic necrosis, cholestasis, and giant mitochondria with paracrystalline inclusion bodies can be detected ( ) . in the myocardium, there is edematous disaggregation of the sarcoplasm and sporadic fragmentation of the myofibrils. paraquat-type herbicides in aqueous solutions have traditionally been determined by colorimetric methods. these involve measurement of the complex formed with some chemical (α-dipicrylamine hexanitrodiphenylmethane). plasma paraquat levels can be assayed by spectroscopy, high-performance liquid chromatography ( ) or radioimmunoassays; levels greater than . μg/ml confirm death by paraquat intoxication. urine paraquat levels can be deter-mined using spectrophotometry, too; levels greater than μg/ml confirm death by paraquat intoxication ( ) . berry and grove introduced an ion exchange and colorimetric method in for the determination of paraquat in urine ( ) . diquat (reglone) is selectively concentrated in the kidneys and causes marked renal tubular damage. in a case of fatal diquat poisoning, mccarthy et al. found esophagitis, tracheitis, gastritis, and ileitis ( ) . autopsy findings and toxicokinetic data in diquat poisoning have been described in detail by hantson et al. ( ) . morfamquat is used far less commonly than the other two bipyridyls, paraquat and diquat. conning et al. have shown that rats that fed on morfamquat developed renal damage ( ). chlorophenoxy herbicides (fig. ) are growth regulators or auxins. they cause abnormal plant growth, thereby ultimately destroying the plant. chlorophenoxy herbicides are commonly used for control of broadleaf weeds in cereal crops and pastures ( ). - dichlorophenoxyacetic acid ( , -d; trimec) has been and continues to be one of the most useful herbicides developed; it is frequently applied to lawns to control broadleaf weeds and is often found in fertilizer products along with other phenoxy herbicides, such as dicamba, mecoprop, and ( -chloro- -methylphenoxy)acetic acid. , -d is easily absorbed through the skin and lungs ( ). on ingestion, , -d causes peripheral neuropathy, muscle weakness, cheyne-stokes respirations, hyperthermia, acidemia, and coma ( ) . the patient is hypotonic, hyporeflexive, hypotensive, and comatose ( ) , and nasogastric aspirate may be guaiac-positive ( ). , -d earned a notorious reputation during the vietnam war as an ingredient of agent orange sprinkled by united states troops over vietnam (see subheading . ). suicidal ingestions of , -d are occasionally reported ( , ) . postmortem findings in deaths caused by chlorophenoxy herbicides are nonspecific. the gastrointestinal mucosa may be intensely congested and/or hemorrhagic. all internal organs are usually congested. confirmatory tests of suspected poisonings with chlorophenoxy herbicides are the demonstration of these herbicides in plasma and urine,which can be detected by radioimmunoassay ( ) and gas liquid chromatography ( ). this category comprises mainly dinitrophenol (dnp), dinitro-orthocresol (dnoc), and pentachlorophenol ( ) . these substances are used in agriculture mainly as selective weed killers for cereal crops. the effects of dnp in stimulating metabolism have been known since , and dnp was used at one time for "slimming." dnp (fig. ) is a potent "uncoupler" of oxidative phosphorylation, causing the energy obtained from the oxidation of nicotinamide adenine dinucleotide and reduction of o to be released as heat. it has been demonstrated that these compounds are dangerous to humans and thus, they are no longer used for medicinal purposes. the principal risk of poisoning is in the agricultural use of concentrated solutions for spraying crops aggrawal (as weed killers). dinitrophenol (dnp) is also used in agriculture for the control of mites and aphids ( ) . absorption occurs by inhalation and thus, breathing apparatus are a must for those who are exposed to this poison. absorption also occurs by ingestion and through the skin. excretion of dnp is extremely slow, so the poison accumulates in the body gradually. the symptoms are fatigue, insomnia, restlessness, excessive sweating, weight loss, and thirst. clinical signs include tachycardia, increase in the rate and depth of respiration, rise in temperature (up to °c and higher) and some yellow discoloration of the sclera. in severe cases, body temperature may keep rising and just before death, it may reach °c. when death occurs, the onset of rigor mortis is rapid. sodium chlorate is a nonselective herbicide. it acts as a soil sterilant at rates of lbs/acre. it is also used as a foliar spray at lbs/acre as a cotton defoliant. it was once avidly advocated as a weed killer, not only because it is effective, but also because it was considered safe. this fallacy was so prevalent that containers of sodium chlorate used to be marked as "nonpoisonous." however, chlorates cause methemoglobinemia. severe hemolysis is a constant clinical feature in sodium chlorate poisoning, with presence of heinz bodies in the red blood cells. acute renal failure and anuria sets in later. anuria occurs because of (a) a direct damaging action of chlorates on the renal tubular epithelium, and (b) mechanical obstruction of the renal tubules by the hemoglobin set free by hemolysis. the fatal dose of sodium chlorate is to g with death occuring within to days. poisoning with sodium chlorate can occur accidentally, suicidally, or even homicidally. accidental poisoning is probably the most common. a -year-old gardner was severely poisoned in a curious way. he was using a concentrated solution of sodium chlorate in an atomizer while a strong wind was blowing. consequently, spray was blown onto his face and he inhaled and ingested some of the solution. symptoms of poisoning started the same evening. he was saved with some heroic effort on the part of the doctors, yet he could only return to full-time work after about year ( ). the skin has a distinctive chocolate-brown color. blood smears may show evidence of hemolysis and heinz bodies. the kidneys are enlarged and their principal change is a brown streaking of the cortex; microscopical examination reveals acute renal tubular degeneration with blockage of tubules by broken red blood cells and brown pigment granules (released hemoglobin owing to hemolysis). glyphosate is an important agricultural chemical from the toxicological viewpoint. out of the deaths caused by pesticides reported by the aapcc annual report ( ) , one was caused by glyphosate. glyphosate is a broad-spectrum, nonselective, systemic herbicide used for control of annual and perennial plants including grasses, sedges, broad-leaved weeds, and woody plants. it can be used on non-cropland as well as on a great variety of crops. although glyphosate itself is relatively harmless, its chemical formulations (e.g., roundup ® , rodeo ® , touchdown ® , gallup ® , landmaster ® , pondmaster ® , ranger ® ) have been used successfully for committing suicide. this is because glyphosate invariably is formulated in a surfactant (polyethoxylated tallow amine), which is quite toxic ( , ) . glyphosate is generally distributed as water-soluble concentrates and powders. mild poisoning results only in gastrointestinal symptoms, such as vomiting, abdominal pain, diarrhea, and nausea, which usually resolve within a day or two. severe poisoning results in intestinal hemorrhage and ulceration, acid base disturbances, renal failure, hypotension, cardiac arrest, pulmonary dysfunction, convulsions, coma, and death. postmortem findings are nonspecific. glyphosate and the concomitant surfactant are demonstrated by toxicological analysis in the gastric contents and other visceral organs. glyphosate levels of mg/ml or more can be detected postmortem in blood, liver, and urine in less than a minute by using p nuclear magnetic resonance ( ). among the several arsenical herbicides available are cacodylic acid, calcium hydrogen methylarsonate, disodium methylarsonate, hexaflurate (asf k), methylarsonic acid, monoammonium methylarsonate, monosodium methylarsonate, potassium arsenite, and sodium arsenite. cacodylic acid (fig. ) is also known as dimethylarsinic acid. cacodylic acid is a white crystalline substance, readily soluble in water and alcohol, and is still used as an herbicide. when it unites with metals and organic substances, it forms salts known as cacodylates. cacodylic acid contains . % of arsenic. fungicides, or antimycotics, are toxic substances used to kill or inhibit the growth of fungi that cause economic damage to crop or ornamental plants. most fungicides are applied as sprays or dusts. seed fungicides are applied as a protective covering before germination. systemic fungicides, or chemotherapeutants, are applied to plants, where they become distributed throughout the tissue and act to eradicate existing disease or to protect against possible disease. bordeaux mixture (cuso cu[oh] caso ) was one of the earliest fungicides to be used ( ) . bordeaux mixture is a liquid composed of hydrated (slaked) lime, copper sulfate, and water. it was accidentally discovered in in the modoc region of france, where farmers, tired of schoolboys pilfering their grapes, sprayed their grapevines with a poisonous-looking mixture of lime and copper sulphate; it was a desperate idea meant just to deter schoolboys from stealing their grapes. however, in , pma millardet from the university of bordeaux observed that the very same mixture effectively controlled the downy mildew of grapes as well. burgundy mixture is a mixture of copper sulfate and disodium carbonate. both bordeaux mixture and burgundy mixture are still widely used to treat orchard trees. copper compounds and sulfur have been used on plants separately and together. synthetic organic compounds are now more widely used because they give protection and control over many types of fungi. cadmium chloride and cadmium succinate are used to control turfgrass diseases. mercury(ii)chloride, or corrosive sublimate, is used as a dip to treat bulbs and tubers. mercury salts used as fungicides include mercurous chloride, mercuric chloride, mercuric oxide, phenylmercury nitrate (fig. ) , tolylmercury acetate, and ethylmercury bromide. organophosphorus fungicides include ampropylfos, ditalimfos, edifenphos, and fosetyl (fig. ) . carbamate fungicides include benthiavalicarb, furophanate, iprovalicarb, and propamocarb (fig. ) ; the toxicity of organophosphates and carbamates has been dealt with earlier. among the most important inorganic fungicides are potassium azide, potassium thiocyanate, sodium azide, and sulfur. other substances occasionally used to kill fungi include chloropicrin, methyl bromide, and formaldehyde. many antifungal substances occur naturally in plant tissues. creosote, obtained from wood tar or coal tar, is used to prevent dry rot in wood. the most important fungicides-from the toxicological viewpoint-aside from organophosphorus and carbamates, are sodium azide and compounds of copper and mercury. copper compounds are also especially important because they are used in agriculture as insecticides and algicides. somerville discussed the metabolism of several fungicides including maneb, mancozeb, zineb, captan, chlorothalonil, benomyl, triadimefon, triadimenol, and cymoxanil ( ). sodium azide is important because it is a potential intentional or accidental poison. aside from being used in agriculture, sodium azide is also used widely in hospitals where it is used as a component chemical in the fluid used to dilute blood samples. sodium azide, like dnp, is an "uncoupler" of oxidative phosphorylation; it also inhibits the enzymes catalase and cytochrome oxidase. ingestion of sodium azide results in nausea, vomiting, diarrhoea, hypotension, and cns symptoms, such as headache, hyporeflexia, seizures, and coma. postmortem findings include edema of the brain and lungs. edema of the myocardium with myocardial necrosis has also been reported ( ) . fig. . fosetyl, an organophosphate fungicide. salts of copper, although mostly used as fungicides, are used for a large number of other purposes in agriculture as well. copper acetate, copper carbonate, cupric -quinolinoxide, copper silicate, and copper zinc chromate are used as fungicidal agents only; copper arsenate is used as insecticide and copper sulfate as algicide, fungicide, herbicide, and molluscicide; copper acetoarsenite is employed as insecticide and molluscicide; copper hydroxide is used as bactericide and fungicide; copper naphthenate is used as fungicide and mammal repellent; copper oleate as fungicide and insecticide; and copper oxychloride as bird repellent and fungicide. chronic exposure to bordeaux mixture in vineyard sprayers causes the socalled "vineyard sprayer's lung." observed mainly in portugal, the disorder includes pulmonary fibrosis ( ) and may lead to lung cancer ( , ) . bordeaux mixture is the only other significant pesticide aside from paraquat that induces significant pulmonary fibrosis with organophosphates coming in a distant third ( ) . the radiological picture in vineyard sprayer's lung resembles that of silicosis with micronodular features in the early stages of the disease ( ) . only in later stages does a picture of massive fibrosis emerge with continuing development of respiratory insufficiency. plamenac et al. ( ) examined the sputum of rural workers engaged for years in spraying of vines. sputum specimens were tested for copper by rubeanic acid. macrophages containing copper granules in their cytoplasm were found in % of the workers engaged in vine spraying compared with none in a control group. other abnormalities, such as eosinophils, respiratory spirals, respiratory cell atypia, and squamous metaplasia, were also found in the sputum. atypical squamous metaplasia was observed in % of vineyard workers who were also smokers ( ). eckert et al. ( ) exposed mice to copper sulfate aerosol for a longer period of time and were able to replicate these changes in the animals' lungs. the authors concluded that the changes seen in vineyard sprayer's lung are a result of copper sulfate toxicity. pimentel and menezes studied the liver of vineyard sprayers by percutaneous biopsy and also at autopsy ( ) . they found histiocytic and noncaseating granulomas containing inclusions of copper as identified by histochemical techniques. they also found that the affected individuals were prone to liver fibrosis, cirrhosis, angiosarcoma, and portal hypertension ( ) . copper sulfate is a popular suicidal poison in india ( ) and copper sulfate was once a very popular homicidal poison ( ) . although no reports of suicide and homicide with bordeaux mixture exist, this is certainly possible. quite possibly such cases did, and still do, occur but have never been reported. mercury is widely used as a fungicide in agriculture. both inorganic and organic salts are used. inorganic mercury fungicides being used as fungicides include mercuric chloride, mercuric oxide, and mercurous chloride. organomercury fungicides include ( -ethoxypropyl)mercury bromide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury , -dihydroxypropyl mercaptide, ethylmercury phosphate, n-(ethylmercury)-ptoluenesulphonanilide (fig. ) , hydrargaphen, -methoxyethylmercury chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide, -phenylmercurioxyquinoline, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride, phenylmercury derivative of pyrocatechol (fig. ) , phenylmercury nitrate, phenylmercury salicylate, thiomersal (fig. ) , and tolylmercury acetate. the ingestion of wheat and barley seed treated with methyl mercury fungicides for sowing by a largely illiterate population in iraq led to a major poisoning with mercury in to with a high fatality rate ( ) . the seed-about , tons of it-was intended for spring planting; there had been ample warning that the seed was unfit for consumption, but this warning was disregarded. there was a latent period of several weeks after which pares- thesias began to appear in several victims. paresthesias involved lips, nose, and distal extremities. more serious cases progressed to ataxia, hyperreflexia, hearing disturbances, movement disorders, salivation, dementia, dysarthria, visual field constriction, and blindness. in the most severe cases, individuals remained in a mute rigid posture altered only by spontaneous crying, primitive reflexive movements, or feeding efforts. there were victims with deaths ( ) ( ) ( ) ( ) . seven children remained permanently incapacitated both physically and mentally. this was the second major mercury disaster after the minamata bay disaster in japan occurring between and , when about people were poisoned and died ( ) . phenylmercury acetate has been found to be embryotoxic and teratogenic ( ). in deaths caused by acute mercury poisoning, the mucosa of the mouth, throat, esophagus and stomach is greyish in color showing superficial hemorrhagic erosions; a softened appearance of the stomach wall is characteristic. in cases where the patient survived a few days, the large bowel may show ulcerations. the kidneys appear pale and swollen owing to edema of the renal cortex. microscopically, the kidneys usually demonstrate necrosis of the renal tubules ( ). sperhake et al. ( ) reported the case of a -year-old chemist who died of mercury poisoning. an autopsy carried out hours postmortem revealed unspecific signs of intoxication including severe edema of the lungs and brain, dilatation of the bowel, and marked congestion of the parenchymatous organs. the stomach contained ml of a reddish fluid. between the gastric folds, the mucosa appeared highly preserved with a brownish discoloration, but streaklike erosions in the exposed parts. the mucosal surface of the oral cavity and esophagus also appeared brownish and discolored. histologically, the pre-served areas of the gastric mucosa were totally unaffected by autolysis with an intact epithelial layer, whereas the eroded areas showed loss of mucosal lining with infiltrates of polymorphonuclear granulocytes and lymphocytes. mercury was detected in the epithelial layer of the gastric mucosa in situ using , diphenylcarbazone staining ( . % in % ethanol). tubular necrosis was present in the kidneys. a case of chronic arsenic poisoning in a -year-old man has been described; the man used a sodium arsenite-based fungicide for cultivating his vine yard ( ). methyl bromide (ch br), also known as bromomethane, monobromomethane, embafume, or iscobrome, is mainly used as a gas soil fumigant against insects, termites, rodents, weeds, nematodes, and soil-borne diseases ( , ) . it has been used to fumigate agricultural commodities, mills, grain elevators, ships, furniture, clothes, and greenhouses. its main advantages are its effective penetrating power and absence of danger of fire or explosion hazards. methyl bromide acts rapidly, controlling insects in less than hours in space fumigations, and it has a wide spectrum of activity, controlling not only insects but also nematodes and plant-pathogenic microbes ( ) . about % of methyl bromide produced in the united states goes into pesticidal formulations. pure methyl bromide is a colorless gas that is heavier than air. odorless and tasteless in low concentrations, it has a musty, acrid smell in high concentrations. occupational exposure to methyl bromide also occurs frequently. it is estimated that about , american workers are occupationally exposed to this gas annually. its toxicity is severe and, despite safeguards, cases of acute and chronic intoxication occur, mainly in the fruit and tobacco industries. the maximum allowable concentration of methyl bromide is ppm. concentrations of ppm or less are considered safe. death has been reported to occur at ppm ( ) . methyl bromide can enter homes through open sewage connections, thus causing fatalities. lagard et al. ( ) reported an interesting case of methyl bromide poisoning where methyl bromide caused toxicity in this manner. the sewage pipes serving two houses (one house was fumigated and in the other the poisoning occurred) had been sucked empty only to hours prior to the start of fumigation. because it depletes ozone into the atmosphere ( ) , methyl bromide has been banned in several industrialized countries, except for exceptional quarantine purposes. phosphine, sulfuryl fluoride (see subheading . .) , and carbonyl sulfide are considered viable alternatives. the mucosa of trachea and bronchi is congested and shows petechial hemorrhages. the lungs show subpleural hemorrhages and pulmonary edema. bilateral bronchopneumonia may also be present. the brain is edematous with necrosis of cortical cells, especially in the frontal and parietal lobes. multiple perivascular hemorrhages may be detected throughout the brain and small subarachnoid hemorrhages may be seen in some cases. circumscribed hemorrhages may also be present in stomach, duodenum, myocardium, spleen, and retina. the kidneys are acutely congested and show tubular necrosis on the micromorphological level; the proximal tubules are most commonly affected. in severe cases, the loops of henle and the distal tubules are also affected. the liver is also congested, but liver cell necrosis is not a common feature ( ) . methyl bromide can be detected and quantitatively determined in various biological samples by headspace gas chromatography ( ). sulfuryl fluoride (f o s) is an important agricultural fumigant. according to the annual report of the aapcc ( ), the only death that occurred as a result of fumigants was caused by sulfuryl fluoride (fig. ) . it is an inorganic gas fumigant used in structures, vehicles, and wood products for control of drywood termites, wood-infesting beetles, and certain other insects and rodents. it is also used as a gas fumigant for postharvest use in dry fruits, tree nuts, and cereal grains. it is available under the trade name vikane™ gas fumigant. because methyl bromide has now been graded as an ozone-depleting substance and is being gradually phased out, sulfuryl fluoride is taking its place. because sulfuryl fluoride is an inorganic material, as opposed to the organic methyl bromide, it does not bind onto items being protected and therefore, less quantities of gas are required for the same insecticidal effect. sulfuryl fluoride is a colorless and odorless gas. it does not cause tears or immediately noticeable eye irritation and lacks any other warning property. chloropicrin is added to products containing sulfuryl fluoride to serve as a warning indicator; chloropicrin is a gas that causes eye and respiratory irritation and vomiting. sulfuryl fluoride acts as a cns depressant. symptoms of poisoning include itching, numbness, depression, slowed gait, slurred speech, nausea, vomiting, stomach pain, drunkenness, twitching, and seizures. inhalation of high concentrations may cause respiratory tract irritation and respiratory failure. skin contact with sulfuryl fluoride normally poses no hazard, but contact with liquid sulfuryl fluoride can cause pain and frostbite-like lesions owing to rapid vaporization. occupational sulfuryl fluoride exposure may be associated with subclinical effects on the cns, including effects on olfactory and some cognitive functions ( ) . the oral ld for sulfuryl fluoride in rats and guinea pigs is mg/kg. scheuerman has reported two cases of suicide by sulfuryl fluoride ( ). according to scheuerman, toxicological analysis should include a plasma and urine fluoride level because the toxic effects of sulfuryl fluoride are probably related to this ion. concentrations of fluoride in his cases were and . mg/l, respectively. however, all values have to be interpreted in the light of all information available (kind and length of exposure, symptoms, autopsy findings, etc.) in a given case. aluminum phosphide (alp) is an ideal grain preservative for a number of reasons. it is highly toxic to almost all stages of insects with remarkable penetration power. alp dissolves well in water, oil, and fat. it is considered an ideal seed fumigant since the seeds' viability is not affected and is practically free from residual toxic hazards-provided the seeds have less than % water content. alp is minimally absorbed and easily desorbed from the treated commod- ity, such as wheat grains. it is inflammable at the prescribed dosage and devoid of tainting on fumigated stock. it has a distinct odor, which has been described as a fishy odor. because of this and also because of delays in evolving, phoshine provides considerable safety in handling this fumigant. safety in handling is due to both these reasons. because it has an odor, it is difficult for handlers to accidently ingest it. because the tablet generates the predetermined weight of gas, it is very convenient to administer the exact dose. cost of fumigation is low and its effects on the fumigated stock last longer. alp is easy to transport and handle. unfortunately, no specific antidote to alp is known. alp is used very extensively throughout agrarian economies like india. on exposure to moisture it releases the poisonous phosphine, which percolates through the grain: alp+h _ al(oh) +ph . as long as the grain is stored in airtight godowns, the liberated phosphine remains in the environment, repelling all pests. when the grain is to be used, it is brought out and aerated. this releases phosphine, leaving behind virtually no or only nontoxic residues. alp is generally available as tablets (alphos ® , celphos ® , fumigran ® ), which are dark brown or grayish in color, g in weight, and measuring mm in diameter and mm in thickness. they come in an aluminum container containing ten tablets. alp is also available as . -g pellets. the tablets are composed of pure alp (the active ingredient) and ammonium carbamate/carbonate (the inert ingredient). the ratio of the active and inert ingredient is generally about : . on contact with moisture, each -g tablet evolves about g of phosphine along with carbon dioxide and ammonia, which prevents self-ignition of phosphine gas. this is why it is also called a "protective gas." carbon dioxide and ammonia are liberated by combination of water with other inert ingredients in the tablets. the main function of the inert ingredients is to produce these gases, so phosphine may not ignite easily. the phosphine gas, once liberated, spreads quickly and kills insects and rodents almost in all stages of their development. after complete decomposition of the tablet, alp is left behind as a harmless and nontoxic grayish white residue, which is less than % of the original tablet weight. alp is the leading cause of accidental and suicidal deaths in india ( ) ( ) ( ) ( ) ( ) . it has been implicated in several homicides including dowry deaths (deaths of newlywed brides occurring in relation to dowry and covered under section b of the indian penal code). the mortality rate for poisoning with alp is almost % ( ) . there is an intense garlic-like odor emanating from the mouth and after opening of the stomach at autopsy. all internal organs are congested and show petechial hem-orrhages. pericarditis may be present ( ) . the stomach contents are hemorrhagic and the mucosa shows detachment. residues of alp may be demonstrable in the stomach contents, but rarely can alp itself be detected because it readily reacts with acid and water within the stomach. misra et al. ( ) described eight cases of alp poisoning after ingestion of alp tablets for attempting suicide; the mean age of the patients was years (age range - years). six of the patients died; the mean hospital stay was hours (range - hours). an autopsy was carried out in two patients, revealing pulmonary edema, congestion of the gastrointestinal mucosa, and petechial hemorrhages on the surface of liver and brain. anger and co-workers ( ) reported the case of a -year-old man who committed suicide by ingestion of alp. autopsy revealed signs of asphyxia with marked visceral congestion. the authors also toxicologically analyzed peripheral blood, urine, liver, kidney, adrenal, brain, and cardiac blood. phosphine gas was absent in peripheral blood and urine but present in the brain ( ml/g), the liver ( ml/g), and the kidneys ( ml/g). high levels of phosphorus were found in the blood ( . mg/l) and liver ( . mg/g). aluminum concentrations were highly elevated in peripheral blood ( . mg/l), brain ( μg/g), and liver ( μg/g) compared with the reference values. histopathological findings in alp poisoning have been described in detail by chugh et al. ( ) . various viscera show congestion, edema, and inflammatory cell infiltration. in the myocardium, there are patchy areas of necrosis, whereas the liver shows fatty changes and the lung parenchyma displays gray/red hepatization. the adrenal cortex shows complete lipid depletion, hemorrhage, and necrosis. chugh et al. assumed that the changes in the adrenal cortex could be both a sequel of shock and/or a cellular toxic effect of phosphine. in out of the patients studied by chugh and associates, there was a significant rise in the plasma cortisol level (> nmol/l). in the remaining patients, the adrenal cortex was critically involved and the cortisol level failed to rise beyond normal levels (< nmol/l). pillay ( ) noted that in alp poisoning the heart shows features of toxic myocarditis, necrosis may be seen histologically in both liver and kidneys, and the lungs may demonstrate evidence of adult respiratory distress syndrome (ards). ards has also been reported by chugh et al. ( ) . the dose of the intoxicant in chugh's cases varied from two g) to three tablets (corresponding to and g, respectively). all patients were in shock at admission and developed ards within hours after ingestion of alp. according to these authors, the exhalation of phosphine (which they detected by a positive silver nitrate paper test) was the possible noxious triggering factor in developing ards. in misra at al.'s series ( ) , histopathological changes included pulmonary edema, desquamation of the lining epithelium of the bronchioles, vacuolar degeneration of hepatocytes, dilatation and engorgement of hepatic central veins and sinusoids, as well as hepatocytes showing nuclear fragmentation. in anger's single case ( ) , microscopic examination revealed congestion of inner organs and pulmonary lesions that were attributed to asphyxia. silo filler's disease is another disorder associated with agrochemical poisoning during preservation. corn used for silage is usually grown under conditions of heavy sunlight and drought and its nitrate content is usually very high. when this silage is stored in a silo, the nitrates are fermented into nitrites, which in turn combine with organic acids to form nitrous acid. nitrous acid decomposes into water and a mixture of nitrogen oxides. these are nitric oxide (no), nitrogen dioxide, and dinitrogen tetroxide. the decomposition starts within approx hours of putting the crops into the silo and continues for about days. when entering these silos (which virtually turn into a kind of gas chamber), farm workers may suffer acute poisoning from these gases, and many such deaths have occurred. this type of death in a silo was first described in , but at that time it was wrongly attributed to asphyxia ( ). nos, being relatively poor soluble in water, can reach the terminal bronchioles and even alveoli. within the lungs, the nos react with water to form nitrous and nitric acids, which cause extensive lung damage, resulting in chemical pneumonitis and profuse pulmonary edema. nos trigger histamine release, which causes bronchoconstriction resulting in increased airway resistance. douglas and colleagues ( ) examined patients of silo filler's disease between and . all exposures had occurred in conventional top-unloading silos. acute lung injury occurred in patients, one of whom died. in the fatal case, autopsy findings included early diffuse alveolar damage with hyaline membranes, hemorrhagic pulmonary edema, and acute edema of the airway walls. poisoning with and fatalities owing to fertilizers are rarely encountered but do occur. the annual report of the aapcc toxic exposure surveillance system reported one death caused by fertilizers ( ) ( table ). used as a fertilizer, anhydrous ammonia is a respiratory irritant, which, in high doses, causes pulmonary edema ( ) . exposure most often occurs during transfer operations. ammonia reacts with water to form the strong alkali ammonium hydroxide, which causes severe tracheobronchial and pulmonary inflammation with bronchiolitis obliterans. normally, the peculiar odor of ammonia warns the potential victim. during world war ii, in london, a brewery cellar having ammonia-carrying condenser pipes was temporarily converted into a bomb shelter. during a bombing, a bomb fragment pierced one such pipe resulting in a mortality rate of the affected individuals as high as % ( ) . saito et al. ( ) described the case of a -year-old male who presumably consumed water contaminated with a nitrate fertilizer. on admission to hospital, the man showed drowsiness, deep cyanosis, and dyspnea; the patient died hours later. at autopsy, no particular morphological changes were noted except for the blood being a chocolate-brown color. postmortem toxicology of the blood revealed a methemoglobin concentration of % and the concentrations of nitrate and nitrite were . and . μg/ml, respectively. in deaths caused by nitrate fertilizers, methemoglobinemia and the presence of appreciable quantities of nitrites and nitrates may be demonstrated in cardiac blood and gastric contents (stored at - °c until toxicological analysis) ( ) . capillary gas chromatography-mass spectrometry and capillary gas chromatography with a nitrogen-phosphorus detector can be used to detect nitrates and nitrites in blood. sato and colleagues ( ) described the case of an -year-old woman who supposedly consumed agricultural fertilizer containing ammonium sulfate. she was found lying dead on the ground outside her house. a thorough autopsy could not determine the cause of her death. a beer can was found next to her, and when it was examined, it was found to contain ammonium sulfate. subsequently, ammonium and sulfate ions were detected in her serum samples and gastric contents. the cause of her death was determined as poisoning by ammonium sulfate. in order to further confirm that this death was indeed a result of an ammonium sulfate fertilizer, the authors administered a total dose of mg/kg of ammonium sulfate to three rabbits. the animals developed mydriasis, irregular respiratory rhythms, and local and general convulsions until they came into respiratory failure with cardiac arrest. electroencephalogram showed slow, suppressive waves and a high-amplitude with a slow wave pattern that is generally observed clinically in hyperammonemia in humans and animals. there was a remarkable increase in the concentration of ammonium ions and inorganic sulfate ions in the animals' serum and blood gas analysis showed severe metabolic acidosis. the authors suggested that when the cause of death can not be clearly determined and the previous history is suggestive of ammonium sulfate intake, measurement of ammonium ions, inorganic ions, and electrolytes in blood, as well as in stomach contents, are a prerequisite for the diagnosis. villar and co-workers reported poisoning and death in animals who drank fertilizer-contaminated water ( ) . the water had been hauled in tanks previously contaminated with a nitrogen-based fertilizer. in udaipur, india, chronic fluorotic lesions in cattle and buffalo have been described following consumption of fodder and water contaminated by the fumes and dusts emitting from superphosphate fertilizer plants ( ) . similar lesions have been reported from australia where the main source of fluoride appeared to have been gypsum that was included in a feed supplement and also ingested from fertilizer dumps on paddocks ( ) . gypsum fertilizers have caused several deaths in animals ( ) . similar morbidity and mortality may be seen in humans who drink contaminated water either intentionally or out of ignorance as well. the latter situation is quite possible among the uneducated farmers of agrarian economies. adrian ( ) drew attention to a very unique situation of poisoning related to fertilizers. in several countries, sewage sludges are used on farms as fertilizers because they do contain these materials. however the sewage-not surprisingly-also contains industrial wastes, such as chromium, lead, zinc, cadmium, and mercury. when this sewage is used as fertilizing material, plants tend to concentrate these heavy metals, especially chromium. ingestion of such farm produce may lead to heavy metal poisoning. several other cases of fertilizer poisoning, especially among animals, have been reported, too ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . in several countries, poisonous plants, such as castor, are used as green manure which can cause poisoning of both humans and animals. soto-blanco and colleagues from the university of sao paulo, brazil, described a case of canine poisoning where castor bean (ricinus communis) cake was used as a fertilizer ( ) . the authors stressed that these cakes may be accidentally ingested by humans as well, and recommended that cake production should include heat treatment to denature the poisonous proteins. nematicides can cause poisoning in banana plantations. wesseling and co-workers, studying pesticide-related illness and injuries among banana workers in costa rica, reported that workers at highest risk per time unit of exposure were nematicide applicators ( ) . slugs are major pests of oilseed rape that are poorly controlled by conventional bait pellets. therefore, compounds, such as metaldehyde and methiocarb, are used as seed dressings to control slugs ( ) . metaldehyde is a popular molluscicide that can cause fatal poisoning; the aapcc annual report ( ) mentions as many as cases of exposure to this agent. kiyota ( ) reported the case of a -year-old mentally retarded man suffering from pica, who ingested about . g of metaldehyde. despite medical treatment, he developed acute lung injury and died after days; he was found to have ascites and splenomegaly. high-performance liquid chromatography revealed . μg/ml metaldehyde in the serum. jones et al. ( ) developed a method to detect metaldehyde in samples of stomach contents by gas chromatography-ion trap mass spectrometry for forensic toxicology investigations. a suicide attempt using metaldehyde was reported by hancock and co-workers ( ) . a case of homicide using metaldehyde has been described by ludin ( ) . detailed overviews of metaldehyde toxicity have been provided earlier by booze and oehme ( ) and longstreth and pierson ( ) . avermectins used as acaricides (avermectin acaricides), insecticides (avermectin insecticides), and nematicides have been used for suicidal poisoning. chung and co-workers ( ) from taiwan studied the clinical spectrum of avermectin poisoning reported to a poison center from september to december . eighteen patients with abamectin (agri-mek; % wt/wt abamectin) exposure and one with ivermectin (ivomec; % wt/vol ivermectin) ingestion were identified ( males, females; age range - years). fourteen out of the patients had been exposed as a result of attempted suicide; one patient died days later as a result of multiple organ failure. algicides have not been reported to cause fatal poisoning in humans; minor ailments owing to algicide exposure include, e.g., contact dermatitis ( ) . aphicides are known to persist in crops ( ) ; their toxicity in house sparrows has been described in detail by tarrant and co-workers ( ) . bird repellants are trigeminally mediated avian irritants ( ) . toxic effects to humans have apparently not been reported so far. chemosterilants are chemicals that aim at destroying the fertility of pests. , -dibromo- -chloropropane is used to induce infertility in rats ( ) . the chemosterilant bisazir is extremely hazardous. ciereszko and co-workers ( ) have recommended that special safety measures are necessary when handling this chemical. however, toxic effects to humans have not been reported in the medical literature so far. antifeedants are chemicals having tastes and odors that inhibit feeding behavior. several chemicals, such as silphinene sesquiterpenes ( ), , , oxadiazoles ( ) , and ryanoid diterpenes ( ) , are used as antifeedants; again, toxic effects to humans have not been reported so far. herbicide safeners are compounds protecting crops from herbicide injury by increasing the activity of herbicide detoxification enzymes such as glutathione-s-transferases ( ) ( ) ( ) and cytochrome p- s. several herbicide safeners are used in agriculture such as benoxacor ( ) and dichloroacetamide ( , ) ; there toxicity in humans has not been reported so far. insect attractants attract or lure an insect to a trap. several of them are available, such as boll weevil attract and control tubes ® (plato industries, houston, tx) ( ), imidacloprid ( ) , and gf- fruit fly bait ( ) . their toxicity has been studied in detail by beroza et al. ( ) . the secondary effects of conventional insecticides on the environment, vertebrates, and beneficial organisms have caused a move to the use of more target-specific chemicals, such as insect growth regulators (igrs) ( ) . igrs are chemicals disrupting the action of insect hormones controlling molting, maturity from pupal stage to adult, or other insect life processes. several igrs are known, such as halofenozide ( ), s-methoprene ( , ) , buprofezin ( ) , tebufenozide ( ) , the chitin synthesis inhibitors teflubenzuron, diflubenzuron ( ) , and hexaflumuron, as well as the juvenile hormone mimic pyriproxyfen ( ) . halofenozide (rh- ) is a novel nonsteroidal ecdysteroid agonist that induces a precocious and incomplete molt in several insect orders ( ) . the antifeedant , , -oxadiazoles also show a considerable amount of igr activity ( ) . the toxicity of these antifeedants to animals has been studied by wright ( ) . pesticide synergists are chemicals that, although they do not possess inherent pesticidal activity, they nonetheless promote or enhance the effectiveness of other pesticides when used combined (synergism). synergists usually increase the toxicity of a pesticide so that a smaller amount is needed to bring about the desired effect. this may reduce the cost of application. an example of a synergist is piperonyl butoxide, often used with pyrethrin, pyrethroid insecticides, rotenone, and carbamate-containing pesticides. piperonyl butoxide is a liver toxicant and a possible human carcinogen ( , ) ; it also inhibits t-cell activation and function ( ) . -chloro-p-toluidine hydrochloride (cpth) is an aniline derivative registered as a selective, low-volume-use (< kg/yr) avicide. rice baits are treated with cpth to cause poisoning in birds harmful to crops ( ) . cpth may be mutagenic. stankowski et al. ( ) conducted three in vitro mutagenicity tests of cpth according to methods recommended by the united states environmental protection agency, e.g., the ames/salmonella assay, the chinese hamster ovary (cho)/hypoxanthine-guanine phosphoribosyl-transferase mammalian cell forward gene mutation assay, and the cho chromosome aberration assay. they found that cpth did not display mutagenic activity using the ames/salmonella or cho/hypoxanthine-guanine phosphoribosyl-transferase assays. however, cpth induced statistically significant, concentration-dependent, metabolically activated increases in the proportion of aberrant cells. the authors concluded that the results were suggestive of minimal mutagenicity effects associated with exposure to cpth ( ) . stahl and co-workers draw attention to the consumption of cpth treated rice baits by nontargeted bird species, such as pigeon (columbia livia) and house sparrow (passer domesticus). cpth can persist in the breast muscle tissues of both targeted and nontargeted birds which may be a potential secondary hazard to scavengers and predators ( ) . toxicity of cpth both in humans and animals has been discussed by several other authors as well ( ) ( ) ( ) ( ) ( ) . if a particular agrochemical poison has been banned in a country, it is not necessarily that poisoning with this agent will not be seen in that particular country. for example, in japan, production of azomite emulsion (an acaricide) has been stopped since . however, moriya et al. in ( ) described a recent azomite-related fatality. poisoning with azomite was confirmed when aramite and azoxybenzene, two effective components of azomite emulsion, were detected in the patient's serum when qualitatively analyzed with gas chromatography-mass spectrometry. the authors concluded that even if an agrochemical poison is banned, the pathologist must still keep the possibility of its ingestion in mind. many times, it is not the active agricultural chemical that is responsible for poisoning but impurities (such as dioxin), surfactants (e.g., polyethoxylated tallow amine used with glyphosate) and adjuvants used along with the chemical. these adjuvants, or "inert" ingredients, could be solvents, stabilizers, preservatives, sticking or spreading agents, or defoamers ( ) and may constitute petrochemical solvents, such as acetone, fuel oil, toluene, and other benzene-like chemicals. these could sometimes be more toxic than the active ingredient. rubbiani drew attention to several of these adjuvants and clinical syndromes produced by them ( ) . according to harry ( ) , toxicity is often due to solvents or surfactants included in the composition of a formula used as an agricultural chemical. when the obligatory declaration on the label about identity and concentration of some of these substances is not provided by the actual legislation in a particular country, the problem becomes more acute. it is also often difficult to determine if the cause of the poisoning is the actual agricultural chemical itself or its adjuvants. metabolites are breakdown products that form when a pesticide is exposed to air, water, soil, sunlight, or living organisms and often the metabolite is more hazardous than the parent compound. an estimated three million cases of agrochemical poisoning are reported from around the world every year, making it one of most serious toxicological problems of the present times. an overwhelming majority of these-more than %-are reported from developing countries, such as india, presumably because these are predominantly agrarian economies. in the united kingdom, pesticides are responsible for only about % of deaths ( ) , whereas in united states, as seen in table , the figure varies between and %. the equivalent figures in india have been reported to be as high as % ( ) . figure shows some common pesticides used in india. accidental poisoning may occur in a number of ways. accidental poisoning can occur if the insecticide is stored inadvertently with foodstuffs ( ) . one of the most shocking cases of mass agrochemical poisonings occurred in the indian state of kerala in (known popularly as the "kerala food poisoning case of ") when bags of foodstuffs, such as wheat and sugar, were inadvertently stored together with those of folidol (parathion) in the same cabin on a ship ( ) . the insecticide leaked and contaminated the foodstuffs; more than people were accidentally poisoned when they consumed these contaminated foodstuffs. out of these, more than people died. mixing of pesticides with foodstuffs may be intentional, albeit entirely because of ignorance and without any criminal intent. such a case came to notice in the late s in lakhmipur in kheri district, in the indian state of uttar pradesh. farmers in this state were found to be preserving food grains with benzene hexachloride. a severe convulsive epidemic broke out among several hundred people because of this ignorance and more than people died. in , improper use and application of benzene hexachloride in the town sunser in the indian state of madhya pradesh resulted in many people falling ill. fortunately, no human died, but there were reports of several bird casualties. in march , a case of agricultural poisoning from india was reported where an entire family was poisoned owing to leakage of pesticides into cereal (sorghum/jowar) stored in the same room ( ) . the indian state of kerala is a major cashew growing region. there have been attempts at aerial spraying of this cash crop with endosulphan. because these areas are close to local residential areas, deleterious effects occurring in humans have caused a major controversy in recent times ( ) . pillay ( ) suggests that accidental poisoning due to pesticides can occur in four different scenarios: (a) occupational exposure among agriculturists and those engaged in the task of pesticide spraying, (b) contamination of foodstuffs on account of negligence, (c) inadvertent ingestion by children, and (d) reusing pesticide containers for storing food or drink (the latter is very common among third-world countries). instances of fatalities among agricultural workers due to accidental exposures have been reported from time to time ( ) . accidental poisoning owing to some pesticides, such as paraquat, occurs in a number of scenarios, e.g., when the mouthpiece of fumigation equipment is sucked by the operator while cleaning and it is suddenly cleared of obstruction, confusion under the influence of alcohol, consumption of contaminated water or foods, accidental ingestion by children, and accidental cutaneous exposure or oral topical application for toothaches by ignorant persons ( ) . robert g. book of bloemfontein, south africa, reported a unique case of accidental poisoning with paraquat: a young woman tried to "achieve a high" by spiking her coca-cola with paraquat. she died after a few days of hospitalization. at the time of her admission she had told the doctor that her husband had maliciously put paraquat in her drink a few days before; however, only days later she changed her version as just mentioned ( ) . it is noteworthy that in india it is very common for married women at the time of their death to shield their murderous husbands by making such statements. whether the woman's first or second statement was correct is anybody's guess. according to harry ( ) , accidental pesticide intoxications are mainly caused by ingestions of diluted fertilizers, low-concentration antivitamin k rodenticides, ant-killing products, or granules of molluscicides containing % metaldehyde, whereas voluntary intoxications are mostly by chloralose, strychnine, organophosphorus or organochlorine insecticides, concentrated antivitamin k products, and herbicides, such as paraquat, chlorophenoxy compounds, glyphosate, and chlorates. suicidal poisoning with agrochemicals, especially organophosphates and alp, is very common in countries like india. one of the main reasons is the easy availability of these agrochemicals. many companies now add an emetic to dangerous agrochemicals, such as paraquat and alp. addition of a "stenching" agent to paraquat has apparently not deterred suicidals from consuming this poison. homicidal poisoning with organophosphorus compounds is possible and from time to time, one gets to hear or read about cases of a homicide commit-ted with these substances. svraka and colleagues have described four cases of homicide with organophosphorus compounds ( ) . however, homicidal poisonings with organophosphorus compounds are rare because of the unpleasant taste of most agrochemicals, especially of organochlorines, such as endrin, but they have been mixed with alcohol, especially toddy (a strong liquor that is very popular in india), which masks its smell and has been used with organophosphorus compounds for homicidal purposes in this way. homicidal poisoning with parathion is much easier ( ) ( ) ( ) ( ) . to prevent this, a coloring agent, such as indigocarmine, is added to parathion. this is, however, not a universal practice. in india for instance, addition of indigocarmine to parathion is not practiced. the commonly used herbicide paraquat is odorless and gives rise to symptoms mimicking viral pneumonitis. these two properties-classically hailed as the properties of an ideal homicidal poison-make it very attractive as a homicidal poison. paraquat is supposed to have a burning taste, but this can be masked in hot liquids or spicy foods ( ) . several homicide cases with paraquat undoubtedly must have gone unnoticed. teare and teare and brown ( , ) described five cases of paraquat poisoning, of which, two were homicidal in nature. the first is a well-documented case (reg vs kenyon and roberts) in which a -year-old man, keith william kenyon, was killed by his wife jennifer kenyon and her friend, david roberts, a consultant on the effects of agricultural chemicals. she purchased gramoxone along with her friend olive hemming (who turned out to be the chief prosecution witness) from a farm shop, and most likely administered it to her husband in repeated small doses. kenyon was taken ill on november , and died days later, on december . during his illness, he displayed all the classical symptoms and signs of paraquat poisoning. postmortem examination confirmed death by paraquat intoxication. mrs. kenyon was convicted of murder, whereas david roberts was acquitted because of lack of evidence against him ( ) . the second case occurred only month later. after christmas , on the falkland islands, four local agricultural workers had been having a boxing day party when some gramoxone was slipped for some unknown reason into one of their beers. the man died after displaying typical symptoms of paraquat poisoning. autopsy confirmed poisoning by paraquat. criminal charges against the other three laborers were contemplated, but eventually it was decided to drop them. paul ( ) described the case of a -year-old woman who killed her husband by mixing paraquat in his steak-and-kidney pie twice. when he developed a sore throat and was prescribed medicine for treatment, she mixed paraquat in the medicine as well. the husband died on june , after suffering a day illness. the cause of death was attributed to cardiac arrest in combination with renal failure and bilateral pneumonia and it was only by a curious chain of circumstances that paraquat was detected in the young man's tissues preserved in the mortuary in a bucket, months after the man's death. his wife and her paramour were found guilty and sentenced. stephens and moormeister from the medical examiner's office of san francisco, ca, reported four cases of homicidal poisoning by paraquat ( ) . of these, the first three murders were perpetrated by one man against members of his immediate family, and the fourth case was equivocal-it could either have been suicide or homicide. the first three murders were committed by a man who had been married five times. his first three wives were alive and healthy. when the fourth wife threatened to divorce him, she found herself ill and died days after the onset of her illness ( days after hospitalization). eight years later, when his fifth wife threatened divorce, she suffered the same fate, and a few months later, his -year-old mother also died. all three showed typical symptoms of paraquat poisoning. the postmortem findings seemed to suggest natural disease of the lungs. although a suggestion of paraquat poisoning was made in all three cases, the concerned pathologist was reluctant to sign death certificates as paraquat poisoning. toxicological analysis in the second and third cases revealed the presence of paraquat in the victims' tissues and this resulted in conviction of the murderer. it was found that the defendant worked as a mechanic on a large agricultural ranch and had easy access to paraquat; his thumb print was found on one of the opened paraquat containers, although he had earlier denied having to do anything with those containers. the fourth case involved a -year-old man, a registered herbicide and pesticide user, who had marital difficulties with his aggressive, "shrew-like" wife who also stood to benefit from a large insurance policy upon his death. while in hospital, the victim denied suicidal ingestion; he died days after the start of his illness. no testing of toxic effects from the compounds he worked with was ever performed, nor was any consideration given to this possibility. the case did not result in court charges for anyone. stephens and moormeister concluded that the reason why such cases will often go unnoticed is because of the reluctance on the part of both clinicians and forensic pathologists to even think in the direction of paraquat poisoning when they see such a clear and typical picture of "viral pneumonia." in their opinion, the clinician should suspect paraquat ingestion in all cases in which there is progressive pulmonary involvement with no features of viral infection ( ) . the pathologist conducting the postmortem would do well to go through the clinical history, if available, in detail to rule out the possibility of paraquat poisoning. in all doubtful cases, a full toxicological analysis should be done and the tissues should be particularly analyzed for paraquat. daisley and simmons from the university of the west indies in trinidad reported two cases of homicide by paraquat poisoning ( ) . both cases occurred in children and the common clinical presentations were gastrointestinal ulceration and acute respiratory distress with pneumomediastinitis. at autopsy, the most prominent finding was bullous lung emphysema. the authors stress that pathologists should be aware of this finding because they feel that if this autopsy finding is seen combined with the typical clinical presentation mentioned in sections . . . and . . ., it is almost diagnostic of acute paraquat poisoning. da costa et al. have dealt with the medicolegal aspects related to paraquat poisoning in detail ( ) . another weed killer that has been used commonly for homicidal purposes is sodium chlorate. in reg vs hargreaves, hampshire (winchester) assizes, april , a -year-old woman was charged with the murder of a -year-old man whom she had known for the last years as an uncle. in august , he made his last will, written out by the accused in her favor. on january , the accused bought the weed killer sodium chlorate apparently for a friend who was a gardener. on january , , the old man died and the postmortem examination showed signs of death from sodium chlorate poisoning. the victim had consumed beer and the remaining beer in the mug contained some mg of sodium chlorate. the jury found the woman guilty of manslaughter and sentenced her to months of imprisonment ( ) . one of the biggest and most well-known medicolegal controversies in connection with herbicides has been that of agent orange. agent orange is the name given to a mixture of herbicides that united states military forces sprayed in vietnam from to during the vietnam war for the dual purpose of destroying crops that might feed the enemy and defoliating forest areas that might conceal viet cong and north vietnamese forces. the defoliant consisted of approximately equal amounts of the unpurified butyl esters of , -d and , , -trichlorophenoxyacetic acid ( , , -t). agent orange also contained small, variable proportions of , , , -tetrachlorodibenzo-p-dioxin-commonly known as dioxin-which is a byproduct of the manufacture of , , -t and is toxic even in minute quantities; dioxin is considered one of the most toxic compounds synthesized by humans. agent orange was delivered in -gallon drums with an orange stripe to distinguish the drums visually from those containing other chemical agents (hence the name). about million liters of agent orange were sprayed over vietnam from low-flying aircrafts. among the vietnamese, it is considered to be the cause of an abnormally high incidence of miscarriages, skin diseases, cancers, birth defects, and congenital malformations (often extreme and grotesque). alterations in manufacturing procedures had reduced the dioxin content in agent orange later to minimal levels. today, , , -t registrations have been cancelled and agent orange was voluntarily removed by the manufacturers in . many united states, australian, and new zealand servicemen who suffered long exposure to agent orange in vietnam later developed cancer and other health disorders. a class-action lawsuit was brought against seven herbicide makers that produced agent orange for the united states military. the suit was settled out of court with the establishment of a $ , , fund to compensate some , claimants and their families. separately, the united states department of veterans affairs awarded compensation to about veterans. agent orange has now been replaced by agent white, a mixture of , -d and picloram, which is longer lasting and more effective. in the united states, the federal insecticide, fungicide and rodenticide act (fifra) was passed in (amended in , , and [ ] ). this act divides all pesticides in four broad classes depending on their toxicity. the label of each pesticide has to contain a signal word depending on its toxicity. the criteria established by the fifra are given in table . according to the fifra, toxic category i pesticides must have the signal words danger and poison (in red letters) and a skull and crossbones prominently displayed on the package label. the spanish equivalent for danger, peligro, must also appear on the labels of highly toxic chemicals. toxic category ii pesticides must have the signal word warning (aviso in spanish) displayed on the product label. toxic category iii pesticides are required to have the signal word caution on the pesticide label. toxic category iv pesticide products shall bear on the front panel the signal word caution on the pesticide label. pesticides formulated in petroleum solvents or other combustible liquids must also include the precautionary word flammable on the product label. this was obviously done to prevent cases of accidental poisoning, and similar acts exist in almost all countries. in india, a predominantly agricultural country, handling of insecticides is governed by the insecticides act and the insecticide rules, (amended in ) ( ) . section of the insecticide rules, classifies insecticides on a similar basis. section also insists on affixing a label to the insecticide container in such a manner that it cannot be ordinarily removed. among other things, it must contain a square, occupying not less than onesixteenth of the total area of the face of the label, set at an angle of °(diamond shape). this square is to be divided into two equal triangles, the upper portion of which shall contain the signal word, and the lower portion the specified color. the classification of insecticides, signal words to be used, and the color of the identification band on the label according to the insecticide rules, of india are given in table . if a pesticide is misused in any way, the person who bought and stored the pesticide may be legally responsible. in the united states, the food quality protection act was passed in as a complementary set of regulations, which, among other important features, specifically recognizes the special situations and usages of pesticides for public health. these laws regulate the registration, manufacture, transportation, distribution, and use of pesticides. the regulations are administered by the environmental protection agency. more than , bright green ld : lethal dose in % of the exposed subjects intoxications caused by plant protection chemicals in forensic toxicology in urban south africa patterns and problems of deliberate self-poisoning in the developing world pesticide poisoning agricultural and horticultural chemical poisonings: mortality and morbidity in the united states 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a case of murder by parathion (e ) which nearly escaped detection homicidal poisoning by paraquat poisoning by paraquat murder under the microscope-the story of scotland yard's forensic science laboratory homicide by paraquat poisoning the forensic medical aspects of paraquat poisonings sodium and potassium compounds fifra- , glp, and qa: pesticide registration the insecticides act, with the insecticide rules, , as amended by the insecticide (amendment) rules, . delhi law house acknowledgment i wish to thank my wife marygold gupta, a chemist, and my son tarun aggrawal for their whole-hearted support during the writing of this chapter. marygold was especially helpful in making me comprehend the chemical structures of several pesticides. tarun drew several chemical structures and figures on his computer. key: cord- -cr br t authors: biswas, debajyoti; sultana, parvin title: policing during the time of corona: the indian context date: - - journal: nan doi: . /police/paaa sha: doc_id: cord_uid: cr br t according to oxford covid- government response tracker, india has the most stringent lockdown as compared to other nations and has scored % in the scale; nevertheless, there had been sporadic incidence of attacks on police personnel and medical workers in different parts of india. this article argues that such resistance comes from two broad factors: (i) a collective scepticism that has built up among certain section of people and (ii) a tool of defiance against the government. in order to quell such resistance, community leaders and the police can play a very crucial role. in order to establish the above hypotheses, a quantitative approach of the events that have occurred in india during the lockdown period of days shall be considered. according to oxford covid- government response tracker, india has the most stringent lockdown as compared to other nations and has scored % in the scale. , despite enforcing such stringent, lockdown from the midnight of march to april (a period of days), there have been sporadic incidence of attacks on police personnel and medical workers in different parts of india. it is indeed a matter of concern as to why certain groups of people are opposing the lockdown while the entire nation is undergoing a threat from the deadly virus? this article argues that such resistance does not necessarily follow from ignorance always but from two other broad factors: (i) a collective scepticism that has built up among certain section of people and (ii) and a tool of defiance against the government. this article further underscores that in order to quell such resistance, community leaders can play a leading role in spreading awareness among the masses and the police can initiate trustbuilding measures as well. in order to establish the above hypotheses, this article shall use the theoretical framework advanced by stephen reicher and clifford stott in a paper titled 'policing the coronavirus outbreak: processes and prospects for collective disorder'. this article shall consider the sporadic events that have occurred in india during the lockdown period of days as the data for this study. reicher and scott stated that riots start between 'ingroup' and 'outgroup' when the former develops 'a sense of illegitimacy and grievance'. in the indian context, this feeling had been brewing among some people for quite some time and the last straw had been the enactment of citizenship amendment act (caa) and the announcement of a decision to update the national population register and national register of citizens nationwide. since then protests in different parts of india have rocked the nation, at times turning violent and inviting strict police crackdown at places where law and order went out of control. , the protests turned violent in delhi on march during the american president mr trump's visit to india. , , furthermore, when the riots in delhi turned communal (hindu versus muslims), many people alleged that the police acted hand in gloves with the government. many videos started doing rounds on social media allegedly showing police officials acting as bystanders while the city burned. under such circumstances when notification about social distancing and prohibition of public gathering were passed, the protest groups took it as government's stratagem to extenuate the intensity of the protest. this resulted in viewing the entire government machinery including medical workers and police as 'them' and the 'outgroup'. however, the protest sites were eventually evacuated as possibility of large-scale contamination loomed large. apart from the anti-caa protestors, these views were also shared by large section of indian population, mainly daily wage earners and labourers who could not anticipate the lockdown and felt that they were not given enough time to prepare for a complete lockdown and were left stranded in metros without any safety net. as desperate time needs desperate measures, the migrant workers were the hardest hit. , they also perceived the state machinery and police as agents of the upper class who are better placed to afford such breaks from work. act resulting from ignorance, helplessness, defiance, and scepticism as the number of covid positive cases steadily rose all across, the indian government started taking a number of precautionary steps from mid-march. regular classes were suspended in schools and colleges. different states also started taking steps to enforce social distancing. the central government invoked the disaster management act and the epidemic disease act of to tackle the crisis arising out of the coronavirus outbreak across india, and from march, the entire country has been undergoing complete lockdown. , nevertheless, there have been blatant violations of the advisories issued by the central and state governments in india. a close scrutiny reveals that these violations are perpetrated by four kinds of people: there are many who are still ignorant about the seriousness of the situation and their own vulnerability and therefore taking the lockdown in a casual manner. some even ventured out into the streets to see what people are doing; some went out in search of smoke and drink or food items (ignorance). the migrant workers and daily wage-earners stuck outside their home-state are left penniless with no income and ration. some of them have walked for miles braving hunger and fatigue for days to reach home (the helpless) , ; then there are the ones who use political and administrative connections, money, and muscle power to violate the lockdown (defiance) , , ; and the ones who are sceptical about it because of their doubt in the ruling party (scepticism). , , incidents this is perhaps for the first time that the entire indian population has experienced a complete lockdown situation for the first time in their lifetime. the prime minister declared a janata curfew to be observed on march, whereby people were asked to stay at home for the entire day and at seven in the evening, the prime minister appealed to the people to step on their balconies and clap to show appreciation for the doctors, nurses, and all other health workers working at the forefront. while the entire day went on well, there were instances where people came out on streets in large groups and defying all the norms of social distancing, creating a chaotic situation. on march evening, the prime minister declared that the entire country will be under a lockdown for days. from the experience of european countries as well as china, south korea, it became clear that social distancing is one of the effective ways to contain the spread of this infection. however, once the lockdown was put in place, there were many instances where the lockdown has been violated. spurts of violent events also took place where police personnel, health workers, and even common wage labourers were at the receiving end. a look at few incidents will throw some light on the trend that such violence and violation took. in punjab, some members from the nihang community (a sect in the sikh religion) have perpetrated the worst brutality on the police when they were stopped during a police checking. the nihangs not only attacked the unarmed police with swords but also severed the hand of one of the police officers. in many places, health workers, doctors have been targeted despite the fact that they are at the forefront of the fight against this virus. , there were incidents reported whereby patients under quarantine made vulgar signals at the nurses. in fact, a video went viral, which shows people throwing stones at two doctors who went to a place in indore to do contact tracing of a covid- positive patient. but the perpetrators have not been only citizens in all cases. in an incident, two all india institute of medical sciences, delhi (aiims)doctors returning from emergency were beaten up by the patrolling police. even when they showed their identity cards, it did not end and one of the doctors was left with a broken arm. as mentioned above, one of the earliest violations of the lockdown came from the most vulnerable section of the people -the daily wage earners. metro cities are home to a large number of migrant workers coming from different parts of the country. most live on their day to day earnings. construction site workers often stay at those sites and do not have a separate space to live at. left with no work and no support, thousands of migrant workers thronged the delhi streets a day after the lockdown to go to their native places. as there were no buses, many workers started thousands of kilometres long journey on foot. it was only later that respective state governments arranged for buses for these migrants. however, migrants were later asked to stay where they are. but not even a week later, violence broke out in surat, ahmedabad in gujarat. around migrant workers clashed with police when they demanded to be sent back to their respective home states as they ran out of money and food. in retaliation, the police fired tear gas shells at those migrant workers. a large number of first information reports (firs) have been filed against the violators of the lockdown both under disasters management act and the epidemic diseases act. while the administration is trying to work on different fronts, sporadic incidents of lockdown violations continued. in some states, violators were slapped with https://www.indiatoday.in/india/story/policeman-s-hand-chopped-off-two-others-injured-in-attack-by-nihangis-inpun- - - - . (accessed april ) https://www.bbc.com/news/world-asia-india- . (accessed april ) https://www.bloomberg.com/news/articles/ - - /doctors-come-under-attack-in-india-as-coronavirus-stigmagrows. (accessed april ) https://www.deccanherald.com/national/north-and-central/tablighi-jamaat-attendees-quarantined-in-ghaziabad-hos pital-make-vulgar-signs-roam-nude-inside- .html. (accessed april ) https://www.bbc.com/news/world-asia-india- . (accessed april ) https://www.thehindu.com/news/national/other-states/aiims-doctors-beaten-up-by-policemen-in-bhopal/art icle .ece. (accessed april ) https://in.reuters.com/article/us-health-coronavirus-southasia/indian-police-fire-tear-gas-at-jobless-workers-defying-cor onavirus-lockdown-idinkbn h or. (accessed april ) https://theprint.in/theprint-essential/modi-govt-is-using-two-laws-to-tackle-coronavirus-spread-but-one-of-themneeds-changes/ /. (accessed april ) national security act. in uttar pradesh, this act was slapped on people who attacked police personnel. however, similar mechanisms have not been followed across all the states. all these incidents show that there are sections of people who are not cooperating with the government in order to make the lockdown effective and fruitful. the actual objective of the lockdown is to contain the spread of the virus; however, with the movement of people from one place to another, this objective may well be defeated. there are some states in india where the lockdown had been effective because of the proper coordination of the administration, the police, the community and religious leaders, social organizations, and the people. one such state is kerala. it has the highest recovery rate and only two deaths; this state may be taken as a model in understanding the effective manner of making the lockdown successful and minimizing the spread of the virus. in the initial days of lockdown, there were cases from certain groups with religious affiliation flouting the laws. the delhi state government issued an order on march to restrict gatherings which saw a conglomeration of more than people. however, on march, the akhil bharatiya hindu mahasabha leader, swami chakrapani organized a 'cow urine party' (gau mutra) at their headquarters in delhi. it saw the participation of more than people. the tablighi jamaat also continued receiving participants from covid- affected countries like malaysia, indonesia, thailand, etc. during this period. while the markaz headquarters are just next door to the nizamuddin police outpost, it was only towards the end of march that the building was evacuated. the markaz headquarters eventually turned out to be a hotspot and accelerated the number of corona-affected cases in india. however, religious and community leaders in some cases have played an important role in taking the government's message to the community. the largest religious minority in india-the muslims have been sceptical of the government in power owing to its alleged majoritarian overtones. in such a scenario, conspiracy theories and fake messages started doing rounds which further alienated the community in the fight where all should have stood united. however, community leaders have been taken on board to a great extent. many from the community condemned the irresponsible behaviour of the tablighi jamaatis and have requested muslims to follow lockdown rules and celebrate religious functions like shab e barat which again includes community prayers in their homes. the chief of the all india imams organisation, imam ahmad ilyasi has issued an appeal in this regard. religious leaders in the state of kerala played an exemplary role. the guruvayur temple authorities asked devotees to not visit the temple, marriages were postponed, and thermal scanning was https://economictimes.indiatimes.com/news/politics-and-nation/nsa-to-be-slapped-against-persons-who-attack-police men-enforcing-coronavirus-lockdown-in-up/articleshow/ .cms?from¼mdr. (accessed april ) https://economictimes.indiatimes.com/news/politics-and-nation/lockdown-violation- -arrested-rs- -lakh-collectedas-fine-in-up/articleshow/ .cms. (accessed april ) https://economictimes.indiatimes.com/news/politics-and-nation/nsa-to-be-slapped-against-persons-who-attack-police men-enforcing-coronavirus-lockdown-in-up/articleshow/ .cms?from¼mdr. (accessed april ) https://www.thehindu.com/news/national/coronavirus-group-hosts-cow-urine-party-says-covid- -due-to-meat-eaters/ article .ece. (accessed april ) https://scroll.in/article/ /tablighi-jamaat-how-did-the-government-fail-to-detect-a-coronavirus-infection-hotspot. (accessed april ) https://www.outlookindia.com/website/story/opinion-in-the-time-of-corona-responsibilities-of-religious-leaders-go-be yond-just-asking-people-not-to-congregate/ . (accessed april ) policing in india during corona article policing installed for those who came. even traditional religious rituals were changed to ensure contamination is contained. kerala chief minister pinarayi vijayan met a number of religious leaders and requested them to cancel religious gatherings. the imams, pastors, and priests readily agreed. kerala has set an example of communal harmony by defeating parochial and petty politics during this hour of crisis when the right wing and the left wing forces joined hands to serve the people and fight against the virus. the appeal made by the religious heads to their community to maintain social distancing in kerala and other parts of india has considerably helped in minimizing the violation related to lockdowns. the appeals made by the minority affairs minister mukhtar abbas naqvi, jamiat ulama-i-hind's general secretary, maulana mahmood madani, all india imams organisation's chief umer ahmad ilyasi, civil servants belonging to the minority community, and political leaders from the muslim community have helped in bringing some order and stability among the minorities in india, although some sporadic attacks on health workers continue in minority dominated areas because of the involvement of some fringe elements. research has shown that the religious leaders have always played a major role in building confidence and maintaining a healthy lifestyle among adherents (anshel and smith, ; heward-mills et al., ) . apart from the role played by the religious leaders, the role of the police has also helped in trustbuilding measures among the people in india. taking cue from the police of other countries, the police in some of the states like west bengal, maharashtra, assam, nagaland, and goa sang some of the famous bollywood songs to keep the public in good humour. , , the cops also tried to sensitize the people about social distancing and sanitization measures apart from distributing food among the needy ones at various cities across india. , , such efforts have helped in overcoming the myth about police brutalities. as mentioned earlier the police had also been alert about the fake messages that try to destabilize communal harmony, and irrespective of the religious of political affiliation of the perpetrators, the police have nabbed the culprits. , , research has shown that such 'distributive fairness' always strengthens the relationship between public and police (sunshine and tyler, ) . since the police are enforcing the government orders, an overall balancing of the relationship among the people, the police, and the government is also very crucial. in achieving that balance, the police have to negotiate between the normative and the pragmatic (suchman, ) . as a result, such measures can eventually lead to the active participation of the people in helping the police to maintain public order and stop violation of the government advisories (jackson and bradford ) . the role of police can therefore not only create awareness among the citizens and build trust in the government agency, but can also indirectly make the citizens more socially responsible and sensitized towards crimes. the violation of the lockdown during the initial days has considerably reduced. the people have become more sensitized and better organized than before. the community leaders too understood their responsibilities and therefore have appealed to their people to follow government advisories. the role played by the police also helped in winning the trust of the common people, thereby bringing down the escalation between the communal forces. apart from the strong role played by the community leaders and police, the role of the government is also important during such epidemic. the stringent measures taken by the chief minister of kerala by issuing strict advisories and warnings against violators have certainly helped in having an effective lockdown. , apart from strict lockdown measures, kerala government has also been doing 'aggressive testing and contact tracing' as reported by stands a good chance of containing the spread of the virus within the state. with proper coordination among the people, the police, the leaders, and the government, the fight against coronavirus has become effective. these lockdowns certainly have various socio-political and economic ramifications, but 'with careful management both at a general policy level and in terms of sensitive community-based and dialogue led policing, it will be possible to maintain a sense of common endeavour and hence to draw on the community as a key resource in dealing with the crisis' (reicher and stott, ) and the difference between 'us' and 'them' will also gradually diminish. the role of religious leaders in promoting healthy habits in religious institutions the role of faith leaders in influencing health behaviour: a qualitative exploration on the views of black african christians in leeds the role of procedural justice and legitimacy in shaping public support for policing managing legitimacy: strategic and institutional approaches what is trust and confidence in the police? policing the coronavirus outbreak: processes and prospects for collective disorder key: cord- -deuvq wf authors: sahasranaman, anand; kumar, nishanth title: network structure of covid- spread and the lacuna in india's testing strategy date: - - journal: nan doi: nan sha: doc_id: cord_uid: deuvq wf we characterize the network of covid- spread in india and find that the transmission rate is . , with daily case growth driven by individuals who contracted the virus abroad. we explore the question of whether this represents exponentially decaying dynamics or is simply an artefact of india's testing strategy. testing has largely been limited to individuals travelling from high-risk countries and their immediate contacts, meaning that the network reflects positive identifications from a biased testing sample. given generally low levels of testing and an almost complete absence of testing for community spread, there is significant risk that we may be missing out on the actual nature of outbreak. india still has an apparently low current caseload, with possibly a small window of time to act, and should therefore aggressively and systematically expand random testing for community spread, including for asymptomatic cases. this will help understand true transmission characteristics and plan appropriately for the immediate future. : the spread of covid- in india (till march , ) . a) change in cumulative caseload over time shows sharp rise of cases in march . b) state-wise distribution of cases in india reveals maharashtra to have the highest burden of cases. the key parameter to characterize an outbreak is the transmission rate, which is a measure of the average number of individuals infected by an individual carrying the virus. a commonly used metric of transmission is the basic reproductive number , which is the transmission rate given that the population has no immunity from past exposures or vaccination, nor any deliberate intervention in disease transmission [ ] . when > , the number of infections grows and spreads in the population, but not for < . is generally modelled from data on the spread of the disease, with the assumption that the dynamic of spread is underway in the community and that the measure therefore parametrizes the extent of intra-community spread. in this work, we look at the data on each individual case of covid- infection and attempt to create the network structure of infections for india. essentially, we attempt to identify how each individual was infected -whether the individual carried the infection from abroad (level ), or if it was local transmission in the country from an individual who had been infected abroad (level ), or if it was community transmission between individuals in the country (level ). using this characterization of individual infections, we create the network of covid- infections in india, and compute the transmission rate as the average number of neighbours of a node in the network. we also simulate different scenarios of transmission using a simple susceptible-infected-recovered (sir) epidemiology model [ ] , to highlight potential pathways of spread. the model considers a system of we use march , as the date on which significant interventions happened in india to restrict the spread of disease, including the suspension of almost all visas for tourists entering the country, in addition to measures adopted by a number of states closing schools and colleges, as well as malls and movie halls. as of this date, we find that there were cases of individuals who had contracted the virus, and we were able to identify the sources of infection in of these cases. because case numbers in india are still close to , we find that newspapers are still tracking individual case histories; and we use these newspaper reports and wikipedia to construct the data set on individual transmission [ , . out of these cases, we identified ( %) as level , ( %) as level or local transmission, and only one ( %) as level or community transmission (fig. a) . a day (fig. a) . this anomaly is resolved when we assess the network structure, which reveals that a majority of infections still being identified are those who contracted the virus abroad ( %, fig. in countries where the virus has seen community spread, has been estimated in the region of . − , which indicates exponential growth dynamics [ ] . while there is emerging research suggesting a degree of climate determination in the spread of covid- as well as a correlation with geographical latitude, these results are very new and need confirmation [ , ] . therefore, in the absence of clinching evidence relating to environmental factors, we ask the question of what is driving this discrepancy in transmission rates between india and other countries experiencing community spread. to answer this question, we must first turn our attention to testing processes on the ground to identify cases of covid- in india. it has been widely reported that the testing in india has been focused on (and limited to) citizens who have travelled from a set of high-risk countries and those who have come in contact with these cases [ ] [ ] . there has been no systematic testing process in place for testing the extent of community spread in india [ ] . given this bias in testing, it should be no surprise that among the observed cases of covid- in the country, a majority are travellers from high-risk countries and their immediate contacts with local transmission (as reflected in the networks structure of infections, fig. b ). recently the indian council for medical research (icmr) confirmed that limited testing on community spread had been initiated - , tests of people without travel history or contact with infected persons were to be done, though details of the randomization process in selecting these cases are not available [ ] . while this is a start, it must be kept in mind that the actual network of spread will continue to reflect the same bias until community testing becomes a significant part of the testing strategy. consolidated data from icmr tells us that india has so far tested a total of , samples [ ] , or tests people per million population, which is very low compared to other countries that have been testing for community spread [ ] , and creates the risk of missing such transmission in case it is already underway in the country. india currently has over covid- positive cases, but is yet to hit the kinds of caseload spikes seen in china, the us and europe [ ] . given this shrinking window of opportunity and the significant lacuna in testing, india must, aggressively and systematically, proceed to widen the scope of testing for possible community transmission immediately. in this context, icmr has just announced the introduction of tests for asymptomatic direct and high-risk contacts of a confirmed case [ ] . however, given the tremendous void in testing for community spread so far, there is a need for larger scale random testing of both symptomatic and asymptomatic cases, in order to better understand the extent of spread in the broader community. this is particularly critical because if indeed community transmission is underway in india, we could see significant proportions of the population being infected by covid- before the epidemic recedeswe simulate these possibilities for = . (which is at the lower end of transmission rates from global evidence on covid- ) and = . (which is close to the median transmission rate from evidence so far) and find that with community spread, we could see maximum infection caseloads of % and % of the population respectively (figs. a and b). a b epidemic spread models used by the uk and us predict much higher infection rateswith = . , they estimate that up to % of the population of the us/uk would be infected in the absence of intervention [ ] . even if we assume that maximum infection load in india peaks at %, (about million people) and even if only % of these cases are most severe requiring intensive care, this means that the indian health system would need to cater for million icu beds, but it is estimated that there are only around , icu beds in indiaor icu bed for people [ ] . given the state of the indian health system, it is essential that we do as much as possible to test randomly for community spreadboth symptomatic and asymptomatic -and attempt to unearth the gravity of spread in india as soon as possible, especially while the current restrictions on international travel, closure of places of gathering (schools, colleges, malls, temples, workplaces etc.), household quarantines, and other social distancing measures that are already in place. briefing by who director-general tedros adhanom ghebreyesus - coronavirus pandemic coronavirus in india: tracking country's first covid- cases; what numbers tell. india today mohfw the reproduction number contributions to the mathematical theory of epidemics-i coronavirus pandemic in india coronavirus cases rise to , italian tourists among them: government coronavirus update: new case reported from ghaziabad, india now has patients coronavirus: delhi resident tests positive for coronavirus, total people infected in india j&k man tests positive for coronavirus; infected in india coronavirus: more positive cases in india, total goes up to , says health ministry ndtv. of family in kerala get coronavirus, total positive cases in india coronavirus update: new cases reported, india now has covid- patients fresh coronavirus cases emerge from punjab, bengaluru; takes total to coronavirus: two test positive in pune; confirmed cases in india. indiatvnews coronavirus: all schools, colleges in kerala to shut down in march; more test positive coronavirus update: more test positive for covid- in maharashtra, number rises to the new indian express. cases reach in india as jaipur person tests positive, one critical in kerala coronavirus cases in maharashtra; budget session to be curtailed the times of india. one more tests positive for covid- uttar pradesh tally is nine sixth case of coronavirus reported in delhi coronavirus update: indian national evacuated from italy with tests positive for covid- two more test positive in yavatmal; maharashtra count rises to four new coronavirus cases confirmed in mumbai, maharashtra total cases at . india today second case of coronavirus confirmed in hyderabad coronavirus: -year-old from jaipur tests positive for covid- , has travel history of spain. india today the reproductive number of covid- is higher compared to sars coronavirus spread of sars-cov- coronavirus likely to be constrained by climate. medrxiv the indian express. one covid- positive infects . in india, lower than in hot zones india needs a more aggressive testing regimen for coronavirus: experts public-health experts raise concerns about india's restricted testing for covid- is india testing enough for coronavirus cases? will know if india is going through community transmission of covid- : icmr worldometers strategy of covid testing in india impact of non-pharmaceutical interventions (npis) to reduce covid- mortality and healthcare demand key: cord- -vobwdcpj authors: jainudeen, m.r. title: buffalo husbandry | asia date: - - journal: encyclopedia of dairy sciences doi: . /b - - - / -x sha: doc_id: cord_uid: vobwdcpj nan tropical asia is the homeland for almost million of the population of million domestic buffaloes (bubalus bubalis) in the world ( estimate). domestic buffaloes in asia are of two types: the swamp type for draught in the eastern half of asia contents asia mediterranean region and the river type for milk in the western half of asia (see dairy animals: water buffalo). once a sadly neglected farm species, the river type buffalo currently produces about million tonnes of milk annually from some of the world's best buffalo breeds in india and pakistan. they breed throughout the year, conceive at ± kg body weight, calve for the ®rst time at ± years following a gestation period of ± days, and produce two calves every years. lactating animals are fed mainly on straw, crop residues and mineral supplements such as urea±molasses±mineral block (ummb). in most rural areas, animals are hand-milked twice daily with the calf present to stimulate milk letdown. lactation is ± days with ®rst lactation milk yields of ± kg. breeding females are retained in the herd until about the ninth lactation ( years of age) with reasonable economic returns. river buffaloes are vulnerable to most infectious and metabolic diseases affecting cattle. in india and pakistan, milk is marketed through a network of milk cooperatives, which guarantee a stable price throughout the year for the farmer. buffalo milk contains twice as much butterfat as cows' milk. besides ghee, several other products are manufactured from buffalo milk, such as butter, cheese, full cream milk powder, skim milk powder and infant formulae. thus, the domestic buffalo is emerging as an alternative source for the manufacture of dairy products worldwide. the term`buffalo' refers to three species in the family bovidae. the african buffalo (syncerus caffer) and the north american buffalo (bison bison ) have yet to be domesticated. on the contrary, the asian buffalo (bubalus bubalis) was domesticated around the same time in history as cattle for draught power, milk and meat. the domestic buffalo is also known as thè water buffalo' because of its fondness of cooling itself in water ( figure ). these two buffalo types differ in their wallowing habits, chromosome numbers and physical features ( table ) . the river buffalo makes up nearly % of the buffalo population in asia ( figure ) . the dairy breeds of river buffaloes in india are the murrah, nili-ravi and surti and in pakistan the nili-ravi and kundi. buffaloes, like cattle, are polyestrous, breeding throughout the year, but the calving pattern is in¯uenced by rainfall, feed supply, ambient temperature and photoperiod. in india and pakistan, most buffaloes calve between november and march. the buffalo attains puberty at a later age than cattle (see oestrus cycles: puberty). on recommended levels of nutrition, most conceptions occur when the female weighs ± kg. in the male viable sperm appear at about months of age. the oestrus cycle length is about days with oestrus lasting to hours and ovulation occurring spontaneously after the end of oestrus ( table ) . unlike cattle, overt signs of oestrus are not pronounced (see oestrus cycles: characteristics). in most smallholder farms, a male buffalo may not be available for oestrus detection. homosexual behaviour or standing to be mounted by another female is observed only occasionally in the buffalo. as a result, most inseminations are based on less-reliable signs such as clear vulval discharge, restlessness, frequent urination, vocalization and reduction in milk (see mating management: detection of oestrus). oestrus commences toward late evening with peak sexual activity at night. since the early s, arti®cial insemination (ai) has been practised in the river buffalo in the indian subcontinent but its progress has been very slow because of the dif®culty of detecting oestrus and low conception rates in smallholder farms. buffalo semen is routinely collected in ai centres with an arti®cial vagina, similar in design to that for cattle. ejaculate volume and concentration of semen are lower in buffalo than cattle. techniques of semen evaluation, processing and cryopreservation are as in cattle with minor modi®cations (see gamete and embryo technology: arti®cial insemination). ai centres in india and pakistan provide an ai service with either chilled or frozen semen. in pakistan, an ai network consisting of over main and about subcentres provides more than million inseminations annually. adapted from jainudeen and hafez ( ) . most inseminations are usually performed between and h from the onset of oestrus. at this time, the cervix is suf®ciently dilated for the deposition of semen in the uterine body with the same insemination equipment as for cattle. both india and pakistan export frozen semen to upgrade or crossbreed indigenous buffaloes in thailand, china and the philippines. several countries are engaged in developing embryo transfer (et) technology in the buffalo. the basic principles of et technology in cattle are applicable to buffalo except that embryos are collected from the uterus on day of the cycle instead on day or adopted in cattle (see gamete and embryo technology: multiple ovulation and embryo transfer). also the pregnancy rates have been less than % in bulgaria and india, as compared with ± % in dairy cattle. poor superovulatory response to gonadotrophins, low embryo recovery rates and the small number of calves born suggest that the technology is not ready for commercial application in the buffalo. in vitro fertilization (ivf) of buffalo oocytes is an alternative to superovulation (see gamete and embryo technology: in vitro fertilization). several laboratories have produced buffalo embryos by ivf. in , the ®rst ivf buffalo calf was born in india. since oocytes can be collected at slaughter from highproducing buffaloes at the end of their lactation (see`feeding the lactating buffalo', below), ivf has potential applications in pakistan and india. gestation is longer in buffalo than cattle, varying from to days for the river buffalo and from to days for the swamp buffalo. pregnancy is routinely diagnosed by rectal palpation of the uterus from about to days following insemination. the birth process is similar to that of cattle (see pregnancy: parturition). the foetus is delivered in anterior presentation with fully extended limbs and foetal membranes are expelled ± h later. twinning is rare, and the incidence is less than per births. birth weights range from to kg with male calves weighing ± kg more than female calves. after calving, the ®rst oestrus and ovulation occur at about and days respectively in well-managed herds. postpartum anoestrus or failure to resume oestrous cycles after calving remains a major problem contributing to long calving intervals (see oestrus cycles: postpartum cyclicity). conception rates based on the nonreturn rates to ai are inaccurate, because of the inherent dif®culty of detecting oestrus (see above). pregnancy rates, based on rectal palpation, usually range from % to % with chilled semen, % to % with frozen semen, and over % for hand matings. a buffalo usually produces, on average, two calves every years. however, in well-managed herds, calving intervals of to months have been achieved. several southeast asian countries have embarked upon crossbreeding the indigenous swamp to the river buffalo. the f crossbreds (river  swamp) possess an intermediate karyotype of n . unlike other mammalian hybrids possessing chromosome complements differing from their parents, both male and female hybrids are fertile. as mentioned previously, seasonal calving patterns in buffaloes have been attributed to ambient temperature, photoperiod and feed supply. in india and pakistan, buffaloes calving in summer or autumn resume ovarian cyclicity earlier than those calving in winter or spring. perhaps decreasing day length and cooler ambient temperatures favour cyclicity. in the past,`silent oestrus' ± ovulation not preceded by oestrus ± was believed to be a major problem in buffalo breeding but recent hormonal studies have revealed that it is due to the farmer's inability to detect oestrus. improvements in nutrition could increase growth rates and hasten the onset of puberty. similarly, early weaning, induction of oestrus with prostaglandin or intravaginal progesterone-releasing devices and better nutrition have hastened the resumption of early postpartum ovarian activity and reduced the calving to conception intervals. induction of oestrus with synthetic analogues of prostaglandin f a and ®xedtime insemination with frozen semen may prove useful in restricting mating seasons so that calving occurs when water and green feed are abundant. male buffaloes show marked seasonal¯uctuations in libido and semen quality, which may be overcome by providing cooling facilities during the hot season. in addition, females could be inseminated with semen collected and cryopreserved during the cooler months. most reproductive management programmes adopted for cattle can be effectively applied for the buffalo but the commercial and smallholder farmers have not realized the bene®ts of such programmes. many asian countries have limited feed resources for feeding their buffaloes. the available resources are essentially tropical pastures (both green and mature), straws and crop residue, which are generally low in protein (see developing countries, cow management: asia). two systems are practised for rearing buffalo calves. in smallholder farms, calves are allowed to suckle their dams both for milk letdown and to suck ± l of milk. as they grow older, suckling time is gradually reduced and replaced by grass and small quantities of concentrate. beyond ± weeks of age, the calf is used only for milk letdown. in commercial farms, calves are weaned at birth and managed as for dairy calves (see replacement management, cattle: preruminant diets and weaning practices). often male calves are neglected and die of starvation. feeding systems of buffaloes for milk can be broadly classi®ed as ( ) extensive, ( ) semi-intensive, and ( ) the intensive system. the second system is most common, with animals tethered in the farmer's backyard and fed mainly on cut fodder and crop residues. lactating animals receive . kg concentrate mixture per litre of milk produced. large herds of high-producing buffaloes are located near big cities in india and pakistan. these animals, purchased from the villages immediately after calving, are transported to cities where they are con®ned in large holding areas and fed with dry fodder and large quantities of discarded bread and other preparations made of¯our.`dry' animals are sent to the abattoir since it is uneconomical to transport them back to their original villages. the energy and protein requirements have been established for maintenance and milk production for the river buffalo (table ) . there is no physiological need for concentrate feed to maintain butterfat content that is about twice as much as cows' milk. feeding concentrates increases milk fat content as high as %, since the buffalo releases unwanted fat into the milk and stores only a minimum in body tissues. several physiological and physical factors contribute to the buffalo's ability to utilize poor quality roughage and crop residues. among these factors are the large rumen volume, high rate of salivation, slower rate of passage of digesta through the reticulo-rumen, slow rumen motility and higher cellular activity. the dry matter intake and digestibility of roughage can be improved by supplementing with a mixture of urea and molasses. the mixture is available as a block lick (ummb). this block supplies fermentable energy, bypass protein, and macro-and microminerals to make the rumen micro¯ora and fauna more ef®cient in digesting roughages. buffaloes fed these supplements show better body condition, shorter calving intervals and higher milk yields. the annual production of buffalo milk in the asian± paci®c region exceeds million tonnes (see table ) with india and pakistan contributing more than over million tonnes (figure ) . almost all the milk is produced in smallholder farms. milk letdown is slower in buffalo than in cattle. the presence of the calf initiates the milk letdown re¯ex. in most smallholder farms, animals are hand-milked with the calf to stimulate milk letdown, whereas in big herds in india and pakistan they are machinemilked as for cattle. normally buffaloes are milked twice a day. the lactation length is about days in the murrah breed and about days in the nili-ravi breed. milk yields range from to kg for the ®rst lactation with a steady increase to a peak in the fourth lactation, and are then maintained at peak levels until the ninth lactation. thus, a buffalo could be retained in the herd up to about the ninth lactation ( years of age) with reasonable economic returns. digestible crude protein dry and lactating animals (g kg À w . ) . to . milk production (g g À of protein in milk) . to . adapted from mudgal ( ) and ranjhan ( ) . with selective breeding, improved management and the establishment of more dairy herds, milk yields are increasing. the individual l-per-lactation female, considered a record years ago, is now common. there are many that yield l in a lactation of days ± some have even attained l. most asians consume buffalo milk in liquid form. surplus milk is processed into butter, ghee, condensed milk, curd and cheese (see milk fat products: anhydrous milk fat ± butteroil, ghee). dairy products that are usually made from cows' milk are also produced from buffalo milk in modern dairy plants. the dairy industry has grown from small creameries to large dairy plants supported by thousands of small farmers who supply between and l of milk per day. the rapid expansion of the buffalo dairy industry in the past two decades can be attributed to the cooperative milk marketing model, ®rst developed in gujarat, india (table ) , then adopted by other states in india and pakistan. in this model, the smallholder farmer is guaranteed a stable price for milk throughout the year, eliminating the middleman from the pro®ts. in addition, these cooperatives provide loans to farmers to purchase superior animals, sell animal feed and provide a routine veterinary and ai service. their extension programmes help producers to increase production and reduce costs. few differences exist between buffalo and cattle in the nutritive value of milk and milk products (see milk: introduction). however, the lower water and higher fat contents make buffalo milk better suited for the manufacture of fat-based and solids-not-fatbased milk products, such as butter, ghee and milk powder ( table ) . calcium, iron and phosphorus in milk are higher in buffalo than in cow. the lower cholesterol content in buffalo milk should make it more popular than cows' milk with the healthconscious public. unlike the cow, the buffalo converts the yellow pigment b-carotene into vitamin a, which is colourless, and is passed on to milk. therefore, buffalo milk is distinctively whiter than cows' milk; the latter is not only pale creamish-yellow but also the milk fat is golden yellow. proteins of buffalo milk, particularly the whey proteins, are more resistant to heat denaturation than those of cows' milk. dried milk products prepared from buffalo milk exhibit higher levels of undenatured proteins when processed under similar conditions. ultra-high temperature (uht) treated buffalo milk and cream are intrinsically whiter and more viscous than their cows' milk counterparts, because greater levels of calcium and phosphorus are converted into the colloidal form. ghee accounts for about % of the total milk produced in india. ghee is clari®ed butterfat and contains about % of milk fat. ghee from buffalo milk has no colour, unlike ghee from cattle, which is golden yellow due to the presence of carotenoids as stated earlier. ghee is the only source of animal fat in the vegetarian diet of the human population in india. cheese made from buffalo milk displays typical body and textural characteristics. for the manufacture of mozzarella cheese, buffalo milk is preferred to cows' milk (see buffalo husbandry: mediterranean region). certain traditional cheese varieties, such as paneer in india or pickled cheeses from the middle east countries, are best made from buffalo milk. amul is a cooperative factory in gujarat which produces a range of milk products exclusively manufactured from buffalo milk. the products include butter, full cream milk powder, skim milk powder, ghee, infant formulae, cheese, chocolates, ice cream and nutramul. amul products are exported to the united states, new zealand and the gulf states. the sales ®gures for amul's butter have increased from tonnes year À in to over tonnes year À in . contrary to the popular belief that domestic buffaloes thrive in the harsh, humid conditions in the tropics, they are susceptible to thermal stress, infectious diseases and disorders similar to those of cattle. with less than one-tenth the density of sweat glands compared to cattle, the domestic buffalo's ability to sweat and lose heat through evaporative cooling is signi®cantly diminished. in addition, their dark body coat promotes heat absorption from the direct rays of the sun whereas the thick epidermal layer prevents heat dissipation through conduction and radiation. thus, the domestic buffalo is more sensitive than cattle to direct solar radiation and high ambient temperatures during the summer months. thermal stress may lead to higher calf mortality, lower milk yields and slow growth, and can depress signs of oestrus (see stress, heat, in dairy cattle: effects on mik production and composition; effects on reproduction). thermal stress can be reduced by providing cooling facilities such as shade and wallows, and by sprinkling water on to the skin during table composition of milk of river buffalo and cow buffalo milk cows' milk water (g l À ) total solids (g l À ) lactose (g l À ) proteins (g l À ) fat (g l À ) cholesterol (mg g À ) . . adapted from rajorhia ( ) and ganguli ( ) . the hotter part of the day and feeding roughage during the night. river buffaloes are susceptible to most diseases affecting cattle (table ) . compared with cattle, buffaloes show greater resistance to foot-and-mouth disease and brucellosis but have a higher incidence of parasitic diseases because of their wallowing habits. the dairy buffalo is as susceptible to mastitis as the dairy cow. bacteria causing mastitis, their treatment and control are similar to those for cattle (see mastitis pathogens: contagious pathogens; environmental pathogens). there is a high incidence of calf mortality caused by toxocara vitulorum, virulent strains of escherichia coli, rota and corona viruses. larvae of to. vitulorum are transmitted from the dam to the calf through the milk during the ®rst month of life. puerperal metritis and retained foetal membranes occur in the buffalo. the high incidence of metritis and other genital infections has been partly attributed to the unhygienic practice of dilating the vagina with either inserting objects or blowing air for stimulating milk letdown. high milk-producing river buffaloes are as susceptible to metabolic disorders as dairy cows. apparently, the aetiology is similar because affected buffaloes respond to therapy and control as for dairy cows. the buffaloes reared in the mediterranean region are the asian buffalo or water buffalo, i.e. bubalus bubalis. this species includes two types: ( ) the river type, with chromosomes, with an adult male weight ranging between and kg, and annual milk production of ± kg; and ( ) the swamp type, with chromosomes, with an adult male weight of ± kg, and annual milk production up to kg. while the major purpose of the river buffalo is milk, the swamp buffalo is reared mainly for draught. only % of the world buffalo population is reared in the mediterranean region, which includes a few buffalo husbandry: mediterranean region. dairy animals: water buffalo. developing countries mastitis pathogens: contagious pathogens; environmental pathogens. mating management: detection of oestrus. milk: introduction. milk fat products: anhydrous milk fat ± butteroil pregnancy: parturition. replacement management, cattle: preruminant diets and weaning practices. stress, heat, in dairy cattle: effects on milk production and composition infectious diseases the water buffalo: new prospects for an under-utilized animal the husbandry and health of the domestic buffalo milk processing and marketing cattle and buffalo energy and protein requirements for dairy buffaloes river buffalo production systems in asia dairy technology applied to buffalo milk text book on buffalo production key: cord- - vhhi g authors: siddiqui, asfa; halder, suvankar; chauhan, prakash; kumar, pramod title: covid- pandemic and city-level nitrogen dioxide (no( )) reduction for urban centres of india date: - - journal: j indian soc remote sens doi: . /s - - - sha: doc_id: cord_uid: vhhi g air pollution poses a grave health risk and is a matter of concern for researchers around the globe. toxic pollutants like nitrogen dioxide (no( )) is a result of industrial and transport sector emissions and need to be analysed at the current scenario. after the world realised the effect of covid- pandemic, countries around the globe proposed complete lockdown to contain the spread. the present research focuses on analysing the gaseous pollution scenarios, before and during lockdown through satellite (sentinel- p data sets) and ground-based measurements (central pollution control board’s air quality index, aqi) for five-million plus cities in india (delhi, ahmedabad, kolkata, mumbai, hyderabad, chennai, bengaluru and pune). the long-term exposure to no( ) was also linked to pandemic-related mortality cases across the country. an average of % reduction in average no( ) values and % improvement in aqi was observed in the eight cities during the first lockdown phase with respect to pre-lockdown phase. also, % of corona positive cases and % of fatality cases were observed in the eight major cities of the country alone, coinciding with locations having high long-term no( ) exposure. the most recently discovered coronavirus disease was declared a global public health emergency on january , , and a global pandemic on march , , by the world health organization ( ). as indicated, the contagious nature of the virus is a matter of grave concern worldwide and has shown a manifold increase since its inception in wuhan, hubei province in china (read et al. ) . when the first covid- patient was diagnosed in india on january , , the world had already crossed the count of cases worldwide, i.e. more than the cases associated with severe respiratory syndrome (sars) in (who ) . covid- is a respiratory disorder accompanied by symptoms of fever, dry cough and breathing difficulty subsequently. the virus was not previously associated with disease in humans; hence, it is also known as novel coronavirus or sars-cov- . some factors responsible for the susceptibility to novel coronavirus are diagnosed as history of diabetes, heart ailments, exposure to smoking and hypertension (jiang et al. ; rodriguez-morales et al. ). as of may , , the world has recorded , , cases and , , deaths with the highest mortality in the usa; india has witnessed a total of , cases and fatalities (who ) . preliminary analysis reveals that the transmission rate for india is . (where the value is ranging from . to . worldwide) (ghosh et al. ) . the respiratory illness symptoms and mortality due to prolonged exposure to gaseous pollutants like nitrogen dioxide (no ), sulphur dioxide (so ), particulate matter (pm), carbon monoxide (co), etc., have been reported earlier in india and around the world in several studies (abbey et al. ; abbey and burchette ; balakrishnan et al. ; beeson et al. ; david et al. ; faustini et al. ; he et al. ; liu et al. ; ogen ; siddique et al. ) . the government of india took note of worsening situation worldwide and to contain the epidemic's effect, imposed the first nationwide public curfew on march , . it was followed by lockdowns in three phases, viz. ( ) march to april , , ( ) april to may , , and ( ) may to may , . the effect of lockdown is quite evident in the first two phases in terms of considerable reduction in the growth rate of the disease (myllyvirta and dahiya ) . the effect could also be noticed on environmental factors around the globe in terms of decreased haze, improvement in air and water quality exuded by limited anthropogenic activities in transport, industrial and domestic sectors (muhammad et al. ) . the use of satellite remote sensing for understanding the growing air pollution levels within the tropospheric column of earth has been demonstrated earlier (liji mary david and nair ; fishman et al. ; martin ; sellitto et al. ). however, canopy-level near-surface air pollution is seen to have a more adverse impact on human health globally, especially in developing countries. the level of ambient air pollution is poorer in countries such as nigeria, bangladesh, india, pakistan, china, far exceeding the standards set by world health organization (who) while leading towards numerous deaths (nearly . million) annually, from all countries around the globe (health effects institute ). in india, numerous researches have indicated very high pollutant concentration over the indo-gangetic plain (acharya and sreekesh ; prasad et al. ; sellitto et al. ; shastri et al. ) . the objective of this research was to analyse the effect of lockdown on improving the levels of air pollution in various cities across india using satellite-derived spatiotemporal data sets and ground-based measurements. additionally, the relationship was explored between mortality and air pollution levels within the selected cities. the long-term status of no as a pollutant and the spatial distribution of tropospheric no for before and during covid- lockdown scenarios were derived using the european space agency's (esa) sentinel- precursor satellite data available through tropospheric monitoring instrument (tropomi). central pollution control board's (cpcb) continuous ambient air quality monitoring system (caaqms) data set was used to study the effect of lockdown on air quality index (aqi) of indian cities. the status of mobility and reduction in traffic-induced pollution were recorded using google-based mobility index report (google ) . additionally, to understand the effect of long term exposure of no on human health, covid- positive cases and number of deaths was obtained for all districts around the country of india as on may . the data set has been retrieved and analysed using google earth engine api (gorelick et al. ) and various government websites dispensing information related to covid- -related deaths. the mean values of no are analysed for pre-lockdown period (march -march , ), lockdown- period (ld ) (march -april , ) and lockdown- period (ld ) (april -april , ) scenarios using arc gis . platform. five-million plus cities were selected for detailed analysis, viz. delhi, mumbai, kolkata, chennai, bengaluru, pune, ahmedabad and hyderabad. the urban boundary of the city was delineated using a city clustering algorithm for calculating the mean, maximum and standard deviation for the concentration of the pollutant during the three phases. for analysing the mortality cases due to the pandemic, the temporal mean of no was obtained using tropomi data for the period from march to february . the maximum values of no and deaths were extracted corresponding to each district. since citylevel mortality information was not available, the maximum value of no within the district was assumed to represent the city. it was observed that the five-million plus cities had more concentration of the pollutant as compared to the other fringe areas within the district. long-term analysis of tropospheric column no (march -february ) ( fig. ) over india indicates hot spots of no at locations dominated by urbanisation or presence of thermal power plants (tpps) (both inland and coastal). the major emission hot spots shown in tro-pomi trop. column no distribution coincide with thermal power plants of capacity more than mw. the hot spots of no were reported from most urbanised locations or the locations dominated by the presence of thermal power plants and other industries during the pre-lockdown period. they were identified in orissa, chhattisgarh, madhya pradesh and jharkhand during the lockdown phase, since they were operational for catering to the electricity demand of the country. the increased concentration of pollution can be attributed to domestic combustion, agricultural waste burning, incomplete fuel combustion in the transport sector, industrial effluents emitted directly in the atmosphere, power generation, construction activity, etc. to name the most salient factors associated with the anthropogenic activities. these factors have contributed to a large extent to increasing asthmatic and other respiratory symptoms amongst masses. a detailed analysis of the no levels for before and during lockdown indicates a - % reduction in the levels of no across the country. very high no values [ lmol/m were observed in districts such as sonbhadra (uttar pradesh), singrauli (madhya pradesh), several locations in chhattisgarh (korba, balrampur, bilaspur, champa, surajpur, koriya), west bengal (bankura, murshidabad, bardhaman, malda), odisha (jharsuguda, sambalpur, angul, dhenkanal), cuddalore in tamil nadu, singhbhum in bihar, bellary in karnataka, etc., majority being thermal power plant locations in india connected through central grid. cities including delhi, mumbai, ahmedabad, kolkata, etc., have shown a considerable decrease in the levels of no as indicated in tables and and figs. , and . the major reduction values as observed through sentinel data can be seen in delhi where the maximum and average values dropped by % followed by bengaluru ( %), mumbai ( %), ahmedabad ( %), hyderabad ( %), pune ( %), kolkata ( %) and chennai ( %) in maximum no values ( table ) . the air quality index (aqi) reported by cpcb suggests % average improvement in air quality cumulatively for the eight major cities of india (five million plus cities) alone (http://www.cpcbenvis.nic.in/) ( table ). the journal of the indian society of remote sensing primary reason behind this reduction is restricted human movement through the motorised mode of transport. google-based tracking report on mobility from march to may , , also indicates a decrease of % in retail and recreation sector and % in the transportation sector in india. the baseline value used to calculate the reduction is the median value for corresponding weekday during january -february , , and is provided. citywide detailed analysis is also provided in the report for better understanding. in delhi, almost % of the total pollution is contributed through the transport sector and saw a major drop as indicated through various reports like (moef), the major share of air pollution was attributed to the motorised vehicles (* %) (agarwal et al. ) . also, termination in construction activities led to reduced dust suspension. another major reason is the closure of industrial activities around the major cities, which is also a major source of air pollution, particularly no . the mixing height increased in several cities, and it helped in vertical dispersion of pollutants, thereby reducing the level of pollution. it is also evident that the lockdown time, specifically between march and april , , could lower the air pollution levels significantly (* %) which rose to by - % in the case study cities of india during mid-april (table , figs. , ) . the reasons could be due to agricultural waste burning in northern parts of pakistan and india, which contributed to this elevated effect. it was observed that several power plants were also operational during the lockdown in madhya pradesh, orissa, chhattisgarh and few other states in the country. the onset of dry conditions due to increasing air temperature after mid-april also led to dust from the gulf area and elevated the air pollution scenario in the country, primarily in the north in terms of particulate matter (central pollution control board (cpcb) ). the relationship of no with the rate of mortality in india due to covid- pandemic revealed that higher mortality was reported in areas which had a long-term exposure to finer gaseous pollutants (particle size \ . nm) like no . it corroborates the fact that long-term exposure to no has weakened the immune system and also had profound effect on inflammation of the lungs. nearly, % of total covid- positive cases and % of deaths ( deaths out of total deaths in india) were reported in the eight major cities of india as on may , (fig. ) (https://www.covid india.org/). covid- related deaths are recorded in districts out of a total of districts in india, the majority of which were reported in major urban centres of the country. the highest deaths were reported in mumbai, ahmedabad, pune, kolkata and delhi. additionally, majority cases were also reported in these major cities indicating a severe impact of air pollution on human health. therefore, considering the association of high no concentration with respiratory mortality (chen et al. ; ogen ) , it can be concluded that exposure to toxic components within the air proves fatal in b fig. observed values of no for a pre-lockdown from march to , ; during lockdown b phase from march to april , c phase from april to april , fig. no levels in indian cities during pre-lockdown and during-lockdown ( and ) scenarios fighting such diseases and could be one of the major factors for elevating the risk of air pollution-induced mortality. the risk of death in a scenario of cytokine storm syndrome due to inflammatory lungs can lead to death, as seen in cases worldwide (arden et al. ; beeson et al. ; blomberg et al. ; bowatte et al. ; chen et al. ; patrick ) . it is also vital to understand that mortality during lockdown scenario may also be dependent upon total covid- tested cases and total reported cases. however, due to restricted and unavailable information, such detailed analysis could not be performed. the research aimed at studying the tropospheric no levels in three phases for india (pre-lockdown and two duringlockdown scenarios of -week each duration). long-term no spatial analysis using tropomi sentinel- p data sets could highlight the hot spots of higher concentration due to varied anthropogenic (domestic, vehicular and industrial) and natural reasons. the -week mean value of no spatial analysis revealed a reduction in the values when compared with status in (first lockdown period) and when analysed with respect to pre-lockdown scenario ( % reduction in ld ) which further rose nominally in the ld- period ( - %) for the five-million plus cities alone. aqi for the major cities also showed an improvement of % during ld- and % during ld- due to reduction in usage of motorised vehicles and nonoperational thermal power plants. it was also observed that % of corona positive cases and % of fatality cases were observed in the eight major cities of the country alone, coinciding with locations having high long-term no exposure. the research could have incorporated detailed analysis of all the cities and various other factors leading to high mortality rates in bigger cities including delhi, ahmedabad, kolkata, mumbai, etc. factors including testing rate, rate of mortality, urbanisation and congestion parameters, etc., could not be included due to paucity of information during pandemic times. certainly, the lockdown across the globe and in the indian subcontinent has helped the environment to regain and to minimise the imbalances. relative power of alternative ambient air pollution metrics for detecting chronic health effects in epidemiological studies estimated long-term ambient concentrations of pm, and development of respiratory symptoms in a nonsmoking population seasonal variability in aerosol 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) levels as a contributing factor to coronavirus (covid- ) fatality health & environmental effects of air pollution health influence of coalbased thermal power plants on the spatial-temporal variability of tropospheric no column over india novel coronavirus -ncov: early estimation of epidemiological parameters and epidemic predictions covid- , an emerging coronavirus infection: current scenario and recent developments-an overview tropospheric ozone column retrieval at northern midlatitudes from the ozone monitoring instrument by means of a neural network algorithm flip flop of day-night and summer-winter surface urban heat island intensity in india effects of air pollution on the respiratory health of children: a study in the capital city of india. air quality, atmosphere and health who guidelines for the global surveillance of severe acute respiratory syndrome (sars) updated recommendations coronavirus disease (p. ). geneva: world health organization acknowledgements the authors are thankful to the european space agency (esa) and the national aeronautics and space administration (nasa) for providing requisite data sets (tropomi sentinel- p and aura omi) for the analysis. we are grateful to mr. nadeem alam and mr. ambadas b. maske for providing requisite support during the analysis of secondary data from cpcb. conflict of interest the author declares no known competing financial interests or personal relationships that could have appeared to influence the work reported in the paper. key: cord- -kdsv v e authors: chathukulam, jos title: the kerala model in the time of covid : rethinking state, society and democracy date: - - journal: world dev doi: . /j.worlddev. . sha: doc_id: cord_uid: kdsv v e kerala, a small state in south india, has been celebrated as a development model by scholars across the world for its exemplary achievements in human development and poverty reduction despite relatively low gdp growth. it was no surprise, then, that the covid pandemic that hit kerala before any other part of india, became a test case for the kerala model in dealing with such a crisis. kerala was lauded across the world once again as a success story in containing this unprecedented pandemic, in treating those infected, and in making needed provisions for those adversely affected by the lockdown. but as it turned out, this celebration was premature as kerala soon faced a third wave of covid infections. the objective of this paper is to examine kerala’s trajectory in achieving the success and then confronting the unanticipated reversal. it will examine the legacy of the kerala model such as robust and decentralized institutions and provisions for healthcare, welfare and safety nets, and especially the capacity of a democratic state working in synergy with civil society and enjoying a high degree of consensus and public trust. it will then examine the new surge of the virus and attempts to establish if this was due to any mistakes made by the state or some deficits in its model of “public action” that includes adversarial politics having a disruptive tenor about it. we will conclude by arguing that the kerala model is still relevant, and that it is still a model in motion. the covid- pandemic that descended upon us suddenly, rapidly spreading across the whole world, has been wreaking havoc on our lives and established habits. it is challenging us to interrogate and rethink many taken-for-granted ideas about our lives and institutions-the relationship between the individual and society, the meaning and value of sociality and communitas, of the common good, and perhaps above all the institutions that serve, govern and constrain us. our focus here is on the institution of the state, the critical actor in dealing with this pandemic. an important fact that has emerged in the wake of this global outbreak is that different states and political regimes behind them responded to the pandemic in very different ways with clearly different outcomes. a seemingly counterintuitive fact that has become clear is that some rich and powerful states (the us and the uk) have emerged as poor performers in effectively responding to the pandemic-in containing the infection by such timely measures as testing and isolating the infected, and in reducing fatalities by providing adequate health care in well-equipped medical centers. on the other hand, there are some relatively poor, so-called under-developed countries and regions, such as vietnam (the economist, ), cambodia and the small state of kerala in india (a state within a state) which have emerged as success stories with a record of early and effective interventions, of controlling the spread of the virus, healing the infected and reducing the death rate. this is a notable and significant fact despite later reversals and second and third wave of covid infections in some of these cases, including that of kerala. this article focuses on the "kerala model" of managing the pandemic. this small state in the south-west coast of india has been well known for nearly half a century for its "model" or pattern of development that achieved high levels of social and human development and rapid reduction in chronic poverty and endemic deprivations despite low economic growth and income (cds, ) i . the "kerala model" ii that has been studied by researchers since the mid- s, is once again in the news across the world as a relative success story in containing the pandemic despite economic constraints and other vulnerabilities such as its dense population iii and constant exposure to foreign contacts iv . indeed, some of these observers see kerala's pandemic management as a decisive test of the the objective of this paper is twofold: to highlight the ways in which kerala handled the pandemic and to analyze the structural and systemic factors behind the state's success. we will especially focus on the state and kerala's model of an effective and vibrant democracy and "public action" in the words of dreze and sen. we argue that while kerala was blessed with good and efficient leaders during this crisis, the more important factors behind kerala's success have been robust institutions of state and governance built over many years with the capacity to take timely and effective measures in handling the crisis. we further examine the unexpected reversal and the rise of third wave of covid infections in an attempt to identify what, if any, mistakes may have been made by kerala and if so if these were due to any deficits inherent in the kerala model. we argue kerala may have made a mistake in relaxing-even abandoning-the rules for the entry of a large wave of nrks returning to the state, and for isolating, testing and tracing these returnees, as kerala had successfully done earlier. while recognizing the unknown and unpredictable nature of this new virus (still being studied by experts) we also identify what may be some deficits in the model such as its tradition of public action that includes adversarial politics having a disruptive tenor about it, especially at a time of impending and contentious election. we argue further that states like kerala which have handled the crisis well have generally been relatively effective models of social democracies in which the state and its institutions work in relative synergy with society and representative social institutions. the paper is organized in four parts. this introductory part is followed by part i which describes the trajectory of the pandemic crisis, timely and effective steps kerala took in managing the pandemic, and then failed to anticipate and prevent a third wave. it also examines deficits in the model that may have been behind the state's failure to prevent a third wave. kerala's adversarial and competitive politics gave birth to public action which in turn laid the foundation for kerala model of development. however, competitive and adversarial politics may have its limitations especially when it comes to managing pandemics like the present one. kerala should have adopted a healthy combination of competitive and adversarial politics and a consensus based democratic approach to tackle the pandemic. part iii analyses the structural and systemic factors behind kerala's relative success, focusing especially on the capacity of the state and its institutions acting in synergy with society. part iv concludes the paper by reflecting upon the kerala experience and attempting to draw some generalizations about the capacity of "effective democracies" such as kerala to eliminate endemic poverty and chronic hunger in contrast to india's abysmal failure in making any serious dent into its record in these as it continues to be home to the single largest pool of chronically poor and hungry people in the world. we suggest that the roots of these lie in a major democratic deficit in the indian system--failed or weak public action, including rational-legal social movements and popular organizations, the space for these increasingly filled by communal, caste and nativist movements (tharamangalam, ) . it also discusses about the dominance of adversarial and competitive politics as the reason of kerala's failure to contain the covid pandemic in its third wave. how did kerala combat this virus better than india and many other countries? through what means? much of the answer to this question is public knowledge by now; for example, italy and the uk were battered by covid in the earlier phase of the pandemic outbreak since they did too little and were too late to take measures to contain the virus by testing, isolating and treating those infected and it resulted in devastating consequences. today, italy, uk, spain or much part of the europe are slowly recovering from the onslaught of the pandemic. the us, the world's richest and most powerful nation, was also confronting this crisis with early denials followed by confusing pronouncements and frequently changing policy initiatives by its authoritarian president even as the virus has spread rapidly turning cities like new york into epicenters of the pandemic. brazil's response to covid has also been a terrible one. india took some bold steps to contain the deadly pandemic by enforcing a stringent nationwide lockdown, but with little consultation, planning or provisioning in place to address the consequences of such a lockdown in a country with high levels of poverty, hunger, homelessness, weak health infrastructure and migrant laborers concentrated in its many urban centers. despite three successive lockdowns, india failed to control the spiraling surge in new covid infections viii . india which is slowly emerging from the lockdown in a phase to phase manner has overtaken brazil and usa and has become the global epicenter of covid pandemic. to see how and why kerala has been effective, we describe a few of the steps it has taken in a short time, then examine the policy priorities and values as well as the institutional structures that enabled kerala to act quickly to battle the pandemic-all of these the legacy of the "kerala model" over a period of time. although, kerala flattened the infection curve during the first two phases of covid ix , it failed to contain the surge in infections in the third phase. kerala's strategies in containing the pandemic in the first and second wave of infections gave way to premature celebrations and it instilled a sense of false safety in the minds of people. the fear factor went completely missing and with the easing of the lockdown people paid little attention to observe physical distancing, hand washing and even wearing masks. deal to collate and handle the health data of those quarantined xi . the major allegation was that the data was collected without the informed consent of the people and the deal lacked strong data protection clauses xii . the government version was that such an exercise was carried out to help medical officials and doctors to make a well-informed choice about possible hospitalization in the case of those quarantined. since the confidential data was collected under the deal made with the us company, questions were raised as to why the government did not disclose any details in the public domain regarding the deal. opposition parties xiii also questioned the rationale behind single handedly appointing the us based sprinklr company that too without putting a global tender for the same. since the cm also manages multiple portfolios including the department of information technology, the controversial deal was enough to rake up a political storm that too in the midst of the pandemic. the logic behind approaching a foreign company when kerala has institutions like centre for development of imaging technology (c-dit) xiv and kerala state it mission xv which are capable of handling big data analytics also raised doubts regarding governments decision. even the government at the centre led by bharatiya janata party (bjp) came down heavily on the state government for inking such a pact with a big data analytics company like sprinklr, when the country has central agencies like national informatics centre (nic) xvi which could easily handle the task assigned to the sprinklr. meanwhile, the kerala government defended its position citing that it took the decision to effectively analyze the covid data quickly. the government version was that it resorted to such a deal as it feared kerala might see an unprecedented jump in covid infection, following the easing of lockdown. it also stated that the ownership of the data lies with the kerala government and not with the sprinklr, which temporarily hosted the data in its server. the state government also said that strong data protection clauses were added to ensure the data privacy. however, the opposition parties weren't satisfied with these explanations and the reluctance of the cm to address the controversy openly added more fuel to the fire xvii . meanwhile, the government constituted a two-member committee to look into the matter. on april there was an outpouring of resentment over kerala government's stand. this unexpected move was dubbed as reluctance to accept more people coming by repatriation flights since the government feared that it will lose control over the fight against the pandemic. the opposition parties including congress, indian union muslim league (iuml) and bjp capitalized the public resentment against the stand of the governments. the opposition parties knew anything involving nrks would be a highly sensitive issue in the state since it has been surviving with the support of the remittances xxvii by overseas workers. it gave the opposition parties an opportunity to exploit the public anger and position themselves as true advocates of nrks. kerala will go to assembly elections next year and keeping it in mind, the ruling ldf, has been trying its best to turn the health crisis into an incredible opportunity to revive its political fortunes. the udf have dubbed the covid management as a mere public relations stunt with an eye on the forthcoming assembly elections. the opposition parties including bjp have accused the ldf for the spike in the infections as the government was too busy with marketing its covid story to international media and conducting debate series called kerala dialogue. the opposition parties in the state have always been skeptical about the kerala model of handling covid pandemic. the criticism by the opposition parties even had misogynistic undertones xxviii . the opposition accused that the health minister was not interested in saving lives and mocked her with misogynistic epithet. xxix however, the segregation of the infected and non -infected returnees from abroad did not happen due to technical difficulties and reluctance of the central government to conduct testing on expatriates boarding aircrafts from overseas. so, state government had no other go but to come up with an alternative strategy, where multi-layer screening facility was set up in airports for returnees xxx .again, on june , the cm wrote to the prime minister to seek the help from the central government to provide facilities for conducting covid test for expatriates returning to kerala via chartered flights. but this move was also met with stiff opposition and criticism from opposition parties and nrks xxxi . in july, a new trend emerged where covid infections through "contact" and local transmission xxxii started to surge in the state with more cases of community spread than imported cases. on july , kerala confirmed its first "covid super spreader" xxxiii incident in the coastal village of poonthura and pulluvila in thiruvanthapuram, the capital of kerala xxxiv . in poonthura and pulluvila, people blocked vehicles of police and attacked health workers. the residents in poonthura and pulluvila alleged that due to stringent lockdown measures they were not even allowed to venture out of their house to buy essential items from shops nearby. the residents complained that no shops in their vicinity were allowed to open and the men in uniform allegedly went around threatening and using bad words against the fishermen coming out of their homes. in addition to that a team of commandoes were but first, a brief overview of kerala and its specific characteristics will be helpful in providing a better context for this discussion. kerala is one of states in india, one of the smallest, but the most densely populated with million people nestled between the arabian sea and the hill ranges of the western ghats xxxvi .kerala is the only state in india without the historically, kerala has had close trade and cultural links with the outside world across the arabian sea; christianity and islam made their substantial presence here in the very early centuries of the founding of these religions making the state one of the most multireligious and multi-cultural. the past few decades saw a mass exodus of kerala's young people seeking employment outside the state, especially in the arabian gulf, but also in europe and north america. the remittances sent by these workers amount to about one third of kerala's state domestic product xxxviii (krishnan, ) . note also that there is a substantial number of migrant workers from other indian states (called "guest workers" by the kerala government) who fill local vacancies at the lower levels of the labor market, attracted by the higher wages and better social security in kerala. in addition to all this, unprecedented income growth and easily available bank loans in recent years have also spurred an exodus of kerala students seeking technical and higher education abroad, not only in the west but even in some remote parts of china and central asia, new destinations for those seeking medical and other degrees at relatively low cost. it is noteworthy that this small state now has four international airports facilitating the high volume of international travel. it is not surprising, then, that kerala was the first state to experience the covid- infection. indeed, the virus was initially brought by keralites returning from wuhan and italy xxxix . how, then, did kerala react to the sudden crisis? the first point to be highlighted here is that kerala may have been among the best prepared states/regions in the world to face this crisis. one reason for this is that it had the experience of successfully handling three crises in the past two years, a very serious nipah epidemic in and two outbreaks of kerala also failed to make use of the vast potential of alternative medical streams like ayurveda and homeopathy in treating covid . meanwhile, as the covid infections have alarmingly increased, the government has started promoting ayurveda as a way of boosting the immunity of the population xlvii . however, government has made it clear that diagnosis, medication and treatment of covid will only be done through scientifically-backed modern medicine. another criticism against kerala was that it was not testing enough. critics point out that kerala was testing less and thus it had relatively few cases earlier. in fact, whether kerala was testing enough was a cause of concern. however, in the beginning kerala, in march, the state was testing the most, followed by maharashtra. kerala with a population of million people conducted tests per million and maharashtra at that time conducted samples per million people. but in mid -april, when covid infections were slowing down in kerala, the aggressive testing strategy was relaxed. there had been allegation that kerala started testing asymptomatic and people with mild symptoms at a later stage. but as on september , , kerala has ramped up its testing from , to , tests per day. critics also argues that kerala invested its energy more in contact tracing than in testing which led to the drastic situation the state is facing now. second, kerala took early steps in monitoring and enforcing the rules of isolation. it has also harnessed and deployed modern technology such as surveillance by drones identifying locations of social gatherings, use of "geofencing" xlviii to enforce quarantine, and location tracking devices to create spatiotemporal maps for re-tracking movements of those infected. government resorted to surveillance technology to track the spread of the covid and to monitor people placed under quarantine. government was forced to resort to technology-based monitoring as the number of lockdown violators and those evading quarantine were increasing in the state. geofencing technology was one among them. what is behind kerala's success, some unique factors specific to kerala, a kerala exceptionalism? this is a complex question, and it is possible to highlight some unique historical and social factors, mentioned above. but our focus here is on institutional and cultural factors that are comparable and amenable to empirical investigation. from this perspective we will highlight the legacy of the "kerala model of development" that has created what some political scientists have called an effective or vibrant democracy (heller, ) , itself the legacy of "public action", as explained by dreze and sen lxxiv . this latter concept includes a proactive and interventionist state that responds to popular demands for basic social security, and a mobilized and politically conscious society that puts pressure on the state and holds it to account. how kerala evolved into such a state, at least close to this ideal, has a relatively long history. when kerala was born as a new state in india in by combining the two princely states of travancore and cochin and the british ruled region of malabar, all the three regions, especially the first two, had a half century old history of anti-caste and social reform movements followed by trade union and socialist movements, these resulting in a mobilized, and a socially and politically conscious population. the new state's first democratically elected government was formed by the communist party of india (cpi), the first time a communist party came to power in a free and multi-party election anywhere in the world lxxv (desai, ) . this government did not last long in a highly contentious political on the negative side, it is important to note two points here. first, the left parties abandoned such critical radical programs as land redistribution. they did enact and implement tenancy reforms that successfully abolished predatory landlordism. the traditional landless classes, of whom the vast majority were (still are) the dalits, received only their house sites or kudikidappu land leaving them where they had been for centuries, landless laborers, now turned into modern types of casual wage laborers lxxix (tharamangalam, ) . second, even the limited distribution of house sites, the most radical among indian states, required organized struggles and intense participation of mass organizations, especially of landless workers. the newly gained home ownership, however limited, did succeed in bestowing a certain sense of dignity to the former hutment dwellers who could no longer be evicted from their houses at the whims of the landlords. we have argued above that the two key elements in the kerala model are ( ) an interventionist state committed to pro-poor policies, and ( ) a mobilized society that engages the state through well-organized mass organizations and parties. in this section we discuss the way in which these two elements have interacted to create and maintain a certain synergy, a "virtuous" relationship. we suggest that this may be critical in understanding why kerala has succeeded where many others such as guatemala, nicaragua, and sri lanka have not been so successful. in examining state-society relations, scholars use different analytical lenses such as "equilibrium," "balance," "synergy," and "state-in-society." we find joel migdal's concept of state-in-society is particularly useful for it shows the state as embedded in society and constructed by social forces, on the one hand, yet enjoying relative autonomy and the capacity to mold and even manipulate social forces and social groups, on the other. .while the state can enjoy relative stability over a period of time, being a system of institutionalized practices, beliefs, and rules, every state is ultimately precarious and vulnerable as an arena in which contesting and changing social forces are continuously at play. we argue that kerala has been successful in maintaining a balance between state and society and among a variety of social groups and organizations. by this we do not mean an equilibrium imposed by some invisible hand, but a synergy created and maintained by institutionalized mechanisms capable of accommodating differences and resolving conflicts. as noted above, in kerala the process involved accommodation and compromise among various interest groups, mediated by rational-legal, modern institutions of the state as well as political parties and other organizations. this is not to suggest that this "virtuous" relationship has been unproblematic, or without dilemmas, strains, or contradictions or that it will be sustained indefinitely and can now be taken for granted. in fact, such a relationship is always precarious and a delicately negotiated one since democratic participation involves and requires critics of a given regime and even political opposition, and states and societies must negotiate inevitable conflicts of interests among social classes and groups. our argument has only been that kerala has not only been successful in maintaining a healthy balance but has, in fact, enhanced the "virtual relationship" between state and society in the context of confronting the four successive crises of floods and epidemics, and that the state's response to the latest and more ferocious covid pandemic, may have been a final test of the "kerala model". unlike the earlier crises, which were of short duration, the covid pandemic is likely to take longer time to resolve. it is therefore a crucial test of resilience of the kerala model. kerala's navodhanam was, indeed a revolution in hope -giving new hope to people who formerly lived without hope, accepting their fate as inevitable and/or unchangeable. kerala historian robin jeffrey (jeffrey, ) has noted, for instance, that by the s large numbers of people in kerala had enthusiastically embraced the belief that they had "entitlements", a concept that figures prominently in the writings of amartya sen. the social reform movements campaigned vigorously for the rights of the lower castes to education. an early associate of sree narayana guru, padmanabhan palpu lxxxi said on the subject: "we are the largest hindu community in kerala. without education no community has attained permanent civilized prosperity. in our community there must be no man or woman without primary education" lxxxii (ramachandran, ) . it is not accidental that universal access to education (first primary and then secondary and even post-secondary) became an issue of high priority in kerala both in terms of public demand and public policy. a notable aspect of mass participation, especially important in health care, has been the pivotal role of "women's agency" (women's empowerment in terms of literacy, education and health, promoting general achievements in human development indicators such as imr, child nutrition and health), as explained by amartya sen (sen, & and ( dreze and sen, the unprecedented covid pandemic has shaken our taken-for granted "common sense" in many respects. kerala which successfully contained the covid in the first two waves of infections is now struggling to contain the pandemic in its third wave. the kerala model of managing and containing covid , which was lauded once across the globe is now looked upon with skepticism. it is also a cautionary tale for the government, media and public at large against celebrating covid success models. kerala's biggest advantage was its robust healthcare system and participatory mode of governance or social democracy when it came to handling the pandemic. however, the pandemic has showed that even a participatory social democratic state face challenges in managing crises and ensuring basic security to all. we will conclude with a brief reflection on the concept of entitlement, made famous by nobel laureate amartya sen in many of his writings but especially in his classic study of famines (sen, ) . his now famous, but somewhat unexpected conclusion was that famines in the modern world are not caused by shortage of food, but by "entitlement failure" lxxxiii . as a corollary to this he also argued that self-governing democracies in the modern world have no famines for the obvious reason that such a government, responding to the needs of the people who elected them, and working in synergy with its citizens and civil society organizations has the knowledge, capacity and the will to take timely and effective steps to obtain and move food to the needy. one of the notable successes of india's sovereign democracy has been the elimination of the periodic famines that had been a recurring feature of colonial india. the country has been free of famines since the s; for the past few decades india has been not just selfsufficient in food supply, but has a substantial surplus, some of it often rotting or eaten by rats in ill-equipped public storages. but here comes india's famous paradox of "hunger amidst plenty" in contrast to kerala, a food deficit state which has eliminated such hunger. as cogently argued by patrick heller, effective democracies put re-distributive pressure on the state. if so, it should be obvious that india fails this test; india is just not an effective democracy --in sharp contrast to kerala which is. atul kohli, who has extensively studied these issues in india supports this conclusion (kohli, (kohli, , (kohli, , (kohli, & . he addresses the class basis of the indian state even better. according to him the redistributive capacity of the indian state, always low, declined even further during the post-reform period. this latter period, he says, has been marked by a shift in the character of the indian state from "a reluctant pro-capitalist state with a socialist ideology to an enthusiastic pro-capitalist state with some commitment to inclusive growth" (kohli, ).he asks if and how democratic politics can counter class power and if "…democracy and activism of the poor (can) modify this dominant pattern of development " (kohli, ) .he sounded an optimistic note as he was writing at a time when popular demands had led to such beneficial legislative measures such as the mgnregs lxxxvi and the national food security act lxxxvii which were beginning to show some success. but the indian state has shifted once again under the bjp which combines even more right-wing economic policies with the ideology and project of hindutva, a militant form of majoritarian hindu nationalism that moved from the fringes of indian society and politics to its mainstream in a short period of time (tharamangalam, ) .no wonder the figures for poverty and hunger are showing no decline as has happened in other southern countries, especially india's own poorer neighbors such as nepal and bangladesh. lxxxviii meanwhile, it is indeed encouraging to see that a few states such as kerala, goa and the so called tribal states mentioned above have continued to follow more promising paths with easily visible outcomes in terms of their social development. we can only hope that the lessons learned from kerala and other states and countries for their best practices during the covid pandemic will continue to resonate with the people of india and the world as they may be re-thinking and re-imagining a better world for the post-covid era. they admitted that they hurled abuses at the health officials and scoffed at them, but residents added that they were forced into doing such activities based on misleading information given to them by external forces. they also said that they have apologized to the health officials in this regard. (interviews with residents on july, lxiii in the wake of nationwide lockdown, guest laborers were housed in shelters in the state. with the easing of the lockdown, many of these the guest labourers are returning to their homes each day. the community kitchens served the guest laborers, the elderly, the homeless, the destitute, and the sick. lxiv a poverty eradication and women empowerment programme of government of kerala why have covid- cases surged in kerala? the hindu -year-old woman in kerala beats covid- in nine days india coronavirus: how kerala's covid success story came undone. bbc news poverty, unemployment and development policy: a case study of selected issues with reference to kerala this is kerala's ayurveda prescription to fight coronavirus and keep infections down. the print congress wins first round over sprinklr deal. the new indian express five years of participatory planning in kerala: rhetoric and reality the sen in the neo-liberal developmental programmes of kerala state formation and radical democracy in india the capabilities approach in the vernacular: the history of capability building in kerala india: development and participation an uncertain glory: india and its contradictions indian development: selected regional perspectives embedded autonomy: states and industrial transformation state-society synergy: government and social capital in development bringing the state back in on our minds: how a southern indian state crushed its coronavirus outbreak. the new york times new delhi: promila & co. in collaboration with the institute for food and development policy limits to kerala model of development: an analysis of fiscal crisis and its implications. thiruvananthapuram: centre for development studies planning commission global hunger index: the challenge of hunger and climate change. welthungerhilfe; and dublin history of kerala: prehistoric to the present do political regimes matter? poverty reduction and regime differences across india social capital as product of class mobilization and state intervention: industrial workers in kerala the labor of development: workers and the transformation of capitalism in kerala degrees of democracy: some comparative lessons from india a virus, social democracy, and dividends for kerala. the hindu land to the tiller: the political economy of agrarian reform in south asia democracy and development in india state and redistributive development in india poverty amid plenty in the new india state-directed development: political power and industrialization in the global periphery row over senior congress leader's "covid rani" remark on kerala health minister foreign remittance, consumption and income. thiruvananthapuram: akg centre for research and studies community kitchen live data state power and social forces: domination and transformation in the third world between euphoria and scepticism: ten years of panchayati raj in kerala taking solidarity seriously: analysing kerala's kudumbashree as a women's sse experiment a study on domestic migrant labour in kerala covid services-norka how a south indian state flattened its coronavirus curve. the diplomat report of the committee for evaluation of decentralized planning and development. government of kerala a decade of decentralisation in kerala: experience and lessons india coronavirus: why celebrating covid- 'success models' is dangerous. bbc news kerala cm's principal secretary removed for alleged connection to gold smuggling accused. the indian express a survey on ageing scenario in kerala senior citizens of india: emerging challenges and concerns indian development: selected regional perspective office of the registrar general. ministry of home affairs(mha). government of india the sample registration system (srs) statistical report in india is carried out by the office of registrar general & census commissioner a store promised buyers cashback of rs , if they got coronavirus within hours of purchase. vice prevalence of risk factors of non-communicable diseases in kerala, india: results of a cross-sectional study education in kerala's development: towards a new agenda carry 'coronavirus -free' health certificate to enter india if flying in from italy, south korea. times of india cm ducks' questions on sprinklr deal. the hindu the coronavirus slayer! how kerala's rock star health minister helped save it from covid- . the guardian kerala could lose rs , cr. in remittances as over lakhs register to return from abroad. the print historical hurdles in the course of the people's planning campaign in kerala, india agrarian class conflict: the political mobilization of agricultural laborers in kuttanad the perils of social development without economic growth: the development debacle of kerala rejoinder" to respondents to the symposium understanding kerala's paradoxes: the problematic of the kerala model of development medical team cornered by mob in kerala covid- hotspot, coughed at, abused. the indian express facebook, twitter followers not impressed by kerala cm pinarayi vijayan's pressers of late. the new indian express kerala sasthra sahitya parishad virus kerala: a portrait of the malabar coast lxv kudumbashree, . on august , authors of this research paper interacted with women who provided support to community kitchens (interview on august , ). lxvi a model that contains multiple centers of sourcing and delivering food, but with a "hub" that coordinates the activities and provides a central point of contact to all the clients. lxvii at present there are a total of janakeeya hotels are functioning in kerala. these days demand for janakeeya hotels are also rising. as per records, , , meals have been provided through these hotels. on july , authors of this research paper interacted with women who manage janakeeya hotels and some of them expressed their doubt towards the sustainability of the hotels. (interview on july , ). lxviii a good example of this is sourcing community-based disaster management plans (cbdms) already prepared by a large number of gram panchayats (village level governments) in the aftermath of the two earlier floods.these plans are based on extensive ward-based data on shelter management, hospital infrastructure, technical resource persons, and trained health workers. this valuable resource is now being used for the fact- lxxxiii take the example of the bengal famine of which killed over million people. sen asks why these million (mostly the rural poor) died while others were well fed, yet others hoarded food and/or exported food out of bengal. the answer has to be sought in the system of food distribution and resource allocation, a complex social, cultural, political and especially legal system. those who starved were the ones who were excluded from access to food in this system, at the center of which was a "war economy" that determined and controlled such access, i.e., "entitlements" to food. lxxxviii it is noteworthy that the best performing indian states in enhancing human development and reducing poverty also include some in the north east such as manipur and nagaland. we would suggest that the critical factor behind the difference between these so-called "tribal" states and the politically powerful, but socially backward north indian states (also the main base of the bjp and the hindutva movement) is the relatively weak presence (if any) of caste in the former and its entrenched and all-encompassing nature in the latter. a second factor may be the early lead of these north east states in literacy and education, mostly due to missionary activities. key: cord- - x yubt authors: sawmya, shashata; saha, arpita; tasnim, sadia; anjum, naser; toufikuzzaman, md.; rafid, ali haisam muhammad; rahman, mohammad saifur; rahman, m. sohel title: analyzing hcov genome sequences: applying machine intelligence and beyond date: - - journal: biorxiv doi: . / . . . sha: doc_id: cord_uid: x yubt covid- pandemic, caused by the sars-cov- strain of coronavirus, has affected millions of people all over the world and taken thousands of lives. it is of utmost importance that the character of this deadly virus be studied and its nature be analysed. we present here an analysis pipeline comprising phylogenetic analysis on strains of this novel virus to track its evolutionary history among the countries uncovering several interesting relationships, followed by a classification exercise to identify the virulence of the strains and extraction of important features from its genetic material that are used subsequently to predict mutation at those interesting sites using deep learning techniques. in a nutshell, we have prepared an analysis pipeline for hcov genome sequences leveraging the power of machine intelligence and uncovered what remained apparently shrouded by raw data. covid- was declared a global health pandemic on march , [ ] . it is the biggest public health concern of this century [ ] . it has already surpassed the previous two outbreaks due to the coronavirus, namely, severe acute respiratory syndrome coronavirus (sars-cov) and middle east respiratory syndrome coronavirus (mers-cov). the virus acting behind this epidemic is known as severe acute respiratory syndrome coronavirus or in short sars-cov- virus. it is a single stranded rna virus which is mainly , to , bases long in average [ ] . the novel coronavirus is spherical in shape and has spike protein protruding from its surface. these spikes assimilate into human cells, then undergo a structural change that allows the viral membrane to fuse with the cell membrane. the host cell is then attacked by the viral gene through intrusion and it copies itself within the host cell, producing multiple new viruses [ ] . as of mid-april, , about , of high-quality complete genome sequences were present in the gisaid initiative database [ ] collected from clinicians and researchers from around the world. to understand the viral evolution and its nature of spread among the different countries, we present an analysis pipeline of the genome sequence leveraging the power of machine intelligence. this paper makes the following key contributions. a. an alignment-free phylogenetic analysis is carried out with a goal to uncover the evolutionary history of sars-cov- . the resulting phylogenetic tree is able to highlight evolutionary relationships that can be explained by facts and figures and has further identified some mysterious relationships. b. several machine learning and deep learning models are used to identify the virulence of the strains (i.e., to classify a virus strain as either severe or mild). additionally, from the classification pipeline, important features are identified as sites of interest (sois) in the virus strains for further analysis. c. several cnn-rnn based models are used to predict mutations at specific sites of interest (sois) of the sars-cov- genome sequence followed by further analyses of the same on several south-asian countries. d. overall, we present an analysis pipeline that can be further utilized as well as extended and revised (a) to study where a newly discovered genome sequence lies in relation to its predecessors in different regions of the world; (b) to analyse its virulence with respect to the number of deaths its predecessors have caused in their respective countries and (c) to analyse the mutation at specific important sites of the viral genome. figure : the whole analysis pipeline consisted of three phases. in the first phase, the genome sequences are divided into subsets based on country and a phylogenetic tree is constructed considering only the "representative" sequences of each such subset using an alignment-free sequence comparison approach. in the second phase, we employed state of the art classification algorithms, leveraging both traditional and deep learning pipelines to learn to discriminate the viral strains of many countries as either mild or severe. we also identify the features that contributed the most as the discriminant factor in the classification pipeline. finally, we use the identified features from the previous stare to predict the mutation of the interesting sites in the viral strain using a deep learning model. figure presents our overall analysis pipeline. below we present the details of the pipeline. we have collected hcov genome sequences upto the date april, (cut-off date) from the gisaid initiative dataset [ ] . these are high quality complete viral genome sequences submitted by the scientists and scientific institutes of individual countries. we also have collected country wise death statistics (upto cut-off date) from the official site of who [ ] . the label was assigned based on a threshold of deaths which is the estimated median of the number of deaths in the data points. any genome sequence of a country having deaths below (above) the threshold were considered a mild (severe) strain, i.e., assigned a label ( ). a sample labelling is shown in the supplementary table . informatively, we have also considered some other metrics for labeling purposes albeit with unsatisfactory output (please see supplementary file for details) . we divided the whole dataset into training and testing subset in / ratio with a balanced number of data points per class for traditional machine learning pipeline and for deep learning classification routine, we created the subsets training/validation/testing in / / ratio. figure : the viral genome sequences were divided into subsets of sequences based on country. for each subset, each viral genome sequence is converted into a vector representation and pairwise euclidean distance was calculated among the vectors to create the distance matrix. as the matrix is very highdimensional, we used principal component analysis to find the principal component matrix from the distance matrix. representative sequences were identified through k-means clustering on the pca matrix, and a phylogenetic tree was constructed from the representative sequence of each country. we aim to identify and interpret the evolutionary relationships among the hcov genome sequences uploaded at gisaid from different regions around the globe ( figure ). to do that we have used an alignment-free genome sequence comparison method as proposed in [ ] as briefly described below. notably, we do not consider any alignmentbased method since it is not computationally feasible for us to align thousands of viral sequences for analysis and clustering purposes [ ] . at first the sequence set is divided into subsets of sequences based on the location. all sequences are converted into representative ℝ vector. pairwise distance among vectors derived from the fast vector method [ ] are computed using euclidean distance. due to the high dimensionality of the resulting distance matrix, we resort to principal component analysis (pca) technique [ ] to reduce the dimension of the matrix. subsequently, we use k-means clustering [ ] to identify the corresponding cluster centers. for the k-means clustering algorithm, we have used the implementation of [ ] and used the default parameters except for the number of clusters which were set to for determining the cluster center for each of the subsets. for each location-based cluster, the representative sequence (i.e., the "centroid" of the cluster) is then identified and used in the subsequent step of the pipeline. the evolutionary relationship among the representative sequences of different clusters (from section . ) has been estimated by constructing a phylogenetic tree. we have used the neighbor joining algorithm [ ] for phylogenetic tree construction since it is more reliable [ ] . we have used euclidean distance among the vectors, as described in the section . , to prepare the distance matrix. while we predominantly have used the alignment-free method of [ ] , in this stage, we have only representative sequences and hence we have also attempted a few other alignment-free and alignment-based methods to estimate the phylogenetic tree; however, these didn't produce satisfactory results (more details are in supplementary file). for traditional machine learning, we use a pipeline similar to [ ] (see figure in supplementary file). we extracted three types of features from the genomic sequence of novel sars-cov- . inspired by the recent works [ ] [ ] [ ] [ ] that focus only on sequences, we also extract only sequence-based features. these features are: position independent features, n-gapped dinucleotides and position specific features (see details in section of supplementary file). we use the gini value of the extremely randomized tree (extra tree) classifier [ ] to rank the features. subsequently, only the features with gini value greater than the mean of the gini values are selected for training a lightgbm classifier model [ ] (with default parameters) and performed -fold cross validation. lightgbm is a highly efficient and fast gradient boosting framework which uses tree-based algorithms. we use shap values and univariate feature selection to compare the importance of the features. shap (shapley additive explanations) is a game theoretic approach which is used to explain the output of a model [ ] . univariate feature selection works by selecting the best features based on univariate statistical tests [ ] . we use selectkbest univariate feature selection to get the top k highest scoring features according to anova f_classif feature scoring [ ] function. we leverage the power of different deep learning (dl) classification models, namely, vanilla cnn [ ] , alexnet [ ] and inceptionnet [ ] . we transform the raw viral genome sequences into two different representations, namely, k-mers spectral representation [ ] and one hot vectorization [ ] to feed those into the dl networks in a seamless manner. details of these representations are given in section . of the supplementary file. for k-mers spectral representation we experimented with different values of k (k = , , for vanila cnn and k = & only for the rest due to resource limitation). for one hot vectorization, we have trained inceptionnet for epochs for both -and -mers and trained alexnet for , and epochs for -, -and -mers respectively. we design a pipeline to predict mutation on specific sites (chosen in an earlier stage of the pipeline) in the sars-cov- genome (figure ). we follow a similar protocol followed by [ ] and adopt it to fit our setting as follows. we divide all the available countries and the states of the usa into different time-steps by the date of the first reported incidence of sars-cov- infected patients of that location. thus, every resulting time-step represents a date (tk for cluster k) and contains the clusters of genome sequences of the countries/states. then the time series samples are generated by concatenating sites from different time-step one-by-one that represent the evolutionary path of the sars-cov- viral strain. for example, t is the very first date when the virus is discovered in china. so, the time-step contains only one country, china. likewise, time-step t contains clusters for those countries where the virus is discovered on date t and so on. (check table in supplementary file for more details). we generate time series sequences by concatenating genome sites from t ,t ,....,tn (in our case, n = ) and then fed the samples to the model which consists of a convolutional one dimensional layer and a recurrent neural network layer [ ] . we experiment with both pure lstm and bidirectional lstm as our rnn layer (see section . of supplementary file). the model has a dense layer of neurons in the end which predicts the probability of the next base pair of the next time-step. so, in a nut-shell the model takes concatenated genome sequences from t ,t ,....,tn- as input and predicts the mutation for time tn. we further use our mutation prediction pipeline to identify and analyze possible parents of a mutated strain. for this particular analysis, we trained the models specifically for some south-asian countries, namely, bangladesh, india and pakistan. we only used the best performing model for this analysis and generated five time series samples. at the time of generating these samples, the country/location having the minimal euclidean distance was taken for each time-step. we have implemented our experiments mostly in python. we have used scikit-learn library [ ] for clustering and plotting the graphs. for deep learning models, scikit-learn, tensorflow and keras neural network libraries are used and for lightgbm classifier, python lightgbm framework has been used. the phylogenetic trees are constructed using the dendropy library of python [ ] keeping default parameters. we use the tree visualizer tools dendroscope [ ] and evolview [ ] for tree visualization and annotation. the experiments have been conducted in the following machines: a) clustering and phylogenetic analyses have been carried out in a machine with intel(r) core (tm) i - u cpu @ . ghz, ubuntu . os and gb ram. b) experiments involving the deep learning pipelines (i.e., both classification and mutation prediction) have been conducted in the work-stations of galileo cloud computing platform [ ] and the default gpu provided by the google colaboratory cloud computing platform [ ] . c) the lightgbm classifier model was trained in a machine with intel core i - u cpu @ . ghz x , windows os and gb ram. all the codes and data (except for the genome sequences) of our pipeline can be found at the following link: https://github.com/pythonloader/analyzing-hcov-genome-sequence. the genome sequence data have been extracted from and are publicly available at gisaid [ ] . we identify the representative sequence of each of the countries as present in the gisaid dataset (upto cut-off date). the estimated phylogenetic tree constructed from the representative sequences is shown in figure . in what follows, we will be referring to this tree as the sc (sars-cov- ) tree. the phylogenetic tree generated is expected to reveal the evolutionary relationship of the viral strains. however, with careful scrutiny we have some apparently unusual but interesting observations. for example, it is generally expected that the countries sharing (open) borders (e.g., countries in europe) should be either neighbours or at least in the same clade in the tree. however, surprisingly from the tree, we do not notice geographically adjacent countries in europe as neighbors; rather we see for example that china and italy are immediate neighbors. it is to be noted that these two countries are also the first countries to get hit by the first pandemic wave. in addition to that, although the usa and canada share the longest un-militarized international border in the world, representative strains do not appear to be sister branches as they should have been. also, we notice that the usa, uk, canada, turkey and russia are in the same clade which have a higher number of deaths than most of the other countries. all our classifiers are trained to learn whether a given strain is mild or severe. the classification accuracy of the lightgbm classifier (~ %) is superior to that of the deep learning classifiers (~ - %), which, while is somewhat surprising, is in line with the recent findings of [ ] . it should be noted that lightgbm had produced better results in significantly less time than deep learning models for this dataset. the results of the classifier models are shown in figure . quantitative results aside, we also have applied our classifiers on the sequences that have been deposited at gisaid after the cut-off date (i.e. april , ). since the cutoff date, the country wise death statistics [ ] has certainly changed significantly and this has pushed a few countries, particularly from asian regions and several states of the united states of america transition from mild to severe state (based on our predefined threshold). interesting, our classifiers have been able to predict the severity of the new strains submitted from these countries/states correctly. table in the supplementary file shows a snapshot of a few such countries/states with the relevant information. we preliminarily identify the top features of shap and selectkbest feature selection (with k= ). from these features, as sois, we have selected the features that are also biologically significant, i.e., cover different significant gene expression regions ( figure ). in particular, we have selected the position specific features pos_ _ , pos_ _ , pos_ _ and pos_ _ as the sois for the mutation prediction analyses down the pipeline. here, pos_x_y indicates the site from positions x to y of the virus strains. the reason for selecting these features as sois are outlined below. according to gene expression studies [ ] [ ], our sois, namely, pos_ _ and pos_ _ encode to two non-structural proteins, nsp and nsp , respectively. and, our other two sois, namely, pos_ _ and pos_ _ correspond to the spike protein of sars-cov- . nsp binds to viral rna, nucleocapsid protein, as well as other viral proteins, and participates in polyprotein processing. it is an essential component of the replication/transcription complex [ ] . so, the mutation in this protein is expected to affect the replication process of the sars-cov- in host bodies. on the other hand, the spike protein sticks out from the envelope of the virion and plays a pivotal role in the receptor host selectivity and cellular attachment. according to wan et al. there exists strong scientific evidence that sars and sars-cov- spike proteins interact with angiotensin-converting enzyme (ace ) [ ] . the mutation on this protein is expected to have a significant impact on the human to human transmission [ ] . therefore, it is certainly interesting and useful to predict the mutation of such sois. cnn-lstm and cnn-bidirectional lstm performed in a similar manner for different sois of the genome registering . % and % accuracy, respectively, considering all sois together. for detailed results please check table and table of the supplementary material. for the model involving only bangladesh, we applied the cnn-bidirectional lstm model (as this is the best performer among the two) and achieved almost % accuracy. then we analyzed the ancestors in the time series test samples and noticed that some of the states of the usa are present in these samples. these states are california, massachusetts, texas, new jersey and maryland. for india and pakistan, we got similar results for some sites but for other sites, accuracy was not as high as bangladesh (check table of the supplementary file for details). our analyses reveal a very close (evolutionary) relationship between the genome sequences of china and italy. also, similarity was found among the virus strains of the usa, germany, qatar and poland. these countries have similar numbers of deaths and although not geographically directly adjacent (except for germany and poland) they have strong air connectivity among them. in fact, a number of interesting relationships can be inferred from the estimated phylogenetic tree as follows. chinese tourists [ ] . this relationship is clearly portrayed in the sc tree where the two strains appear to be immediate siblings. . poland's strain is in the same clade as that of germany, which can be explained by the fact that its strain (through poland's patient zero) came from germany [ ] . . taiwan is geographically very close to china. the virus was confirmed to have spread to taiwan on january , , through a -year-old woman who had been teaching in wuhan, china [ ] . the virus strains from these regions are also close together as can be seen from the sc tree, about branches apart. similar relationship can also be inferred from the tree between china and south korea: the strain of the virus in south korea is believed to be transmitted from china firstly through a -year old chinese woman and secondly by a -year old south korean national [ ] . interestingly, from the sc tree it can also be deduced that the south korean strain is very close to that of taiwan and also near to the strain from china. the incident of a taiwanese woman being deported from south korea after refusing to stay at a quarantine facility can be a probable explanation as to how the south korean strain might have found its path to taiwan [ ] . . on march , , the virus was confirmed to have reached portugal, when it was reported that a portuguese year-old man working in spain was tested positive for covid- after returning home [ ] . subsequently, within a span of days, more cases were reported all originating from spain [ ] [ ] . the fact that the first cases of covid- in portugal originated from spain is clearly captured in our sc tree. . the sc tree suggests that india's strain is closely related to that from china and also italy (around branches) and that it is also connected to that from saudi arabia. these relationships can be explained as follows. a . turkey's first identified case was a man who was travelling europe [ ] . turkey also announced a huge number of cases and subsequent deaths, which were originating from europe [ ] . in our inferred relationship, we can see that the turkish representative strain is quite close to several central and western european countries like russia, iceland and ireland which can be backed up by the two facts stated above. . it is visible from the sc tree that the strain of germany is very close to the strains of both poland and the usa. it might be the case that the community transmission occurred concurrently in both usa and poland from germany which hit the peak of pandemic before both usa and poland [ ] . . qatar has the second highest number of covid- patients in the middle-east [ ] . the first case of qatar was reported on february , to be a man working in iran [ ] . qatar introduced a travel ban to and from germany and the usa as precautionary measures in mid-march, quite a while later following the first occurrence. qatar has air-routes with germany and usa, with more than airlines operating in that route [ ] [ ] . though the first case has originated from iran, it might be the case that subsequent patients were found to be travelling from the aforementioned countries as a result of which the travel ban was introduced. our estimated sc tree places qatar very close to both the usa and germany. . while we can certainly explain many of the relationships identified by the estimated sc tree a above, there are some relationships which are not that apparent. one such example is the direct relationship between vietnam and greece. while apparently, there exists no direct relationship, when investigated further, we identified something interesting. patient zero of greece is believed to have been contaminated during her trip to the milan fashion week which took place during february - , [ ] . interestingly, the first covid- patient in hanoi [ ] left hanoi on february to visit family members living in london, england and three days later, she traveled from london to milan city. could she be in contact with patient zero of greece or any other who had been contaminated by the latter, before returning to london on february ? we can't be certain, but our inferred relationship between vietnam and greece certainly put a lot of legitimacy to that question. . finally, we are unable to find any apparent explanation analyzing the reported news sources for a few other strong relationships inferred by the tree (e.g., congo-iran, panama-malaysia, sweden-singapore, japan-australia, etc). this could be because of the inherent inaccuracies of the distance matrices as well as the limitations of the tree estimation algorithms: none of these algorithms are % accurate. from another angle, perhaps, the tree did identify these relationships correctly; but the relevant incidences were not accurately identified or not documented. in recent times, the number of deaths is increasing rapidly in india. we have been closely following the change in the virus strains of india before and after the cut-off date. a genome sequence (epi_isl_ ) was collected on april , (before our cutoff date) from a patient in ahmedabad, gujrat, india. it was predicted to be a severe strain (with low confidence) even though at that time we trained the classifier to consider the indian sequences as mild. according to our evolutionary relationship, india is very close to both italy and china. so, we calculated the distance between the representative sequence of both italy and china with this strain. we considered another strain (epi_isl_ ) which was collected from another patient from the same place in india on april , (after our cut-off date) and predicted the severity thereof. the classifiers declared this isolate to be severe with very high confidence (about %). we did the distance calculation like before. interestingly, it was identified that this isolate is closer to both italy and china's representative sequence than the previous less severe one. this strongly suggests that there were some mutations that turned the indian sequences from mild or less severe to severe or highly severe, respectively. also, the sequences from the us states of pennsylvania, maryland, indiana, illinois and florida that were collected on may , (about one month after our cut-off date) were analyzed and our classifiers could correctly capture the severity of the genome sequences (see table in the supplementary file). we conduct an analysis to predict possible parents of the (mutated) virus strains of the south asian region (bangladesh, india and pakistan). our mutation prediction pipeline suggests that the strains of some states of the usa, namely, california, massachusetts, texas, new jersey and maryland could be the parents/ancestors of these south asian strains. now, the total deaths in these states up to june , are , , , and respectively [ ] and the strains thereof are also classified to be severe by our classification pipeline. it thus seems quite likely that the sars-cov- situation in these south-asian countries will worsen in near future. bangladesh, india and pakistan are ranked th , th and nd in global health performance compared to the united states of america which is at the th position [ ] . in the majority of lower middle-income countries such as bangladesh, india and pakistan, available hospital beds are < bed per population and icu beds are < bed per , population [ ] . additionally, an uncontrolled epidemic is predicted to have , , deaths having a duration of nearly days in the majority of these countries [ ] . these predictions coupled with our findings call for stern actions (i.e., interventions) on part of these countries. bibliography: covid- ) outbreak situation genomic characterisation and epidemiology of novel coronavirus: implications for virus origins and receptor binding cryo-em structure of the -ncov spike in the prefusion conformation alignment-free sequence comparison: benefits, applications, and tools a novel fast vector method for genetic sequence comparison who coronavirus 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of changes in sars-cov- spike protein in the interaction with the human ace receptor: an in silico analysis measuring overall health system performance for countries. global programme on evidence forhealth policy discussion paper no. qatar reports first case of coronavirus sklearn.feature_selection.f_classif ¶ dendropy: a python library for phylogenetic computing flights from qatar, www.qatar.to/germany/qatar-to-germany flights from qatar, www.qatar.to/united-states/qatar-to-united-states single-stranded rna genome of sars-cov sars-cov- (severe acute respiratory syndrome coronavirus ) sequences antigenic: an improved prediction model of protective antigens dpp-pseaac: a dna-binding protein prediction model using chou's general pseaac key: cord- -ji empe authors: saqib, mohd title: forecasting covid- outbreak progression using hybrid polynomial-bayesian ridge regression model date: - - journal: appl intell doi: . /s - - - sha: doc_id: cord_uid: ji empe in , coronavirus disease (covid- ), caused by the sars-cov- (severe acute respiratory syndrome corona virus ) coronavirus, unforeseen pandemic put humanity at big risk and health professionals are facing several kinds of problem due to rapid growth of confirmed cases. that is why some prediction methods are required to estimate the magnitude of infected cases and masses of studies on distinct methods of forecasting are represented so far. in this study, we proposed a hybrid machine learning model that is not only predicted with good accuracy but also takes care of uncertainty of predictions. the model is formulated using bayesian ridge regression hybridized with an n-degree polynomial and uses probabilistic distribution to estimate the value of the dependent variable instead of using traditional methods. this is a completely mathematical model in which we have successfully incorporated with prior knowledge and posterior distribution enables us to incorporate more upcoming data without storing previous data. also, l( ) (ridge) regularization is used to overcome the problem of overfitting. to justify our results, we have presented case studies of three countries, −the united states, italy, and spain. in each of the cases, we fitted the model and estimate the number of possible causes for the upcoming weeks. our forecast in this study is based on the public datasets provided by john hopkins university available until th may . we are concluding with further evolution and scope of the proposed model. in late december , a group of patients was come up with an unknown etiology to the hospitals having symptoms of pneumonia. later on, the first case of novel coronavirus was reported in the city of wuhan in hubei province in central china [ ] . after taking a basic understanding of the virus, medical experts have given a name as severe acute respiratory syndrome coronavirus (sars-cov- ) and the name of the disease caused by this virus is coronavirus disease (covid- ) [ ]. the cases of covid- pandemic are growing rapidly. till th april , we have , , confirmed and , death cases throughout the world due to this hazardous pandemic, covid- . in india, the first laboratory-confirmed case of covid- was reported from kerala on th january and as of th april , a total of , cases and deaths were reported in india [ ] . to tackle this ongoing pandemic and such events in the future where the lives of millions of people are at high risk, we need a strong health care system and technology that will be the means of making a way to a panacea. whenever such pandemic spread in a country or province it has some patterns and various mathematical models can be proposed to forecast using such technologies and mathematical theories. for example, in [ ] , the authors proposed a model for malaria transmission dynamics of the anopheles mosquito and in [ ] a bifurcation analysis for malaria transmission has been developed. as we are also aware of the menacing of hiv/tb and study [ ] presented the mathematical analysis of the transmission dynamics of the same. according to [ ] , due to being class of β-coronavirus, it has a spreading capability among hosts (primary to secondary source) and that is why the magnitude of infected cases growing non-linearly. non-linearity of any pandemic can be detected in several ways e.g. in [ ] a laplacian based decomposition is used to solve the non-linear parameters in a pine witt disease. similarly, in [ ] , a fractional version of sirs (susceptible -infectious -recovered -susceptible) model has been developed to help, to control the syncytial virus in infants. also, in [ ] , the author has used generalized additive models (gams) to predict dengue outbreaks based on disease surveillance, meteorological and socio-economic data. despite several research works and their documentation, there are huge opportunities for the utilization of ai, machine learning, and data science in this field, due to the novelty of the root cause. for example, in [ ] . this article author has a comprehensive discussion regarding ai applications, constraints, and pitfalls during the covid- pandemic. so, there must be some prediction methods that are required to estimate the magnitude of infected cases, and masses of studies on distinct methods of forecasting are represented so far [ ] . in [ , ] , authors estimate the possible number of infected cases in india using long short-term memory (lstm). same as in [ ] , the study represented virus progression and forecast using the same algorithm for canada and compare with the united states (us) and italy. in [ ] , sujatha performed linear regression (lr), multilayer perceptron (mlp), and vector autoregression model (varm) for expectation on the covid- kaggle information to anticipate the epidemiological pattern of the disease and rate of covid- cases in india. in [ ] author proposed machine learning models (xgboost and multi-output regressor) to predict confirmed cases over the coming days in every province of south korea with . % accuracy. as we have already discussed, a study in [ ] , proposed to control the syncytial virus in infants, same as for china, a modified seir and ai prediction of the trend of the epidemic of covid- has been proposed in this study [ ] . different research also takes place on the cases of india but using different methods, and autoregression integrated moving average model (arima) and richard's model [ ] . moreover predictions, some mathematical models have also estimated the effects of lockdown and social-distancing in india in a practical scenario [ ] but all these studies represented so far are based on inadequate data at the initial stage without any measurement of uncertainty. these models are developed with good accuracy but as well as the data become available, those entire algorithms will not be able to survive without a few evaluations due to the dynamic nature of pandemic escalation of the covid- . so, a distribution based learning model will be more promising rather than doing point estimation. bayesian learning is a very well-known method of making any prediction based on our prior knowledge [ ] . many studies have been already used the bayesian approach for prediction for many pandemics and clinical forecasting like in [ ] authors have been estimated the probability of demonstrating vaccine efficacy in the declining ebola epidemic using the bayesian modeling approach. in this [ ] chapter, the author focuses on the various utility of bayesian prediction and it is not only useful, but simple, exact, and coherent, and hence beautiful. also, the study [ ] illustrated a bayesian analysis for emerging infectious diseases. same as in [ ] , paper presented a bayesian scheme for real-time estimation of the probability distribution of the effective reproduction number of the epidemic potential of emerging infectious diseases and show how to use such inferences to formulate significance tests on future epidemiological observations. besides, a study also proposed a system, able to provide early, quantitative predictions of sars epidemic events using a bayesian dynamic model for influenza surveillance demonstrated [ ] . so, this was the motivation behind the proposed study, the prediction of infected cases by covid- which is also a sars family virus can be formulated using bayesian learning as a study [ ] already represented for influenza surveillance. in the proposed study we are formulating bayesian learning regression with a polynomial of n-degree. furthermore, one issue occurs when working with time-series data (as covid- confirmed cases) is over-fitting particularly when estimating models with large numbers of parameters over relatively short periods and the solution to the over-fitting problem, is to take a bayesian approach (using ridge regularization) which allows us to impose certain priors on depended variables [ ] . another big reason we often prefer to use bayesian methods is that it allows us to incorporate uncertainty in our parameter estimates which are particularly useful when forecasting [ ] . the manuscript is organized as follows. "method and model" explains the methodology used to construct the model and various terminology used in the study. " significance of proposed model in covid- outbreak" describes the important advantages of such a hybrid model and also discussed our novelty of the work in the covid- outbreak. after that three case studies in "case studies" also presented to justify our results and fruition of the model. in the last, we discussed our results, comparison with other developed models, and finding in the section "results and discussion" followed by the conclusion in "conclusion". the datasets collected from johns hopkins university are used in the studies [ ] . the datasets accessed on may . it provides several fatalities and registered patients by the end of each day. the dataset is available in the time series format with date, month, and year so that the temporal components are not neglected. a wavelet transformation [ ] is applied to preserve the time-frequency components and it also mitigates the random noise in the dataset. this dataset consists of six columns ( table ) . the only pre-processing was required to transform the dataset. the observations recorded every day and for each day a new column added. the datasets are divided into two parts training ( %) and testing ( %) datasets. one of the very basic approaches to make a prediction is another version of linear regression is polynomial regression in which the relationship between independent and dependent variables is an n-degree polynomial. mathematically, it can represent as follows: or, where β i is the coefficient and ϵ the measurement error which is f(x) is our polynomial model and to develop a good model we need to tuning, β i so that following loss function with l regularization (ridge regularization) will be as minimum as possible where, the first part of the eq. is the residual sum of squares (rss), the difference between actual value (y i ) and predicted value (f(x i )) of the i th observation. λ is the regularization term, deciding how much regularize the β i . now, for the best fitting our aim to minimize the β by tuning coefficients, β i . according to [ ] , the maximum likelihood estimate of β which reduces the l(y i , now, instead of a vector of coefficients, we have a single value b β, in ℝ p + [ ] . here bayesian regression (br) comes into the picture. in the br, instead of predicting value mentioned as above, it used probabilistic distribution to estimate the value of y i and its follow the following syntax so, from conjugate prior distribution [ ], the eq. is re-written as and v = n − k, n is the number of observations, and k is the number of coefficients in vector β. this suggests a form for the prior distribution is after the formulation of the prior distribution, now we need to generate posterior distribution, which can be formulated as follow (from eqs. , and ), where Λ is ridge regression [ ] used to overcome the problem of multicollinearity normally occurring when the model has large numbers of parameter and it is equal to β i and i is an identity matrix of n × n. now, the posterior mean (μ n ) can be represented in the term of b β and prior mean μ and for the bayesian learning other can be upgraded as follows now we are ready to estimate the probability of y on given conditions (m) using bayes theorem as where m is the marginal likelihood and prior density, here, m is p(y| x, β, σ) (see fig. ). there are many parameters used in the proposed model (table ) and a fit-and-score method implemented to optimize. it also implements predict, predict_proba, decision_function, transforms, and inverse_transform if they are implemented in the estimator used. the parameters of the estimator used to apply these methods are optimized by cross-validated search over parameter settings [ ] . the number of parameter settings that are tried is given by n_iter (≈ in the proposed model). we initialize the parameters with default values and obtain the best-fitted parameters as given in the following tables (tables and ). the optimization of hyperparameters take place by implementing proposed model in python. . using scikit-learn [ ] and used spyder, a publically available software, a gui to debug the code. the piece of code available as follows. but the user-defined value must be greater than or equal to . tol − float, optional, default = .e- it represents the precision of the solution and will stop the algorithm if w has converged. alpha_ − float, optional, default = .e- it is the st hyperparameter which is a shape parameter for the gamma distribution prior over the alpha parameter. alpha_ − float, optional, default = .e- it is the nd hyperparameter which is an inverse scale parameter for the gamma distribution prior over the alpha parameter. lambda_ − float, optional, default = .e- it is the st hyperparameter which is a shape parameter for the gamma distribution prior over the lambda parameter. lambda_ − float, optional, default = .e- it is the nd hyperparameter which is an inverse scale parameter for the gamma distribution prior over the lambda parameter. bayesian_search.best_params_. in the proposed model we have developed concepts of bayesian inference that differ fundamentally from the traditional approach. this is completely mathematical methods in which we have successfully incorporated with prior knowledge. instead of making predictions only, it discovers full probability distribution of the problem-domain even on a small dataset which also encounters the features of the confidence interval, risk aversity, etc. [ ] . moreover, posterior distribution makes the model to incorporate more upcoming data without storing previous data. in the current situation of the pandemic, data are not enough to make any prediction without any measurement of uncertainty. in the introduction section, we have seen many studies for covid- progression with good accuracy but as well as data become available, those entire algorithms will not able to survive without a few evaluations. it will happen because of the dynamic nature of pandemic escalation. for example, if we consider our traditional regression methods (eq. ) and we can discover the best possible values for vector β by using eq. , in this case, β will be more promising on large datasets rather than small datasets (the available data of covid- is not enough yet) because this method failed to quantify the certainty [ ] . here, we need to make little change with β, determine a distribution instead of a single point estimation and it is all that bayesian ridge regression does in this model. now, when β is a distribution instead of a mere number our Þalso turns into stochastic and becomes a distribution too. this means that we have confidence interval in our prediction and it became necessary to encounter uncertainty in the case of covid- progression forecasting when datasets are rapidly growing but not sufficient yet. besides, in eq. of the model, we also used l (ridge) regularization to makes model less prone to overfitting. ridge regression is better to use when all the weights are equal sizes and the dataset has no outliers. clinical trials and diagnosis are very expensive and their outcomes are crucial to the concerned stakeholders and, hence, there is considerable pressure to optimize them. in medical treatments, clinicians and nurses very often have to make various complex and critical decisions during the diagnosis of the patients. in reality, these decisions are full of uncertainty and unpredictability. however, based on the available information, obtained from various clinical and diagnostic tests and situation of the patient, both clinicians and nurses try to reduce their uncertainty in clinical decisions and attempts to shift to span the predictability of the chance of improvement in patient's condition. in the case of the covid- pandemic, the situation is the same as any other clinical trials. many pre-planning and controlling need good prediction for the magnitude of infected cases as well as the measurement of uncertainty. one route of optimization is to make better use of all available information, and bayesian statistics provides this opportunity. bayesian statistics provide a formal mathematical method for combining prior information with current information at the design stage, during the conduct of the trial, and at the analysis stage. the main reason for using a bayesian approach to covid- is that it facilitates representing and taking fuller account of the uncertainties related to models and parameter values. in contrast, most decision analyses based on maximum likelihood (or least squares) estimation involve fixing the values of parameters that may, in actuality, have an important bearing on the outcome of the analysis and for which there is considerable uncertainty. one of the major benefits of the bayesian approach is the ability to incorporate prior information. bayesian inference based approach is really important to conduct for covid- pandemic rather than doing point estimations because it makes it possible to obtain probability density functions for model parameters and estimate the uncertainty that is important in the risk assessment analytics. in the bayesian regression approach, we can take into account other models are developed with good accuracy but as well as data become available, those entire algorithms will not able to survive without a few evaluations due to the dynamic nature of pandemic escalation of the covid- but the proposed model corrects the distributions for model parameters and forecasting results using parameters distributions. this approach has always been used for pandemic and clinical forecasting due to uncertainty measurement for example in [ ] bayesian modeling approach has used to calculate vaccine efficacy in the declining ebola epidemic and [ , ] demonstrated a bayesian scheme for emerging infectious diseases and show how to use such inferences to formulate significance tests on future epidemiological observations. in short, bayesian methods have the following advantages [ ] over other time-series machine learning approaches: & it provides an organized way of combining prior information with data, within a solid decision theoretical framework. & it's an inference based learning approach based on previously available data without reliance on asymptotic approximation and such learning gives the consistency of the results with a small sample and large sample equally. & it is based on the likelihood principle which gives identical inferences with distinct sampling designs. & interpretability of distribution of various parameters used in the model. the method of the present study is unique because the model uses prior and posterior distribution to estimate the confirmed cases. the model should not only judge by the accuracy but also on the reliability of the prediction it makes using prior and posterior knowledge fetched from the data. to test the results and get the accuracy of the model we have proposed a case study of three countries-the u.s, spain, and italy. we implemented the proposed model with hybridization of polynomial fitting of degree , , , and because we have observed the best estimation are happen within this range of degrees. the confirmed cases in italy were the lowest since th march but the deaths remain stubbornly high, have hovered between and for the last few weeks (see fig. ). using pbrr, we fitted polynomials and discovered that degree- is the best fit for the dataset of italy. in fig. the solid blue line demonstrating the actual confirmed cases and dashed green line represented observation calculated by the model. in fig. (a) , the degree- pbrr is suffering from underfitting and poorly estimate the cases for the unseen days. also, in fig. (b) , the model showing overfitting and overestimate on the testing data. fig. (b) , sudden decrement in the number of cases which is not a good prediction considering the ongoing situation of italy. fig. (c) , degree- pbrr given rmse . with an accuracy of % on testing data. in fig. we have plotted four polynomial-curves using pbrr of different degrees and observed degree- is well suited the fig. (a) -degree pbrr fitted but given poor performancetested data due to overfitting on training data. also, in fig. (b) -degree and (d) -degree pbrr fitted so well but after days, it started decreasing which is not suitable for the current circumstances. through our investigation on the dataset of spain, an instant decrement is recorded on the th days of first case arrival. similar to the previous we fitted four different pbrr on spain dataset too and found that -degree is the best fit that not correctly estimates confirmed cases for unseen days but also tracks the decrement happen earlier (see fig. ). the model, in fig. (a) is underfitting that neither predicts the unseen observation nor performed well on the training dataset. the other two models ( fig. (b) and (c)) are not suitable for the present ongoing. the model, in fig. (d) estimates the testing data having rmse . with an accuracy of . %. in the above case studies, we have fitted and found different parameters for the predictions (table ). now, we can predict for the upcoming days. so, we have predicted for days and compare with the actual number of cases on those days (table ). it is demanding to construct a model to predict the dynamic progression of covid- situations. so many researchers are struggling to find and implementing such models with optimal parameters and unknown variables which lead them to uncertainty. pbrr model is different from all the studies published or at least discussed in the literature survey because of its nature of making an estimation. it is a complex mathematical model that more focused to discover distribution instead of making a single value linear prediction of the dependent variable and this feature makes it more promising. as far as we have seen in all the above-mentioned case studies different polynomial based on bayesian belief having a range of degrees between and best fit and enable us to forecast future infected cases of covid- . instead of applying any specific country, we can also estimate the cases on the worldwide dataset. fig. , demonstrates the curve fitting using the pbrr model of degree on world-wide data with accuracy % on testing data. we also estimate the magnitude of confirmed cases in the upcoming days. applying pbrr on world-wide data is means scaling the independent variables but our model also survived in this scenario and showing the consistency of the system. to prove the novelty and superiority of the proposed model, we have compared several models (table ) after the comparison, we finally observed that the proposed model is better than other in the term of rmse and comparable equal in term of accuracy with arima and lstm. although, arima and lstm are giving little bit more accurate results pbrr using the prior and posterior distribution for the model parameters which is not used by any of either arima or lstm. we also experiment with bayesian linear regression with using the prior and posterior distribution for the model parameters which has not given satisfactory result in the term of rmse, accuracy, and sd. in section , we have already discussed the importance of the prior and posterior distribution for the model parameters. no doubt, lstm is a deep learning based advanced approach to forecast time series data but it also has some drawbacks compare to proposed model e.g. longer time to train, more memory, overfitting, sensitive to different random weight initializations etc. the overfitting is one of the major issues of the lstm which has overcome in proposed model by adding ridge regularization. we have a sequential path from older past cells to the current one in lstm hidden layers. in fact the path is now even more complicated, because it has additive and forget branches attached to it. lstm and gru and derivatives are able to learn a lot of longer term information but they can remember sequences of s, not s or , s or more as given here [ ] . moreover, rnns are not hardware friendly. it takes a lot of resources we do not have to train these networks fast. also it takes many resources to run these models in the cloud, the cloud is not scalable [ ] . pbrr modeling not only has sufficient accuracy but also reliable than other methods. in present circumstances when thousands of people are losing their loving ones or own lives a model with more promising algorithms is needed along with good accuracy. prediction with misconceptions may lead to a serious problem for health care professionals as well as governments. although, pbrr is giving reliable results the reality is the forecasting of any pandemic is not only merely dependent on previous observations or time-series analytical inference. many more important factors influence the magnitude of infection like healthcare system stability, education, awareness of people, weather, 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springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. dhanbad. he has been involved in automation in smart grid and applied artificial intelligence in seismology. his area of interest is data analysis, artificial intelligence, and applied statistics. key: cord- -nrxtfl i authors: sharma, vikas kumar; nigam, unnati title: modeling and forecasting of covid- growth curve in india date: - - journal: trans indian natl doi: . /s - - -z sha: doc_id: cord_uid: nrxtfl i in this article, we analyze the growth pattern of covid- pandemic in india from march to july using regression analysis (exponential and polynomial), auto-regressive integrated moving averages (arima) model as well as exponential smoothing and holt–winters models. we found that the growth of covid- cases follows a power regime of [formula: see text] after the exponential growth. we found the optimal change points from where the covid- cases shifted their course of growth from exponential to quadratic and then from quadratic to linear. after that, we saw a sudden spike in the course of the spread of covid- and the growth moved from linear to quadratic and then to quartic, which is alarming. we have also found the best fitted regression models using the various criteria, such as significant p-values, coefficients of determination and anova, etc. further, we search the best-fitting arima model for the data using the aic (akaike information criterion) and provide the forecast of covid- cases for future days. we also use usual exponential smoothing and holt–winters models for forecasting purpose. we further found that the arima ( , , ) model is the best-fitting model for covid- cases in india. the covid- pandemic has created a lot of havoc in the world. it is caused by a virus called sars-cov- , which comes from the family of coronaviruses and is believed to be originated from the unhygienic wet seafood market in wuhan, china but it has now infected around countries of the world. with more than . million people affected around the world and more than , deaths (as of july , ), it has forced people to stay in their homes and has caused huge devastation in the world economy (singh and singh ; ministry of health and family welfare ; gupta et al. ) . in india, the first case of covid- was reported on th january, which was linked to the wuhan city of china (as the patient has travel history to the city). on th march, india saw a sudden hike in the number of cases and since then, the numbers are increasing day by day. as of th july, india has more than , cases with more than , deaths and is world's rd most infected country (https ://www.world omete rs.info/coron aviru s/). since the outbreak of the pandemic, scientists across the world have been indulged in the studies regarding the spread of the virus. lin et al. ( ) suggested the use of the seir (susceptible-exposed-infectious-removed) model for the spread in china and studied the importance of governmentimplemented restrictions on containing the infection. as the disease grew further, ivorra et al. ( ) suggested a θ-seihrd model that took into account various special features of the disease. it also included asymptomatic cases into account (around %) to forecast the total cases in china (around , ). giordano et al. ( ) also suggested an extended sir model called sidharthe model for cases in italy which was more customized for covid- to effectively model the course of the pandemic to help plan a better control strategy. petropoulos and makridakis ( ) suggested the use of exponential smoothing method to model the trend of the virus, globally. kumar et al. ( ) gave a review on the various aspects of modern technology used to fight against covid- crisis. apart from the epidemiological models, various dataoriented models were also suggested to model the cases and predict future cases for various disease outbreaks from time to time. various time-series models were also suggested to model the cases and predict future cases. arima and seasonal arima models are widely used by researchers to model and predict the cases of various outbreaks. in , earnest et al. ( ) conducted a research to model and predict the cases of sars in singapore and predict the hospital supplies needed using this model. gaudart et al. ( ) modelled malaria incidence in the savannah area of mali using arima. zhang et al. ( ) compared seasonal arima model with three other time-series models to compare typhoid fever incidence in china. polwiang ( ) also used this model to determine the time-series pattern of dengue fever in bangkok. for covid- as well, various researchers tried to model the cases through arima. ceylan ( ) suggested the use of auto-regressive integrated moving average (arima) model to develop and predict the epidemiological trend of covid- for better allocation of resources and proper containment of the virus in italy, spain and france. chintalapudi ( ) suggested its use for predicting the number of cases and deaths post -days lockdown in italy. fanelli and francesco ( ) analyzed the dynamics of covid- in china, italy and france using iterative time-lag maps. it further used sird model to model and predict the cases and deaths in these countries. zhang et al. ( ) developed a segmented poisson model to analyze the daily new cases of six countries to find a peak point in the cases. since the spread of the virus started to grow in india, various measures were taken by the indian government to contain it. a nationwide lockdown was announced on march to april , which was later extended to may . the whole country was divided into containment zones (where large number of cases were observed from a relatively smaller region), red zones (districts where risk of transmission was high and had higher doubling rates), green zones (districts with no confirmed case from last days) and orange zones (which did not fall into the above three zones). after the further extension of the lockdown till may , various economic activities were allowed to start (with high surveillance) in areas of less transmission. further, the lockdown was extended to may and some more economic activities have been allowed as per the transmission rates, which are the rates at which infectious cases cause new cases in the population, i.e. the rate of spread of the disease. this was further extended to june , with very less rules and especially the states were given the responsibility of setting the lockdown rules. the air and rail transport became open for general public. post june , we see that the restrictions are nominal with even shopping malls and religious places open for general public. now, the responsibility of imposing restrictions lies with the respective state governments. on the other hand, indian scientists and researchers are also working on addressing the issues arising from the pandemic, including production of ppe kits and test kits as well as studying the behaviour of spread of the disease and other aspects of management. various mathematical and statistical methods have been used for predicting the possible spread of covid- . the classical epidemiological models (sir, seir, siqr etc.) suggested the increasing trend of the virus and predicted the peaks of the pandemic. early researches showed the pandemic to reach its peak by mid-may. they also showed that the basic reproduction number (r ) and the doubling rates are lower in india, with comparison to european nations and the usa. a tree-based model was proposed by arti and bhatnagar ( ) and bhatnagar ( ) to study and predict the trends. they suggest that lockdown and social distancing in india have played a significant role to control the infection rates. but now, as the lockdown restrictions are minimal, the cases in india are growing at an alarming high rate. chatterjee et al. ( ) suggest growth of the pandemic through power law and its saturation at the later stages. due to the complexities in the epidemic models of covid- , various researchers have been focusing on the data to forecast the future cases. chatterjee et al. ( ) , verma et al. ( ) and ziff and ziff ( ) suggest that after exponential growth, the total count follows a power regime of t , t , t and √ t before flattening out, where 't' refers to time. it can, therefore, be realized that there is an urgent need to model and forecast the growth of covid- in india as the virus is in the growing stage here. in india, the most affected states are maharashtra with over , cases (as of july ), tamil nadu (around , cases), delhi (around , cases) and gujarat (around , cases). the greatest number of cases per million has been seen in the national capital of delhi ( cases per million) (refer https ://nhm.gov.in/new_updat es_ /repor t_popul ation _proje ction _ .pdf for population estimates). many states and union territories like, kerala, karnataka, andaman and nicobar islands, daman and diu, etc. which had recovered from majority of the cases have experienced a second wave of infections. this might be attributed to decreased travel restrictions and minimal lockdown measures. in their research, singh and jadaun ( ) studied the significance of lockdown in india and suggested that the new covid- cases would stop by the end of august in india with around , total cases. while some states may see an early stopping of new cases, such as telangana (mid-june), uttar pradesh and west bengal (july end) etc., the badly affected states of maharashtra, tamil nadu and gujarat will achieve this by august end. since a proven vaccine and medication is yet to be developed by the researchers then in such a scenario, modelling the present situation and forecasting the future outcome becomes crucially important to utilize our resources in the most optimal way. therefore, the article aims to study the growth curve of covid- cases in india and forecast its future course. since the disease is still in its growing age and very dynamic in nature, no model can guarantee for perfect validity for future. we, therefore, need to develop the understanding of the present situation of the pandemic. in this article, we first study the growth curve using regression methods (exponential, linear and polynomial etc.) and propose an optimal model for fitting the cases till july . further, we propose the use of time-series models for forecasting the future observations on covid- cases. here, we reach the best-fitted arima model for forecasting the covid- cases. we also compare these results with exponential smoothing (holt-winters) model. this study will help us to understand the course of spread of sars-cov- in india better and help the government and the people to optimally use the resources available to them. in this section, we briefly present the statistical techniques used for analyzing the covid- cases in india. here, we used usual regression (exponential, polynomial), timesseries (arima) and exponential smoothing models. regression is a statistical technique that attempts to estimate the strength and nature of relationship between a dependent variable and a series of independent variables. regression analyses may be linear and non-linear. a regression is called linear when it is linear in parameters, e.g. y = + t+ ∈ and y = + t + t + t + ∈ , ∈∼ n , , where y is response variable, t denotes the indepenet variable, is the intercept and other βs are known as slopes. a non-linear regression is a regression when it is nonlinear in its parameters, e.g. y = e x + . in the beginning of the spread of a disease, we see that the new cases are directly proportional to the existing infected cases and may be represented by dy(t) dt = ky(t) , where k is the proportionality constant. solving this differential equation, we get that, at the beginning of a pandemic, thus, at the beginning of a disease, the growth curve of the cases grows exponentially. as the disease spreads in a region, governments start to take action and people start becoming conscious about the disease. thus, after some time, the disease starts to follow a polynomial growth rather than continuing to grow exponentially. in order to fit an exponential regression to our data, we linearize the equation by taking the natural logarithm of the equation and convert it to a linear regression in first order. we estimate the parameters of a linear regression of order p as follows: let the model of linear regression of order p be: we get the best estimates of these coefficients by solving the following normal equations: which minimizes rss. this technique is referred to as the ordinary least squares (ols). we will use this technique of the ols to estimate the coefficients of our proposed model. (refer montgomery et al. ( ) . since we know that the growth curve of the disease changes after some time point, exponential to polynomial, we propose to use the following joint regression model with change point , where we take f (t) = e t , f (t) = + t + t + ⋯ + p t p + ∈, ∈∼ n( , ) and p is the order of the polynomial regression model and t stands for the time (an independent variable). during the analysis, we found that a suitable choice of f (t) is a quadratic or a cubic model. once the order of the polynomial is kept fixed, an optimum value of the change point can be obtained by minimizing the residuals/errors. we can obtain the ols estimates of the parameters of the model ( ) as given below: the least square estimates (lses) of the parameters, Θ = , , , , , , , … … , p can be obtained by minimizing the residual sum of squares (rss) as given by: where ŷ exp i and ŷ poly i are the estimates value of y i from the exponential and polynomial regression models, respectively, and n is the size of the dataset. the lses of Θ = , , , , , , , … … , p can be obtained as the simultaneous solution of the following n o r m a l e q u a t i o n s , solution to these equations is difficult since the parameter is decenter time point. we suggest to use the following algorithm while is kept fixed. ( in order to find the optimal value of µ, i.e. the turning point between the exponential and polynomial growth, we will use the technique of minimizing the residual sum squares in "analysis of covid- cases in india". we will use mape (mean absolute percentage error) to evaluate the performance of the mode. where y t is the observed value at time point t and ŷ t is an estimate of y t . in order to make the results easy to interpret, we will also use accuracy (%). the auto-regressive integrated moving averages method gauges the strength of one dependent variable relative to other changing variables. it is one of the most used timeseries models in diverse fields of data analysis as it takes into account the changing of trends, periodic changes as well as random disturbances in the time-series data. it is used for both better understanding of the data as well as forecasting, see brockwell et al. ( ) . autoregressive model (ar) is effectively merged with the moving averages model (ma) to formulate a useful timeseries model, arima model. the autoregression (ar) element of the model shows a changing variable that regresses on its own prior values and the moving average (ma) element incorporates the dependency between an observation and a residual error from a moving average model applied to prior observations. however, this model can only be applied to stationary data. since many real-life datasets consist of an element of non-stationarity, to model such datasets, arima model was developed. this model is open for non-stationary data as the integrated (i) factor of the model represents the differencing of raw observations to allow the time-series to become stationary. here, we may refer the reader to follow box et al. ( box et al. ( , for more details on arima model, estimation and its application. the general forms of ar(p) and ma(q) models can be, respectively, represented as the following equations: where ∅ s and θs are auto-regressive and moving averages parameters, respectively, y t represents value of time-series at time point t , t represents the random disturbance at time point t and is assumed to be independently and identically distributed (i.i.d.) with mean and variance . the arma(p, q) model can be represented as: where α is an intercept. the differenced stationary time-series can be modelled as an arma model to use arima model on the timeseries data (ceylan ; he and tao ; manikandan et al. ). the arima model is generally denoted as arima (p, d, q) where, p is the order of auto-regression, d is the degree of difference and q is the order of moving average. the degree of difference, i.e. d is a transformation (operator) that is used to make the time-series stationary as it removes the increasing trends. a higher value of d indicates positive autocorrelations out to a high number of lags. the first step to model the time-series by arima is to determine the time-series data for stationarity. the augmented dickey-fuller (adf) test may be applied to determine if the time series after differencing is stationary or not. ( ) the adf test is applied to test the null hypothesis for the presence of a unit root (which indicates non-stationarity of the series). in order to deduce the arima(p, d, q) model, we can proceed as follows: we have the arma(p � , q) represented as follows (as per eq. ) it can be equivalently written as: has a unit root (i.e. a factor of ( − l) ) of multiplicity d. then, eq. ( ) can be re-written as: or, this can be generalized as: the second step is to plot the graphs of the autocorrelation function (acf) and the partial autocorrelation function (pacf) to determine the most-likely values of p and q. the final step is to obtain the optimal values of p , d and q using the aic (akaike information criterion), for more details see https ://en.wikip edia.org/wiki/akaik e_infor matio n_crite rion. these information criteria may be used for selecting the best-fitted models. lower the values of criteria, higher will be its relative quality. the aic is given by: where k is the number of model parameters, l is the maximized value of log − likelihood function. exponential smoothing is one of the simple techniques to model time-series data where the past observations are assigned weights that are exponentially decreasing over time. we propose the following models, for modelling of covid- cases [see holt ( ) and winters ( ) ]. for single exponential smoothing, let the raw observations be denoted by {y t } and {s t } denote the best estimate of trend at time t. then, s = y , s t = y t + ( − ) s t− , where ∈ ( , ) denotes the data smoothing factor. for double exponential (holt-winters) smoothing, let the raw observations be denoted by {y t } , smoothened values {s t } , and {b t } denotes the best estimate of trend at time t . then, where ∈ ( , ) denotes the data smoothing factor and ∈ ( , ) denotes the trend smoothing factor. for the forecast at t = (n + m) days, ( f n+m ) is calculated by for this study, we have used the data available at github, provided by centre for systems science and engineering (csse) at john hopkins university (see https ://githu b.com/ csseg isand data/covid - /blob/maste r/csse_covid _ _ data/csse_covid _ _time_serie s/time_serie s_covid _confi rmed_globa l.csv). for this study, we use r software. (see r core team ). we have used the data from march to july for continuity of the data. we know that at the beginning of the spread of the disease in india, the growth was exponential and after some time, it was shifted to polynomial. we first obtain optimum turning point of the growth, i.e. when did the growth rate of the disease shifted to polynomial regime from the exponential. we consider both quadratic and cubic regression model for second part of the data. we will also discuss the types of polynomial growth (with their equations) in india. in order to find the turning point of the growth curve, we follow the algorithm , given in the previous section. using that, we evaluate the rss for all the days (from march ) and find the date on which it is minimum. the change points of growth curve for cubic and quadratic regressions are presented in fig. depending upon the size of the data set. from fig. , we can confirm that the growth rate of covid- cases was exponential till april and then after it follows the polynomial growth regime while we use the covid- cases till july (table ) . we call the region of exponential growth in india as region i. the coefficients of the model are presented in table . we see that after the exponential regime (till april ), the growth curve follows a polynomial growth till may . after this, we again see a change in the behavior of the growth curve. in tables , , and , we try to model these growth curves through regression analysis. having evaluated the coefficients for various models (i.e. linear, quadratic and cubic) as well as the important statistics (i.e. r values, p values of the models as well as individual coefficients and f-statistic), we will select the best-fitting models. in order to select the best-fitting models for region ii (april to may ); iii (may to may ), iv (may to may ) and v (june to july ), we have the following steps. we select that model which has high r values, significant p value, high f-statistic and where the p values of all the variables are significant. we see for region ii, from table , that the linear model is having a relatively lower f-statistic and r values in comparison to the quadratic and cubic models. so, we eliminate the possibility of linear fitting. further, we see that the p values, f-statistics and the r values are quite significant in both quadratic as well as the cubic models. but, if we look at the individual p values of the coefficients, we see that the individual p values are not significant for the cubic model. on the other hand, the individual p values are significant for fig. trend of rss and optimum µ for exponential-quadratic regression model for region v, from table , we see that the r values of all the models are very high (quadratic, cubic, quartic and quintic models have exceptionally high). all the models also have significant p-values. the f-statistic of quadratic, cubic, quartic and quintic models is high. f-statistic value of quartic model is the highest. the coefficient individual p values of quartic model are also significant. thus, we conclude that the quartic model is the best-fitting model for region v (june to july ). note for region v, due to spike in the cases, we also checked the fitting of exponential curve in this region (table ) . let the exponential model be-y(t) = e t we obtained the following parameter values: the rse for this model is and mape (%) is . %. both of these values are quite larger than those of quartic model (refer table for rse and mape values of quartic model in region v). thus, we conclude that quartic model is the best-fitting model for region v ( st june to th june). all the anova tables (refer to table ) for region ii, iii, iv and v suggest significant p-values for its coefficients and suggest that the models fit well the respective regions. thus, according to our study, the growth of the virus was exponentially increasing from march to april . then v june st to july th y(t) = − . × + . × t − . × t + . t − . t . after, the virus grew by following a quadratic rate from april to may . after may , we experienced a linear growth. but after may to may , we experienced a sudden rise in the rate of growth of the virus and have seen quadratic growth again. further, for the period of june to july , we see experienced a quartic ( -degree polynomial) growth, which is very alarming (see table for best-fitted regression models). figure shows the best-fitted regression models to the daily cumulative cases of covid- in india from march to july (table ) . we use the daily time-series data of number of cumulative confirmed cases from march to july . first, we check the stationarity of the transformed timeseries using adf tests. dickey-fuller statistic is . with p value . which indicates that the growth of covid- cases is not stationary. the arima models may be useful over the arma models. the acf and pacf plots are shown in fig. . we then obtain the optimal arima parameters ( p , d , q ) using the aic. we take various possible combinations of ( p , d , q ) and compute the aic. then, select the best-fitted arima model that has the lowest aic among all considered models. according to the aic, the arima ( , , ) is the best-fitted model for the covid- cases, india (see table ). estimates of arima ( , , ) parameters and mape are shown in table . we have selected the model parameters using the akaike information criterion. we obtained the parameters as: p = , d = and q = . as p = , it means that the order (number of time lags) of autoregression part of the model is . in general, we can say that the cumulative cases of covid- in a day are dependent on the cases of previous days. as q = , the present value is dependent on the moving average (residuals) of previous days. as d = , the series y * t = y t − y t− + y t− is stationary. a higher value of d indicates positive autocorrelations out to a high number of lags. thus, we can have the equation for our model, using eq. as: where all the symbols have their meanings as per "arima model". estimates of the holt-winters exponential smoothing and exponential smoothing models are given in table . according to the mape and accuracy measures, the arima ( , , ) is a better model than the holt-winters exponential smoothing and usual exponential smoothing models. from this, we can conclude that the arima model is the best fit for the cases of covid- , followed by holt-winters model. the forecasting values along with % confidence intervals are shown in table and fig. . we have used actual data from th june to validate the model. even though most of the actual cases are covered in the % confidence intervals of the arima and holt-winters forecasts, they are seen to be nearer to the upper limits of the confidence intervals and are deviated from the estimates. it might be possible that in the future days, the forecasts might underestimate the actual cases. this might be attributed to the changing pattern of the growth of the pandemic in our country as seen in the regression analysis. thus, we suggest a segment-wise time-series models to forecast the future cases in a more accurate manner. we present the segment-wise arima and holt-winters models for st june to th july. we have seen that our time-series data are non-stationary and, thus, we select the most optimal values of (p, d, q) , which has the least aic. according to aic, ( , , ) is the best-fitting model for the time-series data from june to july , with aic = . . estimates of arima ( , , ) model with the corresponding mape and accuracy are given in table (fig. ) . from fig. , we deduce that the optimal value of d is , as the time series becomes stationary with differencing degree = . estimates of the holt-winters exponential smoothing and exponential smoothing models are given in table . according to the mape and accuracy measures, the arima ( , , ) is a better model than the holt-winters exponential smoothing and usual exponential smoothing models. from this, we can conclude that the arima model is the best fit for the cases of covid- , followed by holt-winters model. the forecasting values along with % confidence intervals are shown in table and fig. . we have used from the interpretations of both the fitted arima models, we can say that as the values of p and d are and , respectively; the daily cumulative cases are dependent on the cases of previous days. also, to convert the time series of daily cases into stationary, we need differencing degree of . from the regression analysis, we conclude that the spread of covid- disease grew exponentially from march to april . further, from april to may , the cases followed a quadratic regression. from may to may , we see a linear growth of the pandemic with average daily cases of . after may to may , we again saw a spike in the cases that lead to a quadratic growth of the pandemic. and, from june to july , we saw a major spike in the growth of the pandemic as it has followed quartic growth. verma et al. ( ) showed the four stages of the epidemic, s : exponential, s : power law, s : linear and s : flat. we saw that the course of covid- in india followed this regime till may . but after the linear trend from may to may , the spread has again reached the quadratic growth and from june to july , india is witnessing a quartic growth. this might be attributed to the relaxation of lockdown measures in the country. though it was much likely that the cases would start to reduce post-linear stage growth as the total cases may start to follow a square root equation, i.e. y(t) ∼ √ t. and this might lead to reduction in the daily number of cases (asy � (t) ∼ ∕ √ t ,) leading to flattening of the curve. but, due to reduced restrictions, we see a reverse trend, which might be alarming and suggest the imposition of strict lockdown to reverse this trend of pandemic growth. if we continue to open our economy in this way, we might go back to the exponential growth of the pandemic and this would lead to huge destruction to human lives and cause a greater impact on our economy. we also observe that some cities have been the hotspots of the disease, such as delhi (more than , cases), mumbai (more than , cases), chennai (more than , cases), thane (more than , cases), etc. as on june, . while the other states and cities have seen a slower growth of the pandemic, these cities have seen explosive growths. due to the opening of air and rail transport in the country, the virus is likely to spread in the other regions as well as people from these cities (especially metro cities) are travelling to different states. thus, it is highly advisable that the country should go back to its lockdown phase until we see reduction in trend. in time-series analysis, we conclude that the arima ( , , ) is the best-fitting model for the cases of covid- from th march to th july with an accuracy of . %. the basic exponential smoothing is not very accurate for our case, but we see that the holt-winters model is around . % accurate. both arima ( , , ) and holt-winters models suggest a rise in the number of cases in the coming days. we observed that both the arima and holt-winters models capture the data well and the actual data from th july validate the forecasts well as they lie in the predicted confidence intervals. but, while validating the model, the actual values are always near to the upper confidence limits, it might be possible that in further days, our model might underestimate the cases. this might be possible because of the changing trend of the growth of the pandemic in india. thus, we used segmented time-series models and took data from st june to th july to build separate arima and holt-winters models. we concluded that arima ( , , ) is the best-fitting model for covid- cases in the given time period with an accuracy of . %. the basic exponential smoothing is not very accurate or this case as well but, the holt-winters model is around . % accurate. we also observe that the arima and holt-winters models capture the data well and the actual data from th july validate the forecasts and lie near to the estimates. we may also conclude that the cases of covid- will rise in the coming days and the situation may turn alarming if proper measures are not followed. since the economic activities have started in the country, people need to be more careful while going out. and explosion of the pandemic in the whole country can cause a serious damage to human lives, healthcare system as well as the economy of the country. thus, there is an urgent need of imposing strict lockdown measures to curb the growth of the pandemic. we must also learn to lead our lives by following all the precautions even if the lockdown restrictions are relaxed and the economic activities are resumed. comparison of indian scenario with that of other countries might not prove fruitful at this stage because of the demographic differences and/or the characteristics of the disease. also, comparison of the indian context with that of the other countries of the world will require to study the spread of the pandemic in those countries in depth and might be considered as an altogether in the future studies. this study was limited to data-driven models using the total covid- cases. in the future studies, the other co-factors (associated with the demographics, social, cultural and medical infrastructure, etc.) can be taken to considerations. modeling and predictions for covid spread in india ceylan z ( ) estimation of covid- prevalence in italy evolution of covid- pandemic: power law growth and saturation amenta francesco covid- virus outbreak forecasting of registered and recovered cases after sixty day lockdown in italy: a data driven model approach using autoregressive integrated moving average (arima) models to predict and monitor the number of beds occupied during a sars outbreak in a tertiary hospital in singapore analysis and forecast of covid- spreading in china, italy and france modelling malaria incidence with environmental dependency in a locality of sudanese savannah area sidarthe model of covid- epidemic in italy coronavirus (covid- ) outbreak in india: a perspective so far international journal of infectious diseases epidemiology and arima model of positive-rate of influenza viruses among children in wuhan, china: a nine-year retrospective study forecasting seasonal and trends by exponentially weighted averages mathematical modeling of the spread of the coronavirus disease (covid- ) considering its particular characteristics. the case of china a review of modern technologies for tackling covid- pandemic a conceptual model for the coronavirus disease (covid- ) outbreak in wuhan, china with individual reaction and governmental action forecasting the trend in cases of ebola virus disease in west african countries using auto regressive integrated moving average models hoboken petropoulos f, makridakis s ( ) forecasting the novel coronavirus covid- the time series seasonal patterns of dengue fever and associated weather variables in bangkok r: language and environment for statistical computing. r foundation for statistical computing covid- pandemic: power law spread and flattening of the curve comparative study of four time series methods in forecasting typhoid fever incidence in china predicting turning point, duration and attack rate of covid- outbreaks in major western countries fractal kinetics of covid- pandemic key: cord- - ggaqf authors: nan title: abstracts of the papers presented in the xix national conference of indian virological society, “recent trends in viral disease problems and management”, on – march, , at s.v. university, tirupati, andhra pradesh date: - - journal: indian j virol doi: . /s - - - sha: doc_id: cord_uid: ggaqf nan patients showed rashes on face, hand and foot. ev detection carried out in vesicular fluid, stool, serum and throat swab specimens by rt-pcr of ncr gene. serotyping was carried out by using rt-pcr of viral protein of vp / a junction region followed by sequencing and phylogenetic analysis using neighbor-joining-algorithm and kimura- parameter model of mega- software. overall ev positivity detected in hfmd patients from kerala, tamil nadu, west bengal and orissa states was found to be . %, . %, . % and . % respectively. typing of vp gene sequences indicated presence of ca- , ev- , echo- strains in kerala and ca- in west bengal, orissa and tamil nadu. phylogenetic analysis indicated ca- , ev- , echo- strains showed . - . % and - . % homology with japanese, australian and french strains. however, ca- strains were closer to malaysian strains with . - . % nucleotide homology. the present study documents the association of multiple types of ev's i.e., ca- , ev- , echo- and ca- strains contributing as prime viral pathogens in hfmd epidemics in the reported regions with new emergence of ca- circulating strain in kerala, india. tasgaon september . sera were collected from suspected hepatitis cases and there contacts and tested for anti hev igm/igg antibodies (elisa) and liver enzymes like alanine aminotransferase (alt). anti hev igm antibodies were detected in . % ( / ) of the suspected cases. the overall attack rate was . %. male to female ratio was : . majority ( . %) of the cases were in the age group - years and recovered without any clinical complications. weekly distribution of cases showed that the majority ( . %, / ) cases occurred between nd and rd week of june. dark urine ( . %), jaundice ( . %), fatigue ( . %), abdominal pain ( . %), anorexia ( . %), vomiting ( . %), fever ( . %), giddiness ( . %), diarrhoea ( . %) and arthalgia ( . %) were the prominent symptoms. sera collected from antenatal cases (ancs) showed anti hev igm antibody in . affected pregnant women had a normal outcome. a death of year, male hepatitis e case was reported during the outbreak period that had cirrhosis of liver with oesophageal varices. sanitary survey revealed that water pipelines were laid down in close proximity of sewerage system, and water posts were without tap. these are the likely sources of faecal contamination of water supplies. among water samples collected from various places, were found to be unfit for drinking based on the routine bacteriological tests conducted at state public health laboratory, pune. no case occurred after the pipelines were repaired. this typical outbreak of hepatitis e re-emphasizes need for proper water supply/sewage disposal pipelines and adequate maintenance measures. jayanthi shastri, nilima vaidya, sandhya sawant, umesh aigal department of molecular biology, kasturba hospital for infectious diseases, mumbai, india dengue and dengue haemorrhagic fever are amongst the most important challenges in tropical diseases due to their expanding geographic distribution, increasing outbreak frequency, hyperendemicity and evolution of virulence. the gobal prevalence of dengue has grown dramatically in recent decades. who estimates - million cases of dengue virus infections worldwide every year resulting in , to , cases of dhf and , deaths each year. public health laboratories require rapid diagnosis of dengue outbreaks for application of measures such as vector control. laboratory diagnosis of dengue virus infection can be made by the detection of specific virus, viral antigen, genomic sequence and/or antibodies. currently basic methods used by laboratories for diagnosis of dengue virus infection are virus isolation and characterisation, detection of genomic sequence by nucleic acid amplification technology assay and detection of dengue virus specific antibodies/antigen. molecular diagnosis based on reverse transcription (rt)-pcr s.a. one step or nested pcr, nucleic acid sequence based amplification (nasba), or real time rt-pcr, has gradually replaced the virus isolation method as the new standard for the detection of dengue virus in acute phase serum samples. several pcr protocols for detection have been described that vary in the extraction method, genomic location of primers, specificity, sensitivity and the methods to determine the products and the serotype. pcr-based dengue tests, due to the specificity of amplification, enable a definitive diagnosis and serotyping of the virus. in addition dna sequencing of the amplification product enables the virus to be genotyped, providing important information on the sources of infection. more recently tests have incorporated flurogenic probe, so called taq man technology for the specific real time detection of dengue - amplicons. product is detected by a specific oligodeoxy nucleotide probe that is labelled with carboxy-fluorescein (fam). this technology offers the advantage of being both rapid and potentially quantitative. second, the detection of product by hybridisation of flurochrome labelled probes increases specificity. third, as the product is detected without the need to open the reaction tube, the risk of contamination by product carry over is minimised. the advantages of speed, contamination minimisation and reduced turn around time justify application of this assay over the currently used nested pcr assay. during the period january to october , molecular laboratory received samples from patients presenting with acute onset fever for dengue . %) samples were tested positive by this method. the disease peaks in the monsoon season with a percentage of . %. rapid tests, igm and igg capture elisa are popularly used tests for diagnosis of dengue infection. its utility is limited for diagnosing dengue in convalescecce ( - days) . specificity is also compromised due to infections with flaviviruses: japanese encephalitis and chikungunya. dengue ns ag elisa with its cost effectiveness, specificity and sensitivity should be considered as the test of choice for diagnosing dengue in the acute phase of illness in the developing countries. molecular diagnosis enables confirmatory diagnosis of dengue in the acute phase of the illness and is suitable for further typing methods. assistant general manager and r&d coordinator, division of quality control and r&d, bharat immunologicals and biologicals corporation ltd., village chola, bulandshahr, up vaccine development in india, though slow to start, has progressed by leaps and bounds in the past years. it was dependent on imported vaccines but now it is not only self-sufficient in the production of vaccines conforming to international standards with major supplier of the same to unicef. the role of drug authorities is to enhance the public health by assuring the availability of safe and effective a indian j. virol. (september ) (suppl. ):a -a vaccines, allergenic extracts, and other related products. vaccine development is tightly regulated by a hierarchy of regulatory bodies. guidelines provided by the indian council of medical research (icmr) set the rules of conduct for clinical trials from phase i to iv studies as well as studies on combination vaccines. these guidelines address ethical issues that arise during a vaccine study. a network of adverse drug reaction (adr) monitoring centers along with the adverse events following immunization (aefi) monitoring program provide the machinery for vaccine pharmacovigilance. genetic modifications have been developed to develop effective and cheaper vaccines by the use of recombinant technology. to ensure safety of consumers, producers, experimental animals and environment, governments all over the world are following regulatory mechanisms and guidelines for genetically modified products. as with other industrializing countries undergoing rapid shifts, india clearly recognizes the need to restructure its regulatory system so that its biopharmaceutical industry can compete in international markets. genetic engineering approval council (geac), recombinant dna advisory committee (rdac), review committee on genetic manipulation (rcgm), institutional biosafety committees (ibsc) are responsible for development, commitment for parameters and commercialization of recombinant vaccines. to centralize and coordinate the whole system, government has taken to form two agencies to regulate the regulation laws to develop recombinant pharmaceuticals products including vaccines. the first is the creation of the national biotechnology regulatory authority (nbra), under the department of biotechnology (dbt), as part of india's long-term biotech sector development strategy. the second major initiative will affect the entire indian pharmaceutical industry. this is the replacement of most state, district, and central drug regulatory agencies with a single, central, fda-style agency, the central drug authority (cda). the cda is expected to have separate, semi-autonomous departments for regulation, enforcement, legal, and consumer affairs; biotechnology products; pharmacovigilance and drugs safety; medical devices and diagnostics; imports; quality control; and traditional indian medicines. it will set up offices throughout india and will be paid for inspection, registration, and license fees. its enforcement powers will be strengthened by a new law increasing the criminal penalties for illegal clinical trials. in the manufacturing area, though, the country has been tightening the rules and enforcement. an amendment to the regulations, ''schedule m'' of the drug and cosmetics act, now specifies the good manufacturing practice (gmp) requirements for factory premises and materials. these requirements were modeled after us fda regulations, to improve regulatory coordination between indian and us regulators. india has realized the importance of regulations in pharmaceutical specially in vaccine field but it will take several years to implementation of these. india has coordinated some of its regulatory functions with western organizations. the us pharmacopoeia established an office in hyderabad in . a representative of the indian pharmaceutical lobby also recently has expressed openness to an expansion of the fda's oversight of indian manufacturing. as india expands its global drug and biologicals production, us and europe, as the world's largest drug importers, will likely expand their regulatory support in the development of the country's regulatory systems. rapid diagnosis of japanese encephalitis virus (jev) infections is important for timely clinical management and epidemiological control in areas where multiple flaviviruses are endemic. however, the speed and accuracy of diagnosis must be balanced against test cost and availability, especially in developing countries. an antigen capture enzyme-linked immunosorbent assay (elisa) for detection of circulating jev specific nonstructural protein (ns ) was developed by using monoclonal antibodies (mabs) specific to recombinant (ns ). the applicability of this jev ns antigen capture elisa for early clinical diagnosis was evaluated with acute phase serum/ cerebrospinal fluid (csf) specimens collected from different epidemics during [ ] [ ] [ ] . jev ns antigen was detected in circulation from day to . the sensitivity and specificity of jev ns detection in serum/csf specimens with reference to reverse transcriptase pcr was %, and . % respectively. no crossreactions with any of the other closely related members of the genus flaviviruses (dengue, westnile, yellow fever and saint louis encephalitis (sle) viruses) were observed when tested with either clinical specimens or virus cultures. these findings suggested that the reported jev specific mab-based ns antigen capture elisa will be a rapid and reliable tool for early confirmatory diagnosis as well as surveillance of je infections in developing countries. manmohan parida the recent emergence of a novel human influenza a virus (h n ) poses a serious global health threat. the h n virus has caused a considerable number of deaths within a short duration since its emergence. a two-step single tube accelerated rapid real-time and quantitative swine flu virus specific h rtlamp assay is reported by targeting the h gene of the novel h n hybrid virus. the feasibility of swine flu h rtlamp for clinical diagnosis was validated with a panel of suspected throat wash samples comprising confirmed positive and confirmed negative cases of ongoing epidemic. the comparative evaluation of h specific rtlamp assay with real-time rt-pcr demonstrated exceptionally higher sensitivity by picking up all the h n positive and additional positive cases amongst the negatives that were sequence confirmed as h n . none of the real-time rtpcr positive samples were missed by rtlamp system. the comparative study revealed that rtlamp was -fold more sensitive than rtpcr with a detection limit of copy number. these findings suggested that rtlamp assay is a valuable tool for rapid, real-time detection as well as quantification of h n virus in acute phase throat swab samples without requiring any sophisticated equipments. because of its recurrent nature. despite considerable progress in understanding of the virus at cellular and molecular levels, the proper management of the disease in its different stages is still a dilemma particularly whether to use antiviral or steroids or both. the risk of using steroids with its attendant complications has to be weighed against the risk of progression of the disease if avoiding the use of steroids. this dilemma can be reduced to a considerable extent if basic principles of virology and pathogenesis are kept in mind. this article reviews current concepts of virological and clinical aspects of hsv keratitis to enable a broad understanding of the disease process. it is recognized several influential host factors including the fact that hsk is more common in men than women. it is observed that the ability of hsv to establish latent infection in sensory neurons and possibly cornea, but have as yet been unable to use this knowledge to prevent the disease limitations. acknowledging limitations may further stimulate application of laboratory knowledge in coping with hsk which constitutes to present major challenge in terms of management. mvo- study on effect of human bhsp in immunity of hcv core protein and hbv hbsag there are more than million individuals with hepatitis b and c in the world. in spite of vaccination in the different areas there are several reports about patients who got vaccine before. also there is not efficient vaccine against of hepatitis c and one of the important problems in vaccine project is development of effective and suitable adjuvant in human vaccines. at present research we applied human bhsp protein as adjuvant and chaperon. this protein injected to balbc mice as adjuvant together with recombinant proteins of hcv core and hbv hbsag. then humoral and cellular immune systems of the mice were studied. core and hbsag genes were cloned into petduet- vector and thermal vector of pgp - was used for human heat shock protein expressions. the different combination of these three proteins was injected to mice and we evaluated the total igg and igg a of mice serums after a week. two weeks after booster injection, we studied the proliferation and cytokine secretion of spleen, inguinal and popliteal lymph nodes lymphocytes in vitro and ex vivo conditions. so the core/hbsag + hsp and core + hbsag + hsp complexes induced total igg and igg a secretion. the spleen lymphocytes proliferation were increased equal to serum igg a level that was constant in second time bleeding with significant different to complexes with freund's adjuvant. at first il- and il- cytokines were increased and then decrease of il- meaned no hypersensitivity. the chaperon effect of hsp on structure of core and hbsag proteins was studied by cd and flourometer. it could fold the proteins after heating and unfolding. hepatitis b virus (hbv) infection is vaccine preventable global public health problem. all commercially available vaccines contain one or more of the recombinant hepatitis b envelope protein or surface antigen (hbsag). measurement of antigen responsible for immunogenicity of vaccine is central to quality assessment. the problems associated with the use of a polyclonal antibody in an assay with regard to its poorly defined nature and batch-to-batch variation has been mitigated by the use of mabs as described in this paper. the initial capture of hbsag by the mab could orientate it such that the same antibody could bind to it as a detection antibody after labeling with out steric hindrance. the development of an immuno-capture elisa (ic-elisa) to measure the hbsag content using a monoclonal antibody (mab) specific to determinant ''a'' of hbsag in the experimental vaccine formulations is being discussed. murine mabs developed against hbsag, subtype adw were found to cross-react with the other subtypes viz. ad and ay too. the mabs have been characterized following which, one mab hbs was chosen for developing ic-elisa format for the quantification of the hbsag in the final algel adsorbed vaccines. the unadsorbed hbsag was used to establish the standard curve of hbsag/a. the elisa had a sensitivity of ng/ml of hbsag. the recovery rate of hbsag/a was found to be around % in the vaccines treated to desorb the antigen from algel. twenty seven experimental batches of monovalent hepatitis b vaccines were analyzed for the hbsag content, both by ic-elisa and a commercial kit (axsym kit, abbott laboratories, usa). the statistical analysis of ic-elisa results indicated that an experimental equation f(x) = . (x) + . , could precisely estimate the amount of hbsag in the adsorbed vaccines. the amounts of hbsag recovered from the adsorbed vaccines as estimated by the ic-elisa format had a good correlation with the estimates derived from a commercial kit, which is being used by several vaccine manufacturers in india for the quality control of vaccine antigen. the varying amounts of vaccine antigens that could be recovered seemed to depend on the quality of the hbsag and the methods of hbsag adsorption to the alum gel during vaccine manufacture. epidemiology of the spread of h n virus. children of school going age have become victim of this deadly virus as evident from the reporting data generated in the past few weeks. the mortality rate has also been slightly increased. the disease spread in wave pattern and presently the world is passing through the second wave of pandemic with more severity in young and otherwise health people with a predilection for lungs leading to viral pneumonia and respiratory failure. now the pandemic gained hold in the developing world affecting more severely as millions of people live under deprived conditions having multiple health problems, with little access to basic health care. current data about the pandemic from developed counties need to be very closely watched in relation to shift in virus sub type, shift of the highest death rate to younger populations, successive pandemic waves, higher transmissibility than seasonal influenza, and demographic differences etc. presently the world appears to be better prepared. vaccine is available in market in many countries. even vaccine trials are actively going on in indian population. effective antivirals are available. although till now h n diagnostic centers worked with cdc/who recommended h n specific primer, probes with taqman chemistry by real time pcr, efforts on the development of indigenous diagnostics, vaccines and chemoprophylaxis is going on to have a better combat against this highly infectious virus. were positive for rotavirus infection by either page or elisa methods. the available data highlights the importance of rotavirus as a cause of diarrhea in children, which is severe enough to deserve specialized care. the observed proportion of . % of all diarrhea cases being associated with rotavirus falls within the range of values reported by other workers. the reported positivity varies from . to . %. in our study a complete concordance of elisa and page results were observed in ( %) of the tested specimens. this finding closely correlates with the findings of other authors who found a . - . % concordance results between elisa and page methods. some authors found rna-page method that is as sensitive and rapid as elisa for detecting rotavirus in stool samples of cases of diarrhea and some others proposed elisa is more sensitive than page method fond to be % specific. the remaining ( %) samples showed conflicting results. in a lone sample in which the od value of elisa test was . , this value was almost at the cutoff level, the possibility of this sample being positive by elisa test is doubtful. negative result of the same sample in page method is difficult to explain, the possibility of presence of lot of empty virus particles or due to low concentration of viral rna in the fecal specimen and insufficient extraction of viral rna could be possible. on the other hand, of the samples which gave positive results by page method were negative by elisa test. these samples had a typical - - - rna pattern. the reason for their being elisa negative thus remains unexplained, however blocking factors or the presence of inhibitory substance in stools might have been responsible. the samples containing predominantly complete particles can also give false negative results. since, the group antigen is not exposed. earlier studies have also reported page to be the most sensitive technique although some are of view that it is laborious procedure. how ever, the page system used in this study was very simple to perform and the results were available on the same day. the main requirement was of trained personnel and proper standardization of the technique. most reports states that the greatest advantage of page and silver stain method are its lack of ambiguity and the fact that it provides information about viral electropherotypes. the modified page system was thus found to be reliable, simple and rapid, no expensive reagents were required. locally available reagents from hi media were used. the cost of the chemical for page per specimen was rs. approximately as compared to rs. per test by confirmatory elisa. a locally produced slab gel electrophoresis system with power pack was the only equipment required. this method could be used for the routine diagnosis of rotavirus infection in the laboratory. vaccine, rapid diagnosis plays an important role in early management of patients. in this study a qc-rt-pcr assay was developed to quantify chikungunya virus rna by targeting the conserved region of e gene. a competitor molecule containing an internal insertion was generated, that provided a stringent control of the quantification process. the introduction of -fold serially diluted competitor in each reaction was further used to determine sensitivity. the applicability of this assay for quantification of chikungunya virus rna was evaluated with human clinical samples and the results were compared with real-time quantitative rt-pcr. the sensitivity of this assay was estimated to be rna copies per reaction with a dynamic detection range of to copies. specificity was confirmed using closely related alpha and flaviviruses. the comparison of qc-rt-pcr result with real-time rt-pcr revealed % concordance. these findings demonstrated that the reported assay is convenient, sensitive and accurate method and has the potential usefulness for clinical diagnosis due to simultaneous detection and quantification of chikungunya virus in acute-phase serum samples. in india, measles vaccine was introduced as part of expanded programme of immunization in . measles, mumps and rubella (mmr) vaccine is still not part of the national immunization schedule of india. the indian association of paediatrics (iap) recommends measles vaccine at months of age and mmr vaccine at - months. however, in a recent policy update, iap committee on immunisation opined that there is a need for a second dose of mmr vaccine for providing adequate immunity against mmr. the aim of the present study was to assess the extent of sero-protection against mmr at - years of age in children who have received one dose of mmr between and months of age. an attempt has also been made to assess the sero-response to the second dose of mmr vaccine in - years old children. a total of consecutive children between the ages of - years who had received mmr vaccine between and months of age and attending the immunization clinic of gtb hospital, delhi were enrolled. the vaccination status, anthropometry and physical examination findings were recorded. three ml of venous sample was again withdrawn for estimation of post vaccination antibody titre. it was observed that . %, . % and . % children were seroprotected for mmr respectively after . - . year of receiving first dose of mmr vaccine. seroprotection rose to . %, % and % for mmr respectively after - weeks of receiving second dose of mmr vaccine. geometric mean concentration of antibody also rose significantly in all three diseases. in view of low seroprevalence of mmr and hence high susceptibility to infection at - years of age, who have already received mmr vaccine, there is need to boost the immune responses against these three diseases by giving a second dose of mmr vaccine. baseline information on the epidemiology of viral agents causing stis and types of risk behaviour of affected persons are essential for any meaningful targeted intervention. the present study documents the pattern of viral stis in patients attending a tertiary care hospital, correlating the syndromic approach and the laboratory investigations to determine the aetiology. three hundred consecutive patients attending the sti clinic were diagnosed and categorized according to the syndromic approach of the who along with detailed history and demographic data. majority of the patients were men ( . %) with a mean age of years. men received education up to middle school. half of the female subjects were illiterate. sixty percent of the patients were married and among these, % were regular condom users. first sexual contact at or before years of age was more in men ( % vs. . % in women). promiscuity was more among male patients who had contact with csw. genital herpes was the commonest viral sti ( / ) followed by genital wart ( / ). concomitant infection with more than one virus was seen in % of patients. hiv was prevalent in . % of sti patients. hepatitis b, hepatitis c, herpes simplex type and molluscum contagiosum were the other viral agents seen in sti clinic attendees at our centre. this disease currently prevalent in more than countries world wide and annually - million people are infected with dengue virus among which . - lakhs cases were dengue hemorrhagic fever (dhf) and dengue shock syndrome (dss) which are serious forms of dengue virus infection and due to this condition , deaths might occur annually world wide and approximately million children were hospitalized for the fast decades. this disease is characterized by sudden onset of high fever with sever headache, pain in the back and limbs, lymphadenopathy macuolo-papulur rash over the skin and retro-bulbar pain. early diagnosis can be established with simple and rapid lgg/ gm antibodies detection in the blood samples of the patients based on the bi-directional immunoassay system for its management and control to reduce morbidity and mortality. details will be presented. myocarditis and dilated cardiomyopathy (dcm) are common causes of morbidity and mortality both in children and adults. the most common viruses involved in myocarditis are coxsackievirus b or adenovirus. recently, the coxsackievirus and adenovirus receptor (car), a common receptor for coxsackieviruses b , b and adenoviruses , has been identified. increased expression of car has been reported in patients with dcm suggesting utilization of car by these viruses for cell entry. the present study was designed to study the expression of car in myocardial tissue of patients with dcm. formalin fixed myocardial tissues were obtained from autopsy cases. a total of cases of dcm and cases of controls which included non-cardiac (group-a) and cardiac disease other than dcm (group-b) were included in the study. expression of car was studied by immunohistochemical staining of myocardial tissue using car specific rabbit polyclonal antibody and biotin conjugated secondary antibody. the tissue sections were considered positive when[ % of the cell showed brown color staining by immunohistochemistry (ihc). the car positivity in dcm cases was found to be % ( / ) as compared to % in control group a and % in control group b respectively. the car positivity was significantly higher in the test group as compared to both the control groups. further car positivity in all the cellular types (myocytes, endothelial cells and interstitial cells) was found significantly higher in test group as compared to both the control groups. the expression of car was significantly higher in myocytes as compared to both endothelial and interstitial cells in all the groups. however, no significant difference was observed in car positivity between endothelial and interstitial cells. the present study highlights the increased expression of car in dcm cases with further significance of car expression in myocytes and endothelial cells. this may help further in understanding the tropism of viruses or cellular susceptibility, which in turn will help in appropriate diagnostic and therapeutic approach in management of viral myocarditis and dcm cases. food security and safety vary widely around the world, and reaching these goals is one of the major challenges, raising public concern for the wellbeing of mankind, in particular. industrialized production and processing as well as improper environmental protection have clearly shown severe limitations such as worldwide contamination of the food chain and water. contaminated water and food during the processes of production, processing and handling are essentially responsible for food and water borne viral infections/diseases. the cases of viral food borne outbreaks are on the rise, creating a threat to human health. recent researches indicate that epidemiological studies are meager to focus the frequently contaminated foods and food borne viral diseases. current paper projects the etiology of select food borne viral diseases, probable reasons for non availability of appropriate methods to detect the viruses responsible for the diseases, routes of water and food borne transmission of enteric viral infections, currently available methods of detection of select viruses and bio safety measures to prevent food borne viral infections. dietary/nutritional management in food borne viral diseases is crucial to control weakness and gastro enteric intolerance due to disease condition and antibiotic therapy. it will principally improve food intake, resulting in better nutritional status leading to optimum immune response. food borne viruses are mainly belong to rotaviruses, enteropathogenic viruses, astroviruses, adenoviruses and caliciviruses, causes acute gastroenteritis (ag) which is an important health problem. the frequency of rotavirus as a cause of sporadic cases of ag ranges between . % and . %. astroviruses cause ag, with a frequency ranging between and %: outbreaks have been described in schools and kindergartens, but also in adults and the elderly. the frequency of identification of adenoviruses and as causes of sporadic ag in non-immuno suppressed children ranges between . % and . %, although there is probably underreporting because the sensitivity of conventional techniques is low. caliciviruses are separated phylogenetically into two genera: norovirus and sapovirus. norovirus is frequently associated with food-and water-borne outbreaks of ag. it is estimated that % of cases of ag due to norovirus are food borne. in sweden and some regions of the united states, norovirus is the first cause of outbreaks of food borne diseases. sapovirus outbreaks due to person-to-person and food borne transmission affecting both children and adults have recently been reported in countries such as canada and japan. it has been predicted that the importance of diarrhoeal disease, mainly due to contaminated food and water, as a cause of death will decline worldwide. evidence for such a downward trend is limited. this prediction presumes that improvements in the production and retail of microbiologically safe food will be sustained in the developed world and, moreover, will be rolled out to those countries of the developing world increasingly producing food for a global market. sustaining food safety standards will depend on constant vigilance maintained by monitoring and surveillance but, with the rising importance of other food-related issues, such as food security, obesity and climate change, competition for resources in the future to enable this may be fierce. in addition the pathogen populations relevant to food safety are not static. food is an excellent vehicle by which many pathogens (bacteria, viruses/prions and parasites) can reach an appropriate colonization site in a new host. although food production practices change, the well-recognized food-borne pathogens, such as salmonella spp. and escherichia coli, seem able to evolve to exploit novel opportunities, for example fresh produce and even generate new public health challenges, for example antimicrobial resistance. in addition, previously unknown food-borne pathogens, many of which are zoonotic, are constantly emerging. awareness and surveillance of viral food-borne pathogens is generally poor but emphasis is placed on norovirus, hepatitis a, rotaviruses and newly emerging viruses such as sars. it is clear that one overall challenge is the generation and maintenance of constructive dialogue and collaboration between public health, veterinary and food safety experts, bringing together multidisciplinary skills and multi-pathogen expertise. such collaboration is essential to monitor changing trends in the well-recognized diseases and detect emerging pathogens. it is also necessary to understand the multiple interactions between these pathogens and their environments during transmission along the food chain in order to develop effective prevention and control strategies. to analyse the effectiveness of these sirnas targeting rabies virus l gene, the bhk- cells expressing sirnas in shrna form were produced by transduction of cells with radv-l. the transduced bhk- cells expressing sirna were infected with rabies virus pv- strain. there was reduction in rabies virus multiplication as analysed by reduction in fluorescent foci forming unit (ffu) count by . % ( ffu in bhk- cells expressing sirna-l compared to ffu in bhk- cells expressing negative sirna). the expression of l gene mrna was reduced by . fold in rabies virus infected radv-l transduced cells compared to radv-neg transduced cells (negative control) as detected using real-time pcr. after analyzing the effectiveness of radv-l in vitro, its effectiveness was also evaluated in vivo in mice after virulent rabies challenge. the mice were inoculated with plaque forming units (pfu) of radv-l in masseter muscle (i/m route) and challenged with ld rabies virus challenge virus standard (cvs) strain. the results indicated % protection with improved median survival from to days compared with group of mice treated with radv-neg. the results of this study indicated that sirnas targeting rabies virus polymerase (l) gene delivered through adenoviral vector inhibited rabies virus multiplication in vitro and in vivo. and were successfully produced and purified from the infected spodoptera frugiperda (sf- ) cells using these recombinant baculovirus. the morphology of the vlps was validated by electron microscopy in comparison to the authentic bt virions. the vlps produced here were stable and were highly immunogenic with intact outer layer which is rapidly lost during normal infection of btv. these btv-vlps elicited long lasting protective immunity in vaccinated sheep against virulent virus challenge. with the use of btv-vlps it was also possible to differentiate the infected and vaccinated animals (diva). vlp-based btv vaccine has potential advantages with regard to controlling the spread of btv with multiple serotypes. it is possible to produce milligram quantities of correctly folded and processed protein complexes using this baculovirus expression system and hence it is a more promising system for producing new generation vaccines like vlp subunit vaccine against any viral diseases in large scale. peste des petits ruminants (ppr), goatpox and orf are oie notifiable diseases of small ruminants especially goat and sheep. these diseases are economically important, in enzootic countries like india and cause significant loss and are major constraints in the productivity. considering the geographical distribution of ppr, goat pox and orf infections and prevalence of mixed infection, in the present study, safety and potency of the experimental triple vaccine comprising attenuated strains of thermostable-ppr virus (pprv jhansi, p- ) grown at °c, high passaged goat poxvirus (gtpv uttarkashi, p ) and attenuated orf virus (orfv mukteswar, p ) was evaluated in sub-himalayan local hill goats. goats simultaneously immunized with ml of vaccine consisting of either tcid or tcid of each of pprv, gtpv and orfv were monitored for clinical and serological responses for a period of - weeks post-immunization (pi) and post challenge (pc). specific immune responses i.e., antibodies directed to pprv, gtpv and orfv could be demonstrated by ppr competitive elisa kit and capripox indirect elisa, snt, respectively following immunization. all the immunized animals resisted infections when challenged with virulent strains of either gtpv or pprv or orfv on day dpi, while in contact control animals developed characteristic signs of respective disease. further, ppr viral antigen could be detected by using ppr sandwich elisa kit in the excretions (nasal, ocular and oral swab materials) of unvaccinated control animals after challenge but not from any of the immunized goats. triple vaccine was found safe at dose as higher as tcid and induced protective immune response even at lower dose ( tcid ) in goats, which was evident from sero-conversion as well as challenge studies. the study indicated that these viruses are compatible and did not interfere with each other in eliciting immune response, paving the feasibility of use of this triple vaccine in combating these infections simultaneously. toll like receptors (tlrs), primary sensors of microbial origin, plays a crucial role in the innate immunity. till now mammalian tlrs have been identified, while there is no information available on tlrs of yak. this study is part of world bank funded-icar project. yak, named bos grunniens for its distinctive vocalization and relationship with cattle, is natural habitant of extremely cold environment. when these animals comes to a lower altitude grazing land, adjacent to villages, become susceptible to the diseases of cattle, buffalo etc. thus, present study was undertaken to with genetic characterization and evolutionary lineage analysis of yak tlrs. we worked on tlr gene, which plays an important role in recognition of ssrna viruses. total rna was extracted from mitogen stimulated pbmcs of yak. the rt-pcr conditions were standardized for full length amplification of tlr gene using specific self designed primers. the expected amplicon of bps was obtained. it was cloned in pgemt-easy vector followed by transformation in e. coli top strain. the recombinant clones were screened, picked up for plasmid isolation and release of tlr was confirmed by restriction digestion. the cloned tlr product was sequenced and analyzed for the nucleotide and deduced amino acid sequences, and d structure analysis. the results revealed that yak shows more than % sequence homology with other bos indicus breeds and bos taurus breeds. however, identity was less than % with other animal species (equine, murine, feline, canine etc.). the evolutionary lineage findings cluster yak more closely with bovine species. point mutations revealed changes at nucleotide positions with corresponding amino acid change at positions. smart analysis of yak protein domain architecture revealed toll-interleukin i receptor (tir), leucine rich repeats (lrr) and signal peptide region. the variations in yak mainly lie in the lrr region. homology modeling revealed horse shoe shaped structure with alpha helix. the additional alpha helix present in bos indicus was not detected in yak. the present study shows existence of genetic variability in tlr gene of yak, in particular the lrr region, which plays an important role in the pathogen recognition and the evolutionary lineage analyses shows its closeness with other bovine species. a.p. aquaculture and fisheries, tirupati in this new millennium, aquatic animal health management strategies in asia expanded and adjusted to the current disease problems faced by the aquaculture sector. this presentation will briefly discuss some of the most serious trans-boundary pathogens affecting asian aquaculture including a newly emerging disease and highlight recent regional and national efforts on responsible health management for mitigating the risks associated with aquatic animal movement. a regional approach is fundamental since many countries share common social, economic, industrial, environmental, biological and geographical characteristics. capacity and awareness building on aquatic animal epidemiology, science-based risk analysis for aquatic animal transfers, surveillance and disease reporting, disease zoning and establishment of aquatic animal health information systems to support development of national disease control programs and emergency response to disease outbreaks are needed. molecular diagnostics with emphasis towards standardization and harmonization, inter-calibration exercises and quality assurance in laboratories, accreditation program and utilization of regional resource centres on aquatic animal health will also be needed. whilst most of these strategies are directed in support of government policies, implementation will require pro-active involvement, effective cooperation and strategic networking between governments, farmers, researchers, scientists, development and aid agencies, and relevant private sector stakeholders at all levels. their contributions are essential to the health management process. generally, aquaculture plays an important role in economy as harvests from natural waters have declined or, at best, remained static in most countries. fish and shrimp, the main aquaculture product sources, have gained the most attention. many factors can cause losses in yields of fish products and infectious disease in fish and shrimp is the biggest threat to the fishery industry. shrimp and fish aquaculture has grown rapidly over several decades to become a major global industry that serves the increasing consumer demand for seafood and has contributed significantly to socio-economic development in many poor coastal communities. however, the ecological disturbances and changes in patterns of trade associated with the development of shrimp and fish farming have presented many of the pre-conditions for the emergence and spread of disease. shrimp and fish are displaced from their natural environments, provided artificial or alternative feeds, stocked in high density, exposed to stress through changes in water quality and are transported nationally and internationally, either live or as frozen product. these practices have provided opportunities for increased pathogenicity of existing infections, exposure to new pathogens, and the rapid transmission and trans boundary spread of disease. not surprisingly, a succession of new viral diseases has devastated the production and livelihoods of farmers and their sustaining communities. this review examines the major viral pathogens of farmed shrimp and fish, the likely reasons for their emergence and spread, and the consequences for the structure and operation of the shrimp farming industry. in addition, this review discusses the health management strategies that have been introduced to combat the major pathogens and the reasons that disease continues to have an impact, particularly on poor, smallholder farmers in asia. btv isolates from the same geographic region have been termed as 'topotypes' and initial observation on segment nucleotide sequences identified a correlation between topotypes and genetic information. later topotyping was proposed based on segment , on the premise that the encoding protein ns , which is involved in virus egress from insect cells, would lead to evolutionary fitness in parallel with the geographic distribution of the different culicoides species. further studies attempted to extend this to nucleotide sequence homology in segments and , but failed to identify clear cut correlations or any evidence for positive selection. for example, south african isolates were found not to cluster into separate african lineage. in this study, we carried out a more extensive analysis of segment sequences. our analysis showed no segregation of isolates into topographically distinct groups. instead we observed topological clustering of the clades, and we attribute this to genetic bottleneck resulting in genetic drift and founder effect leading to homogenous gene pool in a geographical area. we hypothesize that when a new virus enters a geographical area where local btv strains are already circulating, the new genes/segments would enter into a bigger gene pool. consequently, the newer incursions into a heavily endemic area tend to get diluted and disappear from the population because the rate of drift is inversely proportional to the population size, unless they are positively selected. use of live attenuated vaccine in israel, europe, south africa and usa also led to more homogenous population similar to the vaccine strains due to continuous infusion of the vaccine type genes into the gene pool. we conclude that restriction of specific strains to certain geographical areas could generate uniquely imprinted genotypes which would not only indicate origin but also predict movement of viral strains to new areas. vvo- viral diseases of zoonotic importance: indian context k. prabhudas pd-admas, ivri, campus, hebbal, bangalore zoonoses are generally defined as animal diseases that are transmissible to humans. they continue to represent an important health hazard in most parts of the world, where they cause considerable expenditure and losses for the health and agricultural sectors. the emergence of these zoonotic diseases are very distinct, hence their prevention and control will require unique strategies, apart from traditional approaches. such strategies require rebuilding a cadre of trained professionals of several medical and biologic sciences. the article discusses virus infections that have significant zoonotic implications for india. buffalopox is a contagious viral disease affecting milch buffaloes and rarely, cows, with a morbidity rate up to % in the affected herd. although the disease is not responsible for high mortality, it adversely affects the productivity of the animals, resulting in large economic losses. furthermore, the disease has zoonotic implications, as outbreaks are frequently associated with human infections, particularly in the milkers. the causative agent, buffalopox virus (bpxv), is closely related to vaccinia virus. the outbreaks of febrile rash illness among humans and buffaloes were investigated in the villages of districts solapur and kolhapur of western maharashtra. clinico-epidemiological investigations of humans and buffaloes were carried out and representative clinical samples were collected respectively. the samples include vesicular fluid, scab, and blood. laboratory investigations for buffalo-pox virus (bpxv) was done by pcr on blood samples, scabs and vesicular fluid. in vitro virus isolation attempts were carried out by using vero e- cells. negative staining electron microscopy was also employed for detection of virus particles. a total of human cases with pox lesions on hand and other body parts from village kasegaon, district-solapur and cases from different villages of kolhapur district were reported. besides pox lesions patients were having fever, malaise, pain at site of lesion and axillary and inguinal lymphadenopathy. in kasegaon village, attack rate in human cases was . % and in buffaloes . % ( / ). whereas in kolhapur area attack rate in buffaloes was . % ( / ). bpxv was confirmed in blood, vesicular fluid and scab specimens from human cases and scab specimen from buffalo by polymerase chain reaction (pcr) method. the bpxv was also isolated from different clinical specimens and further identified by pcr and electron microscopy. clinical manifestation of the disease in buffaloes from solapur district was as reported earlier like common pox lesions on teats and udders whereas the buffaloes from kolhapur district had lesions on hairless parts of ears and on the eyelids with purulent discharge. bpxv from human and buffalo cases showed similarity. vaccines have been made against several diseases and used for controlling the afflictions. however a few of them were not effective for successfully controlling the disease. the reasons for the failure are many, the major being, either the pathogen is not completely cleared from the vaccinated animal or it reemerges after changing its antigenic structure, thus making the vaccination programme less effective. in addition to this, emergences of newer diseases such as hiv the development of suitable vaccines have become a challenging task. this is especially true in the case of viral diseases. these challenges have warned the researchers ''that protection by vaccination is not that simple and strait forward approach'', and lot need to be understood in terms of host virus interaction and role of environment in perpetuating the disease. so the immediate step that was considered was the environmental safety by way using non infectious materials as vaccines. with the understanding that has been developed in molecular immunology and molecular biology and with the availability of molecular tools that have been developed through recombinant dna technology the field of vaccinology has changed dramatically to emerge as modern vaccinology. this presentation deals with the modern approaches that are being used to produce effective vaccines in the case of foot and mouth disease of cloven footed animals. the similar approach may be worked out for other viral diseases also. despite the availability of an inactivated vaccine that is noted to provide solid immunity against the disease over a short period of time, the search for an ideal vaccine, the criteria for which are; safety of the vaccine for environment, easy in its preparation, does not require a cold chain for its storage, provides longer lasting immunity, economically viable and may be able to clear the virus in case of persistent infection is on. the advent of recombinant dna technology together with the information available on the molecular biology of viruses has enabled to design the development of newer vaccines that can induce strong cellular and humoral responses. the underlying principal in the present vaccine development strategy world over is the virus antigen gene has to be expressed in the tissue and the vaccine backbone has to trigger the immune system for eliciting desired immune response. bangalore campus of ivri has been vigorously pursuing research to develop ideal vaccines for foot and mouth disease keeping above principal in mind to achieve the previously mentioned criteria. the approaches selected are to see that the virus antigen/s replicate transiently in the host. the self replicating vaccines that have been developed are pox virus vectored vaccines, alpha virus replicase based vaccines and fmdv vectored vaccines. the approach and the result obtained so far will be discussed. silkworm, bombyx mori is affected with various diseases caused by viruses viz., nuclearpolyhedrosis (bmnpv), densosnucleosis (bmdnv) and infectious flacherie (bmifv). silkworm viral diseases form major constraints for the silk cocoon production in all the sericultural countries. the losses due to silkworm diseases is estimated about - % and among them viral diseases are most common. in sericulture, prophylactic measures play a vital role in the management of silkworm diseases. these include disinfection of silkworm rearing house and appliances, rearing area, rearing surroundings, silkworm egg and body, and rearing bed disinfection associated with maintenance of general hygiene and personnel hygiene. all these activities are generally carried out as rituals by using general disinfectants often with partial success. recent trends in complete management of silkworm diseases include development of silkworm hybrids evolved from disease resistant/tolerant breeds, effective eco-and user-friendly disinfectants, anti-microbial feed-supplements and use of transgenic silkworms. biotechnological breakthrough in this regard is through rna interference (rnai) approach involving dsrna mediated nuclear polyhedrosis management and this is presently pursued by apssrdi, hindupur in collaboration with centre for dna fingerprinting and diagnostics (cdfd), hyderabad. nadu and karnataka. the disease appears to be more severe in rural flocks than organized farms. our investigations revealed the morbidity, mortality and case fatality rates among rural and organised farms as . %, . %, . % and . %, . %, . % respectively. higher morbidity and mortality in rural areas may be due to stress factors like poor nutrition, parasitic burden, fatigue due to long walks and non availability of veterinary aid. kulkarni et al. also reported the severe bt outbreaks in rural areas of maharashtra with overall morbidity, mortality and case fatality of %, % and % respectively. all the south indian sheep breeds were found to be susceptible and clinical farm of the disease is evident in all of them though saravanabava ( ) reported variations in susceptibility among the indigenous sheep. trichy black and ramnad white sheep were found to be more susceptible than the vambur and mecheri sheep of tamil nadu. prevalence of bluetongue in sheep, goat and cattle appears to be high in the region. serological surveys conducted in andhra pradesh during revealed the prevalence of btv antibodies in sheep ( . %) goats ( . %) cattle ( %) and buffaloe ( %). similar high prevalence of btv antibodies in sheep and goats were also reported from the other states in the region. clinical disease has not been recorded in kerala though btv antibodies were recorded in sheep ( . %) and goats ( . %) (ravi sankar ) . culicoides are the known biological vectors of btv. all the culicoides species are not capable of transmitting the btv. the occurrence of the disease is related to the presence of the competent vectors in the area. jain et al. ( ) established the involvement of the culicoides in transmitting the btv by isolating the virus from culicoides at haryana, the north indian state. c. imicola and c. oxystoma were found to be prevalent in andhra pradesh and tamil nadu. narladakar et al.( ) reported the presence of c. schultzei, c. perigrinus and c. octoni in marathwada region of maharastra. culicoid vectors are significantly affected by the climate and annual variations in the climate reflects the outcome of the disease. the monsoon season (june to dec) with the temperature ranging from . to . °c appears to be favourable period for the multiplication of culicoides. the maximum no of outbreaks were recorded during the north east monsoon period (oct-dec) followed by south west monsoon period (june to sep) in the region. however, details on the distribution of the competent vectors, feeding habits and their dynamics in the region is lacking multiple btv serotypes were found to be circulating in the region. (kulkarni and kulkarni ; janakiraman etal. ; mehrotra et al. ) a total of serotypes viz. - , , , , , and were identified based on the virus isolations. sreenivasulu et al. isolated btv serotype from an outbreak of bt in native sheep of andhra pradesh. btv serotype , and were also isolated from the outbreaks occurred in andhra pradesh. some of the isolates need to be serotyped. deshmukh and gujar ( ) isolated btv type from maharashtra. following is the summary of the distribution of btv serotypes in this region. clinical picture of bt in native sheep appears to be slightly different, the major difference being that swelling of lips and face was less conspicuous. mucocutaneous borders appeared to be very sensitive to touch and bleed easily upon handling. the classical signs of cyanosis of tongue and reddening of coronary band are not the common features of the disease in native sheep. the disease was also confirmed by the virus isolation and identification. clinical disease has not been reported in cattle, buffaloes and goats in spite of high seroprevalence. in conclusion bt is established in native sheep and causes severe economic losses to the farmers. the disease is concentrated in the southern peninsula of the country. the disease is seasonal and is associated with the rain fall. multiple serotypes appear to be circulating in this region. the btv serotypes were of virulent in nature as evident by severe outbreaks. s. janardana reddy*, d. c. reddy department of fishery science and aquaculture, sri venkateswara university, tirupati in less than three decades, the penaeid shrimp culture industries of the world developed from their experimental beginnings into major industries providing hundreds of thousands of jobs, billions of u.s. dollars in revenue, and augmentation of the world's food supply with a high value crop. concomitant with the growth of the shrimp culture industry has been the recognition of the ever increasing importance of disease, especially those caused by infectious agents. in india viral diseases have become an important limiting factor for growth of shrimp aquaculture industry. although more than different viral pathogens have been identified in different species of shrimp world wide, only a few viruses have identified which are causing disease problems in cultured tiger shrimps in india, east coast of andhra pradesh, in particular. diagnostic methods for these pathogens include the traditional methods of morphological pathology (direct light microscopy, histopathology, and transmission electron microscopy), enhancement and bioassay methods, traditional microbiology, and the application of serological methods. while tissue culture is considered to be a standard tool in medical and veterinary diagnostic labs, it has never been developed as a useable, routine diagnostic tool for shrimp pathogens. the need for rapid, sensitive diagnostic methods led to the application of modern biotechnology to penaeid shrimp disease. the industry now has modern diagnostic genomic probes with nonradioactive labels for viral pathogens like infectious hypodermal and hematopoietic necrosis (ihhnv), hepatopancreatic virus (hpv), taura syndrome virus (tsv), white spot syndrome virus (wssv), monodon baculo virus (mbv), and bp. highly sensitive detection methods for some pathogens that employ dna amplification methods based on the polymerase chain reaction (pcr) now exist, and more pcr methods are being developed for additional agents. these advanced molecular methods promise to provide badly needed diagnostic and research tools to an industry reeling from catastrophic epizootics and which must become poised to go on with the next phase of its development as an industry that must be better able to understand and manage disease. within this field, shrimp immunology is a key element in establishing strategies for the control of diseases in shrimp aquaculture. research needs to be directed towards the development of assays to evaluate and monitor the immune state of shrimp. the establishment of regular immune checkups will permit the detection of shrimp immunodeficiencies but also to help monitor and improve environment quality. for this, immune effectors must be first identified and characterised. in the end, however, the assumption may be made that the sustainability of aquaculture will depend on the selection of disease-resistant shrimp, i.e. to develop research in immunology and genetics at the same time. the development of strategies for prophylaxis and control of shrimp diseases could be aided by the establishment of a collaborative network to contribute to progress in basic knowledge of penaeid immunity. however, to improve efficiency, it appears essential also to open this network to complementary research areas related to shrimp pathology, physiology, genetics and environment. bluetongue is an important viral disease of sheep causing severe economic losses to the farmers. lack of effective vaccine is the major impediments in controlling the disease. multiple serotypes were found to be circulating in the state. attempts are being made to develop the vaccine employing the available serotypes to control the disease. hence, it is essential to identify the antigenic relationship among the serotypes to identify the candidate vaccine strains to be incorporated in the preparation of vaccine. reciprocal cross neutralization test was employed to find out the r% values between btv- , - and - which indicated the extent of antigenic relationship between the serotypes. r% value between btv- and btv- was recorded as . r% value of . and . were observed between btv- and - and btv- and - respectively. the r% values recorded in the present study revealed a weak antigenic relationship between the btv serotypes. the extent of antigenic relationship between the btv serotypes was also determined by multiple sequence alignment of the nucleotide and amino acid sequences of the reference btv serotypes , and . the sequence analysis of the vp gene revealed a homology of - % and - % at the nucleotide and amino acid levels respectively. r% values obtained using reciprocal cross neutralization test with the btv- , and serotypes isolated in native sheep of andhra pradesh and the genomic analysis of the reference serotypes of btv- , and revealed very weak antigenic relationship and were highly divergent. diseases especially those by viral pathogens cause greater economic losses in most horticultural crop species throughout the world as compared to agricultural crops. non-genetic methods of management of these diseases include quarantine measures, eradication of infected plants and weed hosts, crop rotation, use of certified virus-free seed or planting stock and use of pesticides to control insect vector populations implicated in transmission of viruses. however, none of these measures is likely to provide an enduring solution against these diseases especially those caused by viruses due sometimes to the huge expenditure involved, but mostly to the questionable effectiveness and reliability of those methods. as key control pesticides are getting increasingly abandoned, development of alternative methods to control diseases has been a felt-need in the recent past. though breeding for disease resistance generally provides a reliable security in a long run, introgression of host plant resistance did not materialise in most important crops. non-availability of an appropriate source of resistance in inter-fertile relatives, linkage to undesirable traits, or often times polygenic nature of such sources of resistance are the stumbling blocks in breeding programs. the limitations of conventional breeding and routine cultural practices prompted the need for the development of other approaches of virus control that could be fully incorporated into traditional methods. in this perspective, the concept of pathogen-derived resistance offers an attractive strategy to evolve newer methods of virus management, by transforming crop plants with nucleotide sequences derived from the pathogen's genome. an increasing number of molecular characterisation of plant virus genomes and the stable transformation of a number of horticultural crop species have in fact opened an avenue for molecular breeding against virus pathogens. successful field-testing of genetically modified crop cultivars renders proof of their supremacy over existing cultivars. it also contributes to demonstrate their capability with regard to environmental safety with a view to winning over public concern and scepticism. in general, the eventual commercialisation transgenic lines expressing virus resistance will rely upon a host of factors including their field performance, genetic stability, public acceptance and the resolution of environmental concerns and patent related issues. as such, elaborate field trials and allied studies are now required to adapt genetically engineered horticultural crops expressing virus resistance for their implementation into practical agriculture. a few examples from current research at tnau, in india or elsewhere will be discussed in this presentation. virology unit, division of plant pathology, iari, new delhi in recent times there has been greater emphasis on vegetatively propagated crops in india to help diversify the indian agriculture. fruit, flower, spice and plantation crops are important vegetatively propagated horticultural crops, which have become a driving force for economic development in several parts of india. however, most of the vegetatively propagated crops are threatened by biotic stress caused by plant pathogens in general and plant viruses in particular. plant viruses produce specific and non specific symptoms and in some cases no symptoms are produced. correct identification and diagnosis of viral diseases is first step in the management of any disease including viral diseases. there have been two major breakthroughs in virus diagnostics during last four decades. the first one was serological assay using monoclonal or polyclonal antibodies in enzyme linked immunosorbent assay (elisa) and the other one was the use of in vitro amplification of dna in polymerase chain reaction (pcr). a significant development in serological assays has been its simplification in form of user's friendly quick strip/dip stick method. the one-step lateral-flow (lf) tests have been developed for the on-site detection and identification of several plant viruses. rapid advancement in virus genome characterization has led to the development of novel approaches of nucleic acid based diagnostics which include conventional pcr, real time pcr, multiplex pcr, micro/macro arrays and biochips. pcr protocols already exist for many plant viruses of citrus, banana, apple, papaya, vegetables, ornamental and spice crops. a further advancement has led to development of realtime pcr assay which is relatively easy but requires training for diagnosticians. in real-time pcr assays, results can be available within min. the nucleic acid template preparation in pcr has been simplified. membrane based dna template protocol and co-isolation of nucleic acid template preparation are novel approaches in pcr detection of virus and virus like pathogens. since many of the horticultural crops are often infected by more than one virus, their individual detection by pcr is not only expensive but also time consuming. therefore, multiplex pcr has been developed where in genome of more than one virus could be amplified and detected in the same reaction mixture. development of nucleic acid based chip is now one of the fastest and recent growing areas in the field of pathogen detection. these nucleic acid based chips have been named as dna/rna chips, biochips, genechips, biosensors or dna arrays. when it comes to applications of microarray technology for plant viruses, it is not too difficult to see the value of a method that could potentially detect a whole range of viruses using a single test. however, microarrays are unlikely to become the only method in use in a diagnostic laboratory. processing of germplasm including transgenic planting material imported for research purposes into the country. during the last two decades, a total of , samples of wheat including transgenics were imported from cimmyt (mexico), icarda (syria) and many other countries. these were grown in post-entry quarantine nursery each year at nbpgr, new delhi and the transgenic samples were grown in national containment facility of level- (cl- ) since its inception to ensure that no viable biological material/pollen/pathogen enters or leaves the facility during quarantine processing of transgenics. in addition, post-entry quarantine inspections of the transgenic wheat grown by indenters are also undertaken by nbpgr quarantine scientists. virus-induced gene silencing (vigs) is a technique in which viral genomes are used, usually after appropriate modifications, for transient gene silencing in plants. the mechanism behind vigs is the phenomenon called rna-interference (rnai), which is widespread in many organisms and is believed to be form of inherent defence system against intracellular pathogens, such as viruses and transposons. double-stranded rna or rna containing strong secondary structures, commonly produced during viral infections, are believed to cause triggering of rnai, which employs a battery of proteins and nucleoprotein complexes to identify and degrade specific viral transcripts. in vigs, viral genomes not causing severe symptoms, but which can accumulate and spread efficiently in the host plant are used as vectors in which a host gene is cloned and introduced into the plant. upon replication, the viral vector triggers rnai response in the host plant, which also targets the host gene, leading to its silencing and subsequently, the silenced phenotype revealing gene function in vivo. vigs has been used extensively to study gene functions in dicot plants, such as tobacco, tomato, pea, soybean, etc., using vectors derived from reference genes are commonly used as an/the endogenous normalisation measure for the relative quantification of target genes. the expression (characteristics) of seven potential reference genes was evaluated in tissues of healthy, physiologically stressed and barley yellow dwarf virus (bydv) infected cereal plants. these genes were tested by rt-qpcr and ranked according to the stability of their expression (characteristics) using three different methods (two-way anova, genorm and normfinder tools). in most cases, the expression (characteristics) of all genes did not depend on the abiotic stress conditions or on the virus infections. all the genes showed significant differences in expression (characteristics) among plant species. glyceraldehyde- -phosphate dehydrogenase (gapdh), beta-tubulin (tubb) and s ribosomal rna ( s rrna) always ranked as the three most stable genes. on the other hand, elongation factor- alpha (ef a), eukaryotic initiation factor a (eif a), and s ribosomal rna ( s rrna) for barley and oat samples; and beta-tubulin (tubb) for wheat samples were consistently ranked as the less reliable controls. the bydv titre was determined in two oat varieties by rt-qpcr by three different quantification approaches. statistically, there were no significant differences between the absolute and the relative quantification, or between quantification using gapdh + tubb + tuba + s rrna and ef a + eif a + s rrna. the geometric average of gapdh, s rrna, tuba and tubb is suitable for normalisation of bydv quantification in barley and oat tissues. for wheat samples, a combination of gapdh, s rrna, tubb, eif a and e fa is recommended. department of microbiology, yogi vemana university, vemanapuram, kadapa large scale production and import of propagative material poses potential risk of introducing several destructive pathogens particularly viruses and mycoplasma like organisms in our country. this demands adequate quarantine safe guards such as growing them under approved post entry quarantine facility for specific period so as to facilitate virus detection, thereby curtailing risk. when such facilities are coupled with propagation by tissue culture will ensure virus free propagative plant material. the requirement of nationwide network of post entry quarantine facility working in close collaboration with crop institutions are very much emphasized for considering import of high risk plant genera for agriculture development. present paper discusses about virus disease of quarantine importance affecting ornamental and fruit plants such as chrysanthimum, dahlia, dianthus, rosabengalensis, cattleya, cymbidium, dendrobium, lilium, citrus, vitis etc. the paper also discusses on immunodiagnostic methods of detection and methods of obtaining virus free propagative material. rice tungro occurs as epidemics in regular cycles and has been reported in the last years from all the major rice growing regions of india, especially prevalent in the southern and eastern states. development of the durable resistant varieties to tungro is crucial for the management of the disease. molecular breeding, involving the use of dna markers linked to the resistant gene(s) for selection, can overcome the difficulties encountered in conventional resistant breeding programs. for successful marker-assisted selection (mas), the identification of closely linked markers through the process of gene tagging and mapping is a prerequisite. attempts have been initiated for identification of tungro resistance genes through molecular mapping and their introgression into the target varieties using marker-assisted selection at drr, hyderabad. the inheritance of resistance to rice tungro virus disease was studied in seven resistant rice cultivars with field evaluation at hot spot locations. the microsatellite markers linked to rice tungro resistance in utri merah was studied and found that resistance genes were linked to rm on chromosome . through molecular mapping two qtl were identified controlling rtv resistance on chromosomes and in 'utri rajapan' explaining . % and . % of the phenotypic variance. in variety 'vikramarya', another two qtl for rtv resistance were detected on chromosomes and explaining . % and . % of the phenotypic variance. the closely linked markers identified in this study flanking the gene of interest through mapping will improve the efficiency and precision of introgression programs in marker assisted breeding for rtv resistance. functional characterization of these qtl for rtv resistance is under progress. there is only a limited pool of natural virus resistance in cassava against cassava mosaic geminiviruses and cassava brown streak ipomovirus hence the development of transgenic resistance in this significant crop might present an option. rna mediated resistance through the expression of inverted-repeat dsrna sequences derived from the virus genome and the modification of plant microrna to produce antiviral artificial microrna are strategies that have recently been proven very effective for induction of virus resistance (immunity) against a number of rna viruses. results from rna interference strategies against geminiviruses never resulted in immunity of transgenes. however, it suggest that viral mrna are targets of rna silencing and that the success of the strategy depends on the relevance of the target gene in the systemic spread of the virus. we have generated a number of rna silencing constructs to induce resistance against cbsv and the indian cassava mosaic viruses icmv and slcmv. due to the serious problems inherent with transformation of cassava and subsequent resistance screening, these constructs were tested for efficiency either by transient-or by transgenic expression in n. benthamiana. complete immunity was reached in transgenic n. benthamiana against cbsv using inverted repeat or amirna constructs. using different species of cbsv for resistance screening, immunity was broken, to show the minimum context for broad spectrum resistance. similarly, highly specific resistance was reached in expression of amirna. in contrast, virus resistance against icmv/ slcmv using single amirna constructs was not successful. results from the experiments to generate virus resistance against cbsv and icmv/slcmv will be shown; methods to evaluate efficiency of rnai gene constructs by transient gene expression in n. benthamiana and strategies to develop efficient resistance against rna and dna viruses in cassava will be discussed. bitter gourd (momordica charantia l.) which is also called bitter melon, balsam apple and balsam pear belongs to family cucurbitaceae. it is an important traditional vegetable of nutritive and medicinal value that is cultivated in tropical and sub-tropical asia, but is considered as a weed host reservoir for viruses in jamaica. viral disease-like symptoms were observed occurring naturally on the crops of bitter gourd grown in the fields of northern india during - . an incidence of . % of diseased plants was recorded which showed chlorotic spots and mosaic ranging from mild mottling to green blisters along with leaf smalling, leaf and fruit deformations, bud necrosis and stunted growth whereas . % plants exhibited leaf curling alone or in combination with mosaic-type disease. a reduction of . % in fruit yield was recorded in mosaic-like disease which could be attributed to lesser fruit setting due to bud necrosis, smaller fruit size and stunted plant growth. such plants produced deformed, notched, irregularly shaped fruits wherein pre-mature yellowing and necrosis on the anterior and posteriors ends made . % fruits unfit for marketability. the dwindling yield and production of unmarketable fruits posed a major constraint for profitable cultivation of this economically important crop, thus warranting for studies on etiology and management of these diseases. the mosaic-like disease was transmitted to healthy seedlings of bitter gourd at -leaves stage by sap inoculation as well as by aphid viz., myzus persicae sulz. and aphis gossypii glov. initially studies were carried out to optimize protocols for efficient plant regeneration and agrobacterium-mediated transformation for nagpur sweet orange, which is a popular and elite citrus cultivar in india. organogenesis was induced in etiolated epicotyl explants of one-month-old axenically raised polyembryonic seedlings by culturing them in mt medium supplemented with g/l sucrose with varying concentrations of plant hormones. it was found that bap at mg/l without auxin was best for efficient shoot regeneration in citrus using epicotyl explants. a % regeneration frequency was obtained and multiple shoot formation was obtained from both the cut ends of all the explants. an average of . well-differentiated shoots per explant were obtained, all of which rooted normally under the influence of mg/l iba. this improved regeneration protocol was utilized in standardizing agrobacterium-mediated transformation of citrus using a. tumefaciens strain eha , containing binary plasmid pcambia that harbors gus reporter gene and npt-ii plant selection marker gene. one-month-old epicotyl explants infected with over-night grown agrobacterium (a . - . ) for min and co-cultured for days were found to be optimum for transformation as assessed on the basis of pcr analysis and gus activity displayed by the stem and leaf sections of putative transgenics. overall transformation frequency ranged from to %. current study focuses on the generation of citrus transgenics for ctv resistance using a. tumefaciens strain eha containing binary plasmid pbinar harboring portion of coat protein gene of ctv and npt-ii gene employing the standardized protocols. several putative transgenic shoots were recovered on selection medium and they are being utilized for molecular analyses and resistance against ctv. work is also in progress on the generation of citrus transformants using rnai construct harboring ctv cp and p genes, singly and in conjunction. our lab was also involved in developing rice transgenics for resistance against rice tungro disease, which is one of the most important and widespread virus diseases of rice in south and southeast asia, causing an annual estimated loss in crop yield of economic losses worth millions of rupees are caused due to these diseases annually. virus diseases are frequently less conspicuous than those caused by other plant pathogens and last for much longer. this is especially true for perennial crops and those that are vegetatively propagated. one further problem with attending to assess losses due to various diseases on a global basis is that what most of the data are from small comparative trials rather than wide scale comprehensive surveys, even the small trials do not necessarily give data that can be used for more global estimates of losses. this is for several reasons, including: ( ) variation in losses by a particular crop from year to year; ( ) variation from region to region and climatic zone to climatic zone: ( ) differences in loss assessment methodologies; ( ) identification of the viral etiology of the disease; variation in the definition of the term 'losses' and ( ) chilli is the major vegetable and spice crop grown in thar desert areas of rajasthan. leaf curl disease (chlcd) is one of the major constrains in chilli cultivation faced by farmers and cause yield loss up to %. a survey was conducted in major chilli growing areas of thar desert; bikaner, nagur, jodhpur and jalore districts of rajasthan during november, to understand the present status of leaf curl disease in chilli. among the four district surveyed for chlcd, the disease incidence was recorded maximum (up to %) in jodhpur district followed by jolore district (up to %). no relation was found between the disease incidence and varieties. the major varieties grown in these area are; mehsana, rch (mandoria), haripur raipur, mathania and local cultivars. the number of whitefly was also counted in top, middle and bottom leaf of chilli grown in these areas. the average number of whitefly per plant ranged from . to . . more number of whitefly ( . ) was recorded in jodhpur district and lowest ( . ) in jalore district. total dna was extracted from three leaf curl infected samples from each district and tested for the presence of begomovirus using coat protein (cp) and dna-b specific primers. all the samples were positive for cp and dna-b amplifications by pcr. the cloning and sequencing of selected cp gene and dna-b fragments are in progress. the preliminary investigations shows that the leaf curl disease of chilli is widespread in the arid region of rajasthan and may be caused by begomovirus associated with satellite dna-b. bittergourd (momordica charantia) is an important vegetable crop of kerala. the crop is affected by several diseases of which mosaic is a prominent one. a field experiment was conducted to evaluate the efficacy of potentised resistance inducing substances (ris) viz., mosaic affected bittergourd plant tissue, ash of mosaic affected bittergourd plant tissue, plumbago and salicylic acid for control of bittergourd mosaic in march . ris were applied as drench and foliar spray at three potency levels twice, before flowering of the crop. the experimental crop was grown as per the package of practice recommendations in split plot design with five replications per treatment. the disease incidence, disease severity and yield of the crop were recorded. the result of the experiment shows that spraying was more effective than drenching of treatments for reducing mosaic incidence and severity. among treatments, infected plant extract at potency was the most effective one for reducing mosaic incidence and it showed the maximum incubation period and minimum disease severity. the spray application of treatments produced significantly higher yield than drenching. among the treatments, ash of infected plant at and potency and infected plant extract at potency were on par and produced comparatively higher yield. elephant foot yam (amoprhophallus paeoniifolius), colocasia (colocasia esculenta) and tannia (xanthosoma sagittifolium) are the major edible aroids cultivated in india. the elephant foot yam cultivation is gaining importance due to its high production potential, nutritional and medicinal values and good economic returns. all these aroids are vegetatively propagated and viral diseases are spreading through planting materials. ctcri has the mandate of producing healthy planting materials of these edible aroids. accurate diagnosis and identification of the virus is essential for production of healthy planting material and effective management of the disease. though occurrences of viral diseases on edible aroids in india were known in s, not much attention was given for detection and identification of the virus involved. in case of elephant foot yam - % mosaic incidence was observed with varying symptoms of mosaic, puckering, filiformy etc. in colocasia and tannia, - % incidence was noticed. rt-pcr amplification with potyvirus group specific primers and subsequent cloning and sequencing of the amplified product has confirmed the association of dasheen mosaic virus (dsmv) with all the three edible aroids cultivated in india. the complete full length coat protein gene of dsmv infecting elephant foot yam was cloned in pgem-t vector and sequenced. further sequence analysis revealed that the cp of dsmv consisted of nucleotides and the utr comprised of nucleotides. blast and phylogenetic analysis showed highest similarity of % with that of dsmv isolate af , reported from usa. the deduced amino acid sequence of cp had . - . % identity with other dsmv isolates. blast analysis of the partial cp gene sequences of colocasia and tannia also confirmed that the virus involved is dsmv. rt-pcr analysis of large number of samples from all the three crops confirmed that the potyvirus group specific primers (mj and mj ) are good for rapid detection of dsmv in these crops. dsmv specific biotinylated cdna and digoxigenin labelled crna probes were also prepared and dsmv in elephant foot yam was detected through nucleic acid spot hybridization. yellow leaf disease (yld) caused by sugarcane yellow leaf virus (scylv) is a recently recorded disease in india and is found wide spread throughout country. in popular varieties, the disease incidence varied from to . % and attained epidemic levels under field conditions. detailed studies on the impact of yld on sugarcane revealed that the virus infection significantly reduces various cane growth parameters, cane yield and juice quality. sequence comparisons of the coat protein (cp) and movement protein (mp) of scylv isolates from india and database sequences showed a significant variation between indian isolates and the database sequences both at nt and aa level in the cp/mp coding regions. the significant variation in our isolates with the database isolates, even in the least variable region of the scylv genome showed that the population existing in india is different from rest of the world. further, comparison of partial sequences encoding for orf and revealed that yld in sugarcane in india is caused at least by three genotypes viz., cub, ind and bra-per, of which a majority of the samples were found infected with cuban genotype (cub). the genotype ind was identified as a new genotype and this was found to have significant variation with the reported genotypes. we have identified specific primers from cp region of the virus and optimized rt-pcr conditions to diagnose the virus. this assay has been found efficient in detecting the virus in asymptomatic plants and tissue culture derived seedlings. elimination of the virus through meristem culture has been demonstrated to purify the virus from the infected planting materials and this technique needs to be adopted to supply disease-free planting materials for effective management of the disease. studies are also in progress to identify the yld-resistant sources in sugarcane germplasm to initiate breeding for yld-resistance in sugarcane. mycoviruses are viruses that infect fungi. they have been identified in all major fungal families. in the present scenario, mycoviruses are the important means of biocontrol of plant fungal pathogens. most identified fungal viruses have double stranded rna genomes, often with more than one dsrna present per virus particle, and have been spherical in shape. these viruses are mostly vesicle bound, as other viruses have protein coatings. to be a true mycovirus, they must demonstrate an ability to be transmitted-in other words be able to infect other healthy fungi through anastomosis and spores. mycoviruses lead 'secret lives', reduce the ability of their fungal hosts to cause disease in plants. this property, known as hypovirulence (hypovirulence is a term used to describe reduced virulence found in strains of pathogens), this phenomenon was first observed in cryphonectria (endothia) parasitica (chestnut blight fungus) on european castanea sativa in italy, where naturally occuring hypovirulent strains were able to reduce the effect of virulent ones. these slower growing hypovirulent strains of c. parasitica contain a single cytoplasmic element of double-stranded rna (ds rna) similar to that found in mycoviruses that was transmitted by anastomosis in compatible strains through natural virulent populations of c. parasitica. hypovirulence has also been reported in many other fungal plant pathogens, including rhizoctonia solani, gaeumannomyces gramini var. tritici, ophiostoma ulmi, sclerotinia homoeocarpa, diaporthe ambigua alternaria alternata, and fusarium sp. etc. hypovirulence has attracted attention owing to the importance of fungal diseases in agriculture and the limited strategies that are available for the control of these diseases. it reduces the use of toxic fungicides which also affect the plant growth. the symptoms resulted by the mycoviruses are reduction in growth, reduction in pigmentation and sporulation, excessive sectoring and aerial mycelial collapse. these are the consequences of alteration in complex physiological and biochemical processes involving interaction between host and virus. cassava (manihot esculenta crantz.) is the major tuber crop in peninsular india, it is grown in an area of . lakh hectares with the annual production of . million tonnes both for direct consumption and the starch grain (sago) producing industries, mainly in the southern states of tamil nadu, kerala and andhra pradesh (fao ) . in tamil nadu, cassava primarily produced for sago producing industries where it is considered as an industrial crop rather than food crop, so the resource rich farmers are cultivating the cassava as irrigated crop in their fertile land and the poor farmers are raising the crop under rainfed conditions. in south india in addition to cassava there is a practice of intercropping important vegetable crops like, tomato, brinjal, legumes and gourds in cassava fields since all the above mentioned crops are short duration and are money spinners for the farmers. unfortunately, the major production constraint in these vegetable crops including cassava is the geminiviruses belonging to the family of in recent years there has been growing concern regarding the standard of scientific researches in india. the strengths, weaknesses, opportunities and threats (swot) analysis on indian scientific research reviewed the progress of science during the last six decades. although the 'strengths' were highlighted in good measure, it was the list of 'weaknesses' that called for attention to upgrade the standard of research and 'opportunities' that provide scope for overall scientific growth. a comparison between india and other countries in terms of research papers published revealed that india's contribution to science has come down enormously. what ails indian science? should we compare the growth of indian science with other developed countries? what criteria should be adopted to judge the quality and standard of scientific research? how to motivate the scientists to improve their scientific output? how do motivate the scientists to improve their scientific output? how do indian journals perform in maintaining quality? this paper analyses critically the scientific journals around the world, based on the scores allotted by the national academy of agriculture sciences (naas) in and for and journals respectively. in general, the indian journals performed poorly irrespective of the disciplines with only - % in the high standard. the paper dealt with the reasons for low impact factor, the anomalies in the allotment of scores to wide spectrum of the journals and the disadvantages the scientists face with the scoring system. a case study was presented of an institute with over scientists whose publications were analyzed to discuss the merits and demerits of the system. the performance of the journals published by prestigious academics, societies and councils was also projected. the paper concluded with the need for enhancing the image of the country through research publications in high standard journals and the role of various scientific bodies with shore and long term measures. poster session herpes simplex virus (hsv) keratitis is a leading cause of corneal blindness throughout the world. the infection can be diagnosed by clinical manifestations but in case of atypical ocular cases, laboratory diagnosis is more helpful in timely management of disease. collection of corneal scrapings in all cases of stromal and epithelial keratitis may not be possible, but collecting tear fluid is a convenient procedure causing less discomfort to the patients. therefore, the present study was intended to evaluate the suitability of tear specimens for detecting hsv by polymerase chain reaction (pcr) and immunofluorescence (ifa). tear fluid and corneal scrapings were collected from patients of suspected herpetic keratitis. hsv- antigen was detected by ifa using rabbit anti-hsv antibodies. pcr was performed to amplify bp region of thymidine kinase (tk) coding gene and bp region from dna polymerase coding gene of hsv. out of patients hsv antigen was detected in ( . %) of corneal scrapings and ( . %) of tear specimens and in ( . %) patients from both the specimens. hsv gene could be amplified in ( . %) of corneal scrapings and ( . %) of tear fluids and in ( . %) patients from both the specimens. although, corneal scraping seemed to be marginally superior material for detection of hsv, tear fluid may also serve as an appropriate alternative clinical specimen, due to ease of collection and least discomfort to the patients. in either cases pcr detected higher number of hsv cases than ifa. therefore if and when feasible, both ifa and pcr should be used simultaneously on each specimen to obtain best results. cytokines play a key role in the regulation of immune responses. in hepatitis c virus infection (hcv), the production of inappropriate cytokine levels appears to contribute to viral persistence and to affect response to therapy. il- is produced by a variety of cells including t cells, phagocytes and fibroblast. cytokine genes are polymorphic at specific sites, and certain mutations located within coding/regulatory regions have been shown to affect the overall expression and secretion of cytokines in patients with hcv infection. to correlate the serum levels and polymorphism of il- gene in chronic hepatitis c patients and healthy controls. forty patients positive for hcv rna attending the medicine out patient department and wards of lok nayak hospital, new delhi as well as forty healthy controls were enrolled for the study. the serum level of il- was detected by using elisa. genomic dna was extracted from whole blood of hcv infected patients and healthy controls by using accuprep genomic dna extraction kit according to manufacture's instruction. the genotyping of il- promoter (- variant) was carried out by pcr and direct sequencing using the method of patricia woo et al. . the serum level of il- was significantly down regulated in hcv infected chronic patients as compared to the healthy controls. genotyping of - promoter variant of il- was performed by pcr and direct sequencing. il- polymorphism in the g/g, g/c and c/c allele was non significant when compared to hcv patients and healthy controls. the il- serum levels were significant among hcv infected patients when compared to healthy controls. the polymorphism in the promoter region of il- (- ) was found nonsignificantly associated in hcv patients compared to healthy controls. in conclusion, the present study suggests that the host il- polymorphism alone may not play a significant role in the outcome of hcv infection. acute gastroenteritis (age) is a global health problem and has been associated with multiple etiological agents, which include bacteria, protozoa and viruses. viral gastroenteritis is considered as the second most common illness in children after upper respiratory tract infection. among enteric viruses, rota, noro, enteric adeno, astro and enterovirus are found to be associated with gastroenteritis. although, association of enteric viruses has been established in children hospitalized for age no such data is available from hospitalized children other than enteric infections. to determine the prevalence of enteric viruses circulating in hospitalized children. fecal samples, n = ( symptomatic and asymptomatic for age) were collected from children \ year of age from three different hospitals across the city of pune from june to feb. . detection of group a rotavirus was carried out by using antigen captured elisa. rt-pcr and pcr was carried out for the detection of norovirus, enterovirus, astrovirus and enteric adenovirus detection by using primers targeted to rdrp gene, ncr gene and consevered gene for serine protease and hexon gene respectively. out of fecal samples tested for enteric viruses in age cases, the prevalence of rota, entero, noro, enteric adeno and astrovirus were . % ( ), . % ( ), . % ( ), . % ( ) and . % ( ) respectively. however, the presence of these viruses in the asymptomatic cases (n = ) was detected at . % ( ), . % ( ), . % ( ), . % ( ) and . % ( ) levels respectively. mixed infections of enterovirus and rotavirus were found in both symptomatic . % ( ) and asymptomatic cases . % ( ). however, mixed infection of enterovirus with adenovirus were found only in asymptomatic cases . % ( ). no marked difference was observed in the seasonal pattern of all viruses in the patients with or without gastroenteritis. the findings of this study document highest circulation of rotaviruses in patients symptomatic and asymptomatic for age. the entero and noroviruses remain second most important enteric viruses in these patients. influenza in humans is a major public health concern and the understanding of its evolution in the light of its ''antigenic drift'' helps prediction of epidemics and update of yearly influenza vaccine. to antigenically characterize influenza a (h n ) isolates and study antigenic drift during to in pune city. patients with influenza like illness were identified using a strict case definition from dispensaries located in different areas in pune and clinical samples (ns/ts) were collected after obtaining informed consent. these clinical samples were processed in vivo (in fertile eggs) and in vitro ( overall, an additional ( . %) positive cases of dengue could be detected when ns antigen assay was also used in the study. highest ns antigen positivity was encountered among the samples collected on the rd day of fever whereas mac elisa for anti igm antibody was positive after th day and gradually there was an increase in the positivity towards the convalescent phase of the disease. the results of this study indicate that ns antigen based elisa test can be an useful tool to detect the dengue virus infection in patients during the early acute phase of disease since appearance of igm antibodies usually occur after fifth day of the infection. concurrent use of both diagnostic assays namely ns antigen as well as mac elisa will improve the overall detection of dengue infection. early detection of acute dengue virus infection is crucial to provide timely information for the management of patients. human parvovirus b , a member of the parvoviridae family, is a pathogen associated with a wide variety of diseases. most commonly, it causes childhood rash erythema infectiosum, but in some cases more serious symptoms such as persistent arthropathy, critical failures of red cell production causing transient aplastic crisis, this infection in pregnancy causes hydrops fetalis and myocarditis. traditional immunosuppressive therapy being unsuccessful, anti-viral therapy might be worthy of consideration. functional annotation would provide role of viral proteome in its survival and pathogenic mechanisms. svmprot functional family annotations of vp protein had deciphered its zincbinding, coat protein, outer membrane, chlorophyll biosynthesis, dna repair and calcium-binding nature. vp protein is having a key role in viral assembly of b virus and being non-homologous to human proteome, it was identified as an attractive molecular target for structure based drug discovery. the vp protein crystal structure was energy minimized using charmm. a structure based virtual screening method was applied using ligandfit to identify potential inhibitors of vp protein from chembank database and ten potential human parvovirus b vp inhibitors were proposed. prism genetic analyzer. the drafting of the sequences was performed using bioedit software and were submitted in genbank. for phylogenetic interpretation denv representing the full extent of genetic diversity in denv- , denv- and denv- were collected from genbank. neighbor joining algorithm was implemented with bootstrap value of , replicates for phylogenetic inference using mega . . . the genomic region to (c-prm gene junction) of denv were amplified directly from patient serum. twelve of samples were positive for dengue viral rna. of these were dengue type , was dengue type and were dengue type . for molecular epidemiological survey and genotyping of the sequences more than sequences from different geographical areas including sequences form previously reported north indian isolates were compared with our present data set. the critical analysis of the sequences revealed: dengue type sequences were clustered within sub-type of genotype iii and all the sequences of den- clustered along with genotype iii. thus, among the dengue types , and currently circulating in north india, dengue type , genotype iii, being the predominant one followed by, genotype iii of dengue type . although there is no specific treatment or vaccine available currently, the confirmative rapid diagnosis based on detection of viral nucleic acid or igm antibodies in serum, an indication of recent infection, helps in epidemiological monitoring, symptomatic treatment of patients and determining prognosis. serological detection of anti-cgv igm antibodies was performed using rapid immuno-chromatographic assay (rica) and igm-antibody capture enzyme linked immunosorbant assay (mac-elisa). eighty convalescent sera were tested by rica and of them were found positive for anti-cgv igm antibodies. twenty-five anti-cgv igm antibody rica positive sera were further assayed using mac-elisa. more sera from the patients are currently being tested to compare the sensitivity of these two serological assays in anti-cgv igm antibody based early serological diagnosis of cgv infection and the findings will be presented. thus the present study was designed to evaluate the utility of multiplex pcr (mpcr) for simultaneous and rapid detection of dengue and chikungunya viral infections. seventy-two acute phase blood samples from clinically suspected dengue cases were subjected for dengue and chikungunya uniplex pcr using dengue genus specific primers and e gene specific primers for chikungunya virus as well as multiplex pcr was developed for simultaneous detection of dengue and chikungunya infection. standard strains of dengue and chikungunya virus were used as controls. of the clinically suspected dengue samples were found to be positive for dengue viral rna by dengue uniplex pcr as well as dengue chikungunya mpcr whereas none of the samples were positive for chikungunya virus infection by both uniplex chikungunya pcr and dengue chikungunya mpcr. the result of dengue and chikungunya uniplex pcr was found to be % concordant with dengue chikungunya multiplex pcr. dengue chikungunya multiplex pcr was found to be a potential rapid test to detect dengue and chikungunya viral infections simultaneously in clinical samples. sheetal malhotra, neelam marwaha, karan saluja, ratti ram sharma department of transfusion medicine, pgimer, chandigarh transmission through blood and blood products can be reduced to a great extent by efficient and reliable testing of the blood. the newer fourth generation elisa assays simultaneously detect antibodies against hiv- and and the presence of p antigen and thus shorten the window period to about days, as compared to days with third generation elisa. to compare the hiv seroprevalance among blood donors using fourth generation elisa (antigen-antibody) versus third generation elisa (antibody) assay. this was a prospective study involving blood donors of which were voluntary donors ( being students and being non students) and were replacement donors. sex workers are one of the core group for transmission of sti/hiv and as a ''bridge group'' to the general population. accordingly, highest priority is given to this group in targeted intervention for prevention of hiv/aids. here we are describing one such female sex worker who was harbouring concomitant sti including viral sti. a year old female sex worker was brought to the sti clinic of a tertiary care hospital by ngo with complaint of genital discharge for days. on per speculum examination, cervix was slightly erythematous, tender with mucopurulent discharge. there was no vaginal discharge or ulcer in anogenital area. however, there was a wart at lateral wall of vagina. as per naco syndromic management guideline, treatment was given for n. gonorrhoeae, c. trachomatis and hpv. cervical swab was taken and subjected to various microbiological investigation for the detection of sti viz n. gonorrhoeae, c. trachomatis, t. pallidum, candida spp., t.vaginalis, hsv- , hsv- , hiv, hbv, hcv, hpv and m. contagiosum. saline wet mount showed pus cells, but no yeast cells or trophozoite of trichomonas vaginalis. gram stained smear showed more than four polymorphonuclear leucocytes in the absence of gramnegative intracellular diplococci and a presumptive diagnosis of non gonococcal urethritis was made. no organism was isolated on any culture media after appropriate incubation. cervical swab was negative for antigen of c. trachomatis. serum was tested positive for hbv, hcv, hsv- and t. pallidum though it was seronegative for hiv. in the present case, the female sex worker was harbouring four viral sti viz hsv- , hbv, hcv and hpv alongwith t. pallidum. however clinically she was diagnosed and treated accurately only for genital wart while cervical discharge due to hsv- was misdiagnosed. it is necessary to try to test alternative approaches such as periodic presumptive therapy of viral sti, because this will not only boost up the efforts of sti control in the target group but also help in hiv control. alternatively, regular clinical and laboratory screening for viral sti may be tried. densonucleosis viruses (dnv) belong to parvoviridae family. they are the etiological agents of insect's disease known as densonucleosis, which leads to death or loss of vital functions of the infected insect. densonucleosis virus of mosquitoes has generated lot of scientific interests because of its tremendous potential in biological control and its application as a transducing vector. earlier, we have reported the isolation and characterization of a dnv from aedes aegypti mosquitoes and its prevalence among different ae. aegypti populations from india. there are reports suggesting that when aedes albopictus mosquitoes co-infected with dengue- and dnv, the multiplication of den- is suppressed. the present study focus on the effect of coinfection of ae. aegypti mosquitoes with dnv and chikungunya virus (chik). the first instar mosquito larvae were infected with dnv and the emerging dnv infected females were then infected with chikv by oral feeding. thus obtained chik infected female mosquitoes were analyzed by real time pcr for both dnv and chikv on alternate days post-infection, up to the th day. the data showed no significant difference in the multiplication of either of the viruses after co-infection. results suggest that chikv neither stimulates the replication of dnv nor is its own replication suppressed due to co-infection. this study forms an initial step in understanding the role played by such endogenous viruses on the vector dynamics. chandipura virus pathogenesis is manifested as encephalitis in young children with a very high mortality rate. this damage could be due to direct replication of the virus in brain parenchymal tissue or immune system mediated. this study aims at elucidating the role of brain infiltrating lymphocytes in pathogenesis using mice as the model system. mice were inoculated intracerebrally with the virus and the perfused brain tissue was used to isolate the lymphocytes. control mice were inoculated with an equal amount of media. in order to standardize the procedure for isolation of lymphocytes from brain tissue, splenocytes were processed to isolate the lymphocytes using histopaque density gradient method. methods to isolate lymphocytes from brain tissue as described by earlier workers were tested for the ease and efficiency of procedure using known suspension of lymphocytes from spleen. percoll density gradient method provided optimum yield of lymphocytes with an ease of handling. in this, brain cell suspension used to prepare % percoll is layered over % percoll prepared using media in : ratio. density gradient centrifugation is carried out at g for min at °c to obtain lymphocyte layer at the interface. leishman staining was performed to analyze the morphological characteristics of isolated lymphocytes. normal lymphocytes showed dark blue stained nucleus. some bigger sized cells with diffused nucleus characteristic of atypical lymphocytes were observed and some of the cells were surrounded by hair like structures. phenotypic characterization was carried out using flow cytometry. the presence of cd + , cd + and cd + cells was observed. the percentages of cd + , cd + and cd + cells was found to be . %, . % and . % respectively in the lymphocytes isolated from infected animal and . %, . % and . % respectively from control animal. hence, cd + cells showed maximum infiltration after infection. (santosh et al. ; pradeep et al. ). in the present study chikv suspected blood samples were collected and the acute phase samples were subjected to rt-pcr for the presence of virus specific rna by using the primer pair dvrchk-f/dvrchk-r as described by us earlier (naresh kumar et al. ). the convalescent phase samples were screened for chikv specific antibodies by using sd bioline chikungunya igm rapid test. six sets of primers were designed to amplify the complete nsp and complete structural genes of chikungunya virus. the products were further gel purified, cloned in ptz r/t vector and the recombinant clones were sequenced and submitted to the genbank. the complete ns gene and structural genes were compared with other available sequences in the genbank. sequence analysis results will be presented. the present study discusses these aspects in detail. . some of these phages (viz. v , v ) showed plaques at °c but not at °c. thus they seem to be lysogenic. for propagating and increasing the titre of all the above isolates, various previously described methods were attempted, but none of these methods were satisfactory. but when siliconized glassware and plastic-ware were used, propagation was successful. we showed that siliconization of glassware and plastic-ware was essential for the propagation of our mycobacteriophage isolates v , v , v , v and v . also, phage dilution medium (pdm) as described by chaterjee et al. ( ) was found to be effective for picking out of the plaques made by the phages. in this way, the phage isolates were propagated up to p . the various passages of the phage isolates v , v , v , v and v (i.e. original, p , p and p ) were stored at - °c. the four major routes of transmission are unsafe sex, contaminated needles, transmission from an infected mother to her baby at birth (vertical transmission) and breast milk. screening of blood products for hiv has largely eliminated transmission through blood transfusions or infected blood products in the developed world. in , globally, about million people died of aids, . million were living with hiv and . million people were newly infected with the virus. hiv infections and aids deaths are unevenly distributed geographically and the nature of the epidemics vary by region. more than % of people with hiv are living in the developing world. there is growing recognition that the virus does not discriminate by age, race, gender, ethnicity, socioeconomic status-everyone is susceptible. however, certain groups are at particular risk of hiv, including men who have sex with men (msm), injecting drug users (idus), and commercial sex workers (csws). the present study indicates the prevalence of hiv infection among the people residing in the northern region of india predominantly among the foothills of the himalayas. the study was carried out on the patients visiting herbertpur christian hospital (a unit of emmanuel hospital association) under the integrated counselling and testing centre scheme at the respective hospital during the - . the study indicates the screening of people groups residing in the respective area through community health schemes. the diagnosis of the hiv infection is done by three types of assays namely. the tridot method which is the rapid method of diagnosis followed by the. hiv coombs test which involves the dot immunoassay principle. the third assay is the enzyme linked immunosorbent assay (elisa). the number of patients screened during the period of september to march is which include patients coming from four different states namely haryana uttarakhand uttarpradesh and himachal pradesh. the number of people who were tested positive are and the number of people who were tested negative are . the people tested positive are sent to the higher centre for other confirmatory tests such as pcr and western blot analysis. these patients are sent for treatment and prophylaxis at a respective recognised centre in dehradun. the present study determines a consistent community hiv screening and treatment approach through diagnostics counselling and awareness programmes. classical swine fever (csf) also known as hog cholera is a highly contagious and fatal disease of swine. csf became rapidly a major issue of pig industries. it still causes important economical losses worldwide. it is considered as a major health problem of swines in india. during the month of august to october there was an outbreak of classical swine fever in bihar. from three districts darbhanga, patna and supol, total numbers of different infected tissue samples like kidney, spleen and lymphnode were collected from the dead morbid/pigs. total rna was isolated from % homogenate of infected tissues in sterile pbs by tri-reagent (sigma, usa) according to the manufacturer's instructions and cdna was prepared by using commercial available kit. the cdna was stored frozen at - °c until used. for the molecular detection of classical swine fever virus specific nested pcr amplification of e and ntr was done along with ns b and e rns amplification. primarily these samples were found positive with these primers. further confirmation by sequencing was done by cloning of these pcr products in pgem-t easy vector. e and ntr sequences were considered for phylogentic analysis along with complete available sequences of csfv. nucleotide sequence alignments were carried out using the clustalw program (dnastar) and phylogenetic tree analysis (dnastar) showed that ntr have close proximity with taiwan strain (accession no. ay ) and e shows close proximity with chinese isolate csfv- (accession no. af ). peste des petits ruminants (ppr) and sheeppox are oie notifiable diseases of small ruminants especially sheep and goat. both the diseases are economically important, in enzootic countries like india and are major constraints in the productivity of animals. considering the geographical distribution of both ppr and sheep pox infections and prevalence of mixed infection, in the present study, safety and potency of the experimental duel vaccine comprising attenuated strains of thermostable-ppr virus (pprv-revati, p- ) grown at °c and attenuated sheep poxvirus (sppv-srinagar, p ) was evaluated in local non-descript sheep. experimental animals were grouped into four groups and each group was comprising six animals, received doses ( tcid ), dose ( tcid ) and / th dose of vaccines and normal saline as control in ml volume subcutaneously, respectively. serum samples were collected on , , , and th day post vaccination. sheep simultaneously immunized with ml of vaccine consisting of either or doses of each of pprv and sppv were monitored for clinical and serological responses for a period of - weeks post-immunization (pi) and post challenge (pc). specific immune responses i.e., antibodies directed to both pprv and sppv could be demonstrated by ppr competitive elisa kit and capripox indirect elisa, respectively following immunization. all the immunized animals' resisted infection when challenged with virulent strain of sppv (srinagar isolate at p- ) on day dpi, while in contact control animals developed characteristic signs of sheeppox. the challenge of the sheep against ppr was not carried out, however, the antibody titre after immunization determined by snt and elisa, indicated that protective titre, as per earlier report on the goats. dual vaccine was found safe at higher dose and induced protective immune response even at lower dose ( tcid ) in sheep, which was evident from sero-conversion as well as challenge study with sppv. the study indicated that both the viruses are compatible and did not interfere with each other in eliciting immune response, paving the feasibility of use of this dual vaccine in combating both infections simultaneously. goatpox is one of the highly contagious, oie notifiable and economically important viral diseases of goats. the disease is caused by goatpox virus (gtpv) is classified of the genus capripoxvirus in the family poxviridae. the disease incurs severe economic losses in terms of high morbidity in adults and heavy mortality in young kids and is a major constraint in goat farming in india. considering the enzotic nature and economic impact of the disease, it is all important to control the infection by developing an effective vaccine. recently, vero cell based a live attenuated goat pox vaccine; using gtpv uttarkashi isolate (p ) has been developed in authors' laboratory and evaluated in goats. the vaccine was found safe, potent and immunogenic experimentally and even at field trials. the vaccine has been evaluated at large-scale at different regions of the country and found suitable for mass vaccination. however, the longevity of potency was not evaluated. therefore, a long term potency trials were studied for a period of years with annual challenge by using virulent goatpox virus and sero-monitoring. a sufficient number of hill goats has been vaccinated with dose of vaccine ( . tcid /ml) and monitored for clinical and serological response. every year, significant number of vaccinated (n = ) and control animals (n = ) were used for challenge with virulent strain ( . srd /ml, gtpv mukteswar). sera of pre-and post-challenged ( dpc) animals including controls have been collected and monitored for serological response in the form of specific antibody production by snt and indirect elisa. all the vaccinated animals were protected on challenge, whereas, all unvaccinated controls developed infections. the same has been reflected in sero monitoring of collected sera. so the developed live attenuated goat pox vaccine was found safe, immunogenic and potent for a period of years of immunization and suitable for mass scale vaccination in control and eradication of goat pox along with a/are suitable diagnostic tool/s in goatpox enzootic country like india. rotavirus infection in avian species varies from subclinical infections to outbreaks of diarrhea. the economic significance of rotaviral enteritis to the poultry industry has not yet been defined, but by analogy to the situation in mammals, it is likely to be significant. unlike the extensive studies performed on rotavirus infection in humans and animals, limited studies have been carried out to determine the extent of exposure of poultry birds to rotaviruses. to determine the prevalence of avian rotavirus antibodies in commercial broiler chickens. a total of chicken serum samples were collected from the lairage of a poultry slaughter house where birds from four different broiler farms in and around pune city were supplied to. the serum samples were tested by an igg antibody capture elisa wherein purified chicken rotavirus ch was used as coating antigen. sera from specific pathogen free (spf) chick (n = ) served as negative control in the test. cut off was calculated as mean negative control ? sd (standard deviation). s/co (mean sample od /cut off) values above ( . - . ) in % ( / ) serum samples were indicating positivity to rotavirus antibodies. the result of the study indicates exposure of the birds to avian rotavirus or similar agent that is circulating in pune city. bluetongue has become established in south india causing regular outbreaks in sheep. btv serotypes , , and were isolated from native sheep of andhra pradesh. the other serotypes circulating in the state need to be identified. however the major constraint is the serotype identification. to overcome the difficulties of traditional serotyping methods (neutralization tests), nucleic acid based tests are being tried. rt-pcr for serotyping was standardized using primers specific to vp gene of btv- , and serotypes. rt-pcr resulted in bp product of btv- , bp product of btv- which was defined by specific primers. however non specific amplification at two different sites i.e. bp and bp was noticed for btv- . specificity of rt-pcr was evaluated. btv- and btv- specific primers could amplify only btv- and btv- respectively where as btv- type specific primers amplified not only btv- but also btv- and btv- . nucleic acid sequence data obtained from btv- pcr product and btv- cloned products were specific to vp gene of btv- and btv- respectively. however, and bp products of btv- were identical to vp gene of btv- , , , , and and vp gene of btv- , and respectively, indicating the non specific amplification of btv- . foot and mouth disease is the most contagions and highly economically impotent disease of cloven footed animals. the disease is controlled by regular vaccination using the vaccine produced from the virus grown in the cell culture. the vaccine strain used for vaccine production is selected from the field isolates based on the adaptability and growth kinetics in bhk cells and antigen coverage. however the field viruses need to be passaged several times to adapt in tissue culture. passage of field viruses in tissue culture may results in development of mutants whose genetic makeup may differ from the field samples also some of the field strains may fail to adapt or may grow poorly in the tissue culture, thus the efficiency of the vaccine gets affected. structural proteins of fmdv carry the sequences which determine the serotype specificity and immunogenicity. thus one may replace the gene coding for structural proteins from the full length cdna copy of the vaccine strain that has been adapted to the tissue culture with the poly-structural protein gene (pi) so that the chimeric virus gets the serotype specificity of the field strain besides retaining the other characteristics that are needed for a vaccine virus. we have made replication competent fmdv asia i full length genome and cloned under t and cmv promoter separately in plasmid vectors. bam h sites were created for inserting pi- a gene of other field strains. the p - a of type 'o' vaccine strain was amplified directly from the cattle tongue material, cloned in plasmid vector and studied the specificity by sequence analysis and gene expression. we have introduced 'o' p - a gene into the full length construct devoid of asia structural protein gene, p - a. the in vitro transcribed rna in case of t promotered construct and plasmid dna in case of cmv promotered construct were transfected into the bhk cells. after the passaging the virus obtained was studied for the speciality. this approach may be used not only for rapid selection of vaccine strain and also as a repository of the cdna copy of the virus. the p is composed of a, b, c and d (vp , vp , vp , and vp ) respectively of which the vp is the most immunogenic and subunit vaccine produced with vp alone was able to induce high level of neutralising antibodies. thus to control the disease in india polyvalent vaccine consisting of the inactivated virus of all the three serotypes are in use. however the conventional vaccines have several drawbacks which include safety and temperature sensitivity. hence alternatively sub-unit vaccines consisting of vp protein has been tried. however this showed limited success due to the antigenic variations occurring in the field viruses thus escaping the neutralization from the antibodies generated from single cloned protein. hence the present study was undertaken with an objective to include all the neutralizing epitopes present in the three serotypes by linking vp ( d) genes and produce a poly valent protein for using as poly subunit vaccine. in this study we have constructed a cassette by linking the genes of three serotypes 'o' ( bp), 'a' ( bp) and 'asia ' ( bp). these genes were cloned individually in commercially pbsk vector and confirmed by sequence analysis before linking in pc dna vector. the linked gene construct was sub-cloned in pet expression vector. the expression of the protein gene from the pet vector was induced with iptg and analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (sds-page). a fusion protein of size kda was observed in page gels. since the protein contains his residues from the vector at the n-terminal end, affinity purification was carried out using nickel nitrilo-tri-acetic-acid (ni-nta) agarose matrix. the immunoreactivity of the purified protein was assayed by western blot with the anti fmdv type 'o' and 'asia ' specific sera. the may be used as a subunit vaccine. silkworm diseases caused by viruses, bacteria, fungi and protozoans form major constraints for the silk cocoon production in all the sericultural countries and among these silkworm viral diseases viz., nuclear polyhedrosis and infectious flacherie caused by bmnpv and bmifv cause severe crop loss. the traditional disease management strategies include prophylactic measures and use of disease free silkworm eggs. the prophylactic measures such as disinfection of silkworm rearing house and appliances, egg surface, silkworm bed disinfection and rearing surroundings. the disinfectants used presently in sericulture are either formaldehyde or chlorine based products, but these chemicals are neither eco-nor user-friendly. the awareness about health hazards caused by formaldehyde and environmental pollution caused by cl necessitated the development of eco-and user-friendly disinfectant products for use in sericulture. these include alternative disinfectant products developed using biodegradable chemicals and plant based ingredients by apssrdi, hindupur and central silk board for the management of silkworm diseases in india. the ideal disinfectant for sericulture would be the one which can inactivate silkworm pathogens of diverse origin and economical for sericulture. the paper discusses on the disadvantages of hcho and cl based disinfectants and advantages of eco-and user-friendly disinfectant for the management of silkworm diseases especially the ones caused by viruses. the baculovirus expression vector system (bevs) is widely used for the production of high levels of properly post-translationally modified, biologically active and functional recombinant proteins and has facilitated basic biomedical research on protein structure, function, drug discovery and the roles of various proteins in disease. bevs is based on the introduction of a foreign gene into nonessential for viral replication genome region via of homologous recombination with a transfer vector containing target gene. the resulting recombinant baculovirus lacks one of nonessential gene (polh, v-cath, chia etc.) replaced with foreign gene encoding heterologous protein which can be expressed in cultured insect cells and insect larvae. insect cell-bev system is widely used to produce recombinant proteins. bevs also eliminates concerns regarding pathogens that could potentially be transmitted to humans as it is non-infectious to vertebral animals. these features make silkworm system an ideal expression and delivery package for producing proteins of medicinal importance. the efficiency, low cost and large-scale production of proteins using bevs represents breakthrough technology that is facilitating highthroughput proteomic studies. the bevs has become a core technology for cloning and expression of genes for study of protein structure, processing and function; production of biochemical reagents; study of regulation of gene expression; commercial exploration, development and production of vaccines, therapeutics and diagnostics; drug discovery research; exploration and development of safer, more selective and environmentally compatible biopesticides. utilization of silkworm larvae and pupae as bioreactor with recombinant bmnpv producing foreign proteins extends the usages of silkworms. due to its large-size and high protein synthesis ability as well as the expediency in mass culture, silkworm is considered as good candidate for producing recombinant proteins. wssbv is the causative agent of a disease, which has recently caused high shrimp mortalities and severe damage to shrimp culture. wssbv has been found across different penaeid shrimp species. in order to develop a effective diagnostic tool, a wssbv genomic library was constructed by cloning wssbv genomic dna extracted from purified virions. in the present study wssv disease free (confirmed by pcr analysis) were collected from hatcheries from different areas of guntur and prakasam districts and analysed to study the effect of various physical parameters like temperature, p h , salinity and turbidity on the prevalence of above disease. the studies on the surface water temperature revealed fluctuations in the ponds ranging between to . °c in diseased ponds and . to . °c in healthy ponds. these results show definite influence of temperature on the prevalence of wssv. present day strategy in vaccine development is to include marker facility that helps in distinguishing antibody response due to vaccination vis-à-vis infection in vaccinated animals. such information becomes relevant for effective disease control programmes especially when using inactivated virus vaccines like foot and mouth disease (fmd). the antibodies generated in the animals, only through vaccination, is the measure of vaccine efficacy and safety. presently inactivated fmd virus (fmdv) vaccines are used to control the disease in the endemic countries like india. the quality assurance of the vaccine depends on the efficacy of the vaccine in generating protective antibody without causing subclinical disease due to improper inactivation. since protective antibody response in vaccinated animals can not be distinguished from that of infected animals one needs to assay the antibody response against non structural proteins (nsps) and the vaccine must be free of contaminated nsps. production of vaccine free of nsps requires the cumbersome method of virus purification which adds to the cost of the vaccine. alternatively one may develop a positive marker vaccine by including a foreign protein or epitope which is not expected to be present in the vaccine and the antibodies generated against which helps in detecting the vaccine related response. here we report a molecular approach by which we introduced a immuno-dominant epitope of green fluorescent protein (gfp) into the structural protein gene of foot and mouth disease virus vaccine strain asia ( / ). our laboratory has produced a mini-genome of fmdv asia that lacks structural protein gene (p - a) coding for all the structural proteins (vp - ) of fmdv asia as a vector (pcfl dasia ). the p - a of the asia vaccine strain was cloned separately into a plasmid vector and by successive pcr mutagenesis and cloning we have introduced nucleotide sequence corresponding to amino acid epitope of gfp into p - a gene. gfp epitope was inserted by replacement at n-terminal region of vp- which is not immunogenic. the modified p - a was expressed in e. coli and studied. the modified p - a gene with gfp epitope was inserted into the pcfl dasia to get full length replication competent cdna cloned under cmv promoter in pcdna (pcflasiagfp). this can be used to produce synthetic virus with gfp epitope that can generate antibodies not only against neutralizing epitopes but also against gfp epitope. presence of antibody against gfp epitope in the vaccinated animal will reveal vaccine efficacy. elisa against gfp can be used as a companion test not only for safety evaluation but also for quick evaluation of efficacy. further absence of nsp antibodies in the serum may reveal the quality of the vaccine in respect of safety. self replicating dna vaccines are developed to achieve robust immune response through enhanced antigen production and gamma interferon expression in vaccinated animals. since self replicating dna vaccines induce gamma interferon expression which helps in viral clearance such vaccines are expected to be useful to cure even the carrier and persistently infected animals. understanding the events that help in the elicitation of both the arms of immune response in vaccinated animals is necessary to understand the effectiveness of the vaccine. the work presented here deals with the immunological evaluation of a sindbis virus replicase based dna vaccine carrying linked fmdv vp genes in vaccinated guinea pigs. we have constructed self replicating dna vaccine vector and to the down stream of a sub genomic promoter we have inserted secretory signal followed by linked-vp genes of fmdv serotypes (o-a-asia ) with glycine and proline bridge in between. guinea pigs were vaccinated with the construct and the sera at days post vaccination were evaluated both for cellular response by studying the cd levels and by mtt and cytokine profiles by real time assays. the humoral response was evaluated by studying cd levels in the whole blood by facs analysis and serum antibody levels by snt and elisa. the animals were challenged with gp infective dose of fmdv type 'o' virus lesions were scored. further the replicative efficiency of the challenge virus was studied by ab elisa. the results showed that all the assays except antibodies against ab protein have positive correlation with the protection. as expected the titre of the antibodies against ab protein was lower indicating that the challenge virus replication was inhibited in the vaccinated animals. the limited studies conducted by us showed that self replicating vaccine has a potentiality to emerge as potent vaccine for fmd. ganjam virus (ganjv) belongs to the genus nairoviruses (family bunyaviridae). these viruses cause diseases in livestock. it has been isolated from different animal hosts and tick vectors from india. genus nairoviruses includes a total of tick-borne viruses, classified into serogroups. the important serogroups are crimean congo hemorrhagic fever (cchf) and the nairobi sheep disease (nsd). the main members of the nsd group are nsd and dubge viruses. their genome consists of three segments of single stranded rna, viz. s, m and l that encodes viral nucleocapsid protein, viral glycoprotein g and g and the viral polymerase respectively. ganjv is very closely related to (nsdv). nsdv is found in east and central africa, causes very high morbidity and mortality in livestock. the present study involves phylogenetic comparison of ganjv isolates from india with other nairoviruses based on complete n gene. it will help to understand the kind of nucleotide (nt) and amino acid (aa) changes that have occurred in ganjv strains from different geographical areas. eight strains of ganjv isolated at niv during - from different parts of india were used in this study. virus stocks were prepared in vero e cell line these were used as the source of viral rna. the n gene was amplified either as a complete gene in one reaction or in fragments whenever necessary. thus obtained sequences were analyzed; annotated to get a consensus sequence, aligned against the sequence of prototype strain of ganjv and other representative nairoviruses. the nt sequences were converted to aa sequences and analysis was done at both nucleotide and amino acid levels. based on what nt or aa phylogenetic tree was constructed and compared with other nairoviruses (cchf, dugv, hazv, kupv and nsdv) where complete s segment sequences were available gen-bank database (ncbi). the phylogenetic data at both the nt and aa levels showed that all the strains of ganjv form monophyletic lineage with the nsdv. cchfv and hazv together formed another clade, whereas dugv and kupv made a separate branch in the tree. the different ganjv strains showed - % difference with nsdv at the nucleotide level and - % difference at the amino acid level. hazv showed - % difference at the nt level and % difference at the aa level with ganjv as well as nsdv. the present data obtained suggests that ganjv and nsdv are minor variants of the same virus. diarrhoeal syndrome is one of the major concerns of the livestock industry. most of the diarrheic cases in animals go unnoticed and limited attention is paid on viral etiology. presence of large amount of fecal matter in animal shed acts as a source of infection for calves via drinking water, feed, or contaminated soil. keeping this in view, investigation was planned to detect the association of rotaviruses with diarrhea in dairy calves and to observe the genomic diversity among the circulating viruses in tarai area of uttarakhand. a total of diarrheic fecal samples collected from instructional dairy farm, nagla, pantnagar, uttarakhand were screened during the study. samples were collected from both cow calves and buffalo calves in - months of age. for the diagnosis of rotavirus, all the fecal samples were subjected to rna-electrophoresis after nucleic acid extraction. viral genome segments were visualized by silver staining. out of the total samples tested, seven were found positive in rna-page showing typical genome segments migration pattern of bovine rotavirus. in the given samples prevalence of bovine rotavirus was . % and % in cow and buffalo calves, respectively. on the basis of migration patterns of rotavirus in rna-page, group a were identified with typical : : : pattern. variation within movement of various genome segments among isolates of bovine rotaviruses was observed during the study that may be indicative of emergence of mutants in the circulating isolates. the vp gene based group a specific rt-pcr was standardized and all the isolates in this area were confirmed to be of group a type. work is in progress to genotype the bovine rotaviruses of this region based on vp and vp genes. this study emphasizes the need to explore the prevalence of bovine group a rotaviruses in different places of uttarakhand and their genetic characterization which could help in selection of control strategies for rotavirus infections. foot-and-mouth disease (fmd) is endemic in india causing enormous economic loss to the animal keepers and trade embargo with fmd free countries in livestock and animal products. rapid diagnosis of fmd is of immense importance in prevention and control of the disease. fmd is initially diagnosed clinically and confirmed by laboratory tests. virus isolation in cell culture and sandwich elisa for antigen detection are commonly practiced in laboratories. the virus isolation though is very sensitive but it can be slow and analytical sensitivity of the elisa is lower and can not be used with certain sample types. the use of molecular techniques in the diagnostic laboratory has greatly increased the speed, specificity and sensitivity of fmd diagnostic tests. molecular techniques like rt-pcr, pcr-elsa and dot hybridization can be used with more success for detecting carrier animals and animals harboring sub-clinical infection and can be applied in a wide range of clinical sample types. these techniques can be used as genus and serotype specific test including detection of particular lineage/genotypes with in the serotype. multiplex pcr has been used to differentiate serotypes of fmdv and the technique is sensitive, experimentally simpler, cost effective and less time consuming. the assay can be used for serotyping on elisa negative samples. the molecular techniques not only help in diagnosis but also useful for epidemiological studies. lineage differentiating rt-pcr has been useful in identifying different lineages of serotype asia (lineage b, c and d) before proceeding with sequencing of d region. similarly genotype differentiating rt-pcr has been developed and used in differentiating two different genotypes of serotype a (genotype vi and vii). these assays have the potential to be applied on clinical samples directly, thereby saving much time needed for sample processing and nucleotide sequencing. recent development of real time rt-pcr methodology has allowed the diagnostic potential of molecular assays to be realised. advancement in real time pcr technology made it possible to combine several assays within a single tube which is in the progress in our laboratory. integration of these assays onto automated high throughput platforms provides diagnostic laboratories with the capability to test large numbers of samples. microarray technology was provided greater screening capabilities for pathogen detection. the microarray allows the addition of large number of oligonucleotide probes for identification of mutant pathogen and also for subtype determination. the combined properties of high sensitivity and specificity, low contamination risk, and speed has made realtime pcr and microarray technology a highly attractive alternative to conventional methods in increasing percentage of outbreaks confirmed and analyzed and for tracing the origin of fmd virus responsible for outbreaks. dna vaccines are expected to elicit both humoral and cellular responses, cellular response being long lasting. however the approach has several limitations like poor stability of dna, poor expression and risk of integration. poor expression becomes the major limitation in the case of fmd as fmdv proteins are poor immunogens. also dna vaccine vectors carrying only eukaryotic promoters elicit strong cmi response and weak humoral response. the methodology to achieve humoral response involves the expression and secretion of the expressed protein so that the antigen presenting cells will be able to process the antigen and produce humoral response. in case of fmd humoral response is as important as cellular response. the present project aims at addressing these issues; achieving higher expression and getting the protein secreted out by constructing self replicating gene vaccines for fmd and studying their efficacy. the vector for humoral immune response contains eef promoter, sindbis virus polymerase gene and secretory and anchoring signals. the integrity of the vectors was confirmed by sequence analysis. the linked polyvalent protein genes of fmdv serotype a, o and asia were cloned into the vectors and the presence of the insert was confirmed by restriction enzyme digestion. the functionality of the constructed dna vaccine vector (pvac self rep ) was assayed by transfecting the dna into bhk cell monolayer and studying the s labeled proteins in immuno-precipitation assays. the studies showed high level of expression in case of constructed vector as compared to infected virus for the specific protein. the secretion of the expressed protein was assayed by immuno-fluorescence assay and found to be positive. encouraged with these studies the preliminary studies were conducted on vaccine efficacy studies in guinea pig model. the immunized guinea pigs showed high antibody titres by snt and elisa, as compared to conventional dna vaccines (pup cd) even at / th of the dose. this approach of constructing self replicating dna vaccine for humoral response is the first report. genetically engineered microorganisms are important sources of industrial and medicinal proteins. over the past decade, plant host system has been investigated as potential host system for expressing proteins of therapeutic and diagnostic use. however concerns regarding the stability and environmental safety need to be addressed. chloroplast engineering is expected to resolve some of these issues since, plastids/chloroplasts are inherited maternally and are not disseminated through pollen. this makes plastid transformation a valuable tool for transgenic creation besides offering biological containment. since foot and mouth disease (fmd) of cloven footed animals is a major concern in the world over. foot and mouth disease (fmd) is the most feared, viral disease of the cloven footed animals causing heavy losses to the live stock industry. the disease is enzootic in many parts of the world including asia. the conventional vaccines for fmd have several limitations which include safety, temperature sensitivity and duration of immunity. attempts have been made to overcome these limitations using recombinant dna technology. amongst the newer vaccines, edible vaccines are cost effective and easy to administer. since the stability of the gene of interest is the major concern in the case of plant transgenics, marker genes are used for regular selection. the detection methods based on the available marker proteins like b glucoronidase (gus) protein/antibiotic selection are cumbersome and cost intensive. however selection based on herbicide resistance is much simpler and easy. hence in the present study, the -enolpyruvylshikimate- -phosphate synthase (epsp) gene was used as a marker along with the immunogen gene of fmdv. epsp is the key enzyme in the shikimate biosynthesis pathway necessary for the aromatic amino acids production. in order to investigate the mechanism of long term immunity and the effect of protective immunity induced by cationic plg micro particle coated dna vaccination. we constructed the expression plasmid containing a foot-and-mouth disease virus (fmdv) id gene sero type a. intramuscular vaccination of guinea pigs with the micro particles coated plasmid dna induced a strong antibody response and neutralization antibodies, cellular mediated immune response which lasted year. we further analyzed the persistence and expression of id gene by polymerase chain reaction and reverse transcriptase polymerase chain reaction and quantitative pcr. the results showed that id gene was present and expressed in the muscle cells up to year after days post vaccination. furthermore, guinea pigs vaccinated with micro particles coated plasmid dna were protected against a challenge with fmdv virus. therefore the micro particles coated plasmid dna vaccination dose induce a protective immunity and long term humoral, cellular immuno responses against fmdv, which could be maintained by persistent expression of id gene in muscle cells. foot and mouth disease virus (fmdv) causes a highly contagious viral disease of cloven hoofed animals, which has a considerable socioeconomic impact on the countries affected. interleukin- (il- ) enhances the il- driven th immune response that is important in immunity against intracellular pathogens. the multiple roles of il- in many physiological and pathological processes have generated a great deal of interest in recent years. antiviral effects of il- have been reported. we evaluated the effects interleukin- (il- ) on the replication of fmdv in vitro in bhk- cells. bovine il- mature protein coding sequence was amplified from the bovine pbmc cells and cloned into prokaryotic expression vector pet a. protein expressed was purified and specificity was confirmed by immunoblotting. bhk- cells were treated with purified expressed il- protein with ( lg/ml) h prior to fmd infection. cell culture supernatants were collected at h post infection were subjected for elisa and virus titration assay. rna extracted from the cells was subjected to real time pcr for viral rna quantification. log titer reduction was observed in the fmd virus titer in il- treated cells compared to the untreated cells where as virus antigen quantified by elisa has shown a reduction of -folds. -fold reduction in the fmd viral rna copy number was observed in the il- treated cell compared to the untreated measured by qpcr. current study demonstrated the potent anti viral activity of il- on fmdv by inhibiting the viral replication. these results further suggests that il- has the potential role of il- as molecular adjuvant in fmd vaccine development and development of therapeutic for fmd. foot and mouth disease is the most contagious viral disease of farm animals. control of the disease in animals is by vaccination and slaughtering of infected animals. conventional oil adjuvant vaccine has its own limitation. alternate to this genetic vaccines where the dna encoding viral antigen may be a promising approach. naked dna vaccine has limitations like poor uptake of dna by cells and more importantly by nucleus. as a result delivery of naked dna through calcium phosphate nanoparticle was attempted. calcium phosphate nanoparticle is a potential delivery agent which proved to enhance the immune response. fmdv p - cd ''o'' vaccine gene constructs in pcdna . ? entrapped by the nanoparticles was prepared by using different molarity of calcium chloride and disodium hydrogen orthophosphate. the nanoparticles entrapping fmdv p - cd ''o'' and naked dna were presented to the guinea pigs through intramuscular injection to study the mrna expression of antigen by rt-pcr. animals were sacrificed at defined time to collect different organs and total rna was extracted. each time blood was collected to analyse the fmdv specific serum antibodies. dna vaccines presented through calcium phosphate produced transcripts in the injected muscle up to days whereas naked dna up to days. serum antibody levels of naked dna vaccine showed antibody titre till days. whereas nanoparticle injected animals showed serum antibody till days. serum neutralization titres of . were observed in calcium phosphate dna vaccines at about - days, where as naked dna sn titers were observed for short period of - days. the study clearly showed calcium phosphate nanoparticle entrapping fmdv vaccine dna may be a better delivery system for dna vaccines as it confirms availability of the antigen and persistence of antibody for longer duration than naked dna. capripox is highly infectious, contagious, and oie notifiable disease of small ruminants, caused by sheeppox and goatpox viruses which are members of capripoxvirus genus of the family poxviridae. in the present study, we analyzed the partial gene sequences of p protein, an immunogenic envelope protein of capripox viruses (capv) to assess the genetic relationship among different sheep pox and goat pox virus isolates from different geographical areas of the country. product of this gene has been shown to be important in attachment of capv to host cell surface receptors during viral entry and host immune response. the following virus isolates have been used in the analysis: gtpv-uttarkashi, p , vaccine virus; gtpv mukteswar, p , challenge virus; gtpv (akola), gtpv bareilly/ , gtpv ladakh/ and gtpv sambalpur/ , field isolates and sppv srinagar, p ; sppv ranipet, p ; sppv-rf, p , vaccine viruses and sppv makdhoom/ , sppv cirg/ , sppv pune/ , sppv bareilly, sppv / and sppv / , field isolates. in this study, all virus isolates were confirmed by pcr amplification and analysed in pcr-restriction fragment length polymorphism (pcr-rflp) using ecori enzyme to confirm their specificity. further, the amplicons were cloned and sequenced commercially. nucleotide and the deduced amino acid (aa) sequences were compared with published sequences of the members of the genus capripox virus. sequence analysis of partial bp sequence has shown high sequence identity among all indian sppv and gtpv isolates at both nt and aa levels. it revealed a . - % and . for gtpv field isolates where as, % for sppv field isolates at both the nt and aa levels. in general, capv isolates in this study shown . - . and . % homology between gtpv and sppv at nt and aa levels as reported earlier. further, it revealed a unique change of g a in all gtpv isolates resulting in formation of drai site in place of ecori and possible development of restriction enzyme specific pcr-rflp for differentiation of sppv and gtpv from field isolates. orf or contagious ecthyma is considered as non-contagious, proliferative disease and is caused by orf virus of the genus parapox virus of the family poxviridae. it is reported most commonly in sheep and goats and also a zoonotic agent. camels are also infected by orf virus and reported in camel rearing countries as a mixed infection with camel pox, the later is caused by an orthopox virus. in india, there are few reports of the orf virus infection in camels and identified by clinical signs and pcr. in this study, we identified the presence of orf virus from clinical samples of suspected case of sporadic infection in camels by serological and molecular techniques. viral dna isolated from processed scabs used initially in nested polymerase chain reaction as diagnostic pcr which successfully amplified bp fragments and also sequenced to check the fidelity of the product. after confirming the infection by pcr, some of the structural and non-structural genes were amplified for sequence analysis. out of the five genes characterized, the major important one selected for sequence and phylogenetic analysis is b l gene which is homologous to a major envelope protein p k of vaccinia virus. full open reading frame of bp from orf b l was amplified by pcr, cloned and sequenced commercially. nucleotide and deduced amino acid sequences of b l were compared with other published sequences of the members of the genus papapox virus. sequence analysis shows a maximum percent identity of . and (indian orf virus isolates); . and . (other orf isolates); . and . (orf-camel/jodhpur/ ); and . (bovine popular stomatitis virus) and finally . and . (pseudo cowpox virus) respectively at nt and aa levels. phylogenetic analysis of the isolate was also performed using the neighbour joining method in mega program to know the phylogeny relatedness of the virus, which revealed that the isolate is well grouped with the jodhpur isolate and closely related to pseudo cowpox virus. it warrants further analysis of other potential genes to confirm the causative agent of the contagious ecthyma in camels as pseudo cowpox virus. chikungunya an arboviral disease is transmitted through the bite of an infected aedes mosquito. it causes a self limited febrile illness along with arthralgia and myalgia. in some cases neurological and severe hemorrhagic manifestations has been observed. chikv epidemic has been reported in africa, india, south east asian countries and during the current out break imported cases of chikv has been encountered in most of the european countries. the causative agent belongs to the genus alphavirus family togaviridae. human beings serve as the chikungunya virus reservoir host during epidemic periods. outside these periods the main reservoirs are monkeys, rodents, birds, and other unidentified vertebrates. antibodies to chikv have been detected in domestic animals. in the present study we surveyed madanapalli, palamaner, b. kotta kota and tirupati and collected a total of rodent samples, bovine samples; sheep samples and canine samples. total rna was isolated from all these samples and subjected to rt-pcr using a primer pair dvrchk-f/dvrchk-r which could amplify a bp e gene product specific to chikungunya virus (naresh kumar et al. ). all the serum samples were further screened for chikv specific igm antibodies using commercially available ctk biotech strips. none of the samples were found positive either for chikv specific rna or chikv specific igm antibodies. more number of samples from domestic animals as well as rodents are being screened to study their possible role if any in the maintenance of chikv in nature and during the inter epidemic periods. the present study discusses these aspects in detail. petunia hybrida is widely used as experimental host plant for begomovirus identification and its characterization. hitherto, natural infection of begomovirus on petunia has not been reported in india. recently, petunia hybrida grown in and around ludhiana were found to be depicting typical symptoms caused by begomovirus. the symptoms include severe reduction in leaf size, downward curling and distorted leaves. severely infected plant became bushy, stunted and produces no flower. total genomic dna was extracted from the plants showing symptoms of begomovirus, by ctab method. the presence of virus was confirmed by using degenerated primers, designed to identify all the begomovirus prevailing in the world. to identify the strain associated with the disease, the positive samples along with healthy control were tested against different strain specific primers of tomato leaf curl virus, so far reported in india i.e. tomato leaf curl new delhi virus, tomato leaf curl palampur virus, tomato leaf curl banglore virus, tomato leaf curl karnataka virus and tomato leaf curl gujarat virus. among these, only tomato leaf curl new delhi virus specific primer was able to give the desired amplicon of * bp. hence, it is confirmed that the leaf curl disease of petunia hybrida is associated with tomato leaf curl new delhi virus. this disease of petunia can become a sever production constraint in coming years. from last years ( and ) it was observed that some varieties of brinjal grown in rainy season, showed typical leaf curl type of symptoms. the symptoms include upward curling of the leaves, cupping, vein thickening, reduction in leaf size and distortion of leaves. the severely infected plant remains stunted and bushy, became unproductive or produces only few fruits. the disease was experimentally transmitted from naturally infected brinjal to healthy seedlings by whiteflies (bemisia tabaci) and grafting, but not by mechanical or aphid transmission. to detect the begomovirus associated, total genomic dna was extracted from the plants showing disease symptoms. the presence of virus was confirmed by using pcr based begomovirus geneus-specific primers designed by deng et al., wyatt and brown and rojas et al. these degenerated primers give the expected product size of * , * and * bp, respectively. core coat protein (cp) gene and dna-b was also amplified in the samples using specific primers. to identify the strain associated with leaf curl virus, dna was subjected against primers of different indian tomato leaf curl virus strain i.e. tomato leaf curl new delhi virus, tomato leaf curl palampur virus, tomato leaf curl banglore virus, tomato leaf curl karnataka virus and tomato leaf curl gujarat virus, using pcr. among these, only tomato leaf curl new delhi virus primer was able to show the desired product size of * bp. therefore, it was confirmed that leaf curl disease of brinjal is caused by tomato leaf curl new delhi virus in association with satellite b-dna. to identify the strain associated with the disease, all samples were further subjected to the specific primers, designed to amplify all the tomato leaf curl virus strains, so far reported from india i.e. tomato leaf curl new delhi virus, tomato leaf curl palampur virus, tomato leaf curl banglore virus, tomato leaf curl karnataka virus and tomato leaf curl gujarat virus, using pcr. among these, only tomato leaf curl palampur virus specific primer was able to give the expected product size of * bp. this shows the association of tomato leaf curl palampur virus with leaf curl disease of calendula and marigold. thus, calendula and marigold can act as a reservoir for the tomato leaf curl palampur virus and may cause severe constrain in the production of these important ornamental plants. groundnut bud necrosis virus (gbnv) belongs to serogroup iv of the genus tospovirus in bynayaviridae family and infects several economically important crops all over india. the nucleocapsid protein (np) encoded by the small rna of gbnv encapsidates the viral rnas. apart from this structural role, the np has also been implicated in the replication, transcription, maturation and cell to cell movement. with a view to study the structure and function, the np of gbnvtomato isolate from karnataka was over expressed in e. coli and purified by ni-nta chromatography. the purified np was present as ribonucleoprotein complex and as heterogeneous mixture containing monomers, tetramers and higher order multimers. in order to determine the regions involved in oligomerization and nucleic acid binding, mutational approach was taken. n-and c-terminal deletion clones were generated (n np, n np, c np and c np), over expressed in e. coli, and were purified by a procedure identical to that used for the wild type protein. initial studies on oligomeric status suggested that in addition to n-and c-terminal regions there may be additional regions or residues which contribute to multimerization of np. the amount of rna bound to the truncated proteins was reduced in case of n np, n np and c np. interestingly removal of amino acid residues (natively unfolded region) from the c terminus resulted in complete loss of nucleic acid binding suggesting that the rna binding domain was located in c-terminal region of np. further np was observed to get phosphorylated in in vitro kinase assays by a kinase present in the soluble fraction of tobacco plant sap. both atp and gtp were utilized as phosporyl donors and mn ? was the preferred metal ion which suggests that np might be phosphorylated by a ck -like protein kinase. phosphorylation studies with n-and c-terminal truncated proteins revealed that the site of phosphorylation lies within the amino acid residues - . by mass spectrometric analysis of the protein threonine- and serine- were identified as possible phosphorylation sites. a naturally occurring isolate of virus infecting gherkin (cucumis anguira l.) showing mosaic symptoms of mosaic, leaf distortion and dark green islands in the lamina was identified in the export cultivars of gherkin grown in commercial fields of kuppam rural, chittoor district, andhra pradesh. the virus infection was deadly prevalent among the field that caused a lot of economic damage to the crop that resulted in yield losses and reduced quality of fruits meant for export. symptoms of the infected fruit included blistering and malformation of the fruit. the virus infected leaf samples were collected and initial host range tests were conducted with different cucurbit species showed that the host range include propagation hosts like cucumis anguira (gherkin), cucumis sativus, cucurbita pepo, cucumis melo, langeneria vulgaris, momordica charantia and local assay host like chenopodium amaranticolor. the virus host range was only restricted to cucurbit species and chenopodium. the virus was maintained for further studies on cucurbita pepo by sap or mechanical inoculation. the virus induced mosaic, vein clearing symptoms on pumpkin. electron microscopy of the leaf dip preparations stained with % uranyl acetate from the pumpkin leaves showing symptoms revealed the presence of a long flexuous filamentous particle measuring nm. the virus positively reacted to the polyclonal antisera of papaya ringspot virus-w, potato virus y, tobacco etch virus and also strongly reacted with the polyclonal antiserum of zucchini yellow mosaic virus in direct antigen coated-enzyme linked immunosorbent assay (dac-elisa). because of very strong reaction to polyclonal antisera of zucchini yellow mosaic virus, we tried to amplify the partial nib and cp genes of the virus along with the utr by using two primers zy gctccatacatagctgag acagc and zy taggctttttgcaaacggagtcta at c . total rna from gherkin infected leaves was isolated using trizol ls reagent (sigma). rt-pcr was performed to obtain an amplicon of * . kbp, cloned into fermentas ptz r/t vector and sequenced at mwg biotech, bangalore. sequence analysis revealed that the virus was isolate of zucchini yellow mosaic virus and was showing % of homology to that of the zucchini yellow mosaic virus strain b genome ay and zucchini yellow mosaic virus nat genome ef which were strains reported from israel. the sequence of the present study was submitted to the genbank gq . the results state a suspicion that the virus could have been mobilized by some infected source brought by the commercial israeli based companies into india due to poor quarantine regulations as the gherkin cultivation in these regions is chiefly supported, purchased, exported and marketed by these private companies that are based from israel. this is the first report on molecular characterisation of zucchini yellow mosaic virus infecting cucumis anguira (gherkin) from india. they also exhibited synergism with other virus which was region specific. fifty percent of the total symptomatic plant population was found be positive only for carla while remaining showed mixed infection of carla with tospo in some regions while in others carla virus was found to be associated with cmv. presence of only carlavirus was up to - % incidence, without association of tospo, cmv, poty or tobamo viruses was also observed in some fields. avijit tarafdar, raju ghosh, k. k. biswas plant virology unit, division of plant pathology, indian agricultural research institute, new delhi citrus tristeza virus (ctv), a brown citrus aphid (toxoptera citricidus) transmitted closterovirus under family closteroviridae, is one of the major limiting factors in cultivation of citrus worldwide. ctv is a longest known plant virus having flexuous particle of nm in size. ctv genome is a positive sense ssrna of about kb nucleotide containing open reading frames (orfs) encoding proteins. several biological as well as genetic variants of ctv are reported in all the citrus growing countries in the world. ctv causes decline and death of millions of citrus trees in the world. in india, ctv is a century old problem, and has killed an estimated one million citrus trees till today. in molecular and genetic level, ctv isolates from india were not fully characterized. genetic diversity and sequence divergence in ctv isolates of india are not fully established. further, evidence of recombination and causes of evolution of ctv variants in india have not been studied till date. therefore, in the present study, effort has been made to characterize several indian ctv isolates in genetic level, examine their genetic diversity, identify recombination events and analyze evolution of divergent ctv. a total number of ctv isolates from different regions of india ( from darjeeling hills, five from bangalore, from delhi and from vidarbha) were under taken for genetic study. two genomic regions of ctv, i.e., entire cp gene (cpg) ( nt) and a gene fragment of orf a (orf a) ( nt) were amplified, cloned, sequenced and nucleotides were analyzed. based on cpg, indian isolates shared - % nucleotide identity, and based on orf a they shared - % identity, among them. incongruence of phylogenetic relationship was observed as on sequence analysis five phylogenetic clades based on cpg, and eight clades based on orf a, were generated suggesting the recombination events have been occurred between the sequences of indian ctv isolates. thus, to identify the potential recombination events, and determine the parental sequences in ctv isolates, six recombination detecting algorithms, namely, rdp, genconv, bootscan, maxchi, chimera and siscan were used. out of indian ctv, cpg of and orf a of isolates of ctv showed recombination events suggesting orf a was more prone and fragile to rna recombination as compared to cpg. this findings indicated that high degrees of genetic diversity and incongruent relationships of indian ctv isolates are due to genetic recombination occurred, which may be the important factors in driving evolution ctv variants in india, that was also supported by a splittree decomposition analysis. b. v. bhaskara reddy, y. sivaprasad, k. rekha rani, k. raja reddy department of plant pathology, regional agricultural research station, acharya n.g. ranga agricultural university, tirupati, andhra pradesh sunflower (helianthus annus l.) is one of the most important oil seed crops in the world which ranks third in area after soyabean and groundnut. the sunflower necrosis disease (snd) is characterized by necrosis of leaves, necrosis streaks on petioles, stem, floral parts and stunted growth. the causal agent of the disease has been identified as tobacco streak virus (tsv) which belongs to genus ilarvirus of the family bromoviridae. the suspected tsv infected sunflower samples collected from chittoor district in andhra pradesh were found positive for tsv-dac elisa. total rna was extracted from sunflower using rnaeasy isolation kit (qiagen). the tsv coat protein (cp) gene, movement protein (mp) gene and replicase (rep) gene were amplified by rt-pcr with specific primers, cloned in ptz r/t vector, sequenced and deposited in genbank (gu , gu and gu ). the size of cloned cp gene was bp and codes for amino acids. the cp gene sequence analysis revealed that the tsv-tpt infecting sunflower has - % homology at nucleotide level with soybean, tagietus-tpt and okra-tn isolates and - % homology at amino acid level. the movement protein gene was bp and codes for amino acids. the mp gene sequence analysis showed that it has - % homology at nucleotide level and - % at aminoacid level. chilli (capsicum annuum), the important commercial vegetable/spice of himachal pradesh, is affected by several viral diseases; of them cucumo, tospo, poty and gemini viruses are the most common genera. however, these viruses are not identified clearly and characterized fully, which are foremost needed to formulate the management strategy. therefore, in the present study, effort has been made to identify and characterize the important viruses causing diseases in chilli. in this study, several farms in major chilli growing areas of bilaspur and kangra districts in himachal pradesh were surveyed and infected plant samples were collected randomly. virus infection in these samples were detected by das-elisa using antisera to cucumber mosaic virus (cmv) and potyvirus (group specific) and through slot-blot hybridization (sbh) using cmv, iris severe mosaic poty virus (ismv), tomato spotted wilt tospo virus (tswv) and chilli leaf curl gemini virus (clcuv). based on das-elisa and sbh, the incidence of disease was estimated and ranged from . to . % by cmv and . to . % by potyvirus. to detect tospo and geminivirus in the infected chilli, sbh test was carried out. infected samples showed maximum virus titer in both das-elisa and sbh test were further confirmed by pcr using specific primers. desired sizes of amplicons; * bp, * bp, * bp and * bp of cmv, poty, gemini and tospo viruses, respectively, were obtained. as the present study clearly indicated that cmv appeared as a major one among the viruses infecting chilli in the hilly region of himachal pradesh, two isolates of cmv were characterized in genetic level. thus the amplified products (* bp) of cmv, palampur and palampur were cloned in pgemt cloning vector, sequenced and the sequences were submitted to ncbi database (palampur : acc-fm and palampur : acc-fm ). the sequences were then analyzed and compared with other sequences available in the data base. based on sequence analysis, it was found that present cmv isolates shared % nucleotide identity between them, are closely related with australian cmv isolate cmv-ly (acc-af ) by % nucleotide identity. in phylogenetic tree analysis, it was observed that indian cmv isolates formed same cluster along with cmv-ly. as it is known that cmv subgroup ii comprises cmv-ly, it is concluded that the cmvs of this hilly region of himachal pradesh belong to subgroup ii. chilli is essentially a crop of the tropics and grows better in hotter regions. chlii (capsicum annuum), a member of family solanaceae is an important vegetable and spice crop of immense commercial importance. the pungency in pepper is due to an alkaloid known as capsaicine and peppers are characterized as sweet, hot or mild depending on capsaicine content. the present investigation were conducted to find out the highly resistant cultivars of capsicum annuum against cmv and tylcv among ten cultivars of chilli in agroclimatic condition of aligarh. the highest ( and ) percentage of infection was observed in hc- and kalyanpur type- by showing the positive reaction to cmv by elisa test. no symptoms was recorded in case of bc- , lca- and jca- and showed negative reaction to cmv by elisa. bc- and lca- also showed negative reaction to tylcv by elisa and these were symptomless. maximum infection ( and ) was registered in hc- and c , cultivar. so, the bc- , lca- and jca- has proved highly resistant varieties against cmv and tylcv and these may be used in breeding programmes against viruses. cotton leaf curl virus belongs to the family geminiviridae, genus begomovirus. the members of this family contain circular single stranded dna molecules as their genomes. there are two kinds of begomoviruses-bipartite viruses with genomes consisting of two dna molecules designated dna-a and dna-b and the monopartite viruses which contain only dna-a but not dna-b. in monopartite viruses, the dna-a is accompanied by a small circular dna molecule called dna-b which is essential for the development of typical disease symptoms. cotton leaf curl virus is a monopartite virus and causes the cotton leaf curl disease which has emerged as a major disease of cotton in the indian subcontinent. the non-structural protein ac of cotton leaf curl kokhran virus-dabawali isolate (clcukv-dab) was cloned into pgex x vector and overexpressed in bl (de )plyss e. coli cells. the overexpressed gst-ac protein was purified by glutathione sepharose chromatography. the purified gst-ac protein was found to possess atpase activity. the optimum temperature and ph for the activity were °c and . respectively. the atpase activity was inhibited in presence of edta, showing that it is dependent on divalent metal ions. the activity was supported by magnesium, manganese and zinc ions but inhibited in presence of calcium ions. it was also inhibited by the non-hydrolyzable atp analogue adenosine-b, c-imido triphosphate and in the presence of other nucleotides like ctp and gtp. the k m and the v max of the reaction for atp as the substrate are . mm and . nmol/min/ mg of the protein respectively. the enzyme could also utilize gtp as the substrate. the fact that ac is specifically an ntpase and not a general phosphatase is revealed by the finding that it does not hydrolyze p-nitrophenyl phosphate to yield yellow colour while a similar reaction carried out in parallel with alkaline phosphatase readily yields the colour. it has been suggested earlier that ac may be involved in cell to cell movement of the virus (rojas et al. ) . it is possible that by its ability to hydrolyze atp, ac serves to power viral movement in the plant. thirteen sugarcane yellow leaf virus isolates causing yellow midrib and irregular yellow spot pattern from six states of india were characterized by rt-pcr assays. scylv- f and scylv- r primers were used as forward and reverse primer pairs and the amplified products were cloned and sequenced. comparative coat protein sequence analysis confirmed that all the scylv-indian isolates were clustered into two major groups confirming the existence of two strains of scylv affecting sugarcane crops of india. in a separate experiment, the member of both of the phylogenetic groups were found to be transmitted by the sugarcane aphid, melanaphis sacchari from infected to healthy sugarcane suggesting its secondary spread in nature. the symptoms produced by the virus causing cotton mosaic disease were little bit different in both sap inoculation and under natural field condition. in natural field condition it has shown clear chlorosis type of symptoms on major leaves of plants but in sap inoculated plants veinal chlorosis and mosaic type of symptoms are found to be common. in field conditions infected plants grows erect and have less boll formation. there is no effect found on seed shape or seed size. the initial symptoms produced on cotton leaves after inoculation were wonderful. local lesions observed in second week from inoculation and then they changes to chlorotic type of symptoms and some are necrotic symptoms also. the plants at early stage are found to be affected, has less lateral branch development and hence reduction in yield production. the naturally field infected plants showing good symptoms are also difficult to identify in lateral stage of plant. because they disappear with time. the virus is very easily sap transmissible. the virus is found to be transmitted by thrips palmi and thrips tobacci in persistent manner. no seed transmission is observed. virus showed same physical properties as it shows in stem necrosis of peanut or sunflower necrosis disease. the physical properties are found to be thermal inactivation point (tip) - °c, dilution end point (dep) - to - and longevity in vitro (liv) h, virus infecting nineteen different host plants are identified belonging to five different types of families viz. malvaceae, chenopodiaceae, compositae, leguminaceae and solanaceae. however they found to produce same types of symptoms as in most of the host that have been tested before. in elisa test report it is found that the virus showing positive test only with anti serum of tsv of a cowpea and cotton but negative reaction with pbnv of cowpea and cotton which clearly denied possibility of presence of pbnv in cotton producing these kinds of symptoms elisa report clearly shows that tsv antiserum of cowpea is showing positive results with clear chlorotic types of symptoms. a powerful approach to functional genomics, and an alternative to the massive generation of transgenic plants, is the use of the recently described virus induced gene silencing (vigs) process, which allows viral vectors to knock out the function of a gene-of-interest. vigs is based on a silencing mechanism that regulates gene expression by the specific degradation of rna. as a tool for reverse genetics, vigs has many advantages over other common ways to study gene function because of the ability of viruses to replicate and move systemically within a plant. vigs can generate a phenocopy of a mutant without all the troubles of traditional methods of mutagenesis. geminiviruses with their small dna genomes and ease of inoculation through agrobacterium, are excellent candidates for vigs vector development. as a first step, the geminivirus bhendi yellow vein mosaic virus, characterized in our lab (jose and usha, virology : [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] ) has been chosen. the satellite b dna associated with this virus has a single open reading frame (bc ). bc is essential for symptom development but not for replication. therefore, bc has been replaced by a multiple cloning site harbouring sali, xbai, bamhi, bsrgi and xhoi, initially in a cloning vector and then in the binary vector containing the partial tandem repeat of the b dna. in the place of the bc orf, the plant phytoene desaturase gene has been cloned and the resulting construct was used for agroinfiltration along with the partial tandem repeat clone of the begomovirus (dna a component chilli (capsicum annuum l.) plants exhibiting prominent symptoms of begomovirus like: leaf curl, vein swelling, shortening of petioles, crowding of leaves and stunting of plants were collected from rorkee, uttarakhand and dhaulpur, rajasthan, india. total genomic dna was isolated from naturally infected chilli samples and pcr was carried out with coat protein (located in dna-a) gene specific primers. as expected to the primers, * bp dna fragments were amplified from the infected chilli samples. to know the bipartite nature of the virus isolates, nuclear shuttle protein (located in dna-b) gene specific primers were employed which also resulted in positive amplification of * bp dna bands with all the coat protein tested positive samples. to ascertain the association of dnab component with the virus isolates, a set of dna-b specific primers were used which resulted in positive amplification of full length (* . kb) dna bands in the chilli samples collected from rorkee, uttarakhand, however, multiple sizes bands were resulted with the samples collected from dhaulpur, rajasthan. these findings confirmed that both the virus isolates under study are bipartite begomovirus associated with dna-b satellite. the sequencing of the pcr products is under progress which analysis will be discussed. groundnut bud necrosis virus (gbnv) belonging to the genus tospovirus, which is a unique member of the family bunyaviridae, infects several economically important crops. the virus has three genomic ssrna segments namely s (ambisense), m (ambisense) and l (negative sense). the s rna codes for nucleoprotein (np) and non-structural protein (nss) from viral complimentary and viral strands respectively. many viral nonstructural proteins such as ns of hepatitis c virus, yellow fever virus, dengue virus, sv large t antigen and cytoplasmic inclusion protein of tamarillo mosaic potyvirus are known to exhibit rna/dna stimulated ntpase, dntpase and helicase activity. nss of gbnv does not have any sequence similarity with any of the above mentioned viral rna/dna helicases but has a ntp binding domain. however, it has been implicated as suppressor of gene silencing in vivo. with a view to elucidate the mechanism by which nss could act as a suppressor of gene silencing and examine the other potential roles of nss in the life cycle of the virus, the gbnv (to) nss was over-expressed in e. coli and purified by ni-nta chromatography. in vitro studies with the purified rnss suggest that it exhibits an rna stimulated ntpase activity. many of the proteins that possess the rna/ dna stimulated ntpase and datpase activity, are also shown to have atp dependent nucleic acid unwinding activity. it was therefore of interest to examine whether nss has the nucleic acid unwinding activity. the helicase assays revealed that nss has dna/rna helicase activity. helicase activity of nss was absolutely dependent on atp and mg ? ion. nss could unwind dsdna substrate with overhang, or overhang. mutation of the crucial lysine in walker motif a (k ) severely affected the unwinding activity where as mutation of aspartate residue in walker motif b (d ) resulted in only % loss of activity. in this regard, rnss is a unique enzyme which does not have the canonical helicase motifs but can catalyze dsdna/dsrna unwinding in an atp and mg ? dependent manner. the rnss might act as a suppressor of by unwinding the dsrna, the substrate for dicer. in addition to being a suppressor of ptgs, nss may also regulate the viral replication and transcription by modulating the secondary structure of the viral genome. this new research finding on nss might pave way for further studies on its role in viral replication and transcription. yellow vein mosaic disease of pumpkin (cucurbita moschata) poses a serious threat to the cultivation of this crop in india. the disease was found to be associated with whitefly-transmitted bipartite begomoviruses were detected in varanasi field using polymerase chain reaction (pcr) with primer design through coat protein conserved region of begomoviruses from ncbi database. all plant samples showing symptoms were infected with begomovirus. the virus species were provisionally identified by sequencing * bp of the viral coat protein gene (av ageratum conyzoides is commonly known as billygoat-weed, chick weed, goatweed and whiteweed. in india it is popularly known as bill goat weed. it is an annual herbaceous plant with a long history of traditional medicinal uses in several countries of the world and also reputed to possess varied medicinal properties including the treatment of wounds and burns. in cameroon and congo, it is used traditionally to treat fever, rheumatism, headache, and colic. during survey in and around gorakhpur in , ageratum plants were found affected with the symptoms of leaf curling, mosaic mottling and leaf yellows. the infected leaf samples were processed for virus identification and association with pcr assays. total dna was extracted and pcr were performed with begomovirus specific primers (tlcv-cp). a * bp band was consistently amplified on % agarose. the pcr products were directly sequenced and sequence was submitted in genbank with the accession no. gq . the blast search analysis showed highest similarity of % with the ageratum enation virus. vernonia cinerea leaves with yellow vein symptoms were collected around crop fields in madurai. a bp product amplified from total dna extracted from symptomatic leaves with degenerate primers designed to amplify a part of the av gene from begomoviral dna a component was cloned and sequenced. based on the above sequences, specific primers were designed and the full length dna a of nucleotides with typical genome organization of begomoviral dna a was obtained and was submitted to embl data base (acc no: am ). the sequence comparison with other begomoviruses revealed the closest identity ( %) with emilia yellow vein virus from china and less than % with all known begomoviruses. the international committee on taxonomy of viruses (ictv) has therefore recognized vernonia yellow vein virus (vyvv) as a distinct begomovirus species. conventional pcr could not amplify the dna b or dna b from the infected tissue. however, the b dna ( bp) associated with the disease was obtained (acc no: fn ) by the rolling circle amplification-restriction fragment length polymorphism method (rca-rflp) using phi dna polymerase. sequence analysis shows that dna b of vyvv has the highest identity ( %) with dna b of ageratum leaf curl disease and - % with the b dna associated with other begomoviruses. infectious clones of vyvv dna a and dna b as dimers were made using the products of rca-rflp. these infectious clones will be used for agroinfection of vernonia and the results will be discussed. this is the first report of the molecular characterization of vernonia yellow vein virus (vyvv) from vernonia cinerea in india. production of bulb and seed crop of onion (allium cepa l.) is hampered by onion yellow dwarf virus (oydv) and iris yellow spot virus (iysv) with an incidence of . % and . % in bulb crop and . % and . % in seed crop, respectively in the popularly grown cv. hisar- . four symptom-based variants of oydv designated as grade a, b, c and d produced varied types of symptoms in onion crop incurring heavy losses in bulb and seed production. iysv caused tiny hay coloured spots of different shapes and sizes on leaves and scapes which later coalesced and led to drying and lodging of scapes. the plant height, bulb weight and bulb size were . cm, . g and . cm in plants infected with oydv, . cm, . g and . cm in iysv infection, . cm, . g and . cm due to their combined infection, as compared to . cm, . g and . cm respectively, in healthy plants of bulb crop. in plants infected with oydv grade a the plant height was minimum ( . cm) whereas the number of umbels was maximum ( . umbels/pl.) but other yield parameters viz., weight/umbel ( . g), number of seeds/umbel ( ), seed weight/umbel ( . g) and seed yield/plant ( . g) were recorded to be the lowest. the minimum reduction in plant height ( . cm), weight/umbel ( . g), number of seeds/umbel ( ), seed weight/umbel ( . g) and seed yield/plant ( . g) were recorded in oydv grade d. the plant height was . cm with . umbels per plant, . g weight/umbel, seeds/umbel, . g seed weight/umbel and . g seed yield/plant in iysv infected plants. the plant height ( . cm), umbels/plant ( . ), weight/umbel ( . g), number of seeds/umbel ( ), seed weight/umbel ( . g) and seed yield/plant ( . g) were found to be the lowest in combined infection of oydv and iysv diseases in comparison to higher values in healthy controls ( . cm, . , . g, , . g, . g, respectively). a minimum reduction in the test weight, germination and seed vigour index were found ( . g, . % and ) due to oydv grade a infection, whereas these were . g, . % and in iysv disease infected plants and . g, . % and in combined infection of oydv and iysv diseases in comparison to . g, . % and in healthy plants. the maximum hampering of seed vigour parameters was recorded due to iysv infection. lodging of scapes caused by this disease was responsible for heavy losses in seed production and seed quality. cotton leaf curl disease is one of the major threats to cotton cultivation from northern india. survey conducted during , observed the disease incidence ranged from to % from bhatinda, abohar, fazilka, sri ganganagar, hanumanghar. in order to study genetic variability in the virus, twelve clcuv isolates were partially characterized ( bp common region, full length av gene and partial sequences of ac and av gene). full length characterization of representative isolates from bhatinda, abohar, fazilka, sri ganganagar, hanumanghar is under progress. partial sequence analysis of clcuv isolates revealed that, the virus isolates collected during cropping season are closely related to cotton leaf curl burewala virus from pakistan and results were discussed. pratibha singh, h. s. savithri department of biochemistry, indian institute of science, bangalore tospoviruses, belonging to the family bunyavirideae, infect economically important plants such as groundnut, tomato, watermelon etc. they have a tripartite genome, with l, m and s segments of rna, in pseudo circular (panhandle) form. the viral genomes encode four structural proteins (l, n, g and g ) in the antisense orientation, and two non structural proteins nss and nsm in the sense orientation. the nsm is the only protein unique to tospoviruseses that infect plants in the bunyaviridae family and hence is proposed to be important for cell to cell movement. ground nut bud necrosis virus (gbnv), a member of the tospovirus genus, is the most prevalent virus infecting several species of leguminosae and solanaceae plants in india. total rna was isolated from gbnv infected tomato leaves and rt-pcr was performed using appropriate primers to amplify the nsm gene. the pcr product was cloned in pgex x vector. the recombinant nsm clone was transformed into bl (de ) e. coli cells and over-expressed by induction with . mm iptg. sds-page analysis of induced and uninduced fraction revealed the presence of overexpressed protein of expected size. the soluble gst-nsm was purified by gsh sepharose affinity chromatography. purified gst-nsm was shown to interact with in vitro transcribed rna transcript by electrophoretic mobility shift assay. further nsm was shown to interact with viral encoded proteins np and nss using elisa and yeast two hybrid system. nsm was also shown to be phosphorylated in vitro by pellet fraction of plant sap. thus the recombinant gbnv nsm possesses the characteristic features of a movement protein such as nucleic acid binding, interaction with nucleocapsid protein, and ability to undergo posttranslational modification. solanum melongena, commonly called as egg plant is one of the most important vegetable crop in the world. it is cultivated widely in the tropical and sub tropical regions. several viruses such as cucumber mosaic cucumo virus (cmv), potato virus-y (pvy), potato virus-x (pvx) and tobacco ring spot virus (trsv) infect egg plant under natural conditions. in india major crop losses due to cmv infection in brinjal is % (fao stat- ) . in the present study the infected leaf samples were collected from local fields of ramapuram, chandamama palli, chandragiri, madanapalli, yadhamari, durgasamudram villages in and around tirupati, were tested for cmv infection by dac-elisa with cmv antisera. the resulting positive samples were further inoculated to the raised brinjal seedlings of selected varieties through mechanical sap inoculation. different varieties of brinjal like mullabadhine, ankhur, ravya, mattigulla, casper and easter egg were used for monitoring the susceptibility to cmv infection. the mosaic symptoms were observed after weeks of inoculation in all varities of brinjal except mullabadhina. among all these susceptible varities ankhur variety is selected to study induced biochemical changes such as chlorophylls, carbohydrates, proteins, nucleic acids and polyphenol oxidases in cmv infected brinjal leaves. in the infected leaves considerable reduction in chlorophyll and starch and increase in total proteins, sugars, rna and polyphenol oxidases was observed when compared to healthy leaves. the amount of total starch, protein and dna decreased to about , and lg/g respectively in infected leaves, where as sugars ( lg/g), rna content ( lg/g) and polyphenol oxidase activity was increased as compared to healthy leaves. the above results suggests that there is an altered concentrations of chlorophyll, proteins, nucleic acids, carbohydrates and polyphenol oxidase activity in the brinjal leaves due to the effect of cucumber mosaic cucumo virus infection. leaf analysis was found to be used as widely accepted diagnostic tool to assess the nutritional status of the vegetables. the present study deals with these aspects in detail. the total rna and dna was isolated from infected leaf samples. rt-pcr assays were performed using sugarcane yellow leaf virus (scylv) specific primers (scylv- f and scylv- r). the infection of scylv was detected in all the collected samples, which showed the expected size (* bp) amplicon during rt-pcr. in another experiment with nested pcr analysis, a phytoplasma characteristic . kb rdna pcr product were amplified from dnas of all infected samples but not in healthy sugarcane plants tested using phytoplasma universal primer pairs p /p and fu /ru . dna extracts from plants with yellow mid rib and leaf yellows produced products of bp, which gave typical phytoplasma profiles when digested with hae iii and hha i. no pcr amplifications were produced using dna from symptomless plants. our results suggest that the yellow mid rib and leaf yellows symptoms on sugarcane varieties in uttar pradesh and uttarakhand states of india exhibiting midrib yellowing and leaf yellows symptoms is mainly caused by mixed infection of scylv and scylp. the affected clumps showed reduction in stalk height as compared to healthy fields. thirty-one sugarcane mosaic isolates belonged to sugarcane mosaic virus (scmv) and sugarcane streak mosaic virus (scsmv were collected from china and india), confirmed in indirect elisa and rt-pcr amplification with scmv and scsmv-specific primers. the amplicons ( . kb) from the coding region of coat protein (cp) were cloned, sequenced and compared to each other as well as to the sequences of scmv isolates from sugarcane (australia, usa, china, brazil, mexico and south africa), maize (australia, china, iranian) and one scsmv isolate from sugarcane (india) in genbank. maximum likelihood and maximum parsimony analyses robustly supported two major monophyletic groups that were correlated with the host of origin: the scmv subgroup that included isolates from china and only isolates from india, and the scsmv subgroup that contained all isolates from india. maize dwarf mosaic virus (mdmv) and johnsongrass mosaic virus (jgmv) were not detected in any of the samples tested. a strong correlation was observed between the sugarcane groups and the geographical origin of the scmv isolates. the millable sugarcane samples from china contained a virus tentatively described as sorghum mosaic virus (srmv). three isolates from nine chewing canes in fujian, yunnan and guizhou provinces of china also contained srmv, and the other samples including five isolates from india was found infected with scmv. no srmv infection has been detected in sugarcane mosaic samples from india. sequence comparisons and phylogenetic analysis indicated that srmv can be considered as the most common and prevalent potyvirus infecting sugarcane in china, however in india sugarcane streak mosaic virus is dominant in causing mosaic symptoms on sugarcane. dig-labeled dna probe complementary to coat protein (cp) region of tobacco streak virus (tsv) sunflower isolate was designed for the sensitive and broad-spectrum detection of tsv isolates, the most devastating virus in india. dot-blot and tissue print hybridizations with the digoxigenin labeled probe were performed for the tsv detection at field levels. here, dot-blot hybridization was used to check a wide number of tsv isolates with a single probe and sensitivity with different sample extraction methods. the probe with cp conserved region prepared from sunflower pcr amplicon was hybridized with the tsv field isolates of gherkin, pumpkin, sunflower, marigold and globe amaranth samples because of highly conserved with little variability in cp region. the sensitivity limits were decreased from total nucleic acid to partially purified and crude extract preparations. in particular, tissue blot hybridization offers a simple, reliable procedure as dot-blot, but requires no sample processing. because there is minimal sample preparation, tissue-print hybridization could be an important component of tsv management programs. thus, the above non-radioactive labeled probe techniques can facilitate in screening the samples during tsv outbreaks and in quarantine services. savita patil, rupali sawant*, k. banerjee virology group, agharkar research institute, macs, g.g. agarkar road, pune two mycobacterium smegmatis strains (ari lab nos. v and v ) were employed for the isolation of mycobacteriophages from soil and sewage samples. mycobacteriophages were isolated from soil samples collected from an area surrounding the tuberculosis (tb) ward, naidu hospital, pune, against m. smegmatis strain v . these were numbered as v , v and v and were isolated by using washed-cell preparation method. the bacteriophages against the other m. smegmatis strain, i.e. v , were isolated from soil samples (collected from around tb ward, sassoon hospital, pune). some of these phages (viz.v , v ) showed plaques at °c but not at °c. thus they seem to be lysogenic. for propagating and increasing the titre of all the above isolates, various previously described methods were attempted, but none of these methods were satisfactory. but when siliconized glassware and plastic-ware were used, propagation was successful. we showed that siliconization of glassware and plastic-ware was essential for the propagation of our mycobacteriophage isolates v , v , v , v and v . also, phage dilution medium (pdm) as described by chaterjee et al. ( ) was found to be effective for picking out of the plaques made by the phages. in this way, the phage isolates were propagated up to p . the various passages of the phage isolates v , v , v , v and v (i.e. original, p , p and p ) were stored at - °c. pvp- effect on pigments due to geminivirus infection on cowpea (vigna unguiculata) shail pande*, naveen pandey, k. shukla mahatma gandhi p. g. college gorakhpur, d.d.u. gorakhpur university, gorakhpur geminiviruses are one of the most important group of viruses causing economic losses in tropics. the symptom produced are yellowing of leaves which directly affect the pigments of diseased plants it in turn affects productivity and yield of diseased plant. cowpea vigna unguiculata is one of the important crop cultivated throughout india for its green pods which are used as vegetables and seeds are used as pulse. cowpea is affected by many viruses amongst them geminiviruses are one of the important virus on the cowpea plant. in the present study total chlorophyll content was studied in leaf of cowpea of diseased and healthy plants using arnon's method. carotenoids were also studied using ikan's method. it was found that chlorophyll content in diseased plants were lower compared to healthy plant similar results were found with carotenoids so the geminivirruses infection lowers the chlorophyll and carotenoid content in diseased plants which reduces yield of diseased cowpea plant. shweta sharma , amrita banerjee , j. tarafdar , r. rabindran , indranil dasgupta * department of plant molecular biology, university of delhi, south campus, new delhi; bidhan chandra krishi vishwavidayalaya, kalyani, nadia, west bengal ; tamil nadu agricultural university, coimbatore, tamil nadu rice tungro disease is an important disease of rice, caused by a joint infection by two viruses: rice tungro spherical virus (rtsv) and rice tungro bacilliform virus (rtbv) in south and southeast asia. the complex of rtbv and rtsv is transmitted by an insect vector green leaf hopper (glh). previously we reported complete genomic sequences of two geographically distinct isolates of rtbv; rtbv-wb (west bengal) and rtbv-ap (andhra pradesh) collected from the field in mid- s. both the sequences showed high homology all along the genome but showed divergence from previously reported southeast asian isolate i.e. rtbv-phil (philippines). to check whether a time period of a decade has resulted into variability in the genomic sequence of different isolates of rtbv in india, we cloned and sequenced the complete genome of rtbv from two geographically distinct regions of india i.e. west bengal and kanyakumari collected from the field in . the complete nucleotide sequence of the dna fragments covering the whole genome of rtbv was determined using universal primers m f and m r and by primer walking, without any ambiguities remaining. the nucleotide sequences of overlapping clones were assembled and analyzed using the dna analysis software generunner and blastn program of ncbi. homology search at the nucleotide and amino acid level were performed using the blastn and blastp (respectively) programs of ncbi. multiple sequence alignments were performed using clus-tal-w software. sequence analysis results thus obtained showed that both the recently obtained complete genomic sequences of rtbv from two geographically distinct regions of india i.e. west bengal and kanyakumari showed very high homology (both at the nucleotide and amino acid levels) with the two previously reported rtbv isolates from india i.e. rtbv-wb (west bengal) and rtbv-ap (andhra pradesh) all along the genome. as observed earlier both the sequences diverged significantly from the southeast asian isolates. this suggests that even after the spatial and temporal difference (a time gap of approx years) between the two previously reported rtbv isolates and the recently reported one, there is very little sequence variability between them. this further strengthens the earlier reports that the rtbv genomes in india are highly conserved. homology search at the nucleotide level using blastn program with the previously existing rtbv isolates revealed a very high percentage identity of % with the rtbv west bengal isolate and % with the rtbv andhra pradesh isolate. this further strengthens the earlier reports that there is not much genetic variability in the rtbv genomes in indian subcontinent. complete genomic rna sequences of two geographically distinct isolates of rice tungro spherical virus (rtsv), a member of the genus waikavirus, family sequiviridae, were determined from india. out of the two previously reported sequences, the indian isolates were closer to the resistance breaking strain rtsv-[vt ] than rtsv- [phila] . between them, the indian sequences showed nucleotide as well as amino acid identities of %. a moderate homology was observed between the leader peptide and a putative helper component protein involved in insect transmission of the maize chlorotic dwarf virus, a closely related waikavirus, indicating its possible transmission-related function. unlike rice tungro bacilliform virus, which causes rice tungro disease jointly with rtsv, and is significantly different between isolates from india and philippines, rtsv genomes were observed to be much more conserved between isolates from the two countries. rice tungro bacilliform virus (rtbv) are believed to be the joint causative agents for the devastating tungro disease of rice prevalent in south and southeast asia [ ] . rice tungro disease has become the major cause of production losses in rice during last three decades in several rice growing states of india. here, we report, for the first time the complete sequence analysis of two geographically distinct indian isolates of rtsv. we analyze the deduced protein sequences and their phylogenetic relationship with the two complete rtsv sequences from philippines as well as with other members of sequiviridae family. we provide molecular evidence that the indian isolates of rtsv are closely related to those from the philippines. we had earlier reported that rtbv isolates between india and philippines differ significantly from each other [ ] . this study was undertaken in order to see whether rtsv isolates from india also show similar difference from those reported from the philippines. frequent outbreaks of tungro were reported near kanyakumari in the last - years. the present work was undertaken to clone and sequence the full-length rtbv and rtsv genomes from the infected rice plants collected from above region and to analyze the similarity of its genetic material with the existing indian isolates of rtbv and rtsv. a . kb dna fragment encoding the reverse transcriptase gene of rtbv genome was amplified and cloned in t/a vector and was sequenced commercially. homology search at the nucleotide level using blastn program with the previously existing rtbv isolates revealed a very high percentage identity of % with the rtbv west bengal isolate and % with the rtbv andhra pradesh isolate. this further strengthens the earlier reports that there is not much genetic variability in the rtbv genomes in indian subcontinent. similarly, the cp region of rtsv was amplified by rt-pcr and was cloned in t/a vector. recently, rice tungro disease has been reported from kanyakumari district of tamil nadu. it is important to determine the genetic nature of this isolate in order to develop resistance strategies. it is thus necessary to clone and characterize the viruses from kanyakumari and to determine the mechanism of virus resistance in transgenic lines. rice tungro disease is an important viral disease of rice. rice tungro is caused by infection by two viruses: rice tungro bacilliform virus (rtbv) and rice tungro spherical virus (rtsv). rtsv is a plant picornavirus with a kb single stranded rna genome. it belongs to genus waikavirus in the family sequiviridae and is necessary for transmission of the two viruses by the leafhopper vector nephotellix virescens. rtsv rna is translated to form a large polyprotein, which is then self cleaved to form the viral proteins, including the three coat proteins, replicase, protease. studies have been conducted on rtsv from philippines. correct information of sequence variability of viral isolates to check whether different geographical conditions like those present in india select for genotypically variable strain and to design for transgenic resistance strategy, information on rtsv from india is absolutely essential. the objective of this study was to clone rtsv isolates from india and compare the genetic diversity of indian isolates from other southeast asian isolates and amongst each other. also develop strategy to impair the attack of virus-complex on rice. the achieve this, complete genomes of two isolates from india were cloned by amplifying different genes by rt-pcr and subsequently cloned in ta vectors, followed by sequencing. subsequently constructs containing cp - , antisense replicase, sense replicase and double stranded replicase were cloned in plant transformation vector. these constructs were used to transform aromatic rice variety from indian-pusa basmati (pb ). pcr analysis of the above plants was done to check the stable insertion of insert in the transgenics. jatropha (jatropha curcas) of the family euphorbiaceae is being grown in india as a major commercial fuel (bio-diesel) crop. jatropha is cultivated in districts of potential states of india. unfortunately, the cultivation of jatropha is limited by the severe mosaic disease. recently, a severe mosaic disease with significant disease incidence was observed in - on j. curcas grown in experimental plots of nbri and j. gossypifolia, a weed growing road side around lucknow and kathaupahadi, madhya pradesh. the disease consisted of the symptoms of severe mosaic, blistering, leaf distortion and stunting of whole plant and no fruit/seed production in severely affected plants. symptomatology and whitefly population observed on them suggested the occurrence of begomovirus infection. to detect the begomovirus infection, the total dna from leaf samples of infected jatropha plants was extracted and polymerase chain reaction (pcr) were performed using three sets of begomovirus genus specific (cpit-i/cpit-t, paliv /paric and paliv /palic ) primers and the expected size * bp, . kb and . kb amplicons were obtained which confirmed the begomovirus infection. further to identify the begomovirus/es and investigate the genetic diversity among them exists if any, the * . kb amplicons were cloned and sequenced. the sequence data were deposited in the genbank database under accession nos.: gq and fj (from j. curcas) and eu and fj (from j. gossypifolia). during blast analysis gq and fj shared highest % sequence identity with each other and - %% with sri lankan cassava mosaic virus (aj , aj , aj , aj and aj ) and indian cassava mosaic virus from india (ay ) therefore, designated as two strains of jatropha mosaic india virus-lucknow. blast analysis of eu showed maximum % similarities with croton yellow vein mosaic virus (aj ), % with tomato leaf curl new delhi virus (dq ) and - % with papaya leaf curl virus (aj and y ), therefore, identified as strain of croton yellow vein mosaic virus. blast analysis of the virus isolate (fj ) showed highest % identities with tomato leaf curl virus-bangalore ii (tolcv-b ii-u ) and - % with tomato leaf curl karnataka virus (tol-ckv, ay , fj ), therefore, considered as new begomovirus species ''jatropha yellow mosaic india virus''. the phylogenetic analysis of gq and fj (from j. curcas) and eu and fj (from j. gossypifolia) was performed along with some selected isolates of begomovirus which showed [ % sequence identities during blast analysis. the isolate eu showed closest relationship with croton yellow vein mosaic virus while fj showed separate clustering of all the four begomovirus from jatropha species. during phylogenetic analysis these isolates formed three separate clusters, therefore, they were considered as three distinct begomoviruses. the above data clearly show that some genetic diversity exists among the begomoviruses infecting jatropha species in india. bitter gourd (momordica charantia l.) of the family cucurbitaceae, also known as bitter melon is extensively cultivated in north eastern region of uttar pradesh, india. it is regarded as one of the world's major vegetable crops and has great economic importance. a severe yellow mosaic disease on bitter gourd (momordica charantia) with a significant disease incidence was observed during the survey of different locations of eastern up, india in the year . the whitefly (bemisia tabaci) population was also observed in the vicinity. the characteristic disease symptoms and whitefly population indicated the possibility of begomovirus infection. total dna were isolated from infected as well as healthy leaf samples. two primer pair (tlcv-cp and roja's primer) were used to study, which resulted * bp with tlcv-cp in / samples and * . kb amplicons with roja's primer in / samples. for further identification of the begomovirus, the pcr amplicons were cloned and sequenced (genbank accession no. eu and eu , respectively). the blastn search analysis of eu indicated - % identity with several isolates of tomato leaf curl new delhi virus (tolcndv). the phylogenetic analysis also showed closest relationships of the isolate (eu ) with tolcndv isolates. based on highest sequence identity and closed relationships with tolcndv the virus isolated from bitter gourd was considered as an isolate of tomato leaf curl new delhi virus. while, blastn search analysis of eu isolate, shared highest - % identites with pepper leaf curl bangladesh virus (peplcbv) isolates. the phylogenetic analysis of the virus isolate with selected begomovirus isolates revealed a closest relationship with peplcbv. these results confirmed the association of peplcbv on bitter gourd. study revealed the variability of viruses on bitter gourd in eastern up, india. tobacco streak virus groundnut isolate was characterized biologically by taking six cultivars (jl , tmv , k , k , k ) and one pre-release culture (k ) using seedlings of - days old under glasshouse conditions. there were clear differences were observed among cultivars tested regarding incubation period, percent seedling wilt and time taken to death of seedlings. k- was least susceptible among all the cultivars tested and it supported least virus titer (a nm: . - . ). both localized (necrotic lesions on leaf, veinal necrosis, leaf yellowing, wilting) and systemic (petiole necrosis, necrotic lesions on young leaves, death of top growing buds not only on main stem but also on all primaries (side shoots), followed by stem necrosis, stunted growth, axillary shoot proliferation with small leaves having general chlorosis, peg necrosis, pod necrosis, pod size reduction, wilt of plants) symptom were observed in all cultivars tested. biological differentiation of tsv and gbnv was made by sap inoculation of both viruses separately using susceptible groundnut cultivar jl under glasshouse conditions. there were certain similarities and differences were observed between these viruses infecting groundnut. seed infection of tsv ranged from . to . % in seeds collected from naturally infected and sap inoculated groundnut cultivars/pre-releases (jl , tmv , k- , k- , k- and k- ) belonging to spanish and virginia types. tsv was detected both in pod shell and seed testa from pod samples produced by sap inoculation under glasshouse conditions. however, seed transmission of tsv was not observed in groundnut. coat protein (cp) gene of three groundnut tsv isolates (gn-ap- - ; gn-ap - ; gn-ap - ) were sequenced and all the three isolates contained a single open reading frame (orf) of bp nucleotide and could potentially code for amino acids (aa). cp gene of tsv isolates originating from different hosts shared high degree of sequence identity both at nucleotide ( . - %) and amino acid ( . - %) levels respectively. tones grown in an area of . . ha (fao stat ). in india papaya is grown in nearly , ha with an annual production of , , tones (fao stat ) and occupies fourth place in the world. the crop is severely affected by a number of viruses. papaya ring spot virus (prsv-p) is the most important virus. the detection of virus infection in plants has traditionally involved either bioassay on indexing plants and or immunological methods (hill , torrence and jones ) . use of nucleic acid probes has improved the detection and sensitivity of viruses. the most common non-radioactive probes are biotynilated probes, which are very specific and sensitive. papaya ring spot virus (prsv-p) is a positive sense ssrna virus belonging to the genus potyvirus family potyviridae and transmitted by aphids. prsv-p coat protein gene region was used as template cdna for probe preparation. dot-blot hybridization with the biotin labeled probe were performed for prsv-p detection. the clarified sap of healthy and infected plants were serially diluted and spotted onto the nitrocellulose membrane, hybridized to biotin labeled probe. biotin labeled rna's are employed as probes, with a subsequent detection based on streptavidin-alkaline phosphatase conjugates. the sensitivity for viral detection of the biotin labeled probe was found to be sensitive than enzyme linked immunosorbent assay (elisa). in recent years tospovirus is causing devastating damage to the yield of vegetables in india. it infects economically important crops viz., tomato, chilli, peppers, groundnut, watermelon and various legumes. now it is emerging as severe disease in brinjal also. in order to monitor the natural occurrence and distribution of tospovirus in vegetable, surveys were conducted in the predominant brinjal growing areas of gujarat, karnataka, maharashtra and andhra pradesh during - incidence ranging from to %, to %, to %, and to . % respectively. samples collected from different places of india were found positive to pbnv in direct antigen coating-enzyme linked immunosorbent assay (dac-elisa). pbnv infected brinjal plants showed mosaic mottling of leaves with leaf distortion, longitudinal streaks on the stem and necrotic rings on leaves and fruits. early infection led to severe stunting and abnormal fruiting. biological and molecular characterization of pbnv-brinjal isolates were compared with other isolates and results are discussed. for identification of virus causing mosaic symptoms on soybean various host plants were tested. plants species belonging to the different families viz. caricaceae, graminae, leguminosae, malvaceae and solanaceae were tested. the virus produced symptoms on diagnostic plant species like chenopodium album, c. quinoa, helianthus anus, phaseolus vulgaris and vigna ungiculata. among tested families the leguminosae that were the host of virus included arachis hypogea, the virus causing mosaic symptoms in soybean is inactivated between and °c and between dilution of - to - . all the inoculated plants of assay host showed the symptoms at °c but not at °c. similarly local lesions produced at - but not at - . the virus in crude sap was infectious up to h but not at h at room temperature. however, the percentage infectivity decreased progressively as the aging of the sap was increased at room temperature. on the basis of reactions on diagnostic hosts pvp- identification and characterization of potyvirus infected chilli (capsicul annum l the virus under study caused mild mosaic and severe mottling symptom in leaves of infected plants. the dilution end point (dep) of the virus was found to be - to - , longevity in vitro (liv) - days at room temperature ( °c), thermal inactivation point (tip) - °c. electron microscopy of purified virus preparation revealed the presence of flexuous particle of size nm long and nm in width with characteristic cytoplasmic inclusions: pinwheels and scrolls. the virus was transmitted by sap and by aphid myzus persicae. the host range study revealed that the host species were restricted to family chenopodiaceae and solanaceae. on the basis of above characteristic, the virus under study was identified as potyvirus associated with mild mosaic and severe mottling symptom in capsicum. phytoplasma causing grassy shoot disease and sugarcane yellow leaf viruses are important pathogens of sugarcane. these pathogens are causing severe losses in sugarcane productivity. with a view to producing virus and phytoplasma free planting material of sugarcane, experiments were undertaken using infected varieties of sugarcane growing at the farms of sugarcane research institute. apical meristems measuring about mm in length, were dissected out, surface sterilized and cultured on agar gelled murashige and skoog's (ms) medium containing growth regulators for shoot induction. the established shoot cultures were multiplied through repeated subcultures on fresh media at - days interval. elimination of gsd and scylv was confirmed through molecular analysis of regenerated plants using specific primers of scylv and gsd. results revealed that apical meristem culture technique is effective in eliminating the pathogens like scylv and phytoplasma (gsd) from the infected clones. this is probably the first report on elimination of grassy shoot disease in sugarcane through meristem culture. papaya ringspot virus (prsv), which causes the most widespread and devastating disease in papaya, isolates originating from different geographical regions in south india were collected and maintained on natural host papaya. the entire coat protein (cp) gene of papaya ringspot virus-p biotype (prsv-p) was amplified by reverse transcription-polymerase chain reaction (rt-pcr). the amplicon was inserted into pgem-t vector by t-a cloning method, sequenced and sub cloned into a bacterial expression vector prset-a using directional cloning strategy. the prsv coat protein was over expressed as fusion protein in e. coli. sds-page gel revealed that cp expressed as a * kda protein. the recombinant coat protein (rcp) fused with his-tag was purified from e. coli using ni-nta resin. the antigenicity of the fusion protein was determined by western blot analysis using antibodies raised against purified prsv. the purified rcp was used as an antigen to produce high titer prsv specific polyclonal antiserum. the resulting antiserum was used to develop an immunocapture reverse transcription-polymerase chain reaction (ic-rt-pcr) assay and compared its sensitivity levels with elisa based assays for detection of prsv isolates. ic-rt-pcr was shown to be the most sensitive test followed by dot-blot immunobinding assay (dbia) and plate trapped elisa. key: cord- -hfmgc ve authors: venigalla, akhila sri manasa; vagavolu, dheeraj; chimalakonda, sridhar title: mood of india during covid- -- an interactive web portal based on emotion analysis of twitter data date: - - journal: nan doi: nan sha: doc_id: cord_uid: hfmgc ve the severe outbreak of covid- pandemic has affected many countries across the world, and disrupted the day to day activities of many people. during such outbreaks, understanding the emotional state of citizens of a country could be of interest to various organizations to carry out tasks and to take necessary measures. several studies have been performed on data available on various social media platforms and websites to understand the emotions of people against many events, inclusive of covid- , across the world. twitter and other social media platforms have been bridging the gap between the citizens and government in various countries and are of more prominence in india. sentiment analysis of posts on twitter is observed to accurately reveal the sentiments. analysing real time posts on twitter in india during covid- , could help in identifying the mood of the nation. however, most of the existing studies related to covid- , on twitter and other social media platforms are performed on data posted during a specific interval. we are not aware of any research that identifies emotional state of india on a daily basis. hence, we present a web portal that aims to display mood of india during covid- , based on real time twitter data. this portal also enables users to select date range, specific date and state in india to display mood of people belonging to the specified region, on the specified date or during the specified date range. also, the number of covid- cases and mood of people at specific cities and states on specific dates is visualized on the country map. as of may , the web portal has about tweets, and each of these tweets are classified into seven categories that include six basic emotions and a neutral category. a list of trigger events are also specified, to allow users to view the mood of india on specific events happening in the country during covid- . covid- pandemic has been severely affecting many countries across the world. the severity of the pandemic is growing very fast across the world. in india, the number of covid- cases have greatly increased, from cases to around k cases, in a span of one month, from march, to april, . the total number of deaths reported in the country have increased from on march, to on april, . there has been a growth rate of more than %, both in view of number of cases and number of deaths in the country, in a span days. increased number of cases being reported, from around k to around k and deaths from to , indicate the rapid growth of the pandemic in the country (from april, to april, ). it has been observed that the sudden outrages of such pandemics affect public emotion and result in either constructive or destructive behavioural changes [hou, du, jiang, zhou, and lin ( ) ]. human behavior has been observed to play an important role in either controlling or scaling up spread of a disease, and is more prominent in case of highly contagious pandemics [siegrist and zingg ( ) ]. the most common emotions witnessed among the people during several pandemics and crisis situations are fear and anger [lin, savoia, agboola, and viswanath ( ) ] [vaughan and tinker ( ) ]. though fear is observed as a basic instinct during the onset of unexpected situations involving danger, researchers also warn that excessive fear results in anxiety disorders, intensifying psychiatric disorders [garcia ( ) ]. also, such psychiatric disorders and anxiety might lead to cardiovascular disorders among the vulnerable population [shin and liberzon ( ) ]. mental health should hence be considered as an important part of pandemic response [douglas, douglas, harrigan, and douglas ( ) ]. lack of proper guidance to face the pandemic situation might sometimes result in acute fear, leading to self harm intentions including suicides [mamun and griffiths ( ) ] [shigemura, ursano, morganstein, kurosawa, and benedek ( ) ]. considering the severity of the pandemic in the context of covid- , it is extremely important to consider the psychological state and motivate the people accordingly, in controlling the spread of covid- . several cases of anxiety, stress and panic have been reported in various countries affected with covid- such s china, japan and so on [j.-b. li et al. ( ) ] [shigemura et al. ( ) ]. providing appropriate guidance to the population helps them to respond in a better way when contracted with covid- [zhao and xu ( ) ]. several organizations across the world such as who and cdc, have suggested various measures to be taken up to protect and enhance mental state of vulnerable population during pandemics, including covid- [cdc ( )][ who ( ) ]. thus, analysing public emotions against covid- helps in understanding the perception and preparedness towards the pandemic among the public [hou et al. ( ) ]. it helps in broadcasting effective public health messages that are inline with public emotions, which could help the public in taking appropriate measures against covid- [van bavel et al. ( ) ]. several countries have issued strict home isolation and quarantine instructions towards battling covid- . governments across the world have taken up health initiatives to reduce the negative psychological impact on the population during the period of home confinement and quarantine [garriga et al. ( ) ] [rubin and wessely ( ) ]. the government of india has taken up several measures towards controlling the pandemic, such as strengthening medical care, issuing strict lockdown instructions, carrying out awareness campaigns and so on . the instructions passed by the government and severity of covid- has greatly affected the day to day lives of citizens in the country. this is also observed to result in psychological stress among few people in the country. several measures to reduce this affect are being taken up by both public and private sector organizations in the country. the government has set up helpline centers that aim towards helping people with psychological issues during the pandemic, through telephone. also, many audio and video awareness clippings are being advertised by many organizations to prevent the psychological stress and to improve awareness among people towards the pandemic. understanding the mood of people across various parts of the country could help various organizations in taking better measures to help citizens of the country in maintaining better psychological balance. social networking platforms such as twitter, facebook and so on serve as a source to analyse and understand emotional state of the public. such platforms play an impor-tant role during pandemics, in assessing the mood and mental health of people across the world. researchers across the globe have made several attempts to understand the emotions of people in various countries towards covid- , with an aim to help health organizations and government in taking up measures accordingly. however, most of the existing studies summarize the emotions of posts on social networking platforms during a specified time interval, but not on day to day posts. depicting the emotion of people on a daily basis could help various organizations in understanding the changing mood of people. hence, we present a web portal-mood of india during covid- , that is aimed to provide visualizations of across various states in the country. the tweets posted on twitter related to covid- are analysed and classified into one of the seven categories that include six emotions -anger, sadness, happiness, surprise, fear and disgust [ekman ( ) ], and neutral category, which are visualized on india map based on the location from which the tweets have been posted. the emotional state of people plays an important role in responding to a pandemic. understanding the psychological state of population helps the governments in formulating guidelines and in taking necessary measures that are intended to motivate the public towards taking appropriate measures to prevent spread of pandemics and to restore mental well being amongst vulnerable population. hence, several studies have been conducted to analyse the emotional state of the public during pandemics, including covid- . the influence of various information sources and awareness campaigns aimed towards educating people about the mode of spread, safety measures to be taken against covid- and so on has been analysed through a open-ended answer based questionnaire based on situational awareness theory and theory planned behaviour [qazi et al. ( ) ]. a user survey has been conducted based on the questionnaire and sentiments of responses received have been analysed. the results of this study indicate that enhanced situational awareness among the people motivates them in adopting better protective measures [qazi et al. ( ) ]. sentiments of responses obtained from an online survey containing open ended questions related to health anxiety have been analysed among people in philippines. the results of this analysis revealed moderate "level of symptoms of hypochondriasis, attitude on acquiring covid- avoidance, and reassurance seeking" among the philippines population [nicomedes and avila ( ) ]. zhao et al. have analysed the attention of public to events related to covid- in china and observed an increase in public attention towards information related covid- . this analysis has been conducted on chinese social media platform -sina microblog, with an aim to help government in formulating better principles in communicating on health related aspects with the public [zhao and xu ( ) ]. another study conducted on data from three social media platforms in china during the period of december , to february , aimed to observe public attention, emotion, behavioral response and so on. this data analysis revealed low public attention in the initial stages of the outbreak, delaying the control of covid- . also, it has been observed that delayed information broadcasting has triggered negative emotions and resulted in panic buying in many cases [hou et al. ( ) ]. li et al. have analysed more than k weibo posts from january to january . the analysis was based on identifying the psychological profile of users based on online ecological recognition and predictive machine learning models, and consequently identified the emotions of users. the results indicate a visible decline in life satisfaction and increase in negative emotions [s. li, wang, xue, zhao, and zhu ( ) ]. twitter is one of the most commonly used platform and a rich medium to analyse various factors of population such as public sentiments, public response to a situation across the world, predict outbreaks of diseases and so on. posts on twitter during january and january related covid- have been extracted have been extracted to understand the changes in sentiments and opinions among people towards covid- . it has been observed that negative emotion tweets are observed in areas having more number of cases reported [medford, saleh, sumarsono, perl, and lehmann ( ) ]. sharma et al. have designed a dashboard that identifies misinformation being spread with respect to covid- , reactions of users to various emergency policies, country-wide sentiments and so on, and displays them on the dashboard [sharma et al. ( ) ]. considering the importance of posts on twitter, a multilanguage twitter dataset has been created by lopez et al. this dataset is also expected to provide insights on public response towards the pandemic across several countries and multiple languages [lopez, vasu, and gallemore ( ) ]. about k posts on twitter during december to february have been extracted and analysed to predict the outbreak of covid- . it has been observed that the number of tweets all over the world were directly proportional to the number of cases being reported in respective countries [jahanbin and rahmanian ( ) ]. chen et al. have analysed posts on twitter during march and april and respective emotions associated with the posts [chen, lyu, yang, wang, and luo ( ) ]. they observed correlations between the nature of terms used in the posts and respective sentiments of the posts. they have classified the terms into two classes -controversial and non-controversial using lda topic modelling and the results of analysis indicated that posts with controversial terms exhibit a higher level of negative emotions [chen et al. ( ) ]. public emotions have been analysed based on twitter data of around million posts, tweeted during january and april [lwin et al. (n.d.) ]. the tweets have been classified into ( )]. it has been observed that positive sentiments have outnumbered the negative ones in the country [barkur and vibha ( ) ]. in spite of several studies being conducted on psychological state of public across the world, there is limited research in understanding the psychological state of public in india. also, most of the existing studies deal with data only during specific timelines. in addition to this, to the best of knowledge, we are not aware of any real time, streaming twitter datasets, that are specific to india. hence, we present an interactive web portal, aimed to display the mood of india during covid- , based on streaming data of twitter. this web portal provides visualizations of number of covid cases reported and emotional states of various states in the country. also, the users are facilitated to select date range and state, and to view respective statistics of emotion change as a graph. mood of india during covid- thus provides a platform to view the sentiment of people across in each state on each day. it also helps in viewing the trends in emotion change across the country during a specific interval. twitter has been regarded as one of the richest platforms to assess trends, predict several activities, understand emotions and response of people towards various scenarios and so on. it has been widely used in analysing mental health and emotions of people during crisis situations. hence, analysing emotions posts on twitter during covid- in india could help in understanding the emotional states of population across the country. several studies have reported that texts in twitter posts could be associated with one of the six basic emotions proposed by ekman [ekman ( ) ]. also, it has been observed that several studies aimed to analyse the sentiment of people based on twitter posts during such pandemics and crisis situations, have classified the twitter posts into the six basic emotions [do, lim, kim, and choi ( ) ]. do et al. have classified emotions on twitter during the outbreak of mers in korea during , into seven categories [do et al. ( ) ]. we observed the idea of classifying tweets into emotion categories during covid- , to be similar to that of classifying them during mers in korea [do et al. ( ) ]. hence, we considered a total seven emotions into which each of the tweets was classified, inline with those considered by do et al. they included the six basic emotions -anger, disgust, fear, happiness, sadness and surprise, and an additional category -neutral. mood of india during covid- provides emotion of a state in india through a six step mechanism as shown in figure . step -data extraction. tweets posted from india with six hashtags related to covid- are downloaded from twitter. these hashtags included -coronavirus, covid- , india fight corona, covid, lockdown all such tweets (not more than , per day), posted during a day are downloaded along with their corresponding locations. based on the location co-ordinates, corresponding states are identified. step -data preprocessing. the downloaded tweets are preprocessed using nltk library. this method first tokenizes all the input sentences in the tweets and the parts of speech of each word in tweet in identified. all nouns and prepositions are removed as they do not convey any emotion. step -sentence ranking. an existing dataset containing synonyms of keywords corresponding to each of the six emotions -anger, disgust, fear, happiness, sadness and surprise has been downloaded from a github repository . the number of keywords for each of the six emotions is presented in table . the resultant tweets after preprocessing are compared to the set of keywords corresponding to each emotion. the tweets are then assigned ranks with respect to each emotion category based on the percentage of keywords of each category present in the tweet. step -emotion based classification. the ranks of all emotions in each tweet are analysed and the highest ranked emotion in the tweet is considered to be the emotion of the tweet. the tweets are then labelled with their corresponding emotion. the tweets having no rank for any of the six emotions indicate the absence of keywords corresponding to all six emotions. such tweets are considered to express neutral emotion and hence are labelled as neutral. all the tweets containing facts also fall into the neutral category. step -identify mood of states. the emotions of all the tweets in a day, in each state are analysed. tweets having similar emotions are grouped together and sum of tweets conveying the same emotion are calculated. the emotion having the largest number of tweets in each state is identified and the states are labelled corresponding to the identified emotion. step -store into database. the tweets and states with corresponding emotions are stored into the database, to be displayed onto the web portal as required. apart from the tweet data, information related to covid- cases, including the number of new cases reported, number of recovered cases and the number of deaths reported are extracted using covid api . this data is rendered on the portal as a heat map, plotted on the country map. apart from choosing to visualize emotion of states in the country, users can also view emotions of any one of the six cities-mumbai, chennai, pune, hyderabad, bangalore and tirupati. the fundamental motivation behind developing the web portal is to provide insights on feelings of people during covid- , based on twitter information. we have used the flask framework as a lightweight back-end system and html for the front-end for the development, which enables us to serve mood of india during covid- as a web portal. using the python scheduler library, we update the previous day's data precisely at : hours daily. we retrieve and store two kinds of data -covid- case data from covid india api and daily tweet data. we then convert this data into .csv files for processing and generate json files with meta-data for reducing the stress on the backend. using the tweet data, we generate two kinds of graphs, a bar graph for a single day evaluation and a line graph for evaluation of a continuous range of dates. these graphs are present for india, it's states and cities. chartjs has been used to generate all the graphs in the application. the covid- case data contains the number of state-wise confirmed, recovered and deceased cases, which is shown to the right of the map. it is visualized by generating a heat map of india. the map shows state-wise covid- confirmed cases based on the selected date. we built the map using an svg image with all the states listed in it and programmed it manually to respond to user interaction. by combining the slider and the map, the user can select a specific state and know the statistics at any point in time. we plot pins in the graph showing the top two highest emotion/emotions in that state. to convert the geographical co-ordinates into a position on the map, we use the amcharts library. a report is generated for the selected date range, which summarises the available details. the web portal, mood of india during covid- , displays the emotion of population towards covid- , across india, with an aim to provide insights about the mood of the country. when the portal is visited on any specific day, emotions of the country from march, to the present day are loaded by default based on twitter data during the range, as shown in figure table depicts the number of tweets classified into each of the seven categories, for every state and union territory of india, along with covid- statistics in the corresponding regions during march , to may , . state, when the extension of lockdown by weeks has been announced on may . this graph is generated by selecting the trigger event -extension of lockdown by weeks. the graph displays mixed emotions, with about % of the tweets expressing happiness, % expressing sadness and so on, indicating that most of the people in the state are happy about the announcement. mood of india during covid- has been developed as a webportal, that is aimed to provide information about emotions of the population during the pandemic. data in the form of posts from twitter are mined on a daily basis, along with the location from which they are posted. each of tweets is classified into one of the seven categories, based on the presence of percentage of keywords belonging to the six emotion categories. the tweets containing facts are classified into the neutral category. currently, our database consists of about k tweets, during the period of march and april. however, more number of tweets for the two months could be mined gradually. also, the maximum number of tweets being mined per day currently is k tweets from each state. though more number of tweets could be mined, we observe that the total number of covid- related posts are around k- k per day across the country, on an average. hence, we assume that the current number of tweets would suffice for analysis. however, this number could be increased if the number of tweets are observed to raise. tweets are being classified into respective emotions based on comparison of the processed tweets with set of keywords present in the dataset extracted from the github repository . tweets containing words that would belong to an emotion, but not present in the set of respective keywords would not be identified to express the specific emotion. the existing list of keywords contains a minimum of keywords per emotion. since the number of keywords in the dataset for each emotion are not equal, the classification might be inclined towards emotions with more number of keywords in the dataset. identifying and implementing natural language processing and machine learning techniques that result in better accuracies could be used to improve the classification of tweets and consequently in better predicting the mood of the country. the existing portal displays mood of the population only upto state level. mood of population in only six cities -pune, hyderabad, mumbai, tirupati, chennai and bangalore is represented. representing the emotions at multiple levels such as nation, state, city, district and so on, could help in understanding the emotional states of people belonging to more specific regions. considering the importance of understanding public emotions and the affects on psychological state of people during a crisis, in this paper, we present a web portal to identify the mood of india during the current covid- pandemic. the web portal marks top most emotions of people across various states and cities in the country based on the sentiments associated with tweets in each region. the emotions of tweets are identified by ranking tweets based on comparison of words in the tweets with preloaded list of keywords for each emotion. the results of emotions in a specific state in the country are displayed on the country map on any day selected by user from march , . also, a heat map of number of new cases reported in the country across all the states is plotted on the country map. the trends of emotions changing across the country in a selected date range are also visualized as line graphs. users can select to view information related to mood of the country. also, bar graphs depicting percentage of tweets expressing specific emotions are presented to the users. viewing the country map on any specific day could help users in understanding the emotion of the region with respect to number of covid- cases reported in the region. in the future versions, we plan to increase the number of tweets being considered for emotion analysis. also, we plan to mine more number of tweets related to covid- in the country during the two month period of march and april to increase the accuracy of emotions being displayed. we also plan to improve the accuracy of classification model by exploring newer nlp and ml based approaches that could classify the tweets based on emotions. furthermore, the existing portal could be improved to display mood of population with more specificity, which could include districts and cities of each state. sentiment analysis of nationwide lockdown due to 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populations the neurocircuitry of fear, stress, and anxiety disorders the role of public trust during pandemics using social and behavioural science to support covid- pandemic response effective health risk communication about pandemic influenza for vulnerable populations global health estimates : disease burden by cause, age, sex, by country and by region chinese public attention to covid- epidemic: based on social media. medrxiv bihar goa punjab uttar key: cord- -catapr authors: baruah, h. k. title: the covid- spread patterns in italy and india: a comparison of the current situations date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: catapr epidemiological mathematical models and time series models can be used to forecast about the spread of an infectious disease. in this article, without using such models, we are going to show how exactly the pattern evolves day by day once a pattern is seen to be approximately followed by the data. although in italy as well as in india the novel corona virus appeared on the same day, in italy the spread is nearly logarithmic by now and in india it is nearly exponential even now. various epidemiological models to study the spread of infectious diseases are available in the literature. meyers [ ] studied the use of the susceptible-infected-recovered (sir) model for infectious diseases affecting a small region. kamp [ ] concluded that the transmission network strongly influences speed and range of spread of epidemics. liu et. al. [ ] studied theoretically the susceptible-infectious-susceptible (sis) pandemic model using time delays in the thresholds. majeed and shawka [ ] studied mathematically the sis model of epidemic growth. wu et. al. [ ] used the susceptible-exposed-infectious-recovered (seir) model in a simulation study of the covid- spread. recently grant [ ] has shown that seir model does not work properly in the case of the spread of covid- . there are certain other models too such as the susceptible-infectious-recovered-dead (sird) model [ ] . indeed, quite a few more epidemiological models are in use to study the spread of infectious diseases. it has been seen that some models do forecast about the spread very nicely while some others have not been very successful. time series models using the auto-regressive integrated moving average (arima) method have also been used successfully by a few authors for forecasting the covid- spread in india. poonia and azad [ ] and azad and poonia [ ] studied the situation in two phases using the arima method. their forecasts were close to the actual values observed later. basu [ ] studied time dependent spread of the virus in india using his own model. as per his forecasts expressed in the form of a graph, the total number of cases in india should have crossed , in the beginning of june, and his forecast has been found to be true. in this work, we have two objectives. first, we shall compare the current spread patterns in italy and india. from the graphs of the current data on total number of cases that includes active cases, recovered cases and deaths, some mathematical pattern would be apparent. we would find out the current approximate patterns of the spread in these two countries. secondly, we would like to show how the patterns evolve day by day. hypothesizing about a particular mathematical model as the underlying spread pattern is one thing, while studying the changes day by day looking into the recent data is quite another. we would show how the logarithmic function is being followed by the total number of cases in italy, and how in india it is following a nearly exponential function, while the patterns are changing slowly and steadily. we would like to state that while trying to find a mathematical model regarding the spread pattern of a pandemic, the epidemiological models assume that in the first phase of the spread the mathematical pattern is exponential. in fact, this assumption is a very simplified one. initially, the pattern would be nonlinear but assuming it to be exponential right from the beginning is not actually valid. indeed, it can in reality be only approximately exponential, because if the pattern is exponential, it would only mean that the pattern would remain so until everything is finished. when the pandemic happens to retard, it is said that the curve is getting flattened. it is important to examine following what pattern the growth starts retarding. in any phase, we cannot say that a particular growth pattern is being strictly followed. when the pandemic would finally come to an end, it would mean that the pattern is a straight line parallel to the time axis. before that happens, the pattern may be approximately logarithmic. indeed a logarithmic growth is also a growth, however slow it is. we are in this article going to discuss and compare the current growth patterns of covid- in italy and india. we would show that in italy the current growth is approximately logarithmic while in india it is still growing approximately exponentially, although as per data published by worldomters.info [ ], on february , , both in italy and in india the total numbers of cases were equal to . where m and c are constants. if we need to fit such a curve from some observed data, we have to estimate the parameters from the data. that would need a method such as the method of least squares to estimate the two parameters. however, in the case that we are currently going to discuss, we would assume that from a certain value of x the concerned curve is logarithmic. therefore taking that starting value of x as , if we want to verify whether the curve is approximately logarithmic, then the value of the constant c is already known to us, and therefore in that kind of a situation we would need to estimate only the value of m. if we now see that the estimated values of m found from . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . although there are two parameters involved, when we proceed to apply this model in the exponential phase of a pandemic, we can take some particular date as the base to describe a few dates thereafter with reference to the base date. accordingly, the value of the constant a would be available to us already and we would have to find an estimate of the parameter b. when we would observe that the estimated values of b are very nearly constant, we would be able to say that the pattern is approximately exponential. as per the worldometers.info data [ ], on february there were cases reported in italy. from the graphs it can be seen that by the middle of march the spread pattern became highly nonlinear. by the end of april, the process of curve flattening had started. in other words, the pattern changed by the end of april from an approximately exponential form to a logarithmic form. we are explaining the matters in a rather simple way. but it can actually be checked whether it was really so. in table- . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint contact network epidemiology bond percolation applied to infectious disease prediction and control demographic and behavioural changes during epidemics sis model on homogeneous networks with threshold type delayed contact reduction the dynamics of an eco-epidemiological model with (si), (sis) epidemic disease in prey nowcasting and forecasting the potential domestic and international spread of the ncov outbreak originating in wuhan, china: a modeling study dynamics of covid- epidemics: seir models underestimate peak infection rates and overestimate epidemic duration data-based analysis, modeling and forecasting of the covid- outbreak short term forecasts of covid- spread across indian states until short term forecasts of covid- spread across indian states until may, , under the worst case scenario fits the data of spread in india [ ] approximately.to estimate the value of the parameter b at some point of time we would need data about the total number of cases for a few days prior to that. if the values of , the first order differences of z are seen to be nearly constant, then we can say that the pattern is nearly exponential. it was observed in [ ] that the values of ∆ ‫ݖ‬ have been following a reducing trend with some irregularities in between which is inherent in the case of a time series of this type of a pandemic. in table- this shows that at least up to june the pattern of spread in india is nearly exponential. our objective was not to forecast, but to show that the nearly exponential pattern is still continuing in india. indeed, our method is valid for short term forecasting only. as has been mentioned earlier, the values of ∆ ‫ݖ‬ were seen to be in a reducing trend. so this method is unsuitable for long term forecasting. although the pandemic had started in italy and india on the same date, february , , the situations soon became very different in the two countries. in italy, the nearly exponential pattern could be observed before the middle of april, and currently it is increasing logarithmically. in india however, in april the spread was just highly nonlinear and currently it is nearly exponential. this shows that a study regarding the total number of cases in the world as a whole cannot follow one single mathematical model, because whereas in india the spread pattern is continuing to be nearly exponential, in italy it is the inverse function -the logarithmic functionbeing followed by the data. key: cord- -gk n slx authors: yadav, pragya; sarkale, prasad; patil, deepak; shete, anita; kokate, prasad; kumar, vimal; jain, rajlaxmi; jadhav, santosh; basu, atanu; pawar, shailesh; sudeep, anakkathil; gokhale, mangesh; lakra, rajen; mourya, devendra title: isolation of tioman virus from pteropus giganteus bat in north-east region of india date: - - journal: infect genet evol doi: . /j.meegid. . . sha: doc_id: cord_uid: gk n slx bat-borne viral diseases are a major public health concern among newly emerging infectious diseases which includes severe acute respiratory syndrome, nipah, marburg and ebola virus disease. during the survey for nipah virus among bats at north-east region of india; tioman virus (tiov), a new member of the paramyxoviridae family was isolated from tissues of pteropus giganteus bats for the first time in india. this isolate was identified and confirmed by rt-pcr, sequence analysis and electron microscopy. a range of vertebrate cell lines were shown to be susceptible to tioman virus. negative electron microscopy study revealed the “herringbone” morphology of the nucleocapsid filaments and enveloped particles with distinct envelope projections a characteristic of the paramyxoviridae family. sequence analysis of nucleocapsid gene of tiov demonstrated sequence identity of . % and . % nucleotide and amino acid respectively with of tiov strain isolated in malaysia, . this report demonstrates the first isolation of tioman virus from a region where nipah virus activity has been noticed in the past and recent years. bat-borne viruses have become serious concern world-wide. a survey of bats for novel viruses in this region would help in recognizing emerging viruses and combating diseases caused by them. bat-borne viruses are considered to be important emerging viruses, as they can pose a serious threat to human and animal health. henipaviruses, coronaviruses, filoviruses and rabies-causing lyssaviruses are all transmissible from bats to humans. bats are primary reservoir host and often the resulting human disease is fatal. they are known to harbor more zoonotic viruses per species than rodents and recognized as a significant source of zoonotic agents (newman et al., ; calisher et al., ; mackenzie et al., ; pavri et al., ; mourya et al., ; raut et al., ; wynne and wang, ) . old world fruit bats of the family pteropodidae, particularly species belonging to the genus pteropus, have been considered as natural hosts for a large number of emerging viruses, especially of the family paramyxoviridae (calisher et al., ) . due to special characteristics, pteropus bats are the perfect reservoir for most of the recently emerging zoonotic pathogens. they often live in large colonies or roosts and travel long distances; thus they are very effective in transmitting viruses among colony members and disseminating them over a considerable distance. interactions among bats, humans and livestock are constantly increasing due to anthropogenic activities, thereby increasing the potential for transmission of viruses. deforestation in tropical areas destroyed the natural habitats of these fruit bat species thus forcing them to live in the vicinity of human settlements. the resulting close contact is responsible for the emergence of highly pathogenic paramyxoviruses, like hendra and nipah virus (niv) in human populations in southeast asia and australia (mackenzie et al., ) . paramyxoviridae is a family of viruses that comprises important pathogens like nipah virus, measles virus, human parainfluenza virus type and human respiratory syncytial virus (aguilar and lee, ) . while investigating niv in urine samples of giant fruit bats of the pteropus genus on tioman island, malaysia, in , researchers isolated a novel virus which was placed in the rubulavirus genus of the paramyxoviridae family. the virus was named as tioman virus (tiov) after the place of isolation from malaysia (chua et al., ) . in this communication, we report the isolation and confirmation of a tioman virus isolated from pteropus species of bats from north-east region of india. the scientific advisory committee, institutional biosafety committee, and institutional animal ethical committee of national institute of infection, genetics and evolution ( ) to determine the presence of niv in pteropus bats, a survey was conducted in two states of north-east region, india i.e. west bengal and assam states that share boundaries with bangladesh. the criteria for selection of the study areas were based on earlier reports of a niv seropositive bat from the myanaguri area in west bengal and confirmed human cases from siliguri and nadia districts of west bengal and roosting areas of pteropus bats (yadav et al., ; chadha et al., ) . sixty-eight pteropus bats were collected from jalpaiguri (n = ) and cooch behar (n = ) districts of west bengal and dhubri district (n = ) of assam on two occasions from march to may . mist nets were used to capture the bats. after capturing the bats, species identification and morphometry was done. further, the bats were euthanized and necropsies were performed in the field following proper biosafety measures. blood, organs (kidney, liver, and spleen), throat swabs, rectal swabs and urine samples were collected from bats. waste disposal was done following guidelines and proper precautionary measures. organ specimens were frozen in liquid nitrogen immediately after necropsy, while blood samples were kept at room temperature for min and centrifuged for min at approximately g. separated serum was aliquoted into labeled cryovials. vials of serum were transported at + °c in styrofoam box to national institute of virology (niv), pune, for further investigation. liver/spleen and kidney tissues of bats were homogenized in sterile minimum essential medium (mem; gibco) using a homogenizer (genogrinder ; bt&c inc., lebanon, nj, usa). further, tissue homogenates were centrifuged at rpm for min, and . ml of the supernatants was inoculated on to monolayers of vero ccl- cells grown in -well cell culture plates after removing the growth medium. the cells were incubated for h at °c to allow virus adsorption, with rocking every min for uniform virus distribution. after the incubation, the inoculum was removed and the cells were washed with × phosphate buffer saline (pbs). finally mem supplemented with % fetal bovine serum (fbs) was added to each well. the cultures were incubated further in % co incubator at °c and observed daily for cytopathic effects (cpe) under an inverted microscope. cultures that showed cpe were harvested and the suspension was centrifuged at rpm for min at °c; the supernatants were processed immediately or stored at − °c in ml aliquots. viral rna was extracted using tripure reagent and rna extraction kit (qiagen, valencia, ca, usa) as per the manufacturer's instruction. virus isolations were also attempted with other specimens of bats (throat and rectal swabs, urine), following the same protocol (chua et al., ) . cell culture supernatants and pellets of vero ccl- infected cells showing distinct cpe were examined by negative-stain transmission electron microscopy (tem) as described previously (brenner and horne, ; gangodkar et al., ) . to identify the virus isolate, various diagnostic tests were undertaken targeting niv and genus paramyxovirus using specific primers by rt-pcr (guillaume et al., ; tong et al., ) . further, the isolates were screened by rt-pcr using primers targeting the nucleocapsid gene and phosphoprotein gene of paramyxoviruses, as described earlier (chua et al., ) . amplified products were further sequenced targeting nucleocapsid and phosphoprotein gene. the sequences obtained by sequencing were curated using sequencher . (gene codes corporation, ann arbor, mi, usa) version software. the curated sequences were aligned using clustal w (embl-ebi, cambridgeshire, uk), and a phylogenetic tree was constructed using the neighbor-joining algorithm (kimura parameter model) with -bootstrap replicates as implemented by mega v . software (tamura et al., ) . in order to study susceptibility of different vertebrate cells to tiov, the infectious virus titer was determined by estimating % tissue culture infective dose (tcid ) using reed and muench method (reed and muench, ) . four vertebrate cell lines vero e- cells, pipistrellus ceylonicus bat embryo cells, baby hamster kidney- (bhk- ) and madine darbey canine kidney (mdck) cells were used for virus infection. the - % confluent monolayer of the cells was infected with multiplicity of infection (m.o.i) virus and observed for seven post-infection days. the methodology of cell infection by the virus was similar as mentioned above in section . . two passages of the virus were made in all cell lines in order to confirm the susceptibility of the cells. all the cells were studied for susceptibility based on cpe and further confirmed using real-time rt-pcr. to explore the possibility of propagation in embryonated chicken eggs, . ml of vero ccl- grown tiov was inoculated in the allantoic cavities of -day-old embryonated white-leghorn chicken eggs. the eggs were incubated at °c for days and were observed for sluggishness and mortality after every h. allantoic fluids from infected eggs were harvested after days of incubation and stored at − °c. first blind passage was performed and allantoic fluid was tested for tioman virus by real-time rt-pcr. cytopathic effect was (cpe) observed in vero ccl- cells inoculated with a kidney tissue homogenate of p. giganteus bat (nivan ). the characteristics of cpe included cell fusion and formation of syncytium with aggregation of the nucleolus. cpe was prominent on post-infection-day and cell detachment was observed on days post-infection- (dpi) (isolation dated st april ) (fig. ). the supernatant was tested by pcr, sequencing and electron microscopy for identification of the suspected virus isolate. negative contrast electron microscopy of the cell supernatant of vero ccl- infected with virus isolate showed the presence of virus particles with the typical paramyxovirus morphology. the "herringbone" morphology of the nucleocapsid filaments, a characteristic of the paramyxoviridae family, was clearly visible (fig. ) . distinct enveloped paramyxovirus particles with envelope projections of approximately nm in length were also visualized. out of bat sample processed, kidney samples from two bats (nivan , nivan ) were found to be positive by rt-pcr. pcr products of bp were observed for nucleocapsid gene of tiov. amplified products were further confirmed by sequencing partial nucleocapsid and phosphoprotein genes of tiov (gene bank accession no. kt , kt , kt . kt ). sequence analysis showed . % nucleotide sequence identity with both nucleoprotein gene and phosphoprotein gene sequences of the malaysian tiov isolate respectively (bat/ /genbank af ) (fig. ) . partial sequences of tiov phosphoprotein and nucleocapsid gene revealed that tiov strains from india and malaysia are from one lineage, it also makes up a clade with menagle virus while tuhoko, achimota and sosuga viruses make up a separate clade. tiov isolated from kidney tissue homogenate of bat showed a titer of . / μl by tcid in vero ccl- cell line. cpe-based susceptibility studies showed that all the studied vertebrate cell lines were susceptible to tiov with varying productivity. cpe in vero ccl- cell line became evident by nd dpi and there was total degeneration of cells by th dpi. vero e- cells, pipistrellus ceylonicus bat embryo cells and bhk- cell line showed cpe by th dpi. ps (porcine stable cell line) cells did not show cpe in first passage; however it showed distinct cpe at th dpi in the second passage. mdck cells showed growth of tiov with rounding and detachment of cells within h post-infection. however, susceptibility study by cpe showed that tiov grows faster in vero ccl- cells in comparison with other vertebrate cells. the study of susceptibility of different vertebrate cells to tiov indicated that vero ccl- cell lines are best suited for propagation of tiov. this may be useful for viral replication studies in future. embryonated eggs did not show any sluggishness or mortality in the initial passage and first blind passage. real-time rt-pcr using tiov specific primers and probe on the allantoic fluid of both the passages did not show any virus amplification. this showed that tiov did not grow in embryonated eggs. the present study reports the isolation of tiov from pteropus giganteus bat from dhubri, assam, india (fig. ) ; this is the second report of tiov isolation besides malaysia (chua et al., ) . tiov is antigenically related to menangle virus (bowden and boyle, ) which is also harbored by pteropid fruit bats; the menangle virus caused an outbreak of fetal deformities in pigs in australia in (philbey et al., ) . all the above-named pteropus-borne viruses group in a single clade, which separates them from other paramyxoviruses. the bats and flying foxes belonging to the order chiroptera are ecologically remarkable. they are among the most abundant, diverse and geographically dispersed vertebrates and are natural reservoirs for a number of highly pathogenic zoonotic viruses. bats are known to have persistent viral infections at a rate higher than other mammals, possibly due to shorter antibody half-life in these animals (calisher et al., ) . detailed studies are needed on their importance as reservoirs of viruses and their potential to harbor important pathogen causing human and animal diseases. there is scanty information available regarding the hosts, reservoirs and transmission of tiov, though direct transmission via ingestion of fruit by humans has been suggested (lehle et al., ) . however, batto-human transmission of tiov has not yet been reported. neutralizing antibodies against tiov have been detected in human serum samples from tioman island in malaysia, from where the virus was first isolated (yaiw et al., ) . tiov's estimated prevalence of . % is suggestive of its potential to cause subclinical infection in humans. experimental studies have shown that tiov is capable of infecting and replicating in pigs and its main cellular targets are lymphocytes, thymic epithelioreticular cells and the tonsillar epithelium in these animals (yaiw et al., ) . hence, pigs could act as an intermediate or amplifying host for human transmission, as has happened during menangle virus and niv outbreaks (parashar et al., ) . during niv outbreaks in malaysia, pigs played a critical role in transmitting the disease to pig handlers by direct contact. pig farms are a source of daily livelihood for a large number of populations in assam and other states like nagaland. the nagaland pig production and marketing project is funded by the national agricultural innovation project with a contribution from the international fund for agricultural development and aims to develop sustainable solutions to livelihood improvement in one of the poorest districts in india. pig farming was rampant during the year and being a good reservoir of many diseases in recent past the number of japanese encephalitis cases and outbreaks were increased in these areas. undetected mild tiov infection could occur in naturally infected pigs and this could facilitate viral transmission to humans via contact with oral secretions; this transmission could cause serious illness by crossing the species barrier. therefore, the role of bats and pigs in transmitting viruses to humans in asia needs to be determined. although no evidence of tiov illness in humans or animals exists, tiov's close relationship to other disease-causing bat paramyxoviruses, including niv, suggests the possibility that it too may cross the species barrier (bowden and boyle, ) . our study has shown the presence of tiov by highlighting its isolation from pteropus bat from dhubri district, assam india. the presence of large colonies of pteropus bats in close proximity of human settlements warrants implementation of necessary steps for detection and identification of emerging bat-borne viruses circulating in north-east region of india. emerging paramyxoviruses: molecular mechanisms and antiviral strategies completion of the full-length genome sequence of menangle virus: characterization of the polymerase gene and genomic -trailer region a negative staining method for high resolution electron microscopy of viruses bats: important reservoir hosts of emerging viruses nipah virus-associated encephalitis outbreak tioman virus, a novel paramyxovirus isolated from fruit bats in malaysia isolation of nipah virus from malaysian island flying-foxes. microbes infect dengue virus induced autophagosomes and changes in endomembrane ultrastructure imaged by electron tomography and whole-mount-grid cell culture techniques specific detection of nipah virus using real-time rt-pcr (taq man) henipavirus and tioman virus antibodies in pteropodid bats, madagascar managing emerging diseases borne by fruit bats (flying foxes), with particular reference to henipaviruses and australian bat lyssavirus malsoor virus, a novel bat phlebovirus, is closely related to severe fever with thrombocytopenia syndrome virus and heartland virus investigating the role of bats in emerging zoonoses: balancing ecology, conservation and public health interest. fao animal production and health manual no. case-control study of risk factors for human infection with a new zoonotic paramyxovirus, nipah virus, during a - outbreak of severe encephalitis in malaysia isolation of a new parainfluenza virus from a frugivorous bat, rousettus leschenaulti, collected at poona, india. am an apparently new virus (family paramyxoviridae) infectious for pigs, humans, and fruit bats isolation of a novel adenovirus from rousettus leschenaultii bats from india a simple method of estimating fifty percent endpoints mega : molecular evolutionary genetics analysis (mega) software version . sensitive and broadly reactive reverse transcription-pcr assays to detect novel paramyxoviruses bats and viruses: friend or foe? detection of nipah virus rna in fruit bat (pteropus giganteus) from india serological evidence of possible human infection with tioman virus, a newly described paramyxovirus of bat origin tioman virus, a paramyxovirus of bat origin, causes mild disease in pigs and has a predilection for lymphoid tissues authors express their sincere gratitude to the secretary and director general, indian council of medical research, new delhi for her continuous support. we would like to acknowledge icmr for funding extramural project 'multi-site epidemiological and virological survey of nipah virus: special emphasis on north-east region of india' (grant number : ). authors are grateful to dr. ms chadha (scientist 'f'& head of department), influenza department for continuous guidance and support and dr. r laxminarayanan, senior administrative officer, niv, pune, for rendering logistic support. technical assistance rendered by divya bhattad, kumar bagmare, amita bargat, shital melag and uk shende (laboratory) is gratefully acknowledged. the authors declare that they have no competing interests. key: cord- -jv mscom authors: nema, shrikant; ghanghoria, pawan; bharti, praveen kumar title: malaria elimination in india: bridging the gap between control and elimination date: - - journal: indian pediatr doi: . /s - - - sha: doc_id: cord_uid: jv mscom india observed a significant reduction in malaria cases in the previous year, reaffirming our trust and efficiency of the existing tools to achieve malaria elimination. on april, , countries around the world marked world malaria day under the theme “zero malaria starts with me”. this provides an opportunity to rejoice the success and re-evaluate ongoing challenges in the fight against this preventable and treatable parasitic disease. we highlight the potential gaps in the malaria elimination program, and underscore potential solutions and strategies to implement, improve and intensify the success of the national goal of malaria elimination by . i ndia has a long history of success and struggles with malaria control. the unsuccessful endeavor to eliminate malaria, and increasing morbidity and mortality bring back the elimination agenda in the health care priorities [ ] . in , there was a massive resurgence of malaria cases and plasmodium falciparum resistance to chloroquine and vector resistance to insecticides were reported [ ] . as a consequence, the modified plan of operations was launched in with a three-pronged strategy: early diagnosis with prompt treatment, vector control, and information education communication (iec)/behavior change communication (bcc), resulting in the decline of malaria incidence again in . subsequently, enhanced malaria control project in and intensified malaria control project in were launched to combat malaria in high transmission areas of the country. new tools for malaria prevention and control were introduced by national vector borne disease control program (nvbdcp) i.e., monovalent rapid diagnostic tests (rdt) for p. falciparum detection in ; artemisinin-based combination therapy (act) in ; long-lasting insecticide-treated nets (llins) in ; antigen detecting bivalent rdts for detection of both p. falciparum and p. vivax in ; and newer insecticides and larvicides in - . however, these strategies failed to build on its expected level of achievements. india moved towards global commitment for malaria elimination and endorsed a plan to eliminate malaria throughout the region by [ ] . world health organization (who) has developed the global technical strategy for malaria under the national framework for malaria elimination in india - to eliminate malaria (zero indigenous cases) throughout the entire country by , and maintain malaria-free status and prevent its re-introduction. therefore, we need to put all our efforts to achieve the desired success this time. in , an estimated million cases of malaria occurred worldwide, compared to million cases in [ ] . in india, a population of million was at risk of malaria with an estimate of million cases in [ ] , while . million confirmed cases of malaria were reported by nvbdcp in [ ] ; although, discrepancies between various sources have been noted [ ] . in india, malaria is highly endemic in rural and tribal areas of madhya pradesh, maharashtra, odisha, rajasthan, gujarat, jharkhand, chhattisgarh, andhra pradesh, west bengal, and karnataka. further, districts with % or more tribal population comprising about % of the country's population contributed to % of total malaria cases, % p. falciparum cases and % malarial deaths in the country [ ] . however, india has shown a % reduction in as compared to and this reduction was achieved by strengthening the surveillance measures, improving diagnosis and treatment, and intensive vector control measures using existing tools. for example, odisha contributed . % of total malaria cases in which reduced to % in using the durgama volume __ july , nema, et al. anchalare malaria nirakaran (daman) initia-tive and compre-hensive case management of malaria. to sustain the achieved reduction and moving forward to the elimination, we have to strengthen all the strategies using existing tools and by developing new tools. accurate diagnosis is the key to success in the elimination goal. among the five plasmodium species, p. falciparum and p. vivax cause the majority of cases and other species are rare, but the diagnosis is complicated by the varied distribution of both mono-infection and mixed infections [ ] . microscopy has always been the gold standard method but it requires highly skilled microscopist with genuine knowledge of different stages of plasmodium species with capability to read low-density parasitemia -fulfilling such a requirement in rural india is a daunting task, as a consequence, more than a quarter of malaria cases are missed by microscopy [ ] . rdts are used where microscopy is not feasible. p. falciparum histidine-rich protein (pfhrp ) antigen targeting p. falciparum is used in more than % of the malaria rdts [ ] . however, deletions of the pfhrp gene in the parasite, fluctuation in the expression level of plasmodium lactic dehydrogenase (pldh), and prozone phenomena are the major problems leading to inaccurate diagnosis of plasmodium species. therefore, other potential biomarkers such as hemedetoxification protein, apical merozoites surface protein pf , glutamate dehydrogenase, and hypnozoites-based serological marker should be validated to strengthen the rdt tool. molecular methods such as polymerase chain reaction (pcr) are feasible for the diagnosis of malaria (particularly low-density infection). however, these methods like conventional pcr, nested pcr, qpcr, multiplex pcr, and loop-mediated isothermal amplification (lamp) are less frequently used techniques due to longer time required, need for advanced equipment, expensive reagents and experienced personnel, and difficultly in organizing in most field conditions. a hemozoin-based magneto-optical detection device (gazelle) may prove an alternative to rdt for accurate diagnosis in the field. these new markers/tools can make an impact on elimination efforts by addressing the problem of missed diagnosis. accredited social health activists (asha) and community health workers are the key players and leading contributors to the malaria elimination program as they are primary healthcare providers in the malaria endemics rural and tribal areas where government hospital and healthcare facilities are inaccessible. they provide diagnosis using rdt, and treatment, as well as advise them about the importance of preventive measures. strengthening the qualitative and quantitative capacity of the asha may prove an asset in malaria elimination as children under the age of are more vulnerable in the community for developing severe malaria. tribal people are mostly dependent on traditional healers and unlicensed medical practitioners (ump), which delays the correct diagnosis, and improper treatment may lead to severe malaria, as well as further transmission in the community [ ] . therefore, the stakeholders may think about providing training to unlicensed medical practitioners on national guidelines for malaria diagnosis and treatment to overcome this issue. an integrated community case management strategy along with asha/ump may be needed to fight against malaria in the community. children aged below years are the most vulnerable group and accounted for % of global malaria deaths in [ ] , and complicated malaria is more common in children than adults. the clinical symptoms (fever, vomiting, cough, difficulty in breathing and inability to eat and drink) of malaria in children may be mistaken for a viral syndrome or acute gastroenteritis. p. falciparum seems to be notorious for severe malaria but vivax is also presenting as severe malaria in children [ ] . in high transmission areas, young children are at high risk of severe vivax-associated anemia, where the relapses phenomenon is frequent [ ] . children need portable, easy to take medicine adapted to their weight and age. therefore, careful consideration should be given to the formulations of child-friendly antimalarials because children absorb and metabolize medicines differently [ ] . although the medicines for malaria ventures (mmv) has taken the initiative for discovering and developing new medicines [ ] . the improper and inadequate drug and doses in the long term may create problems of drug resistance resulting in high morbidity and mortality in children as deaths in infants and children < years of age accounted for . % in india [ ] . pregnant women are more susceptible to malaria, although the prevalence during pregnancy was substantially lower in areas of high transmission [ ] . during placental malaria, p. falciparum-infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus, increasing risk for congenital malaria [ ] . therefore, in the malariaendemic areas, pregnant women should be screened for volume __ july , nema, et al. malaria elimination in india malaria if they have malaria-like symptoms or even in the cases of anemia, which not only helps malaria elimination but also delivering a healthy baby. migration malaria is also an important affair as it serves as a reservoir and seeds local outbreaks. moreover, migrant workers who either take temporary shelter or coming from malaria-endemic areas could impede surveillance. therefore, imported/migratory cases should be tracked by using surveillance networks, similar to geosentinel, eurotravnet and tropneteurop. malaria elimination requires a strong surveillance mechanism that can reliably and rapidly detect the disease using the ' - - ' strategy [ ] and the ' - - ' strategy [ ] during the elimination phase to overcome the problem. additionally, mobile surveillance tools may be efficient in real-time information sharing such as solutions for community health-workers (soch) and integrated health information platform (ihip) to prevent them from spreading disease and outbreak situations [ ] . therefore, the utilization of such networks may have importance in the malaria elimination program in india. afebrile cases do not show presentable routine symptoms but may become a source of parasitic transmission under a favorable setting. asymptomatic malaria (the presence of sexual or asexual parasites and/or absence of clinical symptoms) poses a serious challenge worldwide [ ] . naturally acquired immunity and partial immunity with past exposure and age are the probable factors to asymptomatic malaria in the malaria-endemic areas that plays a significant role in transmission and malaria severity in children to years of age [ ] . therefore, proper attention is warranted in children; else they may act as a key reservoir of malaria infection. schizonticidal and gametocidal drugs have been used to treat and prevent malaria for centuries. chloroquine was first developed in the s; but in , chloroquineresistance (cqr) was initially pointed out in assam, india. the rise in cqr (pfcrt gene, a molecular marker to track the cqr) contributed to a worldwide increase in malaria-related mortality. to combat resistant strains, several alternative synthetic antimalarial drugs (sulfadoxine-pyrimethamine and mefloquine) were deployed to treat and prevent malaria. sulfadoxinepyrimethamine (sp) is utilized as the second line of therapy after chloroquine-resistant in india. however, the mutation at the dhps and dhfr genes make it ineffective against the p. falciparum malaria. the introduction of act has made a thrilling effect on malaria treatment in many countries. at present, these drugs are successful; however, there are already hints that resistance to artemisinin has emerged [ ] . other factors that may contribute to drug resistance are the mutation in resistance markers, counterfeit or substandard treatments, improper doses, and artemisinin monotherapy. to avoid artemisinin resistance, triple artemisinin-based combination therapies such as artemether-lumefantrine plus amodiaquine are already in pipeline for the treatment of uncomplicated p. falciparum malaria [ ] . in the case of p. vivax, a -day course of primaquine (gametocidal drug) is recommended in all transmission settings to overcome the issue of relapse but poor drug compliance is a major challenge. however, the single dose regimen of tafenoquine may be helpful to improve the adherence issues associated with primaquine regimens. clinicians must document the g pd status because primaquine and tafenoquine both may induce hemolytic anemia in patients with a glucose- -phosphate dehydrogenase deficiency (g pd). nevertheless, novel p. vivax anti-relapse medicines that targets hypnozoites are greatly needed. implementation of directly-observed therapy (dot) reduces the antimalarial resistance development, reappearance rate of the parasite, and may subsequently decrease p. vivax transmission [ ] . this ultimate goal of developing new antimalarial drugs and modifying existing ones will take us one step closer to the elimination goal. in india, p. vivax contributed . % of the infections in . it is often termed benign malaria but substantial increases in morbidity and mortality, especially in infants due to weak immunity is considered alarming. pathophysiology of p. vivax such as a low-density bloodstage infection, hypnozoites, transmission facilitated by the early production of infective stages, mature gametocytes and more genetically diverse p. vivax populations have limited understanding. vivax duffynegative phenotype and fy glycoprotein (fya) need proper understanding in the indian context to fight against p. vivax malaria [ ] . the risk of p. vivax parasitaemia is high in coendemic regions (where both p. falciparum and p. vivax are equally prevalent) after treatment for p falciparum infection. this is probably due to fast acting and rapid parasite clearance property of artemisinin-based therapy against the treatment of falciparum malaria, in the area where short periodicity of p. vivax relapse cases occurred. therefore, complete radical cure may be assured to prevent recurrent parasitaemia, reduce ongoing volume __ july , nema, et al. malaria elimination in india transmission to ensure malaria elimination success [ ] . national malaria program has distributed about million long lasting insecticidal nets (llins) to communities during - in india [ ] as an intervention tool for malaria control and prevention to cover the million populations that were under risk [ ] . among children under years of age, llins provide up to % protective efficacy in preventing malaria attributed to mortality [ ] . operational success can only be achieved when universal coverage is attained and is at least % [ ] . the major drawbacks of llins include personal discomfort and feelings of suffocation when humidity and indoor temperature are high. therefore, child-friendly nets using color combinations and cartoon-based print may increase the use of llin. thus, zero vector durable lining (zvdl) is designed to cover interior wall surfaces, utilizing slow-release technology that has the advantages of both llins and irs, i.e. long-lasting residual use and no insecticide dusting [ ] . there is no commercially available malaria vaccine currently. however, efforts to make an effective malaria vaccine are underway for the last three decades. phase trial of rts, s/as (mosquirix) (at month , , and ) in children aged - months showed vaccine efficacy of . % against severe malaria in children [ ] . pfspz based genetically attenuated vaccines which halt the development in the early liver stages were found to offer protection to % recepients [ ] . limited understanding of how immunity develops against malaria poses a great challenge to researchers in designing effective vaccines. recent advances in the generation of recombinant proteins, dna and rna based approaches may be useful in vaccine development [ ] . several government organizations, such as the icmr through malaria elimination research alliance-india and nvbdcp are moving forward to fill the gaps with research and innovative strategies. india health fund and several non-governmental organi-zations such as tata trust and godrej have also taken an initiative to work on parasite control, vector control, technology-integration, and awareness and behavioral change. moreover, the success story of neighboring countries like sri lanka and china echoes the importance of public-private partnerships to accelerate malaria elimination efforts. icmr and sun pharma ltd have partnered for malaria elimination activities in mandla district of madhya pradesh [ ] . healthcare communities have undertook serious efforts to reduce malaria cases in india, but it is still threatening millions in india. this time the elimination efforts would require targeted approaches and strategies starting from the village level to the national level. at the same time, we need to take care of all the possible gaps such as human resources, robust surveillance, and hotspot targeted interventions by proper utilization of existing as well as new tools. all the laboratory-confirmed positive cases should be advised to stay under mosquito net until parasite clearance to avoid community transmission. universal and continuous availability of drugs, diagnostic and essential malaria commodities are to be ensured for effective management of community malaria. if the lessons learned from elimination efforts are properly utilized, the malaria elimination goal mayvery well be achieved on time. contributors: all authors have contributed, drafted and approved the manuscript. funding: none; competing interests: none stated. re-emergence of malaria in india malaria control in india: a national perspective in a regional and global fight to eliminate malaria national vector borne disease control programme (nvbdcp). malaria million death study collaborators. adult and child malaria mortality in india: a nationally representative mortality survey malaria situation in india with special reference to tribal areas strengthening diagnosis is key to eliminating malaria in india submicroscopic infection in plasmodium falciparumendemic populations: a systematic review and metaanalysis plasmodium falciparum glutamate dehydrogenase is genetically conserved across eight malaria endemic states of india: exploring new avenues of malaria elimination unlicensed medical practitioners in tribal dominated rural areas of central india: bottleneck in malaria elimination clinical manifestations, treatment, and outcome of hospitalized patients with plasmodium vivax malaria in two indian states: a retrospective study the anaemia of plasmodium vivax malaria children and malaria: treating and protecting the most vulnerable burden of malaria in india: retrospective and prospective view estimating malaria burden among pregnant women using data from antenatal care centres in tanzania: a population-based study placental sequestration of plasmodium falciparum malaria parasites is mediated by the interaction between var csa and chondroitin sulfate a on syndecan- china's - - surveillance and response strategy for malaria elimination: is case reporting, investigation and foci response happening according to plan? malaria elimination in indonesia: halfway there malaria elimination: using past and present experience to make malaria-free india by asymptomatic malaria and its challenges in the malaria elimination program in iran: a systematic review asymptomatic malaria in the clinical and public health context evidence of artemisininresistant plasmodium falciparum malaria in eastern india triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial directlyobserved therapy (dot) for the radical -day primaquine treatment of plasmodium vivax malaria on the thai-myanmar border duffy antigen receptor for chemokines gene polymorphisms and malaria in mangaluru risk of plasmodium vivax parasitaemia after plasmodium falciparum infection: a systematic review and meta-analysis protective efficacy of interventions for preventing malaria mortality in children in plasmodium falciparum endemic areas school-age children are a reservoir of malaria infection in malawi field evaluation of zero vector durable lining to assess its efficacy against malaria vectors and malaria transmission in tribal areas of the balaghat district of central india vaccines: a step change in malaria prevention? malaria elimination in india-the way forward dna-based vaccines against malaria: status and promise of the multi-stage malaria dna vaccine operation key: cord- -emgxp wg authors: gupta, sourendu; shankar, r. title: estimating the number of covid- infections in indian hot-spots using fatality data date: - - journal: nan doi: nan sha: doc_id: cord_uid: emgxp wg in india the covid- infected population has not yet been accurately established. as always in the early stages of any epidemic, the need to test serious cases first has meant that the population with asymptomatic or mild sub-clinical symptoms has not yet been analyzed. using counts of fatalities, and previously estimated parameters for the progress of the disease, we give statistical estimates of the infected population. the doubling time is a crucial unknown input parameter which affects these estimates, and may differ strongly from one geographical location to another. we suggest a method for estimating epidemiological parameters for covid- in different locations within a few days, so adding to the information required for gauging the success of public health interventions it is generally accepted that in many parts of the world the actual number of infected people is much more than the number of confirmed cases. this is due to limited testing which biased towards the serious cases. the number of documented fatalities on the other hand is likely to be much closer to the actual number. in this note we use a method to estimate the actual number of infections from the documented number of fatalities. this estimate is one of our main results. it is important because it is seems possible that asymptomatic and sub-clinical infections may also infect others [ ] . we find large uncertainties in these predictions at this time, and suggest a method to improve the estimates systematically day by day. this gives us a secondary motivation, which is to refine epidemiological parameters for covid- infections using only the daily statistics of fatalities. we do not utilize detailed epidemiological models. our model input is a hypothesis of exponential growth. there is no data from india at present which contradicts this. the other inputs we need are about the progress of the disease. there is agreement in the literature that post-infection there is a short asymptomatic period. we use statistical models for the progression of the disease from asymptomatic to resolution into recovery or fatality which are parametrized to fit reports. we also need the infection fatality ratio (ifr), which we take from previous studies. using these we make predictions for the infected population now and in future for various scenarios for the exponential growth rate. we discuss how our predictions can be used to validate some of the model assumptions. the distribution of population in india is highly non-uniform, and this could cause geographical fluctuations in the progress of the epidemic. so we apply our estimators to various localized outbreaks seen in india till now, and make predictions for the number of fatalities in these regions for about a week from now. using the statistical inputs which we discuss here, we give confidence limits on the predictions, and discuss how to match them to future data in order to extract the remaining epidemiological parameters. it should be noted that current data is available aggregated over districts. finer details may be very useful for discussing exit strategies from a lock-down. in view of this, the availability of data from each hospital separately would be of great use. in the early stages of a typical epidemic, when the number infected are a very small fraction of the population, the number of infected cases, i, rises exponentially. this may be parametrized as where the doubling time τ = ln /λ, and t is the initial time at which the counting starts. the doubling time τ is related to the basic reproductive rate parameter r . this is affected by both the virulence of the pathogen and the rate of social contact. estimates of r in china vary from as low as . to as high as . , with a cluster of estimates close to the median of . [ ] . see also an interesting estimate of the effect of public health interventions on r using data from the cruise ship diamond princess [ ] . converting r to τ requires an epidemiological model. in this note, we do not use any particular model. our only assumption about the dynamics of the epidemic is the exponential growth of infections given by eq. ( ). due to the extreme heterogeneity of the population in india, r , or τ , could vary from one place to another. the most definitive estimates of population densities are almost a decade old, since they come from the census of india [ ] . according to this source, the population density of indore is /km , whereas that for mumbai is , /km . inside mumbai again there is extreme heterogeneity, with high density areas like dharavi having a density of , , /km . these numbers are indicative of the possibility that different cities, and even districts within a city, may have very different doubling times τ . in view of this, we do not assume a single value for τ , but work with two scenarios: in scenario a infections double every days, i.e., τ = days; in scenario b doubling is twice as rapid, with τ = days. in comparison, the aggregated data on fatalities in india taken until march, indicates a doubling time of roughly days. we note that between march and april , the number of fatalities in the mumbai-navi mumbai-pune area changed from to , which supports the idea that scenario b may not be far from the current doubling time in this location. the aggregated indian fatality numbers could either be dominated by rapid growth in some local outbreaks, or a general spread of the disease. the geographically disaggregated data is capable of indicating which is the case. for covid- infections the incubation period, t i , is estimated to be . days ( % cl . - . days), with a long tail [ ] . early observers reported that the recovery time, t r , the time from the onset of symptoms to recovery, ranged from to days [ ] . the interval from onset of symptoms to release from hospital for a recovery may depend on various factors. it is seen to be larger from the time to death. this latter number is seen to have a mean of . days [ ] , and is the one relevant for our analysis. we will take the duration of the disease, t , to be the sum of these two periods, i.e., t = t i + t r . we will take the incubation period to be a minimum of days and have an exponential distribution after that, so that the mean incubation period is . days. we shall take the recovery time to have a minimum of days, and be exponentially distributed such that the mean time to death is . days. in other words, t i and t r are random variates chosen from the distribution and p (t r ) = for t r < , . e −(tr− )/ . for t i > . ( with these assumptions, the mean infected period, t , is about days, with the % cl being - days. these distributions can be improved in future. the core point to note is that a gaussian distribution is not a good description when the data shows a long tail and skewness. note that each of the random variates is applicable to a different case. the fraction of the infected population which dies is called the infection fatality ratio, ifr. this is most reliably estimated after the end of an epidemic. estimates based on chinese data for covid- give ifr = . (i.e., . %) on average [ ] , with a strong age structure [ ] [ ] [ ] . the analysis of [ ] gives a skewed posterior distribution of this quantity, so we will take ifr to have a minimum value of . , and exponentially after this so that it has a mean of . and a width of . . since the case fatality ratio, cfr, is discussed more frequently, we discuss the relation between cfr and ifr in the final section. note that ifr is a population averaged quantity, and the random values assumed for it are a measure of our uncertainty about this number. we have assumed that there is no correlation between t and ifr, since we have not taken age structuring into account. in a more detailed, age structured analysis, correlations may be important. the remainder of our analysis will use the data on fatalities reported by the ministry of health and family welfare [ ] . before embarking on the analysis it is useful to separate out the data on fatalities into two sets. one is the set of fatalities known to be of persons who arrived from a foreign country and was very soon after diagnosed as being infected with covid- . the statistics of such deaths relate to infections in the country where it was picked up. so this set is not of relevance to our analysis of the infections within the country. it is the complement, namely the set of fatalities to which no travel history can be attributed, which is of relevance to the analysis. this separation is not made in [ ] . however, the data tracked in [ ] adds this information from press reports, and the totals tally with the data of [ ] . this is the data set we utilize here [ ] . due to the extreme variability in population density across india, it is good to avoid a country-averaged analysis if possible. we analyze clusters of fatalities due to covid- in india, with data that was complete at the end of march , . the fatalities of persons with no history of recent foreign travel fell into two groups: sporadic, defined as single fatalities in isolated geographical locations, and clusters, defined as more than one fatality in the same city or in towns very close to each other. we decided not to use sporadic cases, since statistical estimates are meaningless for single incidents. we found four clusters which are listed in table i . these are the epidemic hot-spots in the country according to currently available data. the observation of the number of fatalities, d(t), on day t, may be converted to an estimate of the actual number of infections, i(t), on the same day by using the formula the first factor, d(t)/ifr is an estimate of the number of infections, i(t − t ), on day t − t . the second factor is the exponential growth of eq. ( ) which evolves this older number of infections to its current value, leading to eq. ( ). note that the very broad and skewed distributions of t and ifr will give similarly broad and skewed distributions of i(t). here we suggest how to narrow these estimates progressively. any knowledge of i(t) gives a prediction of i(t ′ ) at a future date t ′ . uncertainties in i(t) expand into larger uncertainties in i(t ′ ) due to exponential growth. however, the number of fatalities up to date t ′ , i.e.. d(t ′ ), is directly observable. a time series for d(t ′ ) allows us to estimate τ directly. furthermore, with each day's data on fatalities, one can run the evolution backwards to rule out some of the uncertainty in the starting prediction i(t) on march. this means that the prediction for d(t ′ ) = i(t ′ ) × ifr further in the future is narrowed down. we show this inference procedure schematically in figure . as the allowed range of the initial i(t) successively narrows, one also narrows the allowed range of t and ifr through a bayesian inference paradigm. there are statistical uncertainties in the parameters t and cfr. we have combined them through a random monte carlo sampling using the probability distribution functions defined above. we implemented the monte carlo in mathematica. the use of eq. ( ) to make estimates of i(t), and the future values i(t ′ ) and d(t ′ ), then gives a statistical distribution of these quantities. these are implemented in the same monte carlo estimator. the basic result is for the amplification factor, i(t)/d(t), which we obtain with this numerical estimate, ( to , ) × d(t) for scenario a ( , to , , ) × d(t) for scenario b the ranges given here are % cl, and have been rounded to two significant digits. the median values are , in scenario a and , in scenario b. we tested the effect of changing the skewness of the distribution by replacing the shifted exponential distributions in eq. ( ) and eq. ( ) by gamma distributions tuned so as to reproduce the same means and variances. however, the gamma distributions then have smaller skewness. ( to , ) × d(t) for scenario a ( , to , , ) × d(t) for scenario b the medians are , in scenario a and , in scenario b. one sees that the medians and lower limits of the % cl change by relatively small amounts, whereas the upper limits are quite different. we list the covid- hot-spots in table i along with estimates of i and d on various dates for each in the two different scenarios defined earlier. we emphasize that different geographical locations may have different doubling times, so both scenarios may be relevant. these are our major results. for later use we also show in figure the % cl predictions for d on april in two different hot-spots in scenario b. any limits that we can extract on disease and epidemiological parameters would help us to plan ahead for the kind of demands that may be put on medical facilities in the near future. from the data on the geographical distribution of fatalities in india, we identified four possible hot-spots for covid- . the clustering of fatalities into hot-spots is an indication that there is perhaps no general spread of the epidemic through the country, and gives hope for partial removal of lock-down if the situation does not change. we used the simple statistical estimator given in eq. ( ) to make a prediction for the total number of infections in each of these hot-spots on march, in two scenarios. estimating i(t) is important, especially since there is a good chance that the part of this population which is pre-symptomatic, non-symptomatic, or has sub-clinical symptoms are all able to communicate the disease to others. our predictions are exhibited in table i . note that the % cl spans an enormous range, due to the spread in the input parameters, mainly the time interval between infection and death. note that the distribution of i(t) is very skew, and the median is close to the lower end of the % cl. in scenario b, the upper end of the % cl is more than % of the population of mumbai. we consider this highly unlikely, although statistically possible. we have outlined a procedure refine these estimates by incorporating daily data progressively into the computation. given the very large values of i(t) which the model predicts, medical professionals may legitimately ask whether one sees so many respiratory cases arriving in hospitals. note however, that a very large fraction are likely to be either asymptomatic, or exhibit sub clinical symptoms. in fact [ ] simultaneously reports ifr and the fraction of infected individuals who are hospitalized, h. this ratio, averaged over the population is reported to be in the range h = - %. in scenario b, therefore one may expect - , people to arrive in a hospital. even among these, some may not be able to consult a physician during a lock-down. nevertheless, current experience strongly disfavours the upper end of this % cl range. one recalls again, that the median is close to the lower end. this estimate again emphasizes how important it is to narrow the range of prediction from the model. we are able to perform another simple estimate from these numbers. the case fatality ratio, cfr, is defined as the number of fatalities divided by the number of cases tested. assuming that the tests are largely done on the people who arrive at a hospital, one can see that cfr ≈ d(t) hi(t) = ifr h . with ifr = . % and h = - %, we find cfr = . - . , i.e., in the range of % to %. this is precisely in the range that is seen in the current data for india. this also means that the current policy for testing is likely to be catching most cases which need to be hospitalized. one hopes that with the decision to administer the faster serum test, it might become possible to sample the larger population more effectively. finally we point out that there is a strong age structure to all the model parameters, which we have ignored. this we plan to do in future. along with the planned bayesian narrowing of the parameter space of covid- pathology and epidemiology, this would provide valuable inputs for more detailed models which can be used to inform future policy. aerosol and surface stability of sars-cov- as compared with sars-cov- the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application positive rt-pcr test results in patients recovered from covid- the reproductive number of covid- is higher compared to sars coronavirus covid- outbreak on the diamond princess cruise ship: estimating the epidemic potential and the effectiveness of public health countermeasures characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china estimates of the severity of coronavirus disease : a model based analysis clinical predictors of mortality due to covid- base on an analysis of data of patients from wuhan, china potential biases in estimating absolute and relative case-fatality risks during outbreaks we make our data set on clusters of fatalities publicly available on google maps at the address drive the authors would like to thank sandhya koushika, gautam menon, and rahul siddharthan for crucial inputs, and many members of the isrc (indian scientists' response to covid- ) mailing list for discussions. key: cord- - zq tln authors: vaz, manjulika; timms, olinda; johnson, avita rose; s., rathna kumari; ramanathan, mala; vaz, mario title: public perceptions on controlled human infection model (chim) studies—a qualitative pilot study from south india date: - - journal: monash bioeth rev doi: . /s - - - sha: doc_id: cord_uid: zq tln research using controlled human infection models is yet to be attempted in india. this study was conducted to understand the perceptions of the lay public and key opinion makers prior to the possible introduction of such studies in the country. respondents from urban and rural bangalore district were interviewed using qualitative research methods of focus group discussions and in-depth interviews. the data was analyzed using grounded theory. safety was a key concern of the lay public, expressed in terms of fear of death. the notion of infecting a healthy volunteer, the possibility of continued effects beyond the study duration and the likelihood of vulnerable populations volunteering solely for monetary benefit, were ethical concerns. public good outcomes such as effective treatments, targeted vaccines and prevention of diseases was necessary justification for such studies. however, the comprehension of this benefit was not clear among non-medical, non-technical respondents and suggestions to seek alternatives to chims repeatedly arose. there was a great deal of deflection—with each constituency feeling that people other than themselves may be ideally suited as participants. risk takers, those without dependents, the more health and research literate, financially sound and those with an altruistic bent of mind emerged as possible chim volunteers. while widespread awareness and advocacy about chim is essential, listening to plural voices is the first step in public engagement in ethically contentious areas. continued engagement and inclusive deliberative processes are required to redeem the mistrust of the public in research and rebuild faith in regulatory systems. a chim is a 'controlled human infection model' study in which a well-characterized strain of an infectious disease agent is administered at a controlled dose by a specified route to healthy adult volunteers to evaluate the disease itself, its treatment, or the efficacy of candidate vaccines, among others. chim studies can lead to better understanding of the mechanism of infection, pathogenesis of disease, contributing host factors, microbial virulence, treatment protocols and vaccine induced responses; and can evaluate potential vaccines. (gordon et al. ; gopichandran ; who ) . chim studies have a varied lexicon and are also known as 'challenge studies' as the body is challenged with a microbial pathogen as part of the research model, and more recently as 'experimental infection' (langenberg et al. ; todnem et al. ) . animal studies may be inadequate in predicting human responses to interventions. aided by advances in immunology, functional genomics, microbiomics, pharmacogenetics, pharmacokinetics and pharmacodynamics, a chim study has evolved as a new methodology in modern infectious disease research (balasingham et al. ; porter et al. ) . however, only % of chim studies are carried out in low, middle income countries (lmic), where the need for research on infectious diseases and vaccines is higher (gordon et al. ; elliott et al. ; selgelid and jamrozik ) . further, cross immunity and biological variability in different populations can alter host-pathogen dynamics and response to vaccines, making extrapolations of study results from other populations difficult. since % of the global infectious disease burden is contributed by india, there is clearly a need for infectious disease research in india and the possible introduction of chim, in particular. chim studies are currently not done in india. chim studies are believed to accelerate vaccine and drug development, making the process efficient and less costly (balasingam and wilder-smith ) , a benefit that could be important for india (gordon et al. ; gopichandran and kang ; dholakia ) . inadequate infrastructure, training and resources, and the absence of a clear regulatory framework are some of the reasons why chim studies are not done in india (gopichandran and kang , timms ). the history of atrocities associated with experimentation in humans could be a cause for apprehension with human testing in chim. (pollard et al. ) as chim studies intentionally infect healthy human volunteers and cause disease, it challenges the bioethical principle of 'primum non nocere' or 'non-maleficence'. thus, these studies would be viewed differently from human studies that typically evaluate therapeutic interventions (balasingham et al. ; rose ; johari ; vaz ) . at present, chim studies are typically conducted in non-endemic, high-income countries where volunteers are usually college students. apart from difficulties with extrapolations due to the genetic profile and environmental factors, it is ethically questionable for a population to be exposed to risk when there is little personal or community benefit. in india, where the understanding of biomedical research itself is low (vaz ) , acceptance of a study design that includes purposeful infection and quarantine, could be a challenge. in addition, research participants here are often less educated or socially disadvantaged with poor 'health literacy' (vaz ) . the validity of chim studies can be questioned in light of the more pressing need to address the social determinants of health. from a social justice viewpoint, chim studies may appear to promote immediate medical/technological solutions over mandates for long-term, sustainable provision of basic human living and environmental conditions that can prevent disease. the scholarly article by bambery et al ( ) , suggests four requirements for human challenge studies to be ethical '(i) conduct independent expert reviews, including systematic reviews; (ii) ensure a publicly available rationale for the research; (iii) implement measures to protect the public from the spread of infection beyond the research setting; and (iv) develop a new system for compensation for harm' (bambery et al. ). there is scarce empirical bioethical literature currently available in india to guide researchers and research ethics committees in navigating the complex ethical issues of purposefully infecting healthy volunteers. it appears that the central ethical dilemma is of individual risk vs public (public health) benefit. deliberative public engagement is recommended for policy development in contested ethical areas (molster et al. ) . interactions with the public on biomedical research, benefits of participation, and protective bioethical guidelines and laws is likely to promote social acceptance and empowerment within the community. it is also important that ethics regulations evolve 'bottom up' and are not exclusively 'expert-based' as the latter risks being "one-sided, biased or ideological-thus illegitimate" (schicktanz et al. ) . listening to the voices of the people also ensures that the notion of 'public good' encompasses multiple perspectives and standpoints (london ) . key outcomes of public engagement are greater transparency of purpose and procedures, the ability to understand and anticipate problems at individual and societal levels, issues of vulnerability and methods to address them; fears and concerns around risks of participation and trust building between the scientific community and the public. public engagement can improve people's participation, trust and confidence in the researcher, and understanding of the safeguards in research. public participation in the development of bioethical guidelines that protect their interests, establishes the public as a key stakeholder in research (blom and de vries ) . since chim research studies have yet to begin in india, it presents an opportunity to do things differently this time around, creating guidelines, processes and infrastructure in a transparent and inclusive manner, to dispel apprehensions born of past clinical trials, and advance vaccine science in a sustainable, safe and cost-effective manner. this paper is the outcome of a study aimed to engage with the public and local stakeholders on their perceptions of acceptability, concerns and participation in chim studies, in the indian context, and thereby influence guidelines to be more people-centered. qualitative research methods and the grounded theory approach (corbin and strauss ) were used in this exploratory study of public perceptions, to generate insights into this new area of medical research. focus group discussions (fgds) and in-depth interviews (idis) were the methods of data collection. the details are described below. the study was conducted in the urban metropolis of bengaluru and in the surrounding villages of bengaluru district. bengaluru is the fastest-growing indian metropolis after new delhi, with an estimated population of . million in its urban area (as of ). about % of residents in bangalore live in slums. much of the population growth in bengaluru is due to migration from other states in india (bangalore population ). bengaluru was selected as the study setting as it is the location of the primary study team and is also a hub of biotechnology and clinical research (pulakkat ) . . % of bangalore district is urban (census - data), with a small proportion remaining rural. mugalur village in the sarjapur hobli (cluster), of anekal taluk (administrative block), bangalore urban district, kms from bangalore city was chosen as the area for collection of rural data. the medical college and the department of community health (arj, rk) conduct an outreach/ community health program at that location. participants were of two types-the general public and key informants. they were selected from bangalore city and mugalur village (anekal block, bangalore district). participation was completely voluntary. participant selection was purposeful and aimed at accessing a cross section of society. the key strata of general public covered were males and females, youth and middle aged, members of the public belonging to specific work categories-college students, information technology professionals (bangalore is the it hub of the country), un-organized sector workers, and mid-income school teachers in the urban areas and members of women's self-help groups, farmers collectives, community health workers and youth groups in the rural areas. local contacts were used to identify potential participants. table provides the number of participants in each category, their age groups and work profiles. fgds were the method of data collection from the general public as it was more practical to meet them as a group. a focussed, guided discussion also makes lay people more comfortable with sharing, as they are not experts in this area. in addition, decision making among these communities in real life is usually through consultation and discussion. the fgd participants were between and years. of the participants, there was nearly equal representation of younger (< years) and older participants (> years). about two thirds were married. majority of the urban respondents were graduates and post graduates while the rural respondents had completed secondary or higher secondary education. people belonged to different religions and caste groups, though many urban respondents were unwilling to disclose religion and caste. they came from various occupational backgrounds: students, salaried employees or daily wage labourers in urban areas. most of the rural women were homemakers, while the rural men were farmers or weavers. many of the urban fgd participants refused to disclose their monthly income. where reported, income levels between the rural and urban participants were extremely disparate. the socio-economic profile of the rural participants was closer to the urban poor. key informants (kis) were in all. in the rural area they were people who understood the community, were influencers in decision making and were engaged with community health outreach work. in the urban area, the kis were those knowledgeable about communicable diseases, infectious disease researchers, ethics committee members and those likely to influence public opinion. they included microbiologists, clinicians, public health workers, social workers, research ethics committee members, media representatives, lawyers, and human rights activists. kis were between and years of age. the in-depth interview method was used for this category, as each was an independent professional with recognised expertise. table has a list of the kis. the research team included the principal investigator (mv), a social scientist with many years of experience working with communities and qualitative research, an ethicist (ot), two public health researchers (arj, rk) and a medical researcher (last author) with many years of experience in epidemiology and social science research. mr is an experienced qualitative researcher and a public health scientist who joined the team at the stage of data analysis and interpretation of data. a focus group discussion guide was developed, pilot tested and fine-tuned. prior to the fgd, participants were reassured that the discussion was not aimed at recruiting subjects for chim research, but intended to understand their views and opinions, there being no right and wrong answers. the discussions flowed naturally and followed the narratives of the respondents and were not limited by the topic guide. a warm up section of the fgd covered a discussion on medical research and ethics. to trigger the discussion on a chim study, a generic case scenario was presented as follows: "a chim study involves giving an infectious agent (a carefully identified low infective form of a germ) at a controlled dose and controlled conditions to carefully selected healthy adult volunteers. the main reasons to conduct a chim study are to understand the exact way that the infection affects humans, human responses and the length for which the germ remains in blood and body fluids…". the three areas of focussed probe included ( ) perceptions of benefit and concern, ( ) understanding who a potential volunteer could be and the nature of consent needed, ( ) issues around compensation and its influence on participation. the last section of the guide focussed on the subject of public good and individual altruism. the topic guide for the idis was similar to that of the fgds but did not include basic awareness of research and ethics. (copies of the topic guides are available with the first author). data collection was done by rk in the rural areas with mv and arj as note takers and was done by mv and arj in the urban areas. an audio recorder was used after the respondents' consent. while english was the language of most fgds and idis in urban areas, kannada, the local language of the region, was used for the rural fgds and idis and the lower socio-economic groups in the urban areas. between june and september , eleven focussed group discussions ( rural, urban) and in-depth interviews ( rural, urban) were completed covering a total of respondents. data collection continued till data saturation was reached. audio recorded data was translated and transcribed into textual documents by an external agency. the transcripts were read by data collectors arj and mv for errors in content or meaning. all the data collected were analysed using the qualitative method of grounded theory and constant comparison. data analysis was an iterative process and began when the first transcript was received. open inductive coding was done by mv and arj, a coding framework was developed consisting of a priori codes (those from the topic guides) and de novo codes (those emerging new from the data) using nvivo software, version . . and was an ongoing process. even when mv and arj were coding independently, both researchers would recheck the codes, and modify or add if necessary, to the coding framework. the coding framework is provided in table . themes have been delineated and presented in the results section. all the study team members were involved in mapping the emerging themes into a conceptual model and this followed a reflexive process. the study was designed following the ethical guidelines of the indian council of medical research. approval of the study protocol, the subject information sheets and consent forms in english and kannada was received from the institutional ethics committee of the primary research team's institution. (iec study ref no / dated th may . after reading and/or discussing the study information sheet, all respondents provided written consent for participation, audio recording and for de-identified quotes to be included in publications. participants were assured of confidentiality, freedom from coercion to speak or participate, and sharing of findings if the participant wished. the perceptions of the general public towards chims have been presented under six major themes (see fig. ). views of the key informants-the health and research experts and the opinion influencers-the media, activists and legal experts have been used to explain the public perceptions or to provide contrasting perspectives. illustrative quotes (with affiliation codes) have been provided to support the themes and sub themes. as a backdrop to the perceptions of the public to controlled human infection trials, we have two subsidiary themes-the basic perception of 'research' among the lay public and their perceptions of ethics and its place in research. there was a clear socio-economic and geographical divide in the understanding of the meaning of research in general. there was less understanding of research among the rural poor. urban groups and individuals had a clearer understanding-some of the notions they expressed were related to the idea of clinical trials, a focus on 'medicines' and the long timeframe for the outcomes of research to reach the public. the ideas about who did research included 'pharma' companies; i know that people go through clinical trials …there are pharmaceutical com-panies… (urban fgd ;); …there are clinical trials [and] all these various aspects, to ensure it [a drug] is completely safe for the public… …you realise it is just a preliminary indication and that whatever the benefit to the public, is around - years later. (urban-idi- ). the idea of ethics went beyond medicine and emphasized desired behavior in everyday life. words that were used to indicate the idea of ethics in the local language included: sabyatha (decency, civilized), sampradaya (traditions, spirituality), maryada (respect, uprightness), naithika (ethical), sambanda (relationship with others), gaurava (honor, prestige), maanavyamoulya (human values), ganathe ( dignity),, vyathiyanadathe (behavior), naithika moulya (following ethics), and siddhantha (principle, tenet) (ventakatasubbaiah ; asian educational services ) . in addition to words, understanding of ethics was also expressed in phrases that appeared to be linked to some of the principles of ethics-for instance, • 'it is about considering others before self' (urban-fgd )-beneficence, • 'no intentional harm to anyone' (urban fgd )-non-maleficence, • 'i think ethics is more like moral rights among the people' (urban fgd )autonomy of choice, • 'we should not underestimate any person or degrade' (urban fgd )-respect and dignity, among others. ethics was seen as important in research to reduce harm-'ethical guidelines should try to avoid collateral damage' (urban fgd- ); 'medical research team should be confident that there will not be harm to that person' (rural idi- ); and, to regulate the processes and purpose of research-'all the procedures and norms in a proper way'(urban fgd ). they did, however, also identify the gap between intent and practice-they [researchers] will concentrate only on research they don't consider anything about ethics (rural fgd ); pharmaceutical companies recruit people from poor backgrounds for human trials (urban fgd ); commercialization has outgrown the benefit of medical research. (urban fgd ). a chim was seen as ethical if there was a clear benefit. this was echoed across both rural and urban settings. ..i feel it is good if it helps in the prevention of diseases (rural fgd ); we can find the treatment for disease… (urban fgd ). however, many felt that they could not understand the benefit of chim clearly. respondents felt that if chim studies had their knowledge base in data from animals it would be more acceptable-this concern seemed to be overwhelmingly about safety. there was also the strong perception that infecting a healthy person was wrong and that studying the natural course of the disease of an already infected person would be the more ethical, alternative option. an exception was during an epidemic when 'to save those many lives this action should be taken… until then i think this is not required.' (urban fgd ). it was also considered important that participation in such studies should be with voluntary consent and with a complete understanding of the study and what it involved. as school teachers in a group discussion said, it should be [done] voluntarily and it should not be the people who don't understand consequences and just do it for the money…they should have the knowledge and decide on their own. so, it depends on the explanation, … time and effort taken to explain how it can be done. (fgd-u- ). the legal expert also cautioned against the enrollment of economically and psychologically vulnerable persons into such studies as it raised ethical and legal suspicions of exploitation. similarly, the legal position of an individual to voluntarily accept self-harm was perceived as being contentious under the law. if economically vulnerable strata are subjected to this … it raises all the wrong alarms… if someone wants to look at a public interest litigation or let us say criminal prosecution… the first question would be to look at psychologically have you misled somebody to self-harm … (u-idi- ). participants in general had no prior knowledge about chim, except for a few key informants who were microbiologists and immunologists. the lay public were able to echo the idea of an infection with a germ, but the extent to which they were able to explain what was communicated to them depended on their education, and prior understanding of medical research, among others. one of the questions they raised, important in the context of advocacy for chim, was why naturally infected persons were not studied? another was, while chim studies were said to be 'controlled', individual response was likely to be unpredictable, so was it really 'controlled'? among non-english speaking communities, the word 'controlled' was misunderstood, while health workers associated the word 'control' with 'prevention'. comparisons with clinical trials were made by key informants with research expertise, who likened the issues of a chim study to a phase i clinical trial. in some ways it is analogous to a phase one clinical trial where you have normal healthy people and give increasing doses of new drugs and study the pharmacokinetics, dynamics, toxicity etc., basically we are doing the same thing except using micro-organisms (urban idi- ). another similarly trained informant felt that chim studies posed less of a risk than drug trials because the infecting agents that were being used were weakened and it was within a controlled (safer) environment. i think that with a chim, germs are being weakened. i think subjects hold a better chance [than a clinical trial]. so, i think the risk factor is slightly less [for chim], because it is controlled, the germs are weakened, and it is in a controlled atmosphere. (urban idi- ). there were concerns and fears across all age groups and in both the rural and urban areas. fears appeared to be greater among those least knowledgeable about the idea of chims and less among the more health literate and technical experts. these included: • fear of the potential consequences to self and those near and dear it is highly dangerous, and it involves something … there are unknown side effects on your body. (urban fgd- ). … we are the earning persons for the family, i may be confident enough that nothing will happen but still i have to take care of my family and i should be saved to take care [of them]. confidence has to be given that nothing will happen to them… (rural fgd ); …but what if something happens to my next generation (urban-idi - ). • fear of something hazardous entering the body where the risk of death was imminent, or the nature of the risk was unknown, …but when it comes to being infected everyone has second thoughts… (rural idi ). what if something happens and if i die… (urban-idi- ); …it may give negative effects to the brain or it may damage organs… (rural fgd - ); we also don't know the long-term repercussions, we actually don't know if the small virus is going to mutate, we want to know what the outcome is (urban fgd- ); but what if that remains in our body till, we die (urban fgd- ); …we are scared that something might happen, so if it is done on the animals initially it would be good. (urban idi- ). • fear of exploitation of the socio economically less endowed groups, … those who are economically less privileged are more likely to take part in a study whether it is risky or not because they really require the benefit that you are providing, that is monetary……not ethical because you are taking advantage of (their) current situation (urban idi- ). • fear and mistrust of a non-responsive health system in case on long term side effects, it might be possible that for months nothing will happen and later on it might start reacting in their life, so that has to be taken care of." (rural fgd- ); after completion of the research will it create any problems in the future and who do we go to then? (rural fgd- ); …there is no guaranteed healthcare, and healthcare not being a standardized thing can be a problem for things that were not diagnosed in that period but later on… (urban idi ); …the frequency with which some of these things go wrong in the indian context is much higher… (urban idi- ); what has happened with vaccine research in india in the past has been so murky and it has been unethical. how does one create an ethical study in such an unethical space…? (urban idi- ). when probed if the risk perception would change if the pathogen was known or unknown, health workers in the rural areas gave examples from their own interactions with local communities, where they implied that the facts didn't matter, but perceptions were what influenced responses. one parallel was drawn to methods of family planning that were advocated and another to any health intervention being prescribed, where negative associations were made with what was actually safe. among the urban respondents, the iec lay member felt that it was not about the germ being known but about the perception of danger: one thing is about a known and unknown pathogen and the other is which is known and known to be …dangerous… (urban-idi ). a health activist suggested that people indulge in riskier behaviours in their daily lives -and seemed to suggest that individuals may be overestimating the risk of chim-…there are so many things that healthy individuals do, there are so many risky behaviours that that healthy individuals indulge in. one cannot say that this is riskier than anything else that you are already doing. (urban idi ). while participants expressed doubts and fears regarding chim, they also perceived some benefits of chim, primarily in relation to the prevention and treatment of diseases. some drew parallels with vaccinations 'i feel it is good, it helps in the prevention of diseases… so we can say it is helpful…like we give vaccine to children' (rural fgd- ), 'the benefits would be in one of two ways, to improve the immune system or to treat similar pathogens' (urban idi- ). perceived benefits were personalised based on how it could help prevent or cure a disease in their own family. at a broader level, the value of the benefit was towards public good, where 'lives could be saved'. there was a clearer articulation of the benefits of conducting chim studies in india among the technically educated, which focused on the opportunity that the method provided to advance science and medical research, relevant to local populations. what would be the objective of the research, broadly one is to test vaccines because you can expose the person to the infective agent with or without achieving illness, and the second is that it could be used for medical treatment, thirdly it could be used to study the natural course of the infection to know how people will behave with the infections (urban idi- ). …it is not like a conventional vaccine trial where you have to take large number and wait for years for natural incidence in the community, here if you have to do to the challenge [chim] method, i can take [volunteers] and i challenge them and i need to follow all hundred and not depend on the natural incidents happening in the community. another advantage is that we have access to multiple geographies and a very large ethnic diversity in india (urban idi- ). …we almost never know what the premorbid state of the individual is, which is something that in the absence of the controlled infection model we have not been able to assess, by the time we get into the picture and start collecting data, especially in the indian context it is fairly late into the infection. (urban idi- ). participants identified people who would likely participate in a chim study and included those in need of money, 'risk takers', those who were impulsive, those without dependents or responsibilities, and those with a heightened sense of altruism and social concern. table provides the details. in identifying potential participants for a chim study, there was a great deal of deflecting-where each group felt that people other than themselves were ideally suited to be participants. it is unclear whether this reflected an underlying fear of a novel method which participants perceived as potentially dangerous. participation was determined by the existing knowledge of the infective agent i.e. a priori evidence and treatment options. another aspect that determined participation was trust; both in individual researchers or medical professionals doing the study, and the overall regulatory environment for support in case of harm. depends on the history of the organization … how they treat patients, how they look at money (rural idi ); if doctor is giving guarantee that nothing will happen then people will agree. (urban fgd- ). research has to be done, if it is done under the protection of government then it will be good… (urban fgd- ); the deflection of the possibility of participation could be indicative of the low levels of trust in individuals and systems for protection of those who are socially and economically vulnerable. therefore, potential participants identified included those in positions of power and authority; such as gram panchayat (village table who will volunteer for a chim study? perceptions of rural participants • those who need money 'people who are desperate for money would come for this, but still we should not take that as an advantage and start doing things like this' (urban fgd- ) there was also a sense that enrolment of the poor should be avoided for this very reason • those who need money 'if they are struggling…if they are paid some money …then they will agree for that' (rural fgd- ) and the contrary position, 'rich people will not come… because they don't accept anything' (rural fgd- ) • those who are 'impulsive' 'more impulsive people will be more willing to take this risk, they may be seeking fame…' (urban idi ) • those who were 'risk takers' • • those who are altruistic and with heightened social concern 'whoever has kind heart…' (rural idi ); 'people who think that when we do something it will be benefited to other people in society' (rural fgd- ); 'if social motive is there then people may come forward…. if someone thinks that it will be helpful for others council) members and politicians, or those with the capacity to deal with adverse consequences; such as medical researchers, wealthy or educated persons. financial incentives for participation had contrary responses across the spectrum of participants-rural women felt that altruism should be encouraged. in their words, 'money should never be there in such kind of a trial…', 'financial incentives would be like a bribe… monetary payments should be avoided, i mean that would then make it into money making thing.' at the other end of the spectrum, urban male youth took a pragmatic view that participants should be paid-but such payments should not be so large as to induce risk taking. college students were seen as particularly prone to such risk taking-all for a bit of 'pocket money'. on the other hand, compensation to participants for time and other costs, was acceptable. in order to ensure fairness in compensation, it was suggested to be commensurate with the engagement-in terms of age of the participant, time or wages lost, social status and number of dependents. even the urban youth were conscious that such compensation should not become undue inducement; they suggested it should not be mentioned at the recruitment stage to pre-empt this possibility. …we should not be giving them anything [in the beginning] so that. will make them real volunteers and in the end, when it is done you can pay them … that would become a reward (urban, fgd ). alternatively, insurance mechanisms that provide not only for persons harmed but for all participants, for a sufficiently long period of time, was also seen as a way of compensation. although the idea of chim was novel to the general public in this study, they identified many ethical issues and specific responsibilities that they believed researchers needed to bear; which could build confidence in people. as specific regulatory guidelines were not yet in place when this study was being conducted, participants' wish list for desired regulations have provided a framework for possible regulations [refer fig. ]. the first issue was the validity of the chim method as opposed to alternate research methods, and the choice and safety of the germ, including the availability of suitable treatment-…let the virus be checked properly before injecting to human being … check if it is not harming and there is treatment…,' (rural fgd ); participants were clear that the research team was ultimately responsible for issues related to the participant, in case there is a sudden side reaction or side effects, providing the person with the medical care required. (urban fgd- ) . …who is doing research must take the responsibility. they should see that nothing will happen to the person who is participating. (rural fgd- ) . to ensure complete voluntariness of participation and protection of every individual's right to life and free choice, the participant in a chim study must do so with a free will, with thorough comprehension of purpose and risks, and without the enticement of financial gain. in the words of a college student, it is the fundamental right of every healthy human being to reject it if they are scared. (urban fgd- ). while consent was unanimously seen as integral to participation in chim, the responses obtained indicated that the public see the current system of consent as inadequate-'…it doesn't mean saying yes or putting a thumbprint there… it means they understand what their body will undergo' (urban fgd- ). the idea of relaying back an understanding of the information received, was a way of testing comprehension. assent from a family member was considered an added protection to the participant's informed consent, as there were implications for the family; not only risk and uncertainty but also confined stay in the research facility away from family and work. any dependents of the participant, may be a wife or children or parents should give their consent… they should be aware of what the individual is going through (urban idi ). this was not meant to take away from the autonomy of the individual, as it was emphasized that the ultimate decision lay with the research participant. the idea of self-harm, even if consented to, appears to be a legal and ethical issue according to the legal expert. there is an underlying perception of having to protect the researcher from legal liability and moral impropriety-we still need to show objectively from our research that what we're doing is not something shocking to the conscience of public morality. contracts are void if the intention is self-harm. sooner or later this can't be left to contract as it must be regulated through legislation. (urban-idi- ). complete information was a repeated request. widespread public interaction and awareness through mass media-television, newspapers and websites were emphasized as a prerequisite, with convincing information about 'the injection', 'why it is given' and 'the benefit that is expected'. public good and the benefit of disease prevention emerge as a required justification from the public's point of view. participants believed that widespread media coverage and public discussion of chim would ensure greater transparency and more ethical conduct of chim. the role of the government in adding credibility to the messaging was also implied. this did not refer to advertisements for recruitment of participants, but an engaged information sharing with the wider public. awareness has to be given to people through media like radio and television by government," (rural fgd- ). of importance to the public was the quality of the research, researcher and institution-and these are judgements that people made, at least partly, based on prior knowledge and interactions with people and institutions-…who is doing the study should take responsibility and should give me confi-dence… (rural idi- ). thus, the responsibility of researchers was beyond what routine clinical trials regulations prescribe and should empower volunteers of chims. the importance of ensuring that the individual was disease and germ free at the end of the study was emphasized as an important regulatory issue, to avoid spread of infections on the one hand, and social ostracization on the other. this was brought up by key respondents through their insights of social and community dynamics. … they are scared if the subject comes back into the community and infects all of them. so, they might not allow the subject to come back or the second thing is that subject might get ostracized in that area and the future of the children would be stake. (urban idi- ). several issues emerged in relation to financial transactions during research protocols. compensation for participation in chim protocols was expected to be formulated and mandated by the government. the focus of compensation for injury and inconvenience needed to include the health of the individual not just during the time of the study, but even afterwards. not only were life insurance and care of family members in case of extreme adverse events required, but health insurance was also advocated. calculation of compensation was not to be based on who the participant was, but on the risk of the chim and the related insurance cover, insurance should be more because of the risk. insurance is compulsory, i think it depends on the risk of the study not on the person who joins the study (urban fgd- ). this was however a highly debated issue among community participants. on the other hand, participants generally agreed that financial incentives to participate needed to be discouraged. 'who should regulate these studies?' evoked much interest among the general public, perhaps because such a question was not generally asked of them and it was left to 'people in authority'. there were varied and interesting responses that emerged, ranging from 'the medical team taking full control and being responsible' (rural fgd- ) to 'a neutral committee with scientists and experts and people from various strata of society… and definitely a few lay people from the public to be involved' (urban it youth-idi- ). rural respondents suggested the presence of government representatives on these committees and mentioned 'gram panchayat' (village self-government body) members. there was however some cynicism of having the government as sole regulator of such research. not many participants in group discussions were aware of ethics committees and their role in overseeing research in the country. there was some skepticism on the motives of such committees-we don't know whether ethics committees are there or not in india. we are not aware whether they are doing it for profit, or they are genuinely concerned. they say watch dog but finally it becomes the dog itself. we have various associations, but we don't know how far all this works. (urban fgd- ). experts from the research fields expressed their doubts on whether the present ethics committees in the country would be equipped to handle these additional areas of oversight and monitoring. an ethics committee member as a key respondent in this study had a contrary view, 'ethics committee do the ground work and icmr (indian council of medical research) is the second layer. i think these two regulators are perfectly fine'. a key regulatory requirement would be to ensure that ethics committees are appropriately trained and that an infectious diseases specialist is brought into the review process as an expert. for controlled human infection studies with its contentious ethical positions, the value of public perceptions in identifying regulatory requirements and researcher responsibilities emerges as critical in the process of ensuring transparency and building trust. studies in africa have shown that understanding perceptions of communities on research activities helps in addressing misconceptions, rumours and concerns which can undermine the ethical underpinnings of a well conceptualized study done by credible medical research institutions gikonyo et al. , ogobara-doumbo . for the lay-person in this study, ethics and being 'ethical' went beyond the word and its usage in purely research contexts. ethics was expected to embody higher virtues of integrity, decency, uprightness, good behavior and relationships with others. this, with the backdrop of people's limited understanding of research, implies that ethical research is not just the way research is done but how it is perceived to be done. the main messages emerging from this exploration of public perceptions of controlled human infection model studies in india reflect that, safety is a key concern of the general public with regard to 'being infected' as has already been established that the protection of participants is an important concern for chims (timms ). a healthy person 'being infected' purposefully appears unethical. the various fears expressed by the public could be a reaction to the novelty of chim and the absence of chim studies in india so far. there was no outright rejection of chims. however, there was an expectation that public good should emerge from such research. indeed, a clear justification of public good would make such research ethically acceptable. the disease chosen was expected to have public health relevance to india and it would be desirable if earlier research had been done on animals or humans in other countries. there was also considerable 'othering' that took place when readiness to participate was explored, with each constituency feeling that people other than themselves may be ideally suited as participants. they created an alternative response to 'the other' than what would be suitable for themselves, thus following a process of 'distantiation' (brons ) . by positioning persons unlike oneself as 'others' and giving them characteristics, seen as unacceptable for oneself demonstrates this 'othering' which also reflects existing or perceived unequal relationships (brons ) , common in indian society. the rural folk identified others whom they perceived to be better off than them as potential participants. urban respondents considered it appropriate for those 'without responsibilities' to volunteer, even the elderly and prisoners. this reflects a utilitarian mindset where the outcome of good for the greatest number makes a certain action acceptable even if it is at the expense of some people i.e. the end justifies the means (khan ) . those who would willingly volunteer were seen to be the economically poor, who would do so to gain monetary benefit. but this motivation was seen as interfering with the person's ability to discern risk and hence it was recommended that such persons be avoided as participants. it was also the legal opinion that such participation would indicate undue exploitation of the vulnerable. comprehension of the procedures and risks emerge as essential pre-requisites for participation. relaying back the explanation of a chim by a potential participant could be a useful means of assessing comprehension. other methods such as q&as and opportunities to discuss concerns and doubts over multiple sittings as suggested in the kenyan malaria studies (njue et al ) could be considered. in addition, psychological wellness was an important criterion for a person to assess risks and provide consent. a gradation of opinion was apparent between the lay public and rural communities on the one side, and health professionals on the other, with the former responding to information provided, while the health professionals and health workers based their responses on their experiences in the field or with similar research. this hierarchy of understanding is dependent not just on education, but technical expertise in research and science. those with health or medical expertise appear more discerning of the risks, benefits and safeguards in research. monetary compensation (seen as a key motivator in the kenyan malarial studies- njue et al. ) emerged as a contested area for chim studies across all groups and strata of respondents. there was a moral rationale presented, especially in the key informant interviews, for compensation not as cash but as 'care', moving the risk-benefit analysis from the immediate to the long term, and from the individual to the family and/or community (third party). it can be argued that in a country like india where comprehensive universal health coverage is absent, a commitment to care can be considered an inducement as well. this, therefore, appears to be a conflicting imperative. however, the duty to care, for the treating physician or the study investigator is an ethical obligation, especially in the context of a chim where the intention to harm is a strong perception, with legal implications in india. these views were also reinforced in recent deliberations on the feasibility and ethics of chims in india, held among wider stakeholders , and also from deliberations in other countries such as vietnam (kestelyn et al. ) . it emerges that in the present context of indian society (of which this study was a small subset), if such research was to begin, the following would be suitable criteria for selection of participants to such studies: • educated persons with reasonable health literacy -for example, science graduates or students, health professionals. • persons not in an economically vulnerable situation for whom financial compensation would not be the sole motivation for participation. • persons who can not only give free, informed, understood consent, but can also get informed assent from a next of kin or close family member. it could be argued that these selection criteria perpetuate a paternalistic approach and that all decision making in a liberal democratic society should be autonomous and free. however, indian culture like that of many other asian countries, tends to be more communitarian. this is reflected in how respondents described ethical research-"a long term relationship with others", the stated need to obtain assent from family, and the concern of social ostracism following participation. if the protection of potentially vulnerable persons requires paternalistic rules, so as to ensure ethical conduct in the early days of chim trials in india, it would be reasonable for regulations to be paternalistic in this regard (timms ) . scholars such as resnik ( ) , support this contention with the reasoning that healthy volunteer participants are not always in a position to understand and assess risk completely, hence need some mechanism, such as a guideline or a committee that can restrict the risk to which healthy volunteers may inadvertently subject themselves to (resnik ) . public engagement begins at the stage of conceptualizing such a study, by listening to diverse voices across a range of people and proactively understanding the public's fears, concerns and expectations (vaz et al. ; vaz ) . the findings of this study highlight areas where public awareness and advocacy are required. the systemic failures of health care delivery, conduct of clinical trials and overall public utilities in india seem to have made the urban, educated sections cynical and wary of government regulation (bhan ) . if chims and perhaps any medical research needs to be successful, it needs to begin with an engaged and empowered public (schicktanz et al. ; cioms ) to develop trust at multiple levels (gopichandran )-at an individual level of the treating doctor and researcher, since a significant amount of clinical research is done in hospitals and not stand-alone research institutions/contract research organisations; at the level of the institution; and at a higher level involving systems related to health delivery and the research regulatory process. the data from the fgds and urban interviews reveal a great distrust-the practice of medicine itself is seen as a commercial enterprise and medical research as problematic, given the understandings of people about 'unethical research'. perceptions of ethics emerge based on 'people's lived experiences and the contexts of their lives and not on a preconceived set of ethical principles (mcintosh ). public engagement for chim studies is therefore required, not to convince the public to participate in chims or facilitate recruitment but to develop public trust in the system and inform regulatory authorities about perceived areas of contention. trustworthiness of the system emerges as an overriding issue. it has three key components in the public engagement paradigm, -consultation where listening to diverse opinions is central (hodgson et al. ) -collectivism where altruism of the participant is reciprocated by altruism of the researcher in terms of benefit sharing and achieving public good (molyneux et al. , lairumbi et al. ) -stake holding, where different players-the lay public, the technical experts, diverse professionals and regulators come together to review regulations and develop contextually appropriate guidelines (vaz ; regulations that are in the best interest of the public and address areas of mistrust and skepticism, are needed for chims in india (srinivasan and johari ; vaz ; ). this will help to redeem the poor public image of medical research, clinical trials and ethics committees in india. regulation that is responsive to public perceptions needs to be widely disseminated (blom et al. ; vaz ) . it would be of value to have the public participate in a watchdog neutral body that can question, review, audit and advise the regulator and researcher on the conduct of the study, and also be the eyes and ears for any community repercussions. this could be on the lines of a community advisory board (cab) that augments the functioning of an institutional ethics committee . the cab's structure and functioning would be mainly to liaise between the community and the researchers, offering a mechanism of contact and mediation. it does not take on the responsibility of recruitment for the study nor is it a gate keeper offering such access. at best, it can be an enabler of responsible decision making. the institutional ethics committee on the other hand has the responsibility of determining risk vs benefit of the study, assessing participant safety and ensuring free and fair participant recruitment. at the end of this study, no simple answer emerged to the question of whether india is ready for a chim or not; that was not the focus of our enquiry. what it does confirm is that the general public has strong views of safety, expectation of safeguards and ideas of how such research can be regulated. these perceptions not only indicate who are likely to participate in chim studies but provide underlying motivations and concerns about these studies being ethical or exploitative. many of the findings that have emerged from this study support the findings of research elsewhere , molyneux et al. , gordon et al. , bambery et al. , njue et al , kestelyn et al. . as this study was qualitative-we cannot conclude that these represent the views of the public everywhere in india-and there may well be a place for an expanded study across geographies, using a quantitative tool. a more nuanced understanding may also be obtained by presenting specific chim scenarios to people and seeking their responses, as was done in a multi-stakeholder workshop in march where a malaria, typhoid and chikangunya chim were discussed . in the light of the covid pandemic and the race to arrive at a safe and efficacious vaccine, additional research in public response to chims in a pandemic and readiness to participate to save lives needs to be explored. what is additionally clear, is that there is a felt need for sustained public engagement, and building awareness and advocacy regarding chims. kittle kannada-english 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ethics'-why and how bioethics expertise should include public and patients' voices ethical challenges posed by human infection challenge studies in endemic settings consultations on human infection studies in india: do people's voices really count? protecting challenge study participants in low-and middle-income settings experimental infection of human volunteers with the heat-stable enterotoxin-producing enterotoxigenic escherichia coli strain tw public engagement in the context of a chim study listening to the voices of the general public in india on biomedical research-an exploratory study the views of ethics committee members and medical researchers on the return of individual research results and incidental findings, ownership issues and benefit sharing in biobanking research in a south indian city consultation on the feasibility and ethics of specific, probable controlled human infection model study scenarios in india: a report kannada-english dictionary acknowledgements this publication was supported by a grant from the translational health science and technology institute (grant no. ). its contents are, however, solely the responsibility of the authors and do not necessarily represent the official views of the translational health science and technology institute. we acknowledge the time and views shared by the participants of this study and the attendees of the chim pre congress workshop of the th world congress of bioethics , where the findings of this study were shared. publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- -zqtjjyoq authors: sundar, k. r. shyam title: covid- and state failure: a double whammy for trade unions and labour rights date: - - journal: indian j labour econ doi: . /s - - - sha: doc_id: cord_uid: zqtjjyoq nan the sudden national lockdown introduced on march initially for days was extended with varying relaxations till may . later even as un-locking took place, local lockdowns have continued. lockdowns meant near-total stoppage of economic activity (not covered by labour laws). trade unions argue that during the lockdown period, the state should assume full control and even responsibility of the economy and welfare of the workers. as the economy gradually even fitfully unlocked, employers came into the picture. so, trade unions have engaged mostly with the state (including the judiciary) and to some extent with employers. the labour ministry merely issued advisories to employers not to retrench workers and pay wages to workers during the lockdown and conspicuous by its absence. the ministry of home affairs (mha) issued a directive (on march ) to employers of factories and shops and establishments to pay full wages to employees during the lockdown period, march to may which as we note below was ineffective. critics have argued that the relief measures announced by the central government are parsimonious and even ill-directed (ghosh ) . along with the relief measures for covid-affected firms and workers, the central government also introduced structural reforms in eight sectors like coal, defence, etc. like introduction of commercial coal mining, increase in fdi in defence manufacturing from % to %, rationalisation of total operating companies to four in strategic sectors (i.e. creating oligopolies in them), and enabling greater role for the private sector in the economy. it must be noted that the structural reforms are not aimed at providing 'direct or indirect relief' to firms or workers but constitute neoliberal reform measures to restructure the product market. several state governments amended the factories act to extend maximum work hours from to - with differential overtime pay. madhya pradesh and uttar pradesh have issued ordinances diluting or suspending important labour laws. several states have increased the thresholds of critical labour laws like chapter v-b of industrial disputes act, (ida), factories act, , the contract labour (regulation and abolition) act, , and introduced fixed-term employment. put simply, these are substantial reforms hurting a wide range of labour rights (shyam sundar and sapkal ; shyam sundar a, b). employees were partially or fully paid and often not paid their wages during the lockdown period (d'souza ; economic times ). during the post-lockdown period, a small proportion of workers were re-employed and often at reduced wages and they were refused wages for the lockdown period. employers have sought resignations from workers with benefits or threaten them with retrenchment or as in the case of air india, employer asked the staff to go on extended leave without pay. in many cases (e.g. bajaj auto, air india, health and care sectors), employees have contracted covid- virus and few succumbed to death (indian express ; toi ). frontline workers especially the vulnerable government-scheme-based employees like anganwadi and asha suffered much. the adverse legal and labour market conditions have pushed trade unions to adopt several strategies to combat them and protect labour rights. trade unions' strategies comprise the following, viz. write memorandums of appeal and protests to the governments (central and state), demand dialogue with government, engage in negotiations with employers, struggles, and seeking the intervention of ilo and a global union, international trade union confederation (ituc)]. given the sensitive covid- context, trade unions needed to adopt softer and distant methods to influence public policy and extend welfare measures to their constituents. organisationally, both at national and state levels, like-minded central trade unions (ctus) have formed coordination fronts (ctus). at the national level, there is a rift between bharatiya mazdoor sangh (bms) and the ten trade unions (intuc, aituc, hms, citu, aituc, aiutuc, tucc, sewa, aicctu, lpf, utuc) who have formed the national platform of central unions (npcu). however, their agenda, thanks to neo-liberal regulatory regime, remains the same despite their differences. the ctus have used the memorandum method quite extensively given the pandemic-imposed constraints. they have appealed to the president, the prime minister, and the union labour minister. the ctus and their allies have among other things(a) demanded multiple welfare measures including direct benefit transfer to non-taxpaying workers, enhanced pension, payment of cash and other forms of assistance to workers from their welfare boards, wide-covering fiscal reliefs, food security (including universal pds), and protective health gear to and safety for the frontline workers, (b) protested against the labour market incidents noted above and provided concrete instances to support their claims, (c) expressed concern at the high and rising unemployment, (d) supported the "industry" their demands for subsidies, and (e) asked for dialogue with them. their demands and concerns covered all kinds of workers including scheme-based employees (mgnrega, anganwadi, asha mid-day meals, etc.) and contract, casual and migrant workers in their petitions. their major demands are: reliefs to surviving migrant workers and compensation to their families, free ration, direct benefit transfer (dbt) of , enhanced pension of to all non-income tax paying workers for six months, aadhar-linked smart cards to all workers, withdraw the proposed privatisation measures and labour law changes, rise in mgnrega wage to ₹ per day, recovery of loans from wilful defaulters, increased budgetary allocation to the health, education, care and agriculture sectors, a fund for social security for unorganised workers, urban employment assurance scheme, protection for frontline workers, etc. the inclusivity and the width of their protest agenda and of employees are significant. trade unions have appealed to the central government to hold dialogue with them and criticised it for holding "web-based consultations". in fact, having ratified the ilo convention, tripartite consultation (international labour standards) convention, (c ), india must hold social dialogue to frame the economic and social policies and laws. it is reported that the labour minister twice met ctus during may and they were ineffective (nath ) . trade unions including bms complained of the absence of social dialogue at both national and state levels. the governments introduced policies and changes in laws unilaterally (shyam sundar a, b). the aggressive reforms and inadequacies in announcement and execution of relief measures have rather forced the ctus to go for direct action. trade unions' protests have taken several forms such as petitions, protest letters, "demands day", posts on social media and whatsapp, black badges, lunch meetings, and raising concerns due to the covid- exigencies. during the partial unlock times, they have conducted open collective protests though often constrained by covid- regulations, viz. demonstrations (at street corners, in front of their houses and government offices), letters to district authorities, hunger strike, processions, courting arrests, and strikes, etc. the protests during the lockdown period shifted from the streets to the social media, processes and mobilisation. owing to rifts in the trade union movement, bms conducted its country-wide protests on may and on may and july the npcu did . there were strikes at the factory and industry levels also. for example, workers at euro clothing company factory (owned by gokaldas exports) struck work protesting the closure of it and retrenchment of more than workers due to cancellation of orders by global brand h&m and took the battle to the social media which made h&m hold dialogue with the trade union at the plant (crumps ). on june - , , the coal workers' unions including bms protested the central government's reforms such as commercial mining, privatisation of coal india. they followed it up with strike during july - as negotiations with the government failed as the latter stuck to its policies . the npcu successfully organised an all-india strike of scheme-based employees on august - and save india day on august , . since the government was not responding to their agitations and representations, the npcu made a detailed representation of aforementioned state policies and laws to the director general (dg) of ilo and the international trade union council (ituc) to seek intervention. both expressed serious concern at the reported developments, appealed to the prime minister to uphold the international commitments made by india and encouraged social dialogue. the personal intervention by the dg of ilo is an exceptional event (joseph ) , and it reflects the seriousness of adversities faced by workers in india. in fact, the central government responded to these pressures positively. it affirmed that complete suspension of labour laws and those reforms such as the extension of work hours contrary to ilo standards would not be permitted (arnimesh ; financial express ). trade unions in india generally shy away from litigation for two reasons. first, the supreme court (sc) has delivered adverse judgments during the post-reform period which weakened or diluted labour rights (e.g. judgments relating to contract and casual employees) period. second, the judge-made laws cannot be reversed. the sc's handling of migrant workers' issues during covid- has been severely criticised even by an ex-sc justice (lokur ) . adjudicating on the clutch of petitions placed by employers on mha's march directive (noted above), the sc firstly ordered no coercive action on wage-defaulting employers (june order) and later left the wage payment issues to direct negotiations between employers and employees (live law ). these decisions by the sc do not inspire confidence in trade unions. a pandemic of this magnitude should ideally create cooperation between the state and trade unions to deal with issues relating to irs. however, covid- has witnessed the continuation of neo-liberal state policies followed during the pre-covid- period such as aggressive labour law and governance reforms and social dialogue deficits. these measures, combined with the pandemic-induced effects, have intensified informality and precarity in the labour market. state unilateralism and aggressive reforms have forced trade unions on the conflict path. trade unions have had to deal with numerous adversities and multiple issues during covid- period. they have resorted to multiple strategies to protect and secure labour and even people's rights to livelihood. on the other hand, even as trade unions defend numerous rights, their voices are far more vocal on the conventional issues like privatisation, fdi, etc., rather than issues like occupational safety and health. for example, during may-june , india witnessed industrial accidents, killing and injuring more than (industriall ). occupational safety and health (osh) issues have not received the attention they deserve from trade unions. the ctus are losing the plot by their excessive focus on issues at the national level since labour law reforms are taking place at the regional level. trade unions must share the responsibility for non-implementation of all laws concerning the unorganised workers which worsened the plight of these workers during covid- period. even now trade unions are not focussing adequately on these critical issues. trade unions need to do a lot of work to stay relevant even as they challenged more stridently by neo-liberal politics. request for coverage in media letter to the president of india urgent issues of scheme workers in the context of covid- pandemic strike notice by npcu to the secretary press statement by bms announcing nationwide agitation in solidarity with the fight against the anti-worker ordinances of up, mp, gujarat, and also other labour issues sacrificing workers on altar of "development letter to prime minister: not to repeal inter-state migrant workmen act ministry of labour and employment, termination and wage cut ( th letter) by citu joint opposition to any move to amend factories act modi govt says suspension of labour laws not reform, raises concern over states changing laws, the print indian factory workers protest after 'h&m cancels orders' leaving , jobless, independent ornella . layoffs, salary cuts become new covid- norms post covid lockdown: workers may face pay cuts, disciplinary action on failure to rejoin companies, economic times state govts cannot increase working hours beyond eight, centre tells parliamentary panel, financial express a critique of the indian government's response to the covid- pandemic bajaj auto unions demand factory halt after workers test positive for covid industriall . india's safety crisis: industrial accidents during covid- kill at least the centre asks for and gets 'one tight slap' from ilo, the week sc gives option to establishments and workers to negotiate on full payment of wages, regardless of mha order, live law justice madan lokur: supreme court deserves an 'f' grade for its handling of migrants, the wire coronavirus lockdown | centre urges unions to convince labour to stay, return to work changes to labour laws by state governments will lead to anarchy in the labour market no dialogue with trade unions, india's labour laws are now a product of unilateralism, the wire times of india (toi) . air india says some employees died of covid- …, times of india key: cord- -njrjepor authors: balsari, satchit; sange, mansoor; udwadia, zarir title: covid- care in india: the course to self-reliance date: - - journal: lancet glob health doi: . /s - x( ) - sha: doc_id: cord_uid: njrjepor nan the public health response to covid- in india has been highly centralised, resulting in a homogenous strategy applied across a sixth of the world's population. india was placed in a nationwide lockdown on march , , with restrictions being relaxed in three phases since june. in may , the prime minister called upon the indian people to be self-reliant. we discuss here opportunities to modify several aspects of the medical response to echo this sentiment. until april , , national guidelines required that all symptomatic patients and families be transferred to health-care facilities and isolated away from their homes, and entire neighbourhoods be declared containment zones. this strategy overwhelmed the health-care system in india's most populous cities, including mumbai and delhi, and precluded access for non-covid care. the resultant fear and stigmatisation has resulted in delays in seeking timely care, and violations of privacy. there was an initial rush to build new covid- hospitals and secure ventilators. the government feared that by not doing this they would be criticised, given the low number of intensive care unit beds per capita. however, intensive care entails not just equipment, but systems in critical care and trained personnel, of which india has few. despite ample scientific evidence against the efficacy of hydroxychloroquine, health departments and physicians continued to promote its use both prophylactically and therapeutically. state agencies have undertaken population-wide distribution of unproven homeopathic and ayurvedic medicines and herbal tea mixes (ukalo), claiming they boost immunity and prevent quarantined individuals from getting infected. practitioners are also prescribing various other medications, including the anti-parasitic drug ivermectin. the attention on wonder drugs and claims about imminent vaccine availability continue to distract from gaps in testing, contact tracing, and safe work environments. for months, physicians were barred from testing asymptomatic patients. although india's daily test count has grown exponentially, it remains low, at around · per people, as of aug , . to date, publicly shared data are not disaggregated enough to shed light on local incidence, or on the demographic determinants that might explain the low reported infection fatality rate. anecdotes and personal testimony should be an impetus for rigorous trials, not a license to promote unproven interventions. a flood of articles, models, and mobile device applications (apps) driven by technocrats and consulting companies has resulted in a high noiseto-signal ratio globally. policy makers must resist the temptation of quick action, and instead rely on those trained to interpret scientific evidence. most people with covid- can be cared for at home, and there is no justification for institutionalising those with mild or no symptoms. where isolation is essential but impossible, dignified quarantine facilities could be constructed in the community, as was done in the densely populated slums of dharavi in mumbai, in the absence of which, mandatory use of facial coverings (which could be inexpensively provided), would also play a substantial mitigating role. india's general practitioners and community health workers, can effectively monitor a patient's vital signs at home via in-person visits or telemedicine, distribute and encourage the use of masks and soap for handwashing, advise selfpronation, and, when possible, use adjuncts like pulse oximeters. providing oxygen therapy (and pronation) in lower tiers of care could avert the need for subsequent ventilation in many patients and help reduce the pressure on hospital bed capacity. some patients might benefit from steroids, and the small minority of people who clinically deteriorate will need intensive care. to meet this demand, existing technicians and nurses must be upskilled and general practitioners recruited to learn the basics of intensive care on the job. liberal use of antivirals should be discouraged, as their benefit is marginal and limited to severe cases, and is cost prohibitive. there is first-hand evidence to show how the indian people have risen to the occasion in helping older neighbours quarantine, sharing chores, and stepping in to feed and assist the millions of migrants stranded by the lockdown. the directive for self-reliance must leverage india's societal fabric and collective sense of purpose to empower communities to say where they would like to quarantine and isolate. local jurisdictions should be provided with more data, as disaster responses are most effective when locally contextualised. community-centred guidelines for people to self-organise and self-care must be vigorously disseminated. health agencies should work with civil society organisations to regain trust. women's empowerment groups in kerala, for example, were marshalled to map where older people live to ensure they had access to medicine and food while selfquarantining-an acceptable, workable, and scalable solution in the indian context. symptomatic patients must be treated at home to the extent possible, and in-patient protocols must only use evidence-based interventions; most patients might only require oxygen and pronation. in summary, what is needed is a plethora of lowtech solutions (especially facial coverings), adherence to science, and societal participation in caring for vulnerable people. there is not always an app for that. but there are the people of india. new guidelines for home isolation of people with very mild symptoms of covid- . the hindu covid- : is india's health infrastructure equipped to handle an epidemic? brookings covid- overwhelms new delhi's hospitals. the wall street journal hydroxychloroquine prophylaxis for covid- contacts in india gujarat govt to try ayurvedic drugs on covid- patients to gauge recovery time. livemint data. coronavirus (covid- ) testing. statistics and research absence of apparent transmission of sars-cov- from two stylists after exposure at a hair salon with a universal face covering policy the role of home pulse oximeters in treating covid- . npr respiratory support in covid- patients, with a focus on resource-limited settings dexamethasone in hospitalized patients with covid- -preliminary report key: cord- -mdsiv tr authors: pattabiraman, c.; habib, f.; pk, h.; rasheed, r.; reddy, v.; dinesh, p.; damodar, t.; kiran reddy, n. v.; hosallimath, k.; george, a. k.; john, b.; pattanaik, a.; kumar, n.; mani, r. s.; venkataswamy, m. m.; shahul hameed, s. k.; kumar b.g., p.; desai, a.; vasanthapuram, r. title: genomic epidemiology reveals multiple introductions and spread of sars-cov- in the indian state of karnataka date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: mdsiv tr karnataka, a state in south india, reported its first case of severe acute respiratory syndrome coronavirus (sars-cov- ) on march , , more than a month after the first case was reported in india. we used a combination of contact tracing and genomic epidemiology to trace the spread of sars-cov- in the state up until may , ( cases). we obtained full genomes of sars-cov- which clustered into six lineages (pangolin lineages-a, b, b. , b. . , b. , and b. ). the lineages in karnataka were known to be circulating in china, southeast asia, iran, europe and other parts of india and are likely to have been imported into the state both by international and domestic travel. our sequences grouped into contact clusters and cases with no known contacts. we found nine of the contact clusters had a single lineage of the virus, consistent with multiple introductions and most ( / ) were contained within a single district, consistent with local spread. in most of the twelve clusters, the index case ( / ) and spreaders ( / ) were symptomatic. of the sequences, belonged to the b/b. lineage, including seven of eleven cases with no known contact, this is consistent with the ongoing transmission of this lineage in the state. genomic epidemiology of sars-cov- in karnataka is consistent with multiple introductions of the virus followed by local transmission in parallel with ongoing viral evolution. this is the first study from india combining genomic data with epidemiological information emphasizing the need for an integrated approach to outbreak response. severe acute respiratory syndrome coronavirus (sars-cov- ), a novel coronavirus that was first detected in individuals with acute pneumonia in china in late , has now spread throughout the world disease (covid ) caused by sars-cov- a pandemic . covid has claimed over , lives (as of july , ) and the pandemic is ongoing . genomic epidemiology from the analysis of viral sequences from all over the world is consistent with the emergence of the virus in late in china and consequent spread and expansion in europe, and other parts of the world , . more than , complete genomes of sar-cov- from all over the world are currently available in public databases such as the gisaid initiative (originally known as global initiative on sharing all influenza data) . while this information is invaluable for understanding evolution of the virus , pathogenesis, and design of diagnostic tools, few studies have been able to combine this with epidemiological data to derive insights on viral spread. these studies have provided information on how the virus is introduced and spread in a population. a comprehensive study of circulating variants of the virus in iceland, which included over complete genomes in combination with epidemiological information (travel history and contact tracing) revealed that while the initial importation of the virus was from china and southeast asia subsequent importations were from different parts of europe . studies based on complete sars-cov- genomes from guangdong province in china highlighted the initial importation of virus to the province by travel and limited local transmission . a study of viral genomes from the east coast of the usa combined with travel data revealed the coast-to-coast spread of virus within the country . initial studies in washington state uncovered cryptic local transmission . these studies reiterate the importance of combining sequencing data with public health information. the first case of covid in india was detected on january , and case numbers have continued to rise inspite of stringent interventions including nationwide lockdowns. in the first few months of the outbreak, between january -april , , test results from all over india could be averaged to a positivity rate of . % . analysis of these cases revealed that the test positivity rate was highest when the samples were from contacts of a known covid positive case . a large number of sars-cov- genomes (about complete genomes as of july , source-gisaid) have been sequenced in different parts of india. the first sequences from india were reported from individuals with travel history to china, italy and iran , . an analysis of complete genome sequences from india showed that five global clades were circulating in india -old nexstrain clades b, b , a a, a , and a distinct clade a i . the a a (european) clade was found to be the most prevalent, followed by a i , . while these studies have added valuable information on circulating lineages of sars-cov- in india, they have not comprehensively linked genomic data with epidemiological information. this study was therefore undertaken to dissect the molecular epidemiology of sars-cov- in karnataka, a state in south india. here we report full-length sars-cov- genome sequences obtained from individuals who tested positive for the virus by rt-pcr and present an analysis of epidemiological information combined with genomic data to elucidate the introduction and spread of the virus in the state. samples with ct value > were included when they were considered critical for representing a cluster or if they were from symptomatic individuals. we used a tiling primer based approach for whole genome sequencing described by the artic network using primal scheme , . briefly, we used the v primer set-these are pairs with amplicons of about basepairs (bp) spanning the whole genome except bp of the ' and a part of the 'utr. pcr was performed by pooling adjacent/overlapping primers into different pools so as to prevent preferential amplification of short fragments between adjacent primer pairs. primers were initially used at a concentration of μm as per the protocol, then modified to amplify regions that were missed by increasing primer concentrations to μm. for four regions additional primers were designed and a separate reaction was set up before the pooling step in order to complete the genome. the resulting pcr amplicons were used for preparing libraries for all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . sequences were basecalled and demultiplexed using guppy (v . ), read lengths between - bp were considered for further analysis. primers were removed from the sequencing reads by trimming bp at the ends and additional trimming based on alignment using bbduk (v ). resulting reads were mapped to the refseq strain (nc_ ) using minimap (v . ) within geneious prime (geneious prime . . ). a consensus was created for regions with coverage > x using the % majority rule and corrected. consensus was aligned to the reference to ensure the correct reading frame and annotation was transferred from the reference. sequences were deposited into the gisaid database. phylogenetic analysis, lineage assignment, detection of snps and amino acid replacements consensus sequences from the genomes from this study were aligned with the reference genome using muscle (v . . ) . the multiple sequence alignment was used to infer the phylogeny using iqtree (v . . ) . a total of dna models were tested, and the tpm u+f+i model was selected based on the bayesian information criterion. maximum likelihood tree was constructed as the consensus tree from bootstraps, using the reference sequence (nc_ ) as the outgroup. nodes with bootstrap values > % were used for interpretation. time scaled phylogenies were constructed using treetime with the multiple sequence alignment described above and the date of sampling as dates. pangolin lineage assignments were performed using the online tool . single nucleotide polymorphisms (snps) and amino acid replacements were detected using the cov-glue web application . both tools use sequences submitted to the gisaid database . the epidemiological data was extracted from the line list and a contact map was constructed using the state line list of positive cases. we identified primary and secondary contacts for a patient from the line list. we then built a graph where each node is a positive individual and is connected by an edge with their contacts who were positive. this gives us the contact map. the graphs were then filtered by size of clusters or clusters containing a node with a particular property to focus on clusters of interest. the graphs are visualized using the d .js all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . karnataka recorded cases between march -may , . most of these cases were from six high burden districts, with bangalore urban (the district encompassing the city of bengaluru) reporting cases ( figure ). in total ( . %) positives were recorded at our centre, of which samples were taken for sequencing ( figure , table ). the features of positive cases in the state of karnataka (state), and those tested and sequenced at our centre are in table (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . table ). of these clusters, clusters were tested at our centre and of the were included for sequencing. these included people and covered ten large clusters (> individuals) from the state (supplementary table ). table ). the location of the clusters was analysed using a contact graph. clusters ( / ) were limited to a single district excepting clusters c , c , c , and c which were spread across districts. time course of the sequenced clusters and cases with no known contacts indicated that i) lineage a.p was introduced recently ii) no new cases from c and c were detected (as of may , ) iii) ongoing transmission was evident for lineage b and lineage b. . (figure , supplementary (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint covid by january , and sustained local transmission was observed in multiple states including delhi, maharashtra, and gujarat . sars-cov- was first detected in the south indian state of karnataka on march , and by may , it had spread to out of the districts of the state resulting in cases. the data from this study using a combination of genomic epidemiology and contact tracing provides evidence for multiple introductions of the virus into the state, with sustained local transmission. we report the circulation of six lineages of sars-cov- in the state namely- a.p , b, b. , b. , b. . , and b. (pangolin lineage nomenclature) . viruses from both lineages are now circulating in different countries of the world . in this study, of the sequences, belong to lineage a.p and were from individuals with travel history to other states within india. this lineage is defined by two snps t c and c t and has been reported from saudi arabia, russia, turkey, and india . no onward transmission was reported from these three cases, however they indicate continued importation of sars-cov- into the state emphasizing the need for active surveillance of domestic travel. of the lineages in the state, b. (related to gisaid clade g, and nextstrain clade a a) and b. . (related to gisaid clade gr and nextstrain clade a a) are european clades. both lineages harbour the d g mutation on the spike protein. it has been suggested that viruses with this mutation are more infectious and the mutation was present at higher frequency in samples across the world , , . of these two lineages, b. was a major contributor to the italian outbreak . in our study, all seven sequenced samples from a large cluster, c (comprising of individuals) belonged to this lineage (figure , supplementary table ). this cluster was restricted to bengaluru city and no new cases were reported from it between - may. the index case for this cluster was a patient with sari. taken together, these observations suggest a hitherto undiscovered link for this cluster to europe. one other sequence from an individual with no known contact with a positive case in mysuru district was also assigned to lineage b. . however, this sequence clustered separately from all the others in the phylogeny and therefore may represent a separate introduction. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . using a maximum likelihood based approach we were unable to completely separate b and b. as some branches had sequences from both clades (figure ) . further, nine of twelve clusters in this study and seven of the eleven cases with no known contact ( . %) belonged to lineages b/b. or both. lineage b is one of the two clades that were circulating in china in late . lineage b. has earlier been reported from philippines, uk, north america, australia, singapore and has also been reported from other parts of india (pangolin). the defining mutations for these lineages are similar to that of the a i clade which has been described as a distinct phylogenetic group in india . indeed, upto a third of the cases in multiple states across the country belong to the a i clade . these lineages were detected throughout the period in this study and across the state including one domestic traveller who entered the state toward the end of the study period ( figure ) . in all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . some studies had initially proposed a link between viral lineages, transmission and disease phenotypes which have not been substantiated by experimental evidence . the analysis of sequences obtained from symptomatic and asymptomatic (at the time of testing) individuals in this study did not reveal any association with a particular lineage. symptomatic individuals were spread across lineages b. , b, and b. along with asymptomatic individuals (figure , supplementary figure ). of the clusters represented in the sequencing data, both the index case and the spreaders were more often symptomatic (figure , supplementary table ). however, sequencing did not reveal any mutations that were specifically associated with clinical state. our study had the following limitations -it is a single point analysis and some follow-up data is not available, for instance we do not know if individuals who were asymptomatic at testing later developed symptoms. further, lineage assignments during an outbreak are dynamic and could change as more data is added and sequencing errors are accounted for. notwithstanding these limitations, our analysis provides insights about introduction, spread, and establishment of sars-cov- in karnataka. further, we were able to capture both geographic diversity and obtain representation from the ten large contact clusters in the state. this was made possible by linking epidemiological information to genomic data. integrating such an approach, in real time, into public health measures is essential for an effective outbreak response. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint a novel coronavirus from patients with pneumonia in china who situation report richard neher tb . genomic analysis of covid- spread richard neher tb . genomic analysis of covid- spread data, disease and diplomacy: gisaid's innovative contribution to global health phylodynamic analysis | genomes spread of sars-cov- in the icelandic population genomic epidemiology of sars-cov- in guangdong province, china coast-to-coast spread of sars-cov- during the early epidemic in the united states cryptic transmission of sars-cov- in washington state laboratory surveillance for sars-cov- in india: performance of testing & descriptive epidemiology of detected covid- full-genome sequences of the first two sars-cov- viruses from india genomic analysis of sars-cov- strains among indians returning from italy, iran & china, & italian tourists in india a distinct phylogenetic cluster of indian sars-cov- isolates analysis of rna sequences of sars-cov- collected from countries reveals selective sweep of one virus type ncov- sequencing protocol v v. . n muscle: multiple sequence alignment with high accuracy and high throughput iq-tree: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies a dynamic nomenclature proposal for sars-cov- to assist genomic epidemiology cov-glue: a web application for tracking sars-cov- genomic variation d data-driven documents spike mutation pipeline reveals the emergence of a more transmissible form of sars-cov- the d g mutation in the sars-cov- spike protein reduces s shedding and increases infectivity no evidence for distinct types in the evolution of sars-cov- key: cord- - a c ee authors: ray, debashree; salvatore, maxwell; bhattacharyya, rupam; wang, lili; mohammed, shariq; purkayastha, soumik; halder, aritra; rix, alexander; barker, daniel; kleinsasser, michael; zhou, yiwang; song, peter; bose, debraj; banerjee, mousumi; baladandayuthapani, veerabhadran; ghosh, parikshit; mukherjee, bhramar title: predictions, role of interventions and effects of a historic national lockdown in india's response to the covid- pandemic: data science call to arms date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: a c ee importance: india has taken strong and early public health measures for arresting the spread of the covid- epidemic. with only covid- cases and fatalities, india - a democracy of . billion people - took the historic decision of a -day national lockdown on march . the lockdown was further extended to may , soon after the analysis of this paper was completed. objective: to study the short- and long-term impact of an initial -day lockdown on the total number of covid- cases in india compared to other less severe non-pharmaceutical interventions using epidemiological forecasting models and bayesian estimation algorithms; to compare effects of hypothetical durations of lockdown from an epidemiological perspective; to study alternative explanations for slower growth rate of the virus outbreak in india, including exploring the association of the number of cases and average monthly temperature; and finally, to outline the pivotal role of reliable and transparent data, reproducible data science methods, tools and products as we reopen the country and prepare for a post lock-down phase of the pandemic. design, setting, and participants: we use the daily data on the number of covid- cases, of recovered and of deaths from march until april , from the novel coronavirus visual dashboard operated by the johns hopkins university center for systems science and engineering (jhu csse). additionally, we use covid- incidence counts data from kaggle and the monthly average temperature of major cities across the world from wikipedia. main outcome and measures: the current time-series data on daily proportions of cases and removed (recovered and death combined) from india are analyzed using an extended version of the standard sir (susceptible, infected, and removed) model. the esir model incorporates time-varying transmission rates that help us predict the effect of lockdown compared to other hypothetical interventions on the number of cases at future time points. a markov chain monte carlo implementation of this model provided predicted proportions of the cases at future time points along with credible intervals (ci). results: our predicted cumulative number of covid- cases in india on april assuming a -week delay in people's adherence to a -day lockdown (march - april ) and a gradual, moderate resumption of daily activities after april is , with upper % ci of , . in comparison, the predicted cumulative number of cases under "no intervention" and "social distancing and travel bans without lockdown" are thousand and thousand (upper % ci of nearly . million and . million) respectively. an effective lockdown can prevent roughly thousand (upper % ci . million) and . million (upper % ci . million) covid- cases nationwide compared to social distancing alone by may and june , respectively. when comparing a -day lockdown with a hypothetical lockdown of longer duration, we find that -, -, and -day lockdowns can approximately prevent thousand (upper % ci . million), thousand (upper % ci . million), thousand (upper % ci . million) cases by june , respectively. we find some suggestive evidence that the covid- incidence rates worldwide are negatively associated with temperature in a crude unadjusted analysis with pearson correlation estimates [ % confidence interval] between average monthly temperature and total monthly incidence around the world being - . [- . , . ] for january, - . [- . , . ] for february, and - . [- . , - . ] for march. conclusions and relevance: the lockdown, if implemented correctly in the end, has a high chance of reducing the total number of covid- cases in the short term, and buy india invaluable time to prepare its healthcare and disease monitoring system. our analysis shows we need to have some measures of suppression in place after the lockdown for the best outcome. we cannot heavily rely on the hypothetical prevention governed by meteorological factors such as temperature based on current evidence. from an epidemiological perspective, a longer lockdown between - days is preferable. however, the lockdown comes at a tremendous price to social and economic health through a contagion process not dissimilar to that of the coronavirus itself. data can play a defining role as we design post-lockdown testing, reopening and resource allocation strategies. software: our contribution to data science includes an interactive and dynamic app (covind .org) with short- and long-term projections updated daily that can help inform policy and practice related to covid- in india. anyone can visualize the observed data for india and create predictions under hypothetical scenarios with quantification of uncertainties. we make our prediction codes freely available (https://github.com/umich-cphds/cov-ind- ) for reproducible science and for other covid- affected countries to use them for their prediction and data visualization work. thousand (upper % ci . million), thousand (upper % ci . million) cases by june , respectively. we find some suggestive evidence that the covid- incidence rates worldwide are negatively associated with temperature in a crude unadjusted analysis with pearson correlation estimates [ % confidence interval] between average monthly temperature and total monthly incidence around the world being - . [- . the lockdown, if implemented correctly in the end, has a high chance of reducing the total number of covid- cases in the short term, and buy india invaluable time to prepare its healthcare and disease monitoring system. our analysis shows we need to have some measures of suppression in place after the lockdown for the best outcome. we cannot heavily rely on the hypothetical prevention governed by meteorological factors such as temperature based on current evidence. from an epidemiological perspective, a longer lockdown between - days is preferable. however, the lockdown comes at a tremendous price to social and economic health through a contagion process not dissimilar to that of the coronavirus itself. data can play a defining role as we design post-lockdown testing, reopening and resource allocation strategies. software: our contribution to data science includes an interactive and dynamic app (covind .org) with short-and long-term projections updated daily that can help inform policy and practice related to covid- in india. anyone can visualize the observed data for india and create predictions under hypothetical scenarios with quantification of uncertainties. we make our prediction codes freely available (https://github.com/umich-cphds/cov-ind- ) for reproducible science and for other covid- affected countries to use them for their prediction and data visualization work. four months since the first case of covid- in wuhan, china, the sars-cov- virus has engulfed the world and has been declared a global pandemic. the number of confirmed cases worldwide stands at a staggering , , (as of : am est april , , microsoft bing coronavirus tracker ). of these, , confirmed cases are from india (figure ) , the world's largest democracy with a population of . billion (compare china at . billion and usa at . million). india has been vigilant and wise in instituting the right public health interventions at the right time including sealing the borders with travel ban/canceling almost all visas, closing schools and colleges in certain states and diligently following up with community inspection of suspected/exposed cases with respect to adherence of quarantine recommendations ( table ) . on march , india took the historic decision of a -day national lockdown starting march , when it had reported only covid- cases and fatalities. in the subsequent days we have seen a steady growth in the number of new cases and fatalities, with growth rates slower than other affected countries but in days, the curve has not yet "turned the corner" or showed a steady decline in the number of newly diagnosed cases (figure ). while india seems to have done relatively well in controlling the number of confirmed cases compared to other countries in the early phase of the pandemic (figure ) , there is a critical missing or unknown component in this assessment: "the number of truly affected cases," which depends on the extent of testing, the accuracy of the test results and, in particular, the frequency and scale of testing of asymptomatic cases who may have been exposed. the frequency of testing has been low in india. according to the indian council of medical research (icmr), only , subjects have been tested as of april . when there is no approved vaccine or drug for treating covid- , entering phase or phase of escalation will have devastating consequences on both the already overstretched healthcare system of india, and india's large at-risk sub-populations (supplementary table ). as seen for other countries like the us or italy, covid- enters gradually and then explodes suddenly. we provide a table listing other highly affected countries along with their first reported case, initial interventions, crude fatality rates, and active case counts in supplementary table for reference. in this article, we take a data-driven approach to explore five extremely time-sensitive and important questions that india faces today in light of the covid- outbreak and the national lockdown: (a) how many cases can india expect at the end of the lockdown period? (b) when will the curve in india reach its apex and will the number of cases go back up after lockdown is lifted? (c) can summer temperatures thwart the outbreak in india? (d) how can the government and the people of india prepare for this crisis during and after the lockdown? (e) how critical is it to have reliable data, data science methods and tools as we envision a long-term strategy during and after the lockdown? this work is the result of the collective public health conscience of a group of interdisciplinary researchers in different parts of the us and in india. we convened virtually after being quarantined in our homes with alternating waves of fear and inspiration surrounding us. we decided to channel our collective energy to study the defining public health and economic crisis of our time and use our data science expertise to search for answers and solutions that can help covid- related policymaking in india. this is our contribution and public service as data scientists. our data science product includes two articles on medium pre and post lockdown announcement, providing critical information for policymakers (reuters, times of india, the guardian, the economic times ) and an interactive app that daily updates forecasts as new case counts are coming in, and publicly available codes for reproducible research. we used the current daily data on number of covid- cases, recoveries and deaths in india to predict the number of cases at any given time. we obtained the data (up to april ) from the novel coronavirus visual dashboard operated by the johns hopkins university center for systems science and engineering (jhu csse). , for our temperature analysis, these counts were aggregated to a month-level for each country, that is, we look at the total number of new cases in the months of january, february and march for each country. we obtained the monthly average temperature for major cities in the countries with covid- outbreak from wikipedia. we analyzed the data from india with standard epidemiologic tools of modeling disease transmission and estimating the theoretical number of cases at any time. one such epidemiologic model is the susceptible-infected-removed (sir) model, which is guided by a set of differential equations relating the number of susceptible people, the number of infected people (cases) and the number of people who have been removed (either recovered or dead) at any given time. recently, this standard sir model was extended to incorporate time-varying transmission rates or timevarying quarantine protocols and is known as the esir model. when using the esir model with time-varying disease transmission rate, it can depict a series of time-varying changes caused by either external variation like government-initiated macro isolation measures, community-level protective measures and environment changes, or internal variations like mutations and evolutions of the pathogen. the r package for implementing this general model for understanding disease dynamics is publicly available at https://github.com/lilywang /esir. to implement the esir model, a bayesian hierarchical framework is assumed where the proportions of infected and the removed people are modeled using a beta-dirichlet state-space model while a latent dirichlet distribution is assumed for the underlying unknown prevalence of the three states. priors for the basic reproductive number r , disease removal rate (consequently, the transmission rate) and the underlying unobserved prevalence of the susceptible, infected and removed states at the starting time are considered. using the current time series data on the proportions of infected and the removed people, a markov chain monte carlo implementation of this bayesian model provides not only posterior estimation on parameters and prevalence of all the three compartments in the sir model, but also predicted proportions of the infected and the removed people at future time point. the posterior mean estimates of the unobserved prevalence at both observed as well as future time points come along with % credible intervals (ci). to get predicted case-counts from the predicted prevalence, we used . billion as the population of india, thus treating the country as a homogeneous system for the outbreak. we made projections of the cumulative number of cases over a time horizon to assess the shortterm impact of lockdown as well as the long-term impact of lockdown and post-lockdown activities. for the short-term forecast on april , we assumed lockdown is implemented until april with either a -or a -week delay in people's adherence/compliance to lockdown restrictions. we compared these projections with two hypothetical scenarios: (a) no nonpharmaceutical intervention (i.e., a constant disease transmission rate over time since the first case was reported in india), (b) a moderate intervention with social distancing and travel bans only (i.e., a decreased transmission rate compared to no intervention). for the no intervention and the moderate intervention scenarios, we chose the transmission rate and the removal rate such that the means for the prior distribution of the basic reproductive number r (the expected number of cases generated by one infected person assuming that the whole population is susceptible) are . and . respectively [the change in r was created based on what we saw in wuhan ]. the value of . was estimated based on the early phase data in india. for the current scenario of lockdown, our chosen mean for r prior starts with . during the period of no intervention, drops to . during the period of moderate intervention, and further drops to . during the -day lockdown period, and moves back up to . after the lockdown ends as described in figure (assuming a gradual, moderate resumption of daily activities). for the longer-term forecast until june , we considered three hypothetical post-lockdown scenarios: (i) people return to normal activities due to the urgent desire for reconnecting after lockdown; (ii) people return to moderate activities as they did during the period with social distancing and travel ban intervention; and (iii) people make a cautious return out of fear for the coronavirus and partake in subdued activities. for these three scenarios, we assume mean for r prior moves back up from . to . , . and . respectively three weeks after lockdown ends on april . we compared these post-lockdown scenarios with another hypothetical scenario involving perpetual social distancing and travel ban only without any lockdown (we fixed the mean for r prior at . over the entire intervention interval). the changes to r values across our simulation scenarios are depicted in figure . to assess the long-term impact of lockdown duration, we considered four scenarios: -, -, -, and -day lockdown periods. in all scenarios, we assume mean for r prior remains at . for the duration of the lockdown and returns to . three weeks after the lockdown period ends (analogous to the "moderate return" scenario). the changes to r values across our simulation scenarios are depicted in supplementary figure . there are many hypotheses regarding the slow growth rate of covid- cases in many countries, particularly low-and middle-income countries (lmics). some of these hypotheses include the use of bacille calmette guerin (bcg) vaccine, younger population, high daily temperature, use of anti-malarials and host genetics. here, we only explore the temperature hypothesis related to covid- incidence. we assessed any correlation between country-wise average monthly temperature and total incidence of covid- . the monthly average temperature for major cities across the world was used to compute the monthly average temperature for each country experiencing covid- outbreak by averaging across the major cities within a country. missing data for average temperature for certain countries was manually appended from www.weatheratlas.com. we computed the pearson correlation coefficient, , between the average monthly temperature and total monthly incidence during each month of january, february and march. we used the fisher's z-transformation to compute z = . log + ,-. ,/. . the standard deviation of , which is known under certain normality assumptions, is used to construct a % confidence interval for . the inverse transform of is then used to obtain the % confidence interval for the correlation . all calculations were carried out in the rstudio platform. under national lockdown (march -april ), our predicted cumulative number of covid- cases in india on april are , and , (upper % ci of , and , ) assuming a -or -week delay (i.e., either a quick or a slow adherence), respectively, in people's adherence to lockdown restrictions and a gradual, moderate resumption of daily activities post-lockdown (figure , supplementary figure ). in comparison, the predicted cumulative number of cases under "no intervention" and the "intervention involving social distancing and travel bans without lockdown" are thousand and thousand (upper % ci of nearly . million and . million) respectively. we are reporting only the upper credible limit here and elsewhere since the lower credible limits are very close to due to the large uncertainty in our predictions arising from many unknowns. we also believe that our point estimates are at best underestimates due to potential under-reporting of case-counts and our model not taking into account the population density, agesex and contact network structure of the whole nation. increase in testing and community transmission may lead to a spike in a single day and that may shift the projection curve significantly upward. regardless of the exact numbers it is clear that, the -day lockdown will likely have a strong effect on reducing the predicted number of cases in the short term. we took a close look at what might be coming in the next few months, based on what we have seen in other countries and an epidemiological model that has been gainfully employed to assess the effect of interventions in hubei province. we estimated that (upper % ci ) and (upper % ci ) cases per , are avoided by may and june , respectively, by instituting a -day lockdown with a -week delay in people's adherence and a cautious release compared to perpetual social distancing and travel ban (without lockdown) ( figure ). this boils down to preventing roughly thousand (upper % ci . million) and . million (upper % ci . million) covid- cases nationwide by may and june , respectively. without some measures of suppression after lockdown is lifted, the impact of lockdown in bringing down the case-counts (the now ubiquitous term, "flattening the curve") can be negated by as early as the first week of june. in fact, in figure a , the pre-intervention ("normal") curve first passes the social distancing and travel ban curve on june . in particular, if people immediately go back to pre-intervention ("normal") activities post-lockdown, a surge in the predicted case-counts is expected in the long-term beyond what we would have seen if there were only social distancing and travel ban measures without lockdown ( . million when post-lockdown activity returns to pre-intervention levels vs. . million under social distancing and travel ban without a lockdown period on july ; figure ). we estimated that (upper % ci ) and (upper % ci ) cases per , are avoided by june and july respectively if people are cautious in their activities post-lockdown compared to the scenario where people return to normal preintervention activities. long-term forecasting under slow adherence ( -week delay) can be seen in supplementary figure . . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint we took the quick adherence epidemiological models and compared the -day lockdown with hypothetical -, -, and -day lockdown scenarios (figure ). when comparing a -day lockdown with a hypothetical lockdown of longer duration, we find that -, -, and -day lockdowns can approximately prevent thousand (upper % ci . million), thousand (upper % ci . million), thousand (upper % ci . million) cases by june , respectively. a -day lockdown does not appear to have a significant impact on cumulative case counts when compared to a -day lockdown. however, purely from an epidemiologic perspective, there appears to be some evidence that suggests a -or -day lockdown would have a more meaningful impact on reducing cumulative covid- case counts in india. we note that longer lockdown periods are accompanied by increasing costs to individuals -notably economicand must be considered. our models suggest that some form of post-lockdown suppression (e.g., extension of social distancing measures, limits of gathering size, etc.) is necessary to observe longterm benefits of the lockdown period. lockdown duration study under the slow adherence ( -week delay) scenario can be found in supplementary figure . we did explore some alternative assumptions and conducted thorough sensitivity analysis before settling on the models presented above. in one example, we assumed that there are actually times the number of reported cases to date to reflect potential underreporting of cases due to lack of testing. in another scenario, we assumed these cases occurred in metropolitan areas to reflect a potential intensification of case clustering. in yet a third scenario, we hypothesized that r prior starts with . instead of . (i.e., a single infected individual would infect . susceptible individuals, on average, instead of ). these scenarios did not appreciably change our conclusions in broad qualitative terms, though the exact quantitative projections are quite sensitive to such choices. across these scenarios, the projected total number of infected cases by the entire first phase of the pandemic varied between - % of the population, again showing the significant variability in these numbers. the estimates we present here may appear conservative and are at best underestimates, and, in all cases, our confidence in these projections decreases markedly the farther into the future we try to forecast. it is extremely important to update these models as new data arise. spatial plots for the average monthly temperatures accompanied by total monthly incidence across all countries from january through march indicate a suggestive pattern of increase in community spread across cities and regions specifically along narrow north east-west directions (figure ). countries in these regions consistently exhibit similar weather patterns. however, in the context of india, a gradual rise in the number of cases is observed starting from january through march. . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . the estimates and the % confidence interval for the correlation coefficient for january was - . [- . , . ] with countries having non-zero incidence, for february was - . [- . , . ] with countries having non-zero incidence, and for march was - . [- . , - . ] with countries having non-zero incidence. although the estimates were negative, the % confidence intervals either include zero or the upper limit is close to , indicating weak evidence for any claim of negative association between case counts and daily temperature. any such affirmation will require further data and investigation that accounts for many possible sources of confounding. our projections using current daily data on case counts until april in india show that the lockdown, if implemented correctly in the end, has a high chance of reducing the number of covid- cases in the short term and buy india invaluable time to prepare its healthcare and disease monitoring system. in the long-term, we need to have some measures of suppression in place after the lockdown is lifted to prevent a massive surge in the number of cases that can quickly overwhelm an already over-stretched indian healthcare system resulting in increased fatalities. specific vulnerable populations will be at higher risk of severity and fatality from covid- infection: older persons and persons with pre-existing medical conditions (e.g., high blood pressure, heart disease, lung disease, cancer, diabetes, immunocompromised persons). , supplementary table provides a description of the approximate number of individuals in these high-risk categories in india. beyond the fragile population characterized by health and economic indicators, we have to remember that healthcare workers and first responders at the front line of this pandemic are amongst the most vulnerable. it is important to note that a massive surge in the number of cases can quickly overwhelm an already over-stretched indian healthcare system. the estimated capacity of hospital beds in india is per , , which is an upper bound on treatment capacity. given an average occupancy rate of %, only a quarter of these are available. moreover, critically ill covid- patients (about - % of those infected) will require icu beds and ventilator support. india has only - thousand icu beds with very high occupancy rates and at most ventilator per icu beds. from a purely public health perspective, this analysis shows the impact and necessity of lockdown and subsequent measures of suppression after lockdown is lifted. all the people in india, regardless of their vulnerability to covid- , need to adhere to the public health guidelines issued by the ministry of health and family welfare in india, and continue to be cautious in their post-lockdown activities to guarantee a long-term benefit of the national lockdown. currently, there are many hypotheses regarding differential covid- infection rates and mortality rates across countries. one such hypothesis is that the bcg vaccine -developed a century back for tuberculosis -has a protective effect on the prevalence of covid- and related . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . mortality. a recent pre-print found covid- attributable mortality in countries with bcg policy is times lower than those without a bcg policy in an ecological analysis, after accounting for country-specific confounders like economic status, percentage elderly (those aged ≥ years) in the population, and relative position of each country along the epidemic trajectory. however, the authors caution against over-interpretation of this negative association between bcg use and covid- due to limitations of country-level analysis and many sources of unmeasured confounders. another hypothesis is that much like the flu virus, summer temperatures will thwart the covid- outbreak. our analysis, based on current data, suggests we cannot rely on the hypothetical prevention (with inconclusive evidence) governed by meteorological factors and need public health actions, regardless of the seasonal weather. the management of this covid- crisis requires strong partnership of the government, the scientific community, the health care providers and all citizens of india (and all global citizens). long term surveillance and management of covid- crisis is needed with not just public health in mind but also to take care of the economic, social, and psychological trauma that it will leave on the people. reviving the economy will be critical in the coming months. below we recommend some healthcare, social and economic reforms that can counter the negative impact of severe public health interventions, some of which india has already begun to make progress. (a) aggressively increase the number of tests administered daily as there are often asymptomatic cases who are spreading the infection without knowing. it is of utmost importance that india adopt widespread testing to identify and isolate the infected. rt-pcr diagnostic test can provide reliable and faster diagnosis of the sars-cov- virus. large scale antibody testing should be launched to assess the true scale of this pandemic. the instrument of isolating nearly everyone with a near universal lockdown not only leads to livelihood losses for millions of families but also starvation for others. as we reopen the country, testing high contact, high density areas and setting up a clever surveillance system is critical. immediately prepare to protect the health care workers and first responders who are at the front line of this pandemic. this involves ensuring a steady supply chain of medical resources (masks, gloves, gowns, ventilators), and protecting our healthcare workers physically and psychologically. full gears (protective suit, medical goggle, cap, face shield, mask and gloves) are absolutely essential when seeing suspected cases. these protection strategies worked in china. (c) reduce all non-essential medical care and expand number of hospital beds, icu beds and ventilators. (d) continue to set up covid- testing mobile labs, hospitals and mobile cabins (e.g. by converting stadiums and trains into quarantine and treatment facilities). ensure the healthcare facilities have adequate supply of medications that are currently . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . being recommended. for instance, antiviral drugs "remdesivir and chloroquine are highly effective in the control of -ncov infection in vitro" indicating promise for treating covid- patients. recently though, the study finding hydroxycholoroquine as an effective treatment for covid- has been retracted for bad study design and not meeting expected scientific standards. (f) use pragmatic real-time data for optimally deploying surveillance, community inspection and health care resources. this is key with limited resources. economic recommendations: (j) provide livelihood assistance over the quarantine period to those who test positive. this will incentivize people to get tested and comply with social isolation protocols. for many people in india, loss of several weeks of earnings can be economically devastating and since symptoms are mild for most infected people, it is unreasonable to expect that all people will tightly follow restrictions unless economically protected. to get a ballpark idea of the fiscal burden involved, assume million detected cases, quarantine of weeks per patient, and inr , monthly compensation. this adds up to a bill of inr billion, which is roughly . % of the annual healthcare budget of the central government. (k) during periods of social distancing and lockdowns, there is grave livelihood threat to a lot of poor people even if they are uninfected -street hawkers, auto drivers, barbers and shopkeepers, etc. providing a universal basic income (ubi), or some mildly means tested version of it, over the period of disruption is needed for a successful lockdown. (l) to prevent shutdowns in badly affected sectors, the government may provide goods and services tax (gst) credit to firms based on the difference between past and current sales. once the pandemic is over and normal business resumes, expansionary monetary and fiscal policy will be needed to revive macroeconomic health. there are many epidemiological models to predict the course of an infectious disease and even many that are india-specific. - some use age-structure, contact patterns, spatial information to finesse their prediction. some consider the possibility of a latent number of true cases, only a fraction of which are ascertained and observed. the model we used here is an extension of a . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . standard sir model, called esir model, where we can create hypothetical intervention scenarios in a time dependent manner. the goal of any intervention is to reduce the chance that an infected person meets a susceptible person. we create models for declines/drops in contact probabilities when an intervention is rolled out. thus, there is some intrinsic ad-hocery to our assumptions. any statistical model is wrinkled with such assumptions. similarly, the predictions themselves have large uncertainty (as reflected by the upper credible limits). as we interpret the numbers from any model, let us use caution in not over-interpreting them. a rigorous quantitative treatment often allows us to analyze a problem with clarity and objectivity, but we recommend focusing more on the qualitative takeaway messages from this exercise rather than concentrating on the exact numerical projections or quoting them with certainty. we see tremendous role of data and data science in governing policy as india reopens post lockdown. the release from lockdown will not be in a binary switch on/switch off process but a modulated slow-varying process. we see the following roles and opportunities for pragmatic use of data science in the post-lockdown phase. (a) flexible, athletic, data driven policymaking will need up-to-date numbers and projections at hand, which require granular data, automation and data transparency (b) understand uncertainty in numbers: all models are wrong, some are useful, but note that takeaway messages for intervention forecasting are often the same (c) using technology to create body temperature/expected health status map (e.g., healthweather.us) (d) assess adherence to social distancing using mobile networks, google (e.g., google mobility reports) (e) use survey to identify potential super-spreaders, manage contact network, oversample high risk areas for testing (f) install syndromic surveillance in hospitals, medical claims systems to set up alert; establish expected number of respiratory and flu-like illnesses so departures can set off an alarm. (g) use community health workers in rural areas, community dwellings to identify and isolate cases and conduct cluster testing (h) targeted communication strategies: regarding tests, treatments, contagion level. misinformation and incorrectly analyzed data lead to panic (i) accurate and consistent reporting of case counts and deaths due to covid- are extremely critical our statistical modeling and forecasts are not without limitations. we have very few data points and a long time-window to extrapolate for the long-term forecasts. the uncertainty in our predictions is large due to many unknowns arising from model assumptions, population . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . demographics, the number of covid- diagnostic tests administered per day, testing criteria, accuracy of the test results, and heterogeneity in implementation of different government-initiated interventions and community-level protective measures across the country. we have neither accounted for age-structure, contact patterns or spatial information to finesse our predictions [ ] [ ] [ ] nor considered the possibility of a latent number of true cases, only a fraction of which are ascertained and observed. increase in frequency and scale of testing, and community transmission of the sars-cov- virus may lead to a spike in a single day and that can shift the projection curve significantly upwards. covid- hotspots in india are not uniformly spread across the country, and state-level forecasts may be more meaningful for state-level policymaking. we are assuming that the implementation and effects of public health interventions and policies are the same everywhere in india by treating india as a homogeneous unit. future opportunities for improving our model include incorporating contagion network, age-structure, estimating seir model, incorporating test imperfection, and estimating true fatality/death rates. regardless of the caveats in our study, our analyses show the impact and necessity of lockdown and of suppressed activity post-lockdown in india. rather than over-interpreting exact numerical projections, we recommend focusing more on the qualitative takeaway messages. one ideological limitation of considering only the epidemiological perspective of controlling covid- transmission in our model is the inability to count excess deaths due to other causes during this period, or the flexibility to factor in reduction in mortality/morbidity due to some other infectious or flu-like illnesses, traffic accidents or health benefits of reduced air pollution levels. a more expansive framework of a cost-benefit analysis is needed as we gather more data and build an integrated landscape of population attributable risks. finally, in our strong commitment to reproducibility and dissemination of our research, we have made the code for our predictions available at github (https://github.com/umich-cphds/cov-ind- ) and created an interactive and dynamic r shiny app (covind .org) to visualize the observed data and create predictions under hypothetical scenarios with quantification of uncertainties. these forecasts will get updated daily as new data come in. we hope these products will remain our contribution and service as data scientists during this tragic global catastrophe, and the model and methods will be used to analyze data from other countries. our epidemiologic and mathematical calculations make a convincing case for enforcing the day national lockdown of the largest democracy in the world, acting early, before the growth of covid- infections in india starts to accelerate. we also notice the public health benefit of extending the lockdown by - weeks in our projections. measures of suppression are needed postlockdown to get long-term benefits from the lockdown. however, these draconian public health . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint measures come at a tremendous price to social and economic health that can last months or even years after the restrictions on social mobility are lifted. thus, there is an urgent need for social and economic immunity: not just coverage for testing and treatment for covid- for everyone in india, but subsidies and incentives for the common man to survive the consequences of the severe interventions that are needed to stop the coronavirus from creating a massive catastrophe in india. we also illustrate the critical role of data in aiding policy decisions. finally, our message to the public is to proceed with prudence and caution, and not panic or drown in despair. we should draw hope from the success of south korea and china and the initial promising containment in india. we need to support the community around us and help the government of india to manage the crisis with the best strategies, resources and science. the lockdown has given us time to prepare and act, let us make the best use of it. we are still in a state of national and global emergency and it will take a considerable time for humanity to recover from this global pandemic and return to normalcy. in the meantime, we root for public health, for innovation and science, for home testing kits [there is none yet], for fda approved drugs [solidarity trial], and for a vaccine [ clinical trials ongoing]. in these frightening times, we find inspiration in the power of the common people and the magic of human kindness. author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . figure . left: country-wise total monthly incidence of covid- in the months of january, february and march. the horizontal lines approximately indicate the equator, the tropic of cancer and the n latitude. right: average monthly temperature (in c) during the months of january, february and march. these maps were created by smoothing the counts as well as the average monthly temperature across geographical locations by spatial interpolation. . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint supplementary figure . short-term daily growth in cumulative case counts in india assuming a -week delay in people's adherence to restrictions. observed data are shown for days up to april . predicted future case counts for april until april are based on observed data until april using the esir model. . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . figure . cumulative (a) and incidence (b) graphs for forecasting models assuming a -week delay under -, -, -, and -day lockdown scenarios using observed data through april . . cc-by-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint who director-general's opening remarks at the media briefing on covid- - microsoft bing covid- tracker. microsoft corporation data for india, united states sars-cov- (covid- ) testing: status update aprilr predictions and role of interventions for covid- outbreak in india historic -day lockdown, predictions for lockdown effects and the role of data in this crisis of virus in india india faces spike in coronavirus cases, says study, in test for health system epidemiologic models show we need aggressive measures in the early phase...lockdown buys us time overcome by anxiety: indians in lockdown many can ill afford. the guardian india could see a reduction in the number of coronavirus cases by next week: study. the economic times an epidemiological forecast model and software assessing interventions on covid- epidemic in china an interactive web-based dashboard to track covid- in real time list of cities by average temperatures evolving epidemiology and impact of non-pharmaceutical interventions on the outbreak of coronavirus disease differentiall covid- -attributable mortality and bcg vaccine use in countries case-fatality rate and characteristics of patients dying in relation to covid- in italy high temperature and high humidity reduce the transmission of covid- regulators split on antimalarials for covid- covid- ): are you at higher risk for severe illness? the world bank hospital utilizationn statistics: thirty-five year trend analysis, a measure of operational efficiency of a tertiary care teaching institute in south india coronavirus: does india have enough ventilators, hospital beds? the times of india can an old vaccine stop the new coronavirus? the new york times centers for disease control and prevention. cdc -novel coronavirus ( -ncov) real-time rt-pcr diagnostic panel new blood tests for antibodies could show true scale of coronavirus pandemic analysis of , lab-confirmed covid- cases in wuhan: epidemiological characteristics and non-pharmaceutical intervention effects india turns trains into isolation wards as covid- cases rise remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus ( -ncov) in vitro hydroxychloroquine and azithromycin as a treatment of covid- : results of an open-label non-randomized clinical trial hydroxychloroquine-covid- study did not meet publishing society's "expected standard prudent public health intervention strategies to control the coronavirus disease transmission in india: a mathematical model-based approach age-structured impact of social distanncing on the covid- epidemic in india covid- for india updates coronavirus statistics: what can we trust and what should we ignore? the guardian covid- community mobility reports food and drug administration. coronavirus (covid- ) update: fda alerts customers about unauthorized fradulent covid- tests world health organization. who director-general's opening remarks at the media briefing on covid- - covid- vaccine tracker. regulatory affairs professionnals society hypertension (women)* † based on est. of . billion from un department of economic and social affairs * age-standardized defined as within -kilometer distance of home or work abbrev.: copd, chronic obstructive pulmonary disease international diabetes federation; nicpr, national institute of cancer prevention and research ¶ date of st case data obtained from jhu csse time series data on covid- † microsoft bing covid- tracker the authors will like to thank the university of michigan advanced research computing services for enabling daily updates to our models and allocating us abundant computational resources. we will also like to thank professor matthew fox from the boston university school of public health for his valuable comments on our rshiny app, key: cord- - ewemyny authors: chugh, tulsi title: snippets date: - - journal: nan doi: . /j.cmrp. . . sha: doc_id: cord_uid: ewemyny nan with concerted efforts of world health organisation (who) since , poliomyelitis is on the threshold of global eradication. wild poliovirus type (wpv ) was eradicated in and wpv in , and wpv is still present but only in pakistan and afghanistan. live attenuated oral polio vaccine (opv) has been the mainstay. it provides durable humoral and intestinal immunity, is easy to administer and has a low cost. however, opv has two major risks due to genetic instability. first, it may very rarely cause sporadic case of vaccineassociated paralytic poliomyelitis (vapp) when the given vaccine dose may revert to neurovirulence and cause paralysis in the vaccine recipient or a non-immune contact, who are otherwise immunologically competent. vapp may also occur in persons who have primary immunodeficiency of antibody production. the second risk is the emergence of genetically divergent neurovirulent vaccine-derived polioviruses (vdpvs). these resemble wpv and can cause outbreaks in areas with low opv coverage. whereas vapp is an adverse event following a dose of opv, vdpvs are polioviruses whose genetic properties show a prolonged replication or transmission. three different types of vdpvs are reported: ( ) circulating vdpvs (cvdpvs) from outbreaks in low opv coverage settings, all cvdpvs seen worldwide are identified and registered with who in geneva. among the cvdpv cases reported since , more than % were associated with cvdpv . an update on vaccine-derived polioviruses worldwide, january -march , has been published recently. four avdpv s were isolated from afp patients from four different states in india during this period. in addition, two vdpv isolates that escaped detection by screening assay by the global polio laboratory network have been reported from mumbai, india. the first was seen in a . -year-old girl with afp in january . it was identified as sabin type . the second was type vdpv found in an immunocompetent girl, . years old, in march . a new confirmed case of vdpv in a . -year-old child has been reported in delhi in november . this has been identified as p . replacement of trivalent opv with bivalent opv will greatly eliminate the risk for circulating vdpv cases and ivdpv infections. maintenance of high levels of immunity through comprehensive ipv coverage will be necessary to protect against ivdpv spread. detection of chronic ivdpv exeretors with suitable antiviral therapy is also important. infections with p. vivax and p. falciparum occur at approximately equal frequencies in states of india where malaria is endemic. the other three species, p. malariae, p. ovale and p. knowlesi, are reported less often. mixed infections are reported in peru, brazil, ethiopia and papua new guinea. malaria diagnosis in india is based primarily on microscopy of peripheral blood smears and rapid diagnostic tests, which cannot differentiate monoinfections from mixed infections. a total of blood samples positive only for p. falciparum by microscopy were subjected to species-specific nested pcr (targeted rrna gene) and ( . %) of these were positive for mixed infections. mixed infection of p. vivax and p. falciparum was seen in ( %), p. falciparum and malaria in ( %), p. falciparum and p. ovale in ( . %) and p. falciparum, p. malariae and p. ovale in ( . %) samples. these mixed infections were seen in all states where malaria is endemic. misidentification of malarial parasites may prolong parasite clearance time and lead to resistance to antimalarial drugs and more severe anaemia. p. vivax and p. ovale both cause relapses and p. malariae can sustain at low rates in the community for decades, and complicate malaria epidemiology and subsequent control. there is thus a need for improved quality of microscopy and rapid diagnostic tests in india. invasive salmonella infections are a huge global burden. worldwide annual estimates are: typhoid fever million, paratyphoid fever . million and invasive non-typhoid salmonella disease (ints) . million. morbidity and mortality are high, especially in resource-limited settings and in compromised hosts. invasive non-typhoid salmonella diseases are principally salmonella typhimurium and salmonella enteritidis. the routine and prospective surveillance for antimicrobial resistance is not readily available. currently resistance to chloramphenicol, ampicillin and cotrimoxazole (mdr) has declined. however, if used, there is a need for multiple dosing, longer course of therapy ( - weeks), risk of chloramphenicol myelotoxicity and higher relapse rates. fluorquinolone resistance is very common and hence unreliable for therapy. third generation cephalosporins, oral and parenteral, are currently the mainstay, safe and effective. however, mic creep and rarely full resistance have been reported. azithromycin is a good alternative: oral, single daily dose, excellent tissue penetration, high intracellular concentration and almost negligible relapse rate. but resistance is already being reported. combination therapy with third generation cephalosporins is under discussion. management of ints disease is as yet not fully determined, due to lack of adequate laboratory and clinical data. third generation cephalosporins for at least weeks is the conventional therapy. improved public health hygiene, wider use of who approved typhoid vaccines and designs of new vaccines which target the other serovars (s. paratyphi a, s. typhimurium, s. enteritidis, s. choleraesuis) are an urgent need to reduce the burden. new approaches to develop live attenuated multivalent salmonella vaccines are also in progress. there is a high prevalence of severe disease in children under two years of age. the presently available vaccines cannot be used in these children. there is a need for conjugate vaccines which can be administered to infants and children. ciprofloxacin-resistant shigella sonnei associated with travel to india shigella spp. is a major pathogen in food borne diseases. shigella dysenteriae serotype causes severe disease, outbreaks or even epidemics. occasional outbreaks by antibiotic-resistant s. sonnei have been reported in industrialised world, especially among children. such outbreaks are also now being reported from developing countries. in india, severe outbreaks of dysentery with high mortality were caused by multidrug-resistant s. dysenteriae type during - . later, it re-emerged with fluoroquinolone resistance and caused several dysentery outbreaks. more recently, food-borne outbreaks due to s. sonnei have been reported in india. the emergence of ciprofloxacinresistant s. sonnei causing such outbreaks and spread among international travellers is a cause of serious concern. antimicrobial drug resistance is a serious worldwide issue more so in countries with poor sanitation and excessive use of antibiotics in humans and animals. several studies show the emergence of ciprofloxacin-resistant s. sonnei in india. in view of this, ciprofloxacin can no longer be recommended for empiric therapy of s. sonnei infections. foodborne-associated shigella sonnei ciprofloxacin-resistant shigella sonnei associated with travel to india the author has none to declare. key: cord- -po wys s authors: singh, a.; gupte, s. s. title: covid- pandemic- pits and falls of major states of india. date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: po wys s covid- , just like sars and mers before it, is a disease caused by corona virus and can lead to severe respiratory diseases in humans. with the outbreak of novel corona virus, who on th january declared it a public health emergency and further on th march , covid- disease was declared a pandemic. india in the initial stages of the pandemic dealt with it in a very effective manner. with timely implementation of lockdown, india was able to contain the spread of covid- to some extent. however with the recently announced unlock . , the sars cov- is expected to spread. this study aims to track and analyze the covid- situation in major states that constitute of percent of the total cases. thus the states selected for the study are: maharashtra, delhi, tamil nadu, gujarat, uttar pradesh and rajasthan. these are the states which had more than ten thousand covid- patients as/on june th . the analysis period is from march th to june th and the data source is india covid- tracker. to assess the previous and current covid- situations in these states indicators such as active rates, recovery rate, case fatality rate, test positivity rate, tests per million, cases per million, test per confirmed case has been used. the study finds that although the absolute number of active cases may be rising, however it is showing a decreasing trend with an increase in recovery rates. with increasing number of covid- cases, testing also has increased however not in the similar proportion and thus by developed nation standard we are lagging. with increasing tpr and cases per million, delhi is well on its way to surpass even mumbai which till now has proven to be worst hit in this pandemic. an interesting finding is that of test per confirmed case which shows that every th person in maharashtra and every th in delhi is showing positive result of covid- test. given such an increase and unlocked india, delhi might soon enter into the third stage of community transmission where source of percent or more cases would be unknown. there has been an increase in the covid- related health infrastructure with the public-private partnership which involved both private hospitals and lab joining hands to battle covid- , however, affordability still remains an issue. if experts are to be believed, pandemic is not over because we have unlocked. the worst is yet to come as covid- is predicted to peak in mid-july to august in india. thus, it would be advisable to not venture out unnecessarily just because restrictions have been lifted. also, following the guidelines- hand-washing, avoiding public gathering, social distancing and covering nose and mouth has now become imperative. been an increase in the covid- related health infrastructure with the public-private partnership which involved both private hospitals and lab joining hands to battle covid- , however, affordability still remains an issue. if experts are to be believed, pandemic isn't over because we 've unlocked. the worst is yet to come as covid- is predicted to peak in mid-july to august in india. thus, it'd be advisable to not venture out unnecessarily just because restrictions have been lifted. also, following the guidelines-hand-washing, avoiding public gathering, social distancing and covering nose and mouth has now become imperative. covid- , like its ancestors sars and mers is caused by a zoonotic pathogen by the name corona virus and can cause severe respiratory diseases in humans [ ] [ ] . world health organization on january th declared novel coronavirus as public health emergency of international concern and on march th covid- disease was stated as pandemic based on its spreads severity [ ] . a peculiar aspect of covid- disease is that its transmission can be symptomatic, mild symptomatic, or even asymptomatic. a study conducted by indian council of medical research said that out of total active cases till april th , percent were asymptomatic and it was also observed that such patients were younger and without comorbidities [ ] . the said study also evaluated covid- patients by age and stated that the attack rate per million was highest among - years old and lowest among children below years old. gender wise attack rate was higher among men compared to women [ ] . india has confirmed covid- cases out of which percent patients constitute the active cases and percent patients have recovered as on june th [ ] . in order to check the spread of cov- at an early stage, a nationwide lockdown was implemented in four phases from march th to may st . many studies asserted that without lockdown, cases would have tripled or quadrupled in comparison to today's figure [ ] . on april th the joint secretary of health ministry, lav agarwal, presented a graph which projected covid cases had lockdown not been implemented and stated the scenario would have been grave as the statistic of confirmed cases and doubling rate would have sky rocketed [ ] . also, the world health organization emergencies programme executive director, michael ryan, on june th said that due to lockdown in india the doubling time for covid- spread is about three weeks at present. [ ] . on st june , around weeks after the first phase of lockdown, india announced unlock . . but the question remains whether lifting the lockdown is a good idea. in accordance to the world health organization recommendations a nation could unlock only if and when daily positivity rates fall below percent and remain so for a period of days. however, india's daily positivity rates was nowhere near percent and stood at . percent (on june st) [ ] . with the increasing spread of corona virus infections, it becomes imperative for the testing to increase in the same or at least similar proportion. testing per million population serves as an important indicator to compare nations in regard to handling covid- disease. enough testing ensures and gives the actual figures of covid- patients. india, although, has conducted more than million tests yet it is not adequate given india's population, the figure for its testing per million population remain less than many other covid- affected countries [ ] . a study while analysing the burden of pandemic in india found that maharashtra having highest number of covid- positive cases is solely responsible for more than one third of cases as on may th followed by gujarat and tamil nadu. also, higher test positivity rate is another issue in these states. along with this the study also forecasted that covid- designated hospitals are less in number and that soon all the ventilators will be occupied due to increasing number of patients along with other patients suffering from communicable and non-communicable disease amidst this pandemic [ ] . this can turn out to be true in forthcoming days as peak of covid- cases is expected in mid-july. therefore, this study aims to track and analyze the covid- situations of the major states which share almost % burden of the total cases. thus, the states taken into consideration for the study are the states which had more than , confirmed covid- patients as/on june th . the six major states so included are: maharashtra, tamil nadu, delhi, gujarat, rajasthan, and uttar pradesh. the covid- related information is taken from the application programming interface (api, http://api.covid india.org). it is a data sharing portal that provides the most recently updated information on daily basis. it gives data related to total tests, confirmed cases, active cases, recovered cases, and deaths for each affected state/ut as well as for whole india. the number of covid- designated public and private laboratories doing covid- testing has been taken from indian council of medical research website as they publishes list of laboratories for each . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) states/uts. the projected population of india and states/ut for the year have been taken from report of the technical group on population projections, [ ] . the analysis for the study has been done from th march (lockdown . ) all the way to th june i.e. ten days after unlock . . for sake of convenience in analysis, this time period is further bifurcated in days interval. in the study, rate of active case is defined as the total number of active cases out of total confirmed cases. recovery rate is defined as the total number of recovered cases out of total confirmed cases. case fatality rate is defined as the total number of deaths out of total confirmed cases. test positivity rate is defined as the proportion of confirmed cases per people tested. tests per million population and cases per million population are also calculated. test per confirmed cases is defined as the number of test done per positive cases. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . figure shows the active cases of india and six selected states. for most of these, active cases have more or less decreased since april th with an exception that of tamil nadu. tamil nadu's active cases are fluctuating with a sudden increase in the duration april th to may th and peaking around th may. post th may , the active cases line of uttar pradesh, tamil nadu and delhi have shown a slight upward trend. across india, in the said duration, the cases are fluctuating with a small peak around th may and then decreasing in the latter part of the taken time period. shows the trend of recovery rates of india and the selected states. the graph shows that the recovery rates are steadily increasing. tamil nadu again stands out as the rates can be seen to fluctuate during the period th april to th may. in this time period, tamil nadu sees both high and low peaks in recovery rates. post th may, the recovery rates can be seen to be increasing gradually for india, maharashtra, gujarat and rajasthan. however, a minor decrease can be observed in the recovery rates of uttar pradesh, delhi and tamil nadu. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . nadu, irrespective of having a higher level of active cases has maintained a very low case fatality rate throughout the duration of analysis. rajasthan, also, in the entire duration has stayed below the national average of case fatality with uttar pradesh rising in the case fatality rates to touch this national average and delhi surpassing it around th june. maharashtra and gujarat from the very beginning have been way higher than the national average case fatality rate. however, where case fatality rate of maharashtra is seen to be decreasing gradually even if still above the national case fatality rate, gujarat's case fatality is increasing at an alarming rate. at the end of analysis period, gujarat's case fatality rate stands at . which is way above the national case fatality rate as on th june which stood at . . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint be seen to be flaring well as far as tests are concerned. as on th june, delhi's stood at tests per million population. delhi is followed by tamil nadu and rajasthan. maharashtra although with higher number of active cases, still seems to be lagging behind in testing. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint figure shows the percentage of government and private laboratories doing covid- tests. more the inclusion of private laboratories for covid- tests shows that state is increasing its efficiency of testing. around percent of covid- designated laboratories are private in india. in states like maharashtra, tamil nadu, and gujarat more than percent of laboratories are private whereas in delhi more than half of the laboratories are private. in uttar pradesh and rajasthan number of private laboratories doing covid- tests is around percent. since the outbreak of novel coronavirus, government of india took a series quick actions and as a part of it announced a nationwide lockdown on march th . measures like social distancing, covering face and nose, maintaining hygiene and avoiding public gathering were made compulsory. the measures were to ensure the break of human chain for transmission and thus ultimately tackle the sars cov- spread. the government has been trying to beat covid- at two fronts, one, flatten the curve of coronavirus positive cases and second, to restrict the exponential growth in the number of positive cases [ ] . however with the announcement of first unlock on june st , the statistics are bound to change. this study, has thus, tried to show how india's numbers have behaved since lockdown to till june th i.e. days into the unlocked india and the strategies used by government of india to counter covid- . the ministry of health and family welfare stated on june th that india's doubling rate of covid- cases has increased from . days when lockdown began (march th ) to . days currently [ ] . along with it india's active cases rate and case fatality rate are decreasing whereas recovery rate is showing an upward trend since the outbreak. at present, recovery rate is higher than active cases rate, however this is not the point to let our guards down as the peak is yet to reach of the pandemic. also, recovery rates talks about cumulative/accumulated numbers whereas active rate give the current situation thus making them non-comparable [ ] . simultaneously, an analysis of the current situation in terms of new active cases and new recovered cases (in the duration of days from unlock . ), the situation is opposite, the active cases are more than recovered cases [ ] . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . this study highlighted the performance of six states but the states that stood out were maharashtra, tamil nadu, and most importantly delhi, which were well below assuring level as there active cases are not only fluctuating but also increasing as india's move to unlock . . number of new cases coming on a daily basis are alarming in these major states making them a contributor to more than percent covid- . test positivity rate clearly show how the cases are accelerating with maharashtra and delhi as the top contributors. however, test per million population of india and in the selected states are increasing. an increase in number of testing can trace an infected person at an earlier stage and thus inhibit its transmission at the same time since its source would be recognizable, it'll save the states from reaching stage three of cov- transmission. indian council of medical research has granted private laboratories the access to conduct testing for covid- and hence this has led to a better and increased capacity and efficiency of testing. with the increase in testing the cases per million population has increased and this comes out as a pressing matter of concern for india. the study has highlighted the situation of delhi and maharashtra that have become major hotspots as test per positive cases in maharashtra is percent and in delhi it is percent which means in maharashtra out of every person tested one is coming as coronavirus positive and in delhi out of every persons tested one is coming positive. this graph is going down steadily for all the selected states and for india as whole meaning that the spread is once again gaining pace. as the daily cases are increasing the government has also realized the need of more hospitals in india. therefore, the number of covid- designated hospitals have been increased by percent i.e. from covid- health centers on may th to covid- health centers on june th [ ] . with the inclusion of private labs and increasing number of health centers government is trying to counter the covid- crisis with increased testing and accessibility of hospitals for infected patients, but even after this we are grappling to match pace with the increasing covid- cases especially in delhi and maharashtra. the number of active and newly infected cases are showing a tremendous increase in these states. india has spent only . percent of gdp on its health infrastructure which is quite less when compared to other developed nation where pandemic is at peak. as per global health expert's prediction india lags in health infrastructure and capability to deal with this pandemic [ ] . though india has performed well in wake of the sars cov pandemic, it can be credited to timely . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint lockdown thereby actively inhibiting its transmission yet it struggled to flatten the curve of infected patients. however lockdown has delayed the peak of coronavirus in indian subcontinent giving it time to strengthen its health infrastructure and thus be better equipped to fight the upcoming challenge. government of india is trying to tackle the pandemic with joining hands and involving both public as well as private laboratories and hospitals to share the burden. however, to ensure the affordability along with accessibility government needs to have an upper ceiling of the charges that people would have to pay in order to get treated. thus it can be said that india fared well at the beginning with timely lockdown and series of quick actions but this was at cost of economy. with new regime of unlock . , india is reluctant to ignore economy anymore and thus india's initial success of containing the spread of cov- seems to be faltering. india is trying to counter the pandemic with public-private partnership as well as an increase in efficiency and accessibility of testing and health care facility but the affordability still remains an aspect that can be worked upon. where on one hand, india is grappling to take control of the situation with increase in daily positivity rates and tests per positive cases, on the other hand, if experts are to be believed, we are yet to see the worst of it in around mid-july to august when cov- would reach its actual peak. hence, it goes without saying that it isn't the end of pandemic and even though lockdown has been lifted, it'd be advisable to not venture out unnecessarily and maintain social distancing, avoiding public places and covering mouth and nose along with the recommended hygiene practices. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . coronavirus disease sars and mers: recent insights into emerging coronaviruses event as they happen (coronavirus disease ) asymptomatic transmission of covid- : why it matters, where evidence stands coronavirus | % of , covid- cases in india till april asymptomatic, says study india covid- tracker assessing the impact of complete lockdown on covid- infections in india and its burden on public health facilities covid- lockdown, successful or not? there are ways to answer this question everything you wanted to know about india's test numbers, in five charts burden of covid- pandemic in india: perspectives from health infrastructure population projection for india and states a comprehensive analysis of covid- outbreak situation in india doubling time of coronavirus cases in india improves to . days: health ministry india coronavirus number explained: more recoveries than active cases, but how relevant is that more hospitals in india designated as covid- treatment centres within four weeks key: cord- -tohbzenc authors: bhola, j.; revathi venkateswaran, v.; koul, m. title: corona epidemic in indian context: predictive mathematical modelling date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: tohbzenc the novel coronavirus pathogen covid- is a cause of concern across the world as the human-to-human infection caused by it is spreading at a fast pace. the virus that first manifested in wuhan, china has travelled across continents. the increase in number of deaths in italy, iran, usa, and other countries has alarmed both the developed and developing countries. scientists are working hard to develop a vaccine against the virus, but until now no breakthrough has been achieved. india, the second most populated country in the world, is working hard in all dimensions to stop the spread of community infection. health care facilities are being updated; medical and paramedical staffs are getting trained, and many agencies are raising awareness on the issues related to this virus and its transmission. the administration is leaving no stone unturned to prepare the country to mitigate the adverse effects. however, as the number of infected patients, and those getting cured is changing differently in different states everyday it is difficult to predict the spread of the virus and its fate in indian context. different states have adopted measures to stop the community spread. considering the vast size of the country, the population size and other socio-economic conditions of the states, a single uniform policy may not work to contain the disease. in this paper, we discuss a predictive mathematical model that can give us some idea of the fate of the virus, an indicative data and future projections to understand the further course this pandemic can take. the data can be used by the health care agencies, the government organizations and the planning commission to make suitable arrangements to fight the pandemic. though the model is preliminary, it can be used at regional level to manage the health care system in the present scenario. the recommendations can be made, and advisories prepared based on the predictive results that can be implemented at regional levels. fight the pandemic. though the model is preliminary, it can be used at regional level to manage the health care system in the present scenario. the recommendations can be made, and advisories prepared based on the predictive results that can be implemented at regional levels. viruses have been considered as inconsequential pathogens in humans for long in comparison to plants. the mortality caused by viruses in humans has been very low in comparison to other diseases such as cancer, cardio-vascular diseases and tuberculosis (cghr report, ). however, viruses have been reported to exacerbate the symptoms and have more serious implications on human health if a person is suffering from some auto-immune disorder, infectious disease and has compromised immune system. in india, for diseases such as tuberculosis, hiv and cancer, the related mortality rate is so high that researchers and funding agencies have under-estimated the implications viral diseases can have on public health and socio-economic security. funding agencies and data scientists have overlooked flu and other human viral pathogens; and in the past years, not much research is funded to work on drug designing or medical research in the field. it is also clear from the recent trends that viral diseases are going to spread at fast pace and many novel viruses will be unearthed in near future. climate change and deforestation is also causing surge in outbreak of viral epidemics. the changing climate is also responsible for increase in number of vectors that accelerate the spread of pathogens (khan et al., ) . in the last few years, who (world health organization) has been continuously emphasizing that the fast-developing nations such as india should triple their expenditure on health care to meet the sdg goals. the outbreak of the sars-cov- has raised the concerns for the government of india, public policy makers and administration as the pandemic has implication on almost all sectors and strata of the society. it is therefore important to understand how the virus will fare in india and how efficiently the country can handle it without causing severe damage to human population. the recent outbreak of the global pandemic covid- has changed the perspective of everyone in the country regarding the viral disease outbreaks as it is affecting and infecting humans around in an exponential manner. this viral disease as well as the causative agent is novel entry to the viral world and hence is posing unforeseen challenges. sars-cov- , commonly known as n o v e l coronavirus, is a single, positive-stranded, rna virus belonging to order nidovirales (cascella, ) (peeri, et al., ) . both these viruses emerged from animal reservoirs to cause global epidemics with alarming morbidity and mortality (chavang, ) . the reservoirs of the novel coronavirus are mostly animals found in the wild. scientists also believe that peri-domestic mammals may also serve as for long, human viruses have not been considered severe pathogens as infected people develop flu like symptoms and then get cured on their own as innate immune system triggers antibody formation that provides resistance against the diseases (chiu, ; kistler et al., ; wrammert et al., ) . in both developed and developing countries the signs of common flu have not been a cause of concern though some vaccines have been developed recently and elderly are advised to take shots yearly as they have compromised immune systems (voordouw et al., ) . however, the spread of novel covid- has alarmed people all over the world. it is important to understand how the virus will fare in the alien environments. therefore, interdisciplinary research involving biologists, data scientists, mathematicians, clinicians is required in order to work towards stopping the spread of these diseases and design appropriate methods, drugs to contain it before the situation gets out of hand. . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint the present virus that first manifested in wuhan is different from other corona viruses known to humankind, and that is the reason for being cautious. basic symptoms resemble the normal flu-like symptoms that can result in cough, cold, headache and body ache. the more severe consequences include acute respiratory tract infections that culminate into pneumonia (who report, ). in more severe cases, especially old people also develop secondary infections that start affecting other vital organs and in worst cases leading to death of any individuals which can be cured for most infected individuals (xu et al., ) . the fast pace at which it is spreading from human to human contact is the current major reason of worry, and this what we show through a concise mathematical model in this paper. the infections can spread through air (if the infected individual is less than one meter apart from uninfected individuals), mostly through the droplets of infected people since the virus stays alive in droplets on the surfaces for many days. as soon as it gets into the host, it replicates in the body, and the body becomes a reservoir (rothan and byrareddy, ). however, in some cases, the virus can stay latent inside the body and may not cause any disease symptoms, but if this person is a carrier, then he/she can spread the disease to others who come in contact with the droplets of the person that are released during coughing or sneezing. the symptoms resemble people who catch seasonal flu like symptoms ranging from cough, cold, fever to shortness of breath (who, ; wu, ). as the symptoms shown by the person infected with novel covid- are similar and over lapping with other common flu, it is not easy to identify the carriers and therefore, the transmission cannot be easily contained. india tops the list of countries with highest population and has been trying hard to negotiate . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint the problems and challenges thrown by this overwhelming population (ministry of health, goi, ). the rise in population has already created crisis for health sector, education and has caused poverty elevation. with the outbreak of the novel coronavirus covid- , the country must gear up to confront it. it is important for indian scientists to come together and study the pathogenicity in the indian context. in india, the first case was reported in the end of january this year, and the number has grown to touch as on march , . but india is a peninsula and the temperature, humidity and topography is variable, hence the factoring of variables will also have an implication on mortality and morbidity. also, education, awareness and understanding of people, socio-economic status is variable, so the infection percentage, the magnitude of impact will also be different. this calls for regional data assessment and modelling. besides, mathematical and ecological modelling can help in predicting the disease course. the data generator through these models can consider various variables that are specific to the country and give some predictions. this can help in a fair assessment and put all the fake and unscientific assumptions on hold. this data can also help in giving recommendations to the health care agencies. brockmann, ). scientists have also been using dynamic bipartite graphs to model the physical contact patterns that result from movements of individuals between specific locations based on the trends available each day . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint we used the software mathematica to do predictive modelling based on the data that is presently available on the mortality due to the pandemic spread by covid- . in the present context, population of india can be classified into three broad classes; namely this can be seen as a three-compartment model (figures and ) and what is our interest is to have the minima of the i(t) compartment under the prevailing circumstances. cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint figure from what is known about corona viruses, it is evident that the per capita rate of increase in the number of infectives is directly proportional to the number of susceptible in the vicinity of an infective and hence, the total intake in the first compartment looks like (ks)i ; where k signifies the rate of transmission indicated by the average number of people who will catch the virus from one infected person. . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint the basic differential equation system [sir-model] ( barnes and fulford, ) that captures the problem is given by: where r is the rate at which infectives recover or die; and clearly, these individuals can no longer remain infective. looking at the statistics worldwide (https://www.who.int/) the value of k is somewhere between . and . . for the sake of visualization let us take the total world population to be and a single infective to begin with. a plot code in mathematica for k= (which is much lower than the actual k for many countries at present) gives a striking sketch (figure ). . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint figure starting with just a single infective, the infection peaks up to almost the total population size before starting to fall down. the situation in india is summarized in the https://www.mohfw.gov.in/ website. at present, community transmission has not been validated and the k value is significantly less than in india. the infection will still continue growing initially before attaining a peak lower than the total susceptible population this time, as indicated by figure . . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint figure to contain the transmission of this virus, it is extremely important to contain the value of k. this k value is supposedly dependent on many factors that involve both natural (temperature, humidity) and non-natural factors or personal provisioning measures such as physical distancing, infectives wearing masks, good hygiene practices such as washing hands with soap for seconds, and so on. if k is greater than , then the disease will grow exponentially after a critical stage and become an epidemic. the exponential growth occurs because every infected individual replaces himself or herself by more than one new infected person on an average. scientists classify this value as r or basic reproduction number. the r for measles is around , the r for covid is around . , and for seasonal flu it is around . . figure shows how the number of new cases (per transmission) for seasonal flu is negligible as compared to covid . . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint figure however, the exponential growth process can only continue ) if there are sufficiently many susceptible individuals available. once a larger fraction of the population has gone through the infection and has become immune, the probability of an infected person transmitting the infection decreases. but as shown in the previous figures, in every transmission from person to person, the numbers increase exponentially, and we would not have enough hospitals beds, medical staff and equipment to treat all infected individuals if exponentially increasing number of people have to be admitted in hospitals every day! we cannot risk such a situation because any healthcare system (of even the richest and most developed country) will breakdown and we would have unnecessary deaths. as humans, we have the knowledge to overcome such situations. we have the knowledge of science, and we should use this to avoid unnecessary deaths. this is where the second option becomes important to practice, that is ) physical distancing to ensure we do not spread (or receive) the virus to (or from) other people. this way, the virus surviving within the bodies of already infected individuals can no longer survive by jumping to other persons. the viruses would stop surviving in the infected persons' bodies after its -day incubation period in that host. this way, we can reduce the number of deaths, and also reduce the number of infected by blocking the virus from spreading. all this standard epidemiology is going to work in the covid- case only if this new strain of virus behaves in a decent way, i.e. within our current grasp of understanding. what if the virus mutation occurs causing re-infection ( figure ) or what if there comes a second wave of infection affecting large numbers? all these apprehensions need a more detailed analysis. scientists are working on getting a full picture of the evolution of the virus, but it might take some time. we need to give scientists this time; we all need to give medical and healthcare . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint workers the time to deal with new patients every day. we can deal with both these situations only by lockdown, physical distancing and personal hygiene methods. the cooperation of every citizen is required. the sate wise scenario in india as on march , is tabulated as under: the above table shows the maximum number of covid- cases in maharashtra. maharashtra is densely populated with mumbai being an overcrowded city that has a population size of more than million people to which this highest number is being attributed to. this has happened in maharashtra even when the state has not been the first one to get the infection in india. the same can be paralleled with the influenza epidemic a century ago which took a toll of estimated - million people in india alone and warns us of what lies ahead of us, if the present situation goes uncontrolled, unattended or casually attended. also, from the above plots (figures and ) , though the transmission rate is very low in india now, the number of infectives is bound to increase with time. the only way to get the graph of infectives as a decreasing function of time as per the proposed model is that the interaction term ksi in the equation ( ) tends to zero. that can only happen when infectives are totally isolated from the susceptible population. the variables will keep on changing with each passing day as the virus has just reached stage of its disease cycle where there are no mass causalities and things are under control. data suggests that the country is going to see a surge in the cases. however, we have to understand that variables such as hygiene, physical distancing, staying indoors, and boosting immune system can flatten the curve. raising awareness through various platforms including the social networking websites like facebook and twitter is one way of containing the disease. each household must be reached and that can be done through vernacular language since large section of the population is still not conversant in english and hindi. government has already taken measures such as setting testing centres and has designated isolation blocks in hospitals. this would ease the burden on the existing ones. new makeshift health centers can also be created as they did in china, which helped them win over the battle despite the high cases there. also, the country-lockdown announced by the government is surely going to act as infection controller and hopefully help india attend to this new challenge in the desired form. strict measures have been announced for people who are not following government advisory. it is important to boost the morale of front-line workers (such as medical practitioners and paramedical staff, nursing staff, cleaning staff and house-keeping departments of the hospitals and health care centres) who are interacting directly with the patients. people who are showing anxiety symptoms due to restrictions and lock downs need constant counselling. psychologists, self-help groups need to offer counselling through electronic media. indians also need to fight the menace of superstitions and myths that are being propagated regarding the cure of corona related illness. scientists need to gear up for the task and come forward to do collaborative research work to understand the spread, containment and eventualities of the pandemic outbreak. for this, interdisciplinary teams must work together to come out with some concrete strategy. research teams have to develop vaccines for which funding, infrastructure, and adequate facilities are required. so, covid- is a reminder that science cannot take a back seat and health care, education and research should always hold a top priority. faith in science and scientists, and optimism is important at this juncture so that india comes out as a winner in the battle. mathematical modelling with case studies, a differential 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coronavirus disease (covid- ) outbreak annual revaccination against influenza and mortality risk in community-dwelling elderly persons report of the who-china joint mission on coronavirus disease rapid cloning of high-affinity human monoclonal antibodies against influenza virus characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention pathological findings of covid- associated with acute respiratory distress syndrome. the lancet respiratory medicine epidemiological and clinical features of the novel coronavirus outbreak in china transmission and epidemiological characteristics of severe acute respiratory syndrome coronavirus (sars-cov- ) infected pneumonia (covid- ): preliminarily evidence obtained in comparison with -sars estimating the serial interval of the novel coronavirus disease (covid- ): a statistical analysis using the public data in hong kong from key: cord- -np exds authors: sharma, surbhi; kundu, aayushi; basu, soumen; shetti, nagaraj p.; aminabhavi, tejraj m. title: indians vs.covid- : the scenario of mental health date: - - journal: nan doi: . /j.sintl. . sha: doc_id: cord_uid: np exds the fight with covid- pandemic seems nowhere near the end and is extremely daunting. an upsurge in cases of mental illness in india post the pandemic is a clear indicator of its scary impact. the situation of lockdown is causing the feeling of distress, agitation and helplessness among the people. healthcare workers, poverty-stricken people, elderly, kids and persons with some pre-existing medical condition are more vulnerable to anxiety currently. practicing a healthy lifestyle; yoga, meditation, avoiding reading too much about the pandemic and being with family are the ways to assuage stress. coronavirus disease (covid- ) is a contagious disease caused by severe acute respiratory syndrome coronavirus (sars-cov- ) which is a single standard rna genome [ , ] . the continuously rising number of the affected patients and deaths across the globe is overwhelmingly daunting. more than , people globally and , people solely in india have succumbed to this disease as of august , [ , ] . the number of active cases of covid- in india by august , is [ ] . since there is currently no drug or vaccine available against this virus, keeping social and physical distancing is the preferred way to slow down the spread by interrupting the chain of transmission [ ] . minimization of contact with infected surfaces, regular hand washing, wearing mask compulsorily, physical distancing (at least meter), and avoiding crowding are a few measures that each and every individual is advised to incorporate in their routine lives [ , ] . the present times are not only a test of physical immunity but also a test of mental strength and resilience [ ] . covid- pandemic is accompanied by increased stress, anxiety, sleep disturbance, and panic amongst the people [ ] . the horrific pandemic led to an unprecedented situation of nationwide lockdown in many countries including india [ , ] . the sudden changes in routine life because of the lockdown and prolonged isolation cause psychological distress [ ] . the people living alone amidst the lockdown tend to get agitated feeling confined. people whose family member has some serious complications of covid- could feel anticipatory grief [ ] . in addition, the shortage of supplies can also augment the stress [ ] . j o u r n a l p r e -p r o o f healthcare workers, unemployed/ poverty-stricken individuals, elderly people, children, pregnant women and those suffering from a pre-existing mental condition like obsessivecompulsive disorder (ocd) and depression are likely to feel more distressed [ , [ ] [ ] [ ] [ ] . the front-line workers who have direct involvement in handling covid- patients are at greater risk to develop psychological distress over others. excessive working hours, inadequate personal protective equipment, and sensationalized news stories contribute to the anxiety [ ] . the pandemic situation worsens the anxiety issues for people with major symptoms of ocd and individuals who overrate dangers. such people worry about becoming contaminated and unintentionally spreading contamination [ ] . children and adolescents can find it very hard to spend such a long time at home continuously with a lack of personal meetings with friends causing them to feel agitated and bored [ ] . there is also reportedly an increase in the violence against children during such a time which is fearsome for kids [ ] . in the period of complete lockdown, sudden travel ban, no work, and financial crisis caused grievous panic amongst internal migrant workers in india forcing them to walk several thousands of kilometers to reach their respective native places. they are vulnerable to develop severe, acute and chronic mental health issues [ ] . moreover, massive job losses, salary cut, unemployment and mounting economic crisis have exacerbated the situation for the majority of the public causing obvious psychological distress [ ] . lockdown has encouraged excessive use of digital platforms and social media that can influence sleep patterns and negatively impact mental well-being eventually. moreover, depressive symptoms in students and office workers during the period of lockdown have been reported to be greater when compared to before lockdown, possibly due to home confinement, stress as well as anxiety [ ] . the indian j o u r n a l p r e -p r o o f psychiatry society reported a % increase in mental illness cases since the pandemic [ ] . the rate of suicide could be escalated possibly due to the fear of infection and feeling helpless [ ] . the mental health situation during the pandemic situation is quite the same globally. around % of adults reported an impact on mental health in the us [ ] . the situation is reportedly quite similar in australia where adolescents and young adults are excessively affected because of the pandemic [ ] . in a web survey conducted in albania during th march- th april , around . %, . %, and . % out of participants expressed minimal, mild, and moderate depression after just weeks after the commencement of quarantine [ ] . furthermore, investment in the infrastructure has been put by taiwan to support clinical as well as psychosocial aspects of care in the course of the pandemic. people in taiwan and spain have been suggested to limit the consumption of news stories related to covid- to only minutes every day to minimalize the feelings of despair [ ] . the frontline workers, doctors, nurses, healthcare staff, sanitation workers, police personnel, as well as volunteers are to be credited for the earnest efforts to curtail the number of covid- cases [ ] . people having mild symptoms may be given symptomatic treatment like an antipyretic drug for fever and pain. hydroxychloroquine may be deliberated for persons having high-risk features for the severe disease under strict medical supervision [ ] . convalescent plasma therapy is another treatment strategy followed in india. moreover, 'arogyasetu' mobileapplication is also available which helps to inform people about the covid- situation in their vicinity and self-assess their health [ ] . on the vaccination front, three vaccine contenders oxford/astrazeneca's contender chadox ncov- which is known as covishield in india and is being tested and manufactured by the pune-based serum institute [ ] . discussing mental health problems is considered a social stigma because of which seeking treatment for mental disorders is still not thought to be normal by a large proportion of people [ ] . nonetheless, a special task force and helpline concerning mental health issues during the pandemic has been set up by the national institute of mental health and neuroscience (nimhans), india. a continuum of care service has been established for persons with psychiatric, neurological as well as neurosurgical issues. telemedicine facilities and teleconsultation are being provided to the patients [ ] . india's strong socio-cultural framework and family culture can act as a savior during hard times where family members can comfort, cheer and motivate each other. staying calm, keeping one self busy with routine activities, and rediscovering hobbies and interests are some way outs to assuage boredom. healthy lifestyle and eating habits are also helpful; the use of ayurvedic herbs known for boosting immunity like tulsi, cinnamon, turmeric, etc., is also common in indian households [ ] . indians commonly practice meditation and yoga which can aid in alleviating stress and anxiety [ ] .stress management, counseling and communication are essential during these hard times. feeling anxious amidst the pandemic and lockdown is inevitable. but, india is a country where people are used to hardships and compromises from a very early age. however, the current battle is a tough one where mental strength, patience and resilience are being tested. more communication with close ones, avoiding sensationalized news-stories, practicing healthy lifestyles with a positive mindset is the way out to keep anxiety away. the authors don't have any conflict of interest in the publication of the manuscript. sars-cov- : virus dynamics and host response invasion of novel corona virus (covid- ) in indian territory government of india, home|ministry of health and family welfare covid- coronavirus pandemic current treatment protocol for covid- in india world health organization, advice for the public, who coronavirus dis the covid- paradox: impact on india and developed nations of the world ministry of health & family welfare -government of india, minding our minds during the covid- psychiatrist in post-covid- era -are we prepared? the lancet, india under covid- lockdown covid- pandemic and lockdown: cause of sleep disruption, depression, somatic pain, and increased screen exposure of office workers and students of india mental health of family, friends, and co-workers of covid- patients in japan loss and grief amidst covid- : a path to adaptation and resilience recognising and addressing the impact of covid- on obsessive-compulsive disorder resilience, covid- -related stress, anxiety and depression during the pandemic in a large population enriched for healthcare providers mental health status of pregnant and breastfeeding women during the covid- pandemic: a call for action mitigate the effects of home confinement on children during the covid- outbreak mental health problems faced by healthcare workers due to the covid- pandemic-a review parenting in a time of covid- covid pandemic: mental health challenges of internal migrant workers of india aggregated covid- suicide incidences in india: fear of covid- infection is the prominent causative factor covid and its mental health consequences international experiences of the active period of covid- -mental health care effect of covid- pandemic on mental health among albanian people residing in the country and abroad -implications for mental care ministry of health and family welfare, clinical management protocol : covid- india's first covid- vaccine covaxin appears safe in early trials mental health in india: neglected component of wellbeing in covid- era national institute of mental health & neurosciences, covid- pandemic mental health in the times of covid- pandemic ayurveda and covid- : where psychoneuroimmunology and the meaning response meet public health approach of ayurveda and yoga for covid- prophylaxis ms. surbhi sharma is grateful to ugc, new delhi, india for the research fellowship. key: cord- -m qabh k authors: kadi, adiveppa s.; avaradi, shivakumari r. title: a bayesian inferential approach to quantify the transmission intensity of disease outbreak date: - - journal: comput math methods med doi: . / / sha: doc_id: cord_uid: m qabh k background. emergence of infectious diseases like influenza pandemic (h n ) has become great concern, which posed new challenges to the health authorities worldwide. to control these diseases various studies have been developed in the field of mathematical modelling, which is useful tool for understanding the epidemiological dynamics and their dependence on social mixing patterns. method. we have used bayesian approach to quantify the disease outbreak through key epidemiological parameter basic reproduction number (r ( )), using effective contacts, defined as sum of the product of incidence cases and probability of generation time distribution. we have estimated r ( ) from daily case incidence data for pandemic influenza a/h n in india, for the initial phase. result. the estimated r ( ) with % credible interval is consistent with several other studies on the same strain. through sensitivity analysis our study indicates that infectiousness affects the estimate of r ( ). conclusion. basic reproduction number r ( ) provides the useful information to the public health system to do some effort in controlling the disease by using mitigation strategies like vaccination, quarantine, and so forth. influenza is an emerging infectious disease and influenza-like illness (ili) is a clinical illness caused by the influenza virus, which gave rise to human pandemics such as spanish flu (h n ), asian flu (h n ), hong kong flu (h n ), and most recently h n pandemic . influenza a (h n ) was originally referred to as "swine flu" because laboratory testing showed that many of the genes in this new virus were very similar to those found in pigs in north america. further on, it has been found that this new virus has gene segments from the swine, avian, and human flu virus genes. the scientists call this a "quadruple reassortant" virus and hence this new (novel) virus is christened "influenza-a (h n ) virus" [ ] . a reassorted influenza was first detected in mexico on march , , and rapidly spread to the united states, canada, and subsequently all regions worldwide including india. the first case of h n was reported in india on may , , at hyderabad airport in a young boy who travelled from the usa and later it spread throughout the country [ ] . according to world health organization (who) update of november , , virus spread across more than countries resulting in deaths [ ] . in june world health organization (who) raised the level of pandemic alert phase to phase [ ] . according to the directorate general of health services, government of india, new delhi, update on november , , there have been laboratories confirming cases recorded in india resulting in deaths [ ] . to formulate the valid and reliable estimate of transmissibility and spread of an outbreak we have utilised statistical modelling, which facilitates our understanding of mechanism of disease spread. to access the intensity of an outbreak, transmission potential can be quantified by reproduction number , that is, average number of secondary cases generated by a single primary case in a completely susceptible population [ , ] . the importance of basic reproduction number becomes more apparent when an emerging infectious disease strikes a population which is a key concept in the epidemic theory. if is less than or equal to one, then transmission in the population goes stochastically extinct with probability of one after a small number of infections. if is greater than , then there is a positive probability of a large epidemic. statistical estimation of is used to understand the transmission dynamics and evolution of the infectious disease which facilitate designing the effective public health intervention strategies and mitigation policies [ ] . the aim of present study is to quantify the intensity of pandemic influenza a/h n in india. to achieve this goal we have calculated basic reproduction number from time series data set of h n through bayesian approach to contact patterns. we have estimated basic reproduction number with % credible interval. time series data for the influenza a/h n pandemic in india was obtained from the ministry of health and family welfare (mohfw), government of india [ ] . , infected cases with deaths were reported during may , , to may , , with two complete waves of epidemic. we have represented the data of the first wave from may to october (see figure ). for the analysis we have used daily reported cases (incidence) for initial phase of an epidemic from june to august , [ ] . statistical inference of is still in progress, and it is recognized that the estimate is very sensitive to dispersal of the disease progression [ ] . estimation of can be illustrated by employing time-since-infection model and suggests origin of transmission of infectious diseases which is the counterpart of compartmental models like si, sis, and so forth. both models are originated in the basic paper of kermack and mckendrick [ ] , and both the sir model and the simplest time-since-infection model are known as "the kermack-mckendrick age structure model. " it is used to identify key epidemiological parameter by using a simple renewal process which adheres to the basic reproduction number . let ( ) represent the number of new infections or incidence at calendar time ; that is, each infected individual on an average generates secondary cases at a rate ( ) at timesince-infection which is a specific case of renewal equation of birth process [ ] [ ] [ ] . consider ( ) since represents average number of secondary cases that a primary case generates during entire his/her infectious period, the estimate is given by [ , ] under kermack and mckendrick assumption "single infection causes an independent process of infection with host" which allows an age representation for the state of infection, that is, infectivity of an individual. the time elapsed since infection is called the infection age or time since infection, whereas ( ) is expected infectivity of an individual with time-since-infection whereas ( ) becomes the rate of secondary transmission per single primary case at time-sinceinfection [ ] : where ( ) is the transmission rate which depends on frequency of contact and infectiousness at infection age and Γ( ) is the probability of being infectious at infection age . further, we consider a probability density of the generation time where generation time is defined as time from infection of an individual to the infection of a secondary case by that individual, denoted by ( ) through normalized density of secondary transmission [ , , ] . we have using ( ) in ( ) we get then, the basic reproduction number is as in in reality, the case incidences are rather in discrete form as daily/weekly reports. the discretized analogy of ( ) can be derived as computational by taking the inverse of both sides of ( ) we get where is the discretized form of time since infection (usually in days), is discretized calendar time (usually in days/weeks), and is the generation time distribution for an infectious disease which is the probability distribution function for the time from infection of an individual to the infection of a secondary case by that individual [ , ] . from figure the concept of through contact patterns has been illustrated here before taking up the bayesian method of estimation. from figure (a), the transmission tree with = represents who infected whom, where each primary case on an average generates " " secondary cases. secondary transmissions from primary to secondary cases are given by the basic reproduction number = . from figure (b) restructuring the transmission tree, given that all the potential contacts made by primary cases with the probability of each possible contact resulted in a secondary transmission, is / . this type of transmission tree represents who infected whom which is unobservable in nature unless rigorous contact tracing is implemented [ , ] . the numerator of the right hand side of ( ) represents the total number of effective contacts made by a possible primary case in day/weeks which have an equal probability of resulting in the secondary transmission; that is, the probability that a secondary case is linked to an effective contact made by a single primary case at time is given by / . effective contacts lead to potential secondary cases with equal chance of getting the infection from the primary cases at time . it has been seen that every contact does not lead to successful transmission of infection; that is, the effective contacts are uncertain which is defined as the contact that is sufficient to lead to the transmission of infection between infectious and susceptible population. the total number of effective contacts made by a potential primary case at time is the sum of the product of incidence cases and generation time distribution during the generation interval of length . this indicates a simple binomial law of uncertainty in effective contacts [ ] . total number of effective contacts become = ∑ = − , during the th day, that is, ∼ bin( , / ), ∀ = , , . . . , , where / is the probability of effective contacts. let denote incidence or new cases at calendar time and denotes generation time distribution at time-sinceinfection . then the probability mass function of effective contacts becomes the likelihood function of / is as follows: here, bayesian inferential approach is used to estimate parameter which provides us with different but related estimate by combining prior belief and the evidence observed. as more evidence is gathered the prior distribution is modified into the posterior distribution that represents the uncertainty over the parameter values. posterior distribution is derived from the bayes formula [ ] where ∫ ⋅ Θ ( / ) ( ) is a normalization constant, indicated data, is the unknown quantity, ( ) is the prior distribution, ( / ) is the likelihood function, and posterior distribution ( / ) completely describes the uncertainty. there are two key advantages of bayesian theory: (i) once the uncertainty in the posterior distribution is expressed via probability distribution then the statistical inference can be automated and (ii) available prior information is reasonably incorporated into the statistical model. now, the posterior estimate of parameter is derived using its prior information, where likelihood function follows binomial distribution with conjugate prior as beta distribution of first kind [ ] . that is, / ∼ beta( , ), with realistic choice of parameters ( , ): now posterior distribution of / is proportional to the likelihood times prior. therefore, we are interested in estimating with its % credible interval (cri) which has been derived by considering the sampling transformation of / through simulation from the above posterior distribution with different choices of priors for beta distribution. theoretically, it is hard to find the posterior distribution of where / is a beta variable. through simulation we have generated samples from beta posterior distribution and also estimated % cri. we have considered beta distribution with several combinations of mean (ranges from . to . ) and accordingly we chose different values of ( , ). the second and fourth column of table represent our estimates of which are posterior means along with % cri. figure displays the posterior distribution of with different prior choices. generation time is another most important characteristic in infectious disease epidemiology, since indicates only the average number of secondary infections one primary infection produces in one disease generation. when we consider disease transmission in real time scale such as days or weeks, it matters a lot how long one disease generation lasts. generation time is the average time taken for secondary infections produced by a primary infection [ ] . generation interval or generation time distribution is assumed to be known as weibull distribution which is a biologically plausible choice [ , [ ] [ ] [ ] with a mean of . and . days and a standard deviation (sd) of . and . days for = and days [ , ] (tables s and s computational and mathematical methods in medicine all the sensitivity analysis was done by using matlab (supplementary material, algorithm). sensitivity analysis is a statistical technique which provides insight into how uncertainty in input variables affects the model outputs and which input variable tends to derive variation in the outputs [ ] . we performed sensitivity analysis to quantify the effect of changes on . it has been used to determine how sensitive an estimate of the parameter is. it is usually performed as series of tests in which one can use different set of hyperparameter values to see the change in the estimate. our analysis is based on the pandemic influenza a/h n in india through the bayesian estimates of basic reproduction number; we used the daily reported cases to calculate effective contacts. we have calculated posterior distribution of using prior as beta distribution with different values of parameter choices. from figure we have seen that as prior choice changes the shape of the posterior distribution also changes. the estimates of for the h n influenza pandemic were mainly reported based on the data obtained in the first few months of pandemic or based on whole first wave data. most of these estimates ranges from . to [ ] [ ] [ ] [ ] [ ] [ ] . our estimated value of the basic reproduction number indicates the milder intensity of disease transmission in india. interestingly, this estimated with % credible interval is consistent with several other studies on the same strain [ ] , along with many european countries [ ] . notably, it has a smaller credible length which is more reliable estimate; see table . statistical inference of is based on incidence (reported cases) and known generation time distribution. some differences among these estimates are due to the choice of generation time distribution because estimation relies much on the assumptions of the generation time distribution [ ] . in general, shorter mean generation time may lead to smaller estimates. since, the estimate of crucially depends on generation time distribution. from table , we conclude that generation time or infectiousness of an individual affects the basic reproduction number. this method does not require exponential growth assumption. still our estimate is greater than one so one has to make effort in controlling the disease through control strategies, which are typically targeted to bring this number below one and maintain it, as this will lead to eventual extinction of the epidemic. limitations. this method is applied only for initial stage of the epidemic (exponential phase) when there is no intervention like quarantine, isolation vaccination, and so forth. if basic reproduction number is < , then the probability / terminates because it exceeds the law of probability. pandemic influenza: a h n clinical management protocol and infection control, guidelines pandemic h n 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reproductive numbers quantifying the transmission potential of pandemic influenza a note on generation times in epidemic models different epidemic curves for severe acute respiratory syndrome reveal similar impacts of control measures the construction and analysis of epidemic trees with reference to the uk foot-and-mouth outbreak correcting the actual reproduction number: a simple method to estimate r from early epidemic growth data monte carlo statistical methods, springer texts in statistics bayesian statistics, academic class notes epidemiology, transmission dynamics and control of sars: the - epidemic a likelihood based method for real time estimation of the serial interval and reproductive number of an epidemic the transmissibility of highly pathogenic avian influenza in commercial poultry in industrialised countries estimation of the serial interval of influenza household transmission of pandemic influenza a (h n ) virus in the united states st rategies for containing an emerging influenza pandemic in southeast asia uncertainty and sensitivity analysis of the basic reproduction number of a vaccinated epidemic model of influenza the transmissibility and control of pandemic influenza a (h n ) virus the early transmission dynamics of h n pdm influenza in the united kingdom initial human transmission dynamics of the pandemic (h n ) virus in north america vaccination against pandemic influenza a/h n v in england: a real-time economic evaluation the infection attack rate and severity of pandemic h n influenza in hong kong bayesian modeling to unmask and predict influenza a/h n pdm dynamics in london time variations in the transmissibility of pandemic influenza in prussia the authors thank the university grants commission (ugc) through research fellowship in science for meritorious students (rfsms) and dst (science & engineering research board) project (no. sr/s /ms: / ) new delhi, india, for research funding support. they are thankful to sheikh taslim ali for his motivation and suggestions. the authors declare that there is no conflict of interests regarding the publication of this paper. key: cord- - dsx pey authors: maitra, arindam; sarkar, mamta chawla; raheja, harsha; biswas, nidhan k; chakraborti, sohini; singh, animesh kumar; ghosh, shekhar; sarkar, sumanta; patra, subrata; mondal, rajiv kumar; ghosh, trinath; chatterjee, ananya; banu, hasina; majumdar, agniva; chinnaswamy, sreedhar; srinivasan, narayanaswamy; dutta, shanta; das, saumitra title: mutations in sars-cov- viral rna identified in eastern india: possible implications for the ongoing outbreak in india and impact on viral structure and host susceptibility date: - - journal: j biosci doi: . /s - - - sha: doc_id: cord_uid: dsx pey direct massively parallel sequencing of sars-cov- genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in eastern india. seven of the isolates belonged to the a a clade, while one belonged to the b clade. specific mutations, characteristic of the a a clade, were also detected, which included the p l in rna-dependent rna polymerase and d g in the spike glycoprotein. further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. g v in spike (s) protein, r k, and g r in the nucleocapsid (n) protein. the n protein mutations reside in the sr-rich region involved in viral capsid formation and the s protein mutation is in the s( ) domain, which is involved in triggering viral fusion with the host cell membrane. interesting correlation was observed between these mutations and travel or contact history of covid- positive cases. consequent alterations of mirna binding and structure were also predicted for these mutations. more importantly, the possible implications of mutation d g (in s(d) domain) and g v (in s( ) subunit) on the structural stability of s protein have also been discussed. results report for the first time a bird’s eye view on the accumulation of mutations in sars-cov- genome in eastern india. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. sars-cov- is the causative agent of current pandemic of novel coronavirus disease which has infected millions of people and is responsible for more than , deaths worldwide in a span of just months. the virus has a positive sense, singlestranded rna genome, which is around kb in length. the genome codes for four structural and multiple non-structural proteins (astuti and ysrafil ) . while the structural proteins form capsid and envelope of the virus, non-structural proteins are involved in various steps of viral life cycle such as replication, translation, packaging and release (lai and cavanagh ) . although at a slower rate, mutations are emerging in the sars-cov- genome which might modulate viral transmission, replication efficiency and virulence in different regions of the world (jia et al. ; pachetti et al. ) . the genome sequence data has revealed that sars-cov- is a member of the genus betacoronavirus and belongs to the subgenus sarbecovirus that includes sars-cov while mers-cov belongs to a separate subgenus, merbecovirus (lu et al. ; wu et al. ; zhu et al. ) . sars-cov- is approximately % similar to sars cov at the nucleotide sequence level. epidemiological data suggests that sars-cov- had spread widely from the city of wuhan in china (chinazzi et al. ) after its zoonotic transmission originating from bats via the malayan pangolins . global sequence and epidemiological data reveals that since its emergence, sars-cov- has spread rapidly to all parts of the globe, facilitated by its ability to use the human ace receptor for cellular entry (hoffmann et al. ) . the accumulating mutations in the sars-cov- genome have resulted in the evolution of clades out of which the ancestral clade o originated in wuhan. since the first report of sequence of sars-cov- from india, there have been multiple sequence submissions in global initiative on sharing all influenza data (gisaid, https://www.gisaid.org/). extensive sequencing of the viral genome from different regions in india is required urgently. this will provide information on the prevalence of various viral clades and any regional differences therein, which might lead to improved understanding of the transmission patterns, tracking of the outbreak and formulation of effective containment measures. the mutation data might provide important clues for development of efficient vaccines, antiviral drugs and diagnostic assays. we have initiated a study on sequencing of sars-cov- genome from swab samples obtained from infected individuals from different regions of west bengal in eastern india and report here the first nine sequences and the results of analysis of the sequence data with respect to other sequences reported from the country until date. we have detected unique mutations in the rna-dependent rna polymerase (rdrp), spike (s) and nucleocapsid (n) coding viral genes. it appears that the mutation in nucleocapsid gene might lead to alterations in local structure of the n protein. also the putative sites of mirna binding could be affected, which might have major consequences. the possible implications of the mutations have been discussed, which will provide important insights for functional validation to understand the molecular basis of differential disease severity. the regional virus research & diagnostic laboratory (vrdl) in indian council of medical research-national institute of cholera and enteric diseases (icmr-niced) is a government-designated laboratory for providing laboratory diagnosis for sars-cov- (covid ) in eastern india. nasopharyngeal and oropharyngeal swabs in viral transport media (vtm) (himedia labs, india) collected from suspect cases with acute respiratory symptoms/travel history to affected countries or contacts of the covid- confirmed cases were referred to the laboratory for diagnosis. the test reports were provided to the health authorities for initiating treatment and quarantine measures. residual deidentified positive samples for sars-cov- were used for rna isolation and sequencing in accordance with ethics guidelines of govt. of india. extraction of viral rna from the clinical sample ( ll) was performed using the qiaamp viral rna mini kit as per manufacturer's protocol (qiagen, germany). the extracted rna was tested for sars-cov- (covid- ) by real time reverse transcription pcr (qrt-pcr) (abi , applied biosystems, usa) using the protocol provided by niv-pune, india (https://www.icmr.gov.in/pdf/covid/labs/ _sop_for_first_ line_screening_assay_for_ _ncov.pdf; https://www. icmr.gov.in/pdf/covid/labs/ _sop_for_confirmatory_ assay_for_ _ncov.pdf). briefly, first line screening was done for envelope e gene and rnase p (internal control). clinical samples positive for e gene (ct b . ) were subjected to confirmatory test with primers specific for rdrp and hku orf (hku-orf -nsp ). positive control and no template control were run for all genes. a specimen was considered confirmed positive for sars-cov- if reaction growth curves crossed the threshold line within cycles (ct cut off b . ) for e gene, and both rdrp, orf or either rdrp or orf. rna isolated from nasopharyngeal and oropharyngeal swabs were depleted of ribosomal rna using ribo-zero rrna removal kit (illumina, usa). the residual rna was then converted to double stranded cdna and sequencing libraries prepared using truseq stranded total rna library preparation kit (illumina inc, usa) according to the manufacturer's instructions. the sequencing libraries were checked using high sensitivity d screentape in tapestation system (agilent technologies, usa) and quantified by real time pcr using library quantitation kit (kapa biosystems, usa). the libraries were sequenced using miseq reagent kit v in miseq system (illumina inc, usa) to generate x bp paired end sequencing reads. for viral genome amplification in samples which did not generate sufficient viral reads, the rna samples were converted to double stranded cdna and amplified using qiaseq sars-cov- primer panel (qiagen gmbh, germany) according to the manufacturer's instructions. the multiplexed amplicon pools were then converted to sequencing libraries by enzymatic fragmentation, end repair and ligation to adapters. the sequencing libraries were checked and quantified as above and sequenced using miseq reagent kit v nano in miseq system (illumina inc, usa) to generate x bp paired end sequencing reads. the sequencing reads obtained in shotgun rna-seq experiment were mapped to reference viral sequence, variants detected and consensus sequence for each sample built using dragen rna pathogen detection software (version ) in basespace (illumina inc, usa). for amplified whole genome sequencing, the viral sequences were assembled using clc genomics workbench v . . (qiagen gmbh, germany). in both cases, the severe acute respiratory syndrome coronavirus isolate wuhan-hu- as reference genome (accession nc_ . ) was used as the reference sequence. each variant call generated in either pipeline was manually verified in integrated genome viewer igv v . . (jt robinson et al. ) . clustal omega was used to display the mutations in the context of the sequence alignments. bioedit software (v . ) was used to extract the cds from consensus sequence and to check codon usage. nucleotide to amino acid conversion was done in emboss transeq online tool (f madeira et al. ). to generate the clustering patterns of the viral sequences from west bengal, a subset of representative virus sequence data (n = ) were downloaded from gisaid global database (supplementary table ). only high coverage data (where the entries have less than % n's and less than . % amino acid mutations), complete genome (entries with base pair greater than , ) and excluding low coverage entries (entries having more than % n's) were used in the analysis. all of the sequences were aligned using mafft (multiple alignment using fast fourier transform). we used the nextstrain pipeline to process the sequence data. nextstrain with the augur pipeline was used to build phylogenetic tree based on the iqtree method, which is a fast and effective stochastic algorithm to infer phylogenetic trees by maximum likelihood. the tree building process involves the use of these subtypes 'wuhan-hu- / ', 'wuhan/wh / ' to generate the root of the tree. the tree is refined using raxml (randomized axelerated maximum likelihood). a web-based visualization program, auspice was then used to present and interact with phylogenetic and phylogeographic data. we investigated the potential mirna binding site in the region coding for n protein, found to be mutated in our samples. starmir (http://sfold.wadsworth.org/cgibin/starmirtest .pl) software was used for this purpose. the whole human mature mirna library was obtained from mirbase database. the sequence in query was taken nt upstream and nt downstream from the site of mutation. the mirnas which bind to the mutation site through seed sequence were shortlisted. the change in bases can prevent certain mirna binding and support the binding of others. therefore, mirna binding was checked for both, original and mutated site. we checked the levels of mirnas in the cancer conditions around the upper respiratory tract in the dbdemc database (https://www.picb.ac.cn/ dbdemc/). the tissueatlas database (https://ccbweb.cs.uni-saarland.de/tissueatlas/) was used to analyse the presence and correlation of mirnas in body fluids. all patients were diagnosed positive for sars-cov- rna by real time pcr as described above. five of the patients suffered from fever, while seven patients exhibited some symptoms of infection like sore throat, cough with sputum, running nose or breathlessness. one patient suffered from acute respiratory distress syndrome (ards). two patients did not exhibit any symptom (table ) . five individuals had contact with covid- patients in particular; both s and s had contact with the same patient (table ). one individual had history of international travel while another had history of domestic travel. the shotgun rna-seq data resulted in high coverage (greater than x median depth of coverage) of complete genome sequences of the sars-cov- in five samples (s , s , s , s and s ) in which greater than % of the viral genome was covered at greater than x and greater than % of the viral genome was covered at greater than x. a negative correlation was found between viral load (represented by the threshold cycle or ct value of the rna samples in the real time pcr based diagnostic assay) and the number of reads mapped to the viral genome in the rna-seq library. even with samples, the pearson correlation coefficient was found to be - . (p value = . ) (table ). in particular, it was observed that samples with ct values greater than mostly resulted in generation of low counts of viral sequence reads leading to less than x median depth of coverage of the viral genome. in the remaining four samples (s , s , s and s ), the median depth of coverage was less than x and hence the viral genome sequencing was achieved after amplification of the viral genome by a multiplex pcr approach. all the nine sequences have been submitted in the global initiative on sharing all influenza data (gisaid) database. phylogenetic tree analysis of the sequences, along with other complete viral genome sequences submitted from india in gisaid, revealed that seven of these sequences belonged to the a a clade while only one sequence belonged to clade b (figure and table ). we were unable to classify one of the nine sequences, s , into any clade due to low sequence coverage. to understand transmission histories of these nine sars-cov- isolates from west bengal, we aligned these sequences with more than global sequences, including thirty sequences submitted in gisaid from india (at the time of our analysis) to identify specific mutations that occur at the highest level of the tip in a branch leading to the specific subtype. the predicted origin of the transmitted subtype in each case was identified with - % confidence from the branch in which our samples were located in the phylogenetic tree (table ) . the list of mutations detected in the sequences from nine samples are provided (table ) . seven sequences harboured the important signature mutations of a a clade. these consisted of the c/t mutation resulting in a change of p l in the rdrp and the a/g mutation resulting in a change of d g in the spike glycoprotein of the virus. in addition to these, g/t mutation in the gene coding for spike glycoprotein (g v) and triple base mutations of - ggg/aac in the gene coding for nucleocapsid resulting in two consecutive amino acid changes r k and g r were detected in s , s and s , s , s respectively. while the g/t s gene mutation was unique to these samples and could not be found in any other sequence from india or the rest of the world, the nucleocapsid mutations could be detected in only three other sequences from india (figure ). out of these, two sequences were obtained from individuals with contact history of a covid- patient who had travelled from italy. interestingly, two out of three sequences harbouring these mutations obtained by us belonged to kolkata and with contact history with one covid- patient who had travelled from london (uk). the third sequence was obtained from a covid- patient from darjeeling, india who had history of travel from chennai, india. these mutations have been found in % of sars-cov- sequences reported world-wide from countries like uk, netherlands, iceland, belgium, portugal, usa, australia, brazil, etc. rdrp (nsp ) gene of the sars-cov- codes for the rna-dependent rna polymerase and is vital for the replication machinery of the virus. we detected a total of six mutations in this gene in the nine samples, out of which four were nonsynonymous, including the a a clade specific c/t (rdrp: p l) mutation. two individuals, s and s , harboured viral genome sequences that shared a unique c/t (a v) mutation which was not found in any other sequence reported from india or rest of the world. one individual s , whose viral sequence belonged to b clade, harboured mutations in rdrp, which appear to be clade specific, out of which were nonsynonymous. to study the functional relevance of the mutations, we investigated the alteration in mirna binding in the nucleocapsid coding region, predicted to be caused by the - ggg/aac mutations. we found seven mirnas which bind to the original sequence and three which bind the mutated sequence exclusively (table and figure ). the number of bases in the sequence (ggg/aac) which bind the seed sequence of mirna were also identified. the strength of mirna prediction is reflected by the dg value mentioned in the figure . mutant base s s s s s s s s s lesser the value, stronger is the binding. the values are comparable to some of the experimentally validated mirna bindings like mir binding to hcv rna has dg value of - . kcal/mol for s binding site and - . kcal/mol for s binding site (data not shown). the values of dg obtained for the mirnas binding to n protein coding region are comparable to these values, suggesting their relevance in the in vivo conditions. we checked the levels of these mirnas in cancer conditions around the upper respiratory tract in the only two samples from west bengal (s and s ) harbour this mutation. (d) c/t, c/a and t/c mutations in the rdrp gene in clustal omega. only one sample from west bengal (s ) harbour these mutations. dbdemc database. we found that mir- - - p and mir- - p were downregulated in most of the cancers. mir- - - p was found to be upregulated in esophageal cancer (esca), head and neck cancer (hnsc), lung cancer (luca) and downregulated in nasopharyngeal cancer (nsca) (supplementary figure ). assuming that the binding of mirnas would inhibit the viral replication/stability, higher abundance of that mirna would be protective against infection and lower abundance would increase the susceptibility towards infection. to comprehend the results, we have found that if a patient suffering from esca, hnsc, luca is infected with the original virus containing ggg sequence, the upregulated mir- - - p would be protective against the infection. but, if the same patient is infected with the mutated virus containing aac sequence, mir- - - p will not be functional anymore and mir- - p which targets the mutated site is also downregulated. this could make the patients suffering from described cancers, highly susceptible to infection with the mutant virus. we also checked if these mirnas are associated with other disease conditions and found that mir- - p is down regulated in type diabetes mellitus (t dm) and hence could serve as one of factors for increased susceptibility of t dm patients for the mutated viral subtype and increase the risk of comorbidity (huang et al. ) . another mir- - p, targeting original subtype, is reported to be higher in asthma patients (fang et al. ) . this could be one of the factors limiting the original viral propagation, but the loss of its targeting site in mutated viral subtype could increase the host susceptibility towards viral infection. we further checked if there are some other conditions that could alter the availability of these mirnas at the site of infection. therefore, we used the tis-sueatlas database to analyse the presence and correlation of these mirnas in body fluids. we found that there is differential expression of certain mirnas in the saliva of patients suffering from pancreatic cancer. mir- b- p, mir- - p and mir- - p were found to be upregulated in the saliva of pancreatic cancer patients which could provide similar protective/susceptible effect as mentioned of mirnas before (supplementary figure ) . mirnas have been known to affect viral replication and stability by binding to protein coding regions of the genome of h n , ev , cvb and many more viruses (bruscella et al. ; trobaugh and klimstra ) . in most of the cases, binding of mirnas leads to translational repression of the targeted protein and hence directly affects viral rna replication. targeting by mirnas could decrease the levels of n protein, which is involved in various steps of viral life cycle including replication, translation and coating of viral rna to form the nucleocapsid. hence, altered levels of the shortlisted mirna could regulate various viral processes and severity of sars-cov- infection. the effect of mirnas would be opposite if they assist in viral replication/stability, but that needs to be experimentally confirmed and still holds the importance of mirnas targeting the original and mutated sites. we analysed the - ggg/aac mutations in the nucleocapsid gene which results in contiguous amino acid changes of r k and g r for their potential role in alteration of structure of the encoded protein. the sites of these mutations at position are located in the sr-rich region which is known to be intrinsically disordered (chang et al. ). in addition, this region is known to encompass a few phosphorylation hsa-mir- - p hsa-mir- - p hsa-mir- - p hsa-mir- - p hsa-mir- - p hsa-mir- hsa-mir- - - p hsa-mir- - p hsa-mir- b- p hsa-mir- - - p sites (surjit et al. ) , notably the gsk phosphorylation site at ser and a cdk phosphorylation site at ser which are in close proximity to these mutations. the sequence motifs and are entirely consistent with gsk and cdk phosphorylation motifs, respectively. when ser is phosphorylated which incorporates a large negative group tethered to the sidechain of ser, as seen in many other substrates of kinases, it is likely that charge neutralization takes place involving positively charged sidechains in the sequential and spatial vicinity. arg is a part of gsk phosphorylation motif and its sidechain could potentially contribute to charge neutralization at p-ser . given the sequential, and therefore spatial proximity of arg to p-ser the sidechain of arg could potentially be involved in interaction also with phosphate group at position . this interaction would contribute to reduction of conformational entropy. similarly, arg , a part of cdk phosphorylation motif, would contribute to charge neutralization at p-ser . arg and gly are mutated to lys and arg respectively (figure ). spike protein (s) of coronaviruses is a class i viral fusion protein which is synthesized as a single chain precursor that trimerizes upon folding. it is composed of two subunits: s (in the amino terminal) containing the receptor binding domain (rbd) and s (in the carboxy terminal) that drives membrane fusion ( in all the three structure, d lies in a loop at the interface between any two out of the three protomers. the co-ordinates for the d side-chain in chain a and c of vyb are available only up to c b -atom and the orientation of these atoms are similar to that observed in the respective atoms of d in vxx. the co-ordinates of all the side-chain atoms of d in chain b of vyb are available and they are similar to that observed in chain b of vxx. the side-chain of d in all the protomers of vxx and chain b of vyb point outward from the core of the protein toward the solvent. the side-chain orientation of d in all the three chains of vsb is different from the former two structures. this differential orientation of d side-chain in vsb facilitates formation of hydrogen bond between d (present in s subunit) and t (present in s subunit) from the neighbouring chain in two out of the three interfaces found in vsb ( figure ). taken together, these facts suggest that d is highly flexible and support the wobbly nature of the inter-protomeric hydrogen bond observed between d and t . contribution of this transient hydrogen bond toward stability of the pre-fusion state cannot be negated. interestingly, s protein of mouse coronavirus (mhv-a ) which has a similar structural topology as that of the sars-cov- s protein but shares a low overall sequence identity (* %), has a conservative substitution at the position equivalent to d of the latter. the asn (n ) of mouse coronavirus (mhv-a ) is replaced with asp (d ) in sars-cov- ( figure and figure ) . in earlier literature, n has been suggested to offer inter-protomeric interactions that contribute toward maintenance of the s fusion machinery in its metastable state (ac walls et al. ) . given the conservation of asp at this position in closely related coronaviruses (bat coronaviruses: btcov-ratg and btcov-hku ; sars-cov) and its conservative substitution in mouse coronavirus (mhv-a ), it is likely that d is important for structural stability of s protein. as gly lacks a side-chain, the transient hydrogen bond as observed in the wild-type s protein would be lost in the variant with d g mutation. this can potentially compromise on the structural stability of pre-fusion state of s protein possibly interfering with conformational transitions. moreover, replacement of asp with gly at this position would come with higher conformational freedom at the backbone (c ramakrishnan and gn ramachandran ) of the polypeptide resulting in enhancement of local conformational entropy. the gly at this position is solvent exposed and is present at the tip of the c-terminal end of a b-strand. this position is proximal to the region where the s protein attaches itself to the viral membrane (figure ). it is to be noted that the gly at this position is conserved among the closely related coronaviruses (bat coronavirus ratg and hku , sars-cov) hinting toward its possible role in maintenance of structure and function of the s protein (figure ). in general, as explained above, gly backbone has higher conformational freedom than any other amino acid residues (ramakrishnan and ramachandran ) . therefore, figure . conformation of d in three structures ( vxx, vyb, vsb). (a), (b), (c) overlay of d ( vxx: yellow carbon; vyb: white carbon; vsb: dark pink carbon) from chain a, b and c of the three structures, respectively. to maintain visual clarity, only the backbone of respective chain of vxx is shown in cartoon representation. (d), (e), (f) orientation of d (green carbon) from chain a (purple cartoon) and t (dark blue carbon) from chain b (teal cartoon) in vxx, vyb and vsb, respectively. hydrogen bond is depicted as black dashed line. (g), (h), (i) orientation of d (green carbon) from chain c (orange cartoon) and t (dark blue carbon) from chain a (purple cartoon) in vxx, vyb and vsb, respectively. hydrogen bond is depicted as black dashed line. the side-chain co-ordinates for d in chain a and c of vyb are unavailable. protein rendering has been done using pymol (schrödinger, llc). substitution of gly with val would impart rigidity to the local region. the possible implication of such rigidity on the association of s protein with viral membrane could be understood from a structure of s protein in association with the viral membrane. however, such a structure is currently unavailable. substantial uncertainties surround the trajectory of the recent epidemic of covid- in india. it is extremely important to track the outbreak by analysing the phylogenetic relationships between different sars-cov- genomes prevalent in india and compare them with genomes reported from rest of the world. the errorprone replication process of all rna viruses in general, results in introduction of mutations in their genomes which behave as a molecular clock that can provide insights into the emergence and evolution of the virus. the data till date suggests that sars-cov- emerged not long before the first cases of pneumonia in wuhan occurred . in this study, direct massively parallel sequencing of the viral genome was undertaken on nasopharyngeal and oropharyngeal swab samples collected from infected individuals from different districts of west bengal. we have analysed the first nine sequences in this report. recent analysis of sars-cov- sequences from all over the globe has revealed that the outbreaks have been initially triggered in most countries by the original strain from wuhan, clade o, which thereafter have diversified into multiple clades (yadav et al. ; biswas and majumder ) . temporal sweeps leading to replacement of the ancestral o and other clades by a a, have been detected. until our report, initial sequences from samples obtained from individuals with travel history to china, reported genetic similarity to the clade o, which was obtained at the beginning of the outbreak in wuhan, china. rest of the sequences reported from india mostly belonged to either clade a ( %) or a a ( %) (supplementary table ), with evidence of the temporal sweep where the a a is emerging as the predominant clade (biswas and majumder ) . the a a clade is characterized by the signature nonsynonymous mutations leading to amino acid changes of p l in the rdrp which is involved in replication of the viral genome and the change of d g in the spike glycoprotein which is essential for the entry of the virus in the host cell by binding to the ace receptor. notably, the d g mutation is close to the furin recognition site for cleavage of the spike protein, which plays an important role in virus entry. whether both these mutations have resulted in the evolution of a more transmissible viral subtype i.e. the a a clade, is yet to be verified by in vitro and in silico analyses. interestingly, we also found that one of viral sequences in our study belonged to the b clade, which originated in china (gonzalez-reiche et al. ). b clade sequences have not been reported from india earlier and are only less than % of sequences reported worldwide. probably, the individual s was transmitted this subtype by contact with others who had travel history to china although this information was not available in the patient clinical history. emergence of viral subclones in an outbreak can affect the transmission patterns and disease severity, which are immensely important for public health (harvala et al. ; jones et al. ) . given the large size of the infected population in india, with the possibility of regional differences in the population and host-related factors, this can have the potential to affect the course of the outbreak. population surveillance is essential for early detection of emergence of such subclones. we analysed the mutations detected in each sequence that we generated and found preliminary evidence of this. we found that three individuals of this study, viz. s , s and s , shared rare set of three contiguous mutations in their genome which resulted in the consecutive alterations of r k and g r. these mutations were also found to be shared with other sequences reported from western india. interestingly, while two out the three sequences harbouring these mutations were from individuals who shared contact history with a covid- patient with history of travel from italy, two out of the three samples from west bengal shared contact history with the same covid- patient with history of travel from uk. the third individual whose sample harboured these mutations, viz. s , was found to have history of travel from chennai, india, but the possibility of the patient having contact in transit with an individual with international travel history cannot be excluded. additionally, origin of the viral subtypes infecting s and s has also been predicted by phylogenetic analysis to be europe (uk). s had been infected in delhi, india where he had contact with an infected individual who travelled from europe. one of the individuals s , harboured a viral subtype which is predicted to have been transmitted in china. s and s , who shared an identical sequence of the virus, also harboured one unique mutation resulting in the amino acid alteration of g v in the spike protein. this correlates with the fact that these two individuals had also been known to have contact with the same covid- patient. viral rna sequences obtained from two samples s and s shared all mutations except a v l mutation at orf harboured by s and not by s . interestingly, both these individuals belonged to the same district of east medinipur, had history of contact with covid- patients and did not exhibit any clinical symptom. thus our findings indicate that the viral subtypes transmitted in the eastern region of india, in particular west bengal, have mostly originated from europe and also china. sequencing of large number of samples are being presently undertaken to confirm and elaborate these initial findings. rdrp is essential for replication of viral rna genome and hence this gene is expected to be conserved. interestingly, we detected multiple mutations in this gene, the majority of which were non synonymous and hence result in alteration of protein sequence. in particular, the p l was present in all a a sequences in our samples. this mutation is located adjacent to a hydrophobic cleft in rdrp which is a promising target for potential drugs (pachetti et al. ) . sequences from two samples, s and s , shared a unique rdrp mutation at a v which has not been detected until date in rest of the sequences submitted from india or worldwide. as observed earlier, these two samples harbour viral subtypes whose genomes are strikingly similar. sequence obtained from one of the samples s , which belonged to the clade b , did not possess the p l mutation. instead, it harboured three different mutations resulting in two non-synonymous changes of h y, p t and a synonymous mutation which were not found in any other sequences reported from india until date and are specific for the b clade. it remains to be seen whether these amino acid alterations result in substantial changes in structure or function of rdrp, resulting in emergence of drug resistant subtypes or enhancement in mutation rate in the viral genome. we investigated the potential of the mutations detected in the nucleocapsid region to effect alterations in the viral and host processes. we found that this mutation results in considerable alterations in the predicted binding of mirnas, which might play a role in the establishment and progress of infection in the patient. we also found that some of the mirnas which are predicted to bind to the mutated subtype might be downregulated in multiple cancer types. this raises the possibility that cancer patients might have higher susceptibility to the mutated sub-clone due to the reduced ability to contain the virus in vivo, compared to infection by the original virus of the same clade. the leads obtained from this study need to be pursued to develop mirna based novel therapeutic approaches. we also analysed the predicted structural alterations in the viral nucleocapsid protein, which might be caused by consecutive alterations of r k and g r. as a result of these mutations, we have two strong positively charged residues in close sequential positions as opposed to only one positively charged residue in the other genotype. given the structural vicinity of p-ser and p-ser and the long sidechains of lys and arg with high positive charge and significant side-chain conformational freedom in this genotype, both these residues potentially could contribute to charge neutralization of the phosphorylated serine residues. this contributes to further reduction of conformational entropy compared to the other genotype. while lys is likely to offer electrostatic interactions to p-ser , arg (with a greater number of positively charged centres as compared to lys) could potentially simultaneously interact with the phosphate groups at both p-ser and p-ser . together, these two positively charged residues (lys and arg ) have the potential to offer additional interactions to the phosphorylated serine residues at and positions as opposed to only one of them (arg ) in the other genotype. consequently, one can expect a significant difference in conformational entropy as well as in the inter-residue interaction structural network between the two genotypes especially when ser and ser are phosphorylated. further, gly at position in one of the genotypes would confer significantly higher conformational freedom at the backbone (ramakrishnan and ramachandran ) of the polypeptide chain compared to arg in the equivalent position in the other genotype. this mutation adds another dimension to the likely structural differences in this local region of the two genotypes. subsequently, phosphorylation-mediated functional events might be different in the two genotypes (surjit and lal ; surjit et al. ). these proposed differences in the inter-residue structural network between the two genotypes are depicted schematically in figure . admittedly, the proposed network of interactions is fraught with uncertainty. however, given two positively charged residues in one genotype compared to only one in the other genotype, the charge neutralization structural interaction networks involving p-ser and p-ser has to be certainly different going by the highly established literature on kinase substrates (kitchen et al. ; krupa et al. ) . interestingly, the mutations d g (in s d domain) is supposed to confer flexibility in the s d domain and the mutation g v might impart partial rigidity in the conformation of s domain. obvious question is whether such structural alterations in local region would have any consequence in receptor binding affinity of spike protein. since the mutation resides in rbd domain-s subunit of spike protein, residue is not directly involved in the interaction with ace . but the mutation might have some effect on the positioning of the residues involved in interaction. now to address the concerns whether these mutations are expected to affect the sensitivity of the existing diagnostic kit, we have again explored the implications of the structural changes. most likely, the presence of mutation should not affect the rapid detection kits because these kits detect the presence of specific igg/igm antibody against viral n protein or viral s protein. the whole protein is coated for the test and therefore polyclonal antibodies would provide the result here. change in just one epitope might not affect the overall result. we have further checked if the mutation sites fall in immunodominant epitopes. this data is available for sars proteins and the sites where we have found mutation have been shown to be conserved in sars and sars-cov- . while the mutation site of n protein does not elicit much antibody response, region - of the s protein of sars has been shown to be a major immunodominant epitope in s protein (he et al. ) . change in this epitope by mutation could alter the sensitivity of the igg/igm tests conducted. also, there are certain diagnostic kits being designed to check the presence of viral antigen in the clinical sample. the abundance of antibodies targeting the mutation sites needs to be checked in those kits, to be more effective across the viral strains harbouring different mutations. we also detected interesting relationships between ct value of diagnostic assay as a surrogate of viral copy number and viral sequence reads obtained. we recommend that for future sequencing studies, the shotgun rna-seq approach should be used for high viral copy number represented by low ct values while for rest, a viral genome amplification method should be used. although the sample size of our preliminary report is small, follow up studies are underway to confirm these observations for understanding the impact of the same in the ongoing outbreak of covid- in india. we have not commented on the relationship of the viral sequence alterations with disease severity due to the limited sample size of this analysis. we hope to provide valuable information on this aspect based on the expanded number of samples being sequenced at present. our findings provide leads which might benefit outbreak tracking and development of therapeutic and prophylactic strategies to contain the infection. finally, we conclude that the initial sequences generated by us from first nine samples in west bengal in eastern india indicate a selective sweep of the a a clade of sars-cov- . however, the viral population is not homogenous and other clades like b also exist. we have also detected emergence of mutations in the important regions of the viral genome including spike, rdrp and nucleocapsid coding genes. some of these mutations are predicted to have impact on viral and host factors, which might affect transmission and disease severity. this preliminary evidence of emergence of multiple subclones of sars-cov- , which might have altered phenotypes, can have important consequences on the ongoing outbreak in india. during the ongoing covid- pandemic. we also acknowledge the assistance provided by dr. sillarine kurkalang (nibmg), mr. sumitava roy (nibmg) in reviewing the sequence data, ms. soumi sarkar (nibmg) for assistance in statistical analysis, and mr. anand bhushan and ms. meghna chowdhury for providing assistance in laboratory support and logistics. sd and ns would like to acknowledge support from j c bose fellowship. we also thank dbt-iisc partnership programme at iisc, bengaluru, and the national genomics core at nibmg. hr and sc would like to acknowledge support from csir-spm fellowship and dst-inspire fellowship, 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origin of sars-cov- associated with the covid- outbreak a novel coronavirus from patients with pneumonia in china we acknowledge the financial and overall support provided by the department of biotechnology, ministry of science and technology, india, and indian council of medical research and all laboratory staff of the niced-vrdl network for laboratory support key: cord- -ff j i i authors: siqueira, andré m; lacerda, marcus vg; magalhães, belisa m l; mourão, maria pg; melo, gisely c; alexandre, márcia aa; alecrim, maria gc; kochar, dhanpat; kochar, sanjay; kochar, abhishek; nayak, kailash; del portillo, hernando; guinovart, caterina; alonso, pedro; bassat, quique title: characterization of plasmodium vivax-associated admissions to reference hospitals in brazil and india date: - - journal: bmc med doi: . /s - - -y sha: doc_id: cord_uid: ff j i i background: the benign character formerly attributed to plasmodium vivax infection has been dismantled by the increasing number of reports of severe disease associated with infection with this parasite, prompting the need for more thorough and comprehensive characterization of the spectrum of resulting clinical complications. endemic areas exhibit wide variations regarding severe disease frequency. this study, conducted simultaneously in brazil and india, constitutes, to our knowledge, the first multisite study focused on clinical characterization of p. vivax severe disease. methods: patients admitted with p. vivax mono-infection at reference centers in manaus (amazon - brazil) and bikaner (rajasthan - india), where p. vivax predominates, were submitted to standard thorough clinical and laboratory evaluations in order to characterize clinical manifestations and identify concurrent co-morbidities. results: in total, patients ( . % above years old) were hospitalized at clinical discretion with pcr-confirmed p. vivax mono-infection ( in manaus and in bikaner), of which ( . %) presented at least one severity criterion as defined by the world health organization ( ). hyperlactatemia, respiratory distress, hypoglycemia, and disseminated intravascular coagulation were more frequent in manaus. noteworthy, pregnancy status was associated as a risk factor for severe disease (or = . ; % ci = . - . ; p = . ). the overall case fatality rate was . / , cases in manaus and . / , cases in bikaner, with all deaths occurring among patients fulfilling at least one severity criterion. within this subgroup, case fatality rates increased respectively to . % in manaus and . % in bikaner. conclusion: p. vivax-associated severity is not negligible, and although lethality observed for complicated cases was similar, the overall fatality rate was about -fold higher in india compared to brazil, highlighting the variability observed in different settings. our observations highlight that pregnant women and patients with co-morbidities need special attention when infected by this parasite due to higher risk of complications. electronic supplementary material: the online version of this article (doi: . /s - - -y) contains supplementary material, which is available to authorized users. malaria is a major public health problem in most tropical regions, and despite impressive reductions in the number of cases and deaths in the last decades, malaria resulted in an estimated million episodes and , deaths in [ ] . although the attention of the scientific community has focused in past decades on the burden and consequences of p. falciparum infections [ , ] , in recent years there has been a renewed interest in p. vivax-associated morbidity, as a result of the increasing report of its potential hazards to health [ ] [ ] [ ] [ ] . p. vivax is the most geographically widespread parasite causing malaria in humans, with over . billion individuals exposed to the risk of infection; it is the predominant species in latin america and some areas of the asian and pacific regions [ , ] . in a context of renewed and intensified commitment of the international community towards figure epidemiological profile of the two studied sites: p. vivax annual parasite index in brazil (a) and india (b) (reproduced from the malaria atlas project [ ] ); malaria transmission scenarios in the rainforest, manaus, brazil (c) and in the desert, bikaner, india (d); reference tertiary care center façades in manaus (e) and bikaner (f). malaria eradication [ , , ] , a surge of interest has emerged regarding this species, possibly because of the major challenges posed for its control, ensuing from its poorly understood ability to present clinical relapses [ , ] , but also due to its capacity to cause a more complicated disease [ ] [ ] [ ] . p. vivax benign clinical course has now been completely reconsidered, as the evidence of life-threatening disease has been reported from diverse endemic areas, such as latin america [ , , ] , india [ , ] , and southeast asia and the pacific regions [ , ] . in spite of the world health organization (who) recognition as early as of the potential of p. vivax to cause severe disease [ ] , there are still several gaps in knowledge to be filled [ , , , ] . the diverse range and rate of occurrence of clinical complications associated to p. vivax infection widely differ according to reports from different endemic regions, suggesting that many unaccounted factors, including those related to the parasite, the host, or the context in which the infection is produced may interact in causing the clinical presentation [ ] . indeed not all endemic areas have been reporting severity attributed to infection with this parasite, such as the thailand-myanmar border, where severity was reported only very recently [ ] . in the absence of adequate experimental models, or the paucity of postmortem samples to further elucidate the pathophysiology of this infection [ , , ] , systematic multisite clinical studies become a unique opportunity to better understand this geographic variability and characterize the severe vivax malaria syndrome. indeed, comprehensive reviews of the literature demonstrate that severe vivax malaria occurrence is an old, and not infrequent, phenomenon that was not being properly recognized [ , , ] . we have used a common protocol in order to prospectively follow vivax malaria patients admitted to two distinct reference centers located in brazil and india, aiming to comprehensively characterize and compare the clinical complications of p. vivax infection. the enrollment of cases was performed at two different reference tertiary hospitals located in brazil and india. fundação de medicina tropical dr heitor vieira dourado (fmt-hvd) is located in the city of manaus, in the brazilian western amazon, with beds for hospitalization. this hospital is the reference tropical medicine and infectious disease center for the area, and receives patients from all over the amazonas state, referred or not to this service. admission is free of charge, and admission criteria for malaria patients are any clinical complications suggestive of severe malaria, or complications impacting proper antimalarial treatment, such as severe vomiting. six other hospitals in town are the reference for pediatric diseases. anopheles darlingi is the major malaria vector in the region, with transmission occurring continuously throughout the year with peaks in the beginning of the dry and the wet season. in recent years there has been a decrease in the number of reported episodes paralleled to an increase in the proportion of cases attributed to p. vivax, which is now responsible for more than % of cases of malaria in the region [ ] . sardar patel medical college (spmc) hospital is located in bikaner in the rajasthan state of india, where, as a result of environmental and climatic reasons, malaria transmission has a well-defined seasonal pattern with practically no cases being reported during the dry season, and p. vivax is responsible for % of the cases [ ] . an. stephensi, an. culifascies, and an. annularis are the major malaria vectors in the region ( figure ). the hospital includes around beds for hospitalization in general, and a specific malaria ward, which remains closed except for the duration of the malaria season. the hospital receives referrals from the entire rajasthan state, although other hospitals (including private ones) are also available for patients in the area. admission is free with the exception of certain subsidized procedures, and during the malaria season most of the patients are routinely admitted to this ward, often because they are being referred. neither of the two hospitals is a specifically pediatric referral center, although pediatric patients may be admitted in both. this was a hospital-based study of patients admitted with vivax malaria at the two study centers, regional references mostly for the adult population. enrollment in manaus occurred in two distinct periods (between april and march , and between january and december ), while in bikaner patients were recruited between august and october . all initial microscopy-confirmed p. vivax infections (or patients with negative thick blood smears (tbss) but with history of previous recent diagnosis in use of antimalarials) requiring admission, at clinician's discretion (for example, for the presence of jaundice, thrombocytopenia, bleeding, vomiting, diarrhea, abdominal pain, non-lithiasic cholecystitis, spleen rupture, or overall compromised clinical status), regardless of age, were eligible for enrollment provided patients or their legal representatives signed an informed consent. all enrolled patients were hospitalized in separate wards designed for clinical research and were followed and evaluated daily until discharge, when the final outcome of each case was registered after consensual discussion performed by the clinical team involved in the study. the same protocol for clinical and laboratory investigations was applied at both sites, including standard operating procedures (sops) and questionnaires. the study procedures were standardized and supervised by coinvestigators from both sites and supervised by study monitors from isglobal (authors qb and cg) to minimize potential discrepancies in their application. at enrollment all patients underwent an initial comprehensive clinical assessment based on a clinical history and physical examination. data were prospectively collected using a standardized questionnaire, which included the description of the duration and intensity of the clinical symptoms, a thorough clinical examination, and complementary tests (complete blood cell count and biochemical analyses). the history of previous malaria infections and antimalarial use was obtained through medical history and health surveillance and health unit records revision. blood samples were collected for pcr confirmation of p. vivax mono-infection and for a detailed evaluation of coexisting acute and chronic morbidities, when suspected by the clinicians, while women of reproductive age were additionally tested routinely for their pregnancy status. when available at each site, and according to individual clinical presentation, imaging exams were performed, such as abdominal or trans-vaginal ultrasound, computerized tomography, and fundoscopy. treatment was provided according to who recommendations and national guidelines, with the use of chloroquine ( mg/kg over days) in non-complicated patients, or parenteral artemether or artesunate in patients with suspicion of severe malaria or severe vomiting, followed by primaquine ( . mg/kg over days in brazil, and over days in india) [ , ] . in india, patients with severe criteria were also systematically prescribed wide spectrum antibiotics upon admission. clinical assessments and tbs were performed on a daily basis. additional and follow-up laboratory tests were performed at the physician's discretion. for the diagnosis and quantification of parasitemia, the tbs was prepared as recommended by the walker technique [ ] . in addition to the reading performed for patients' diagnosis, each blood slide was analyzed independently by two microscopists. a slide was recorded as negative if no parasite was detected in the -field reading. if parasites were detected on the slide, quantification was performed by counting the number of asexual and sexual parasites until either leukocytes or parasites were counted (whichever occurred first). in case of discordance (species-specific, or in the density quantification whenever discrepancy was higher than %), a third reading was performed by a different microscopist. the parasite density was calculated by the arithmetic mean of two concordant readings and the white blood cell count obtained from the total blood count analysis as previously described [ ] . in addition, species-specific real-time pcr for plasmodium was performed to confirm p. vivax mono-infection status and exclude p. falciparum co-infection. p. malariae was not tested considering previous data from both sites confirming the absence of circulation of this species in the study areas. the extraction of total dna from whole blood was performed using the qiaamp dna blood mini kit w (qiagen, usa), according to the manufacturer's protocol, and amplification was done in an applied biosystems fast system w using primers and taqman fluorescence labeled probes [ ] . patients were classified in relation to their clinical symptomatology and laboratory results. the presence of the who-defined severe malaria criteria and syndromes was systematically assessed at admittance and during the whole length of hospitalization at both sites, with cases being classified accordingly to the criteria described in table [ ] . the results for the worst tests were recorded in the case report form (crf) and the last results were used for case closure purposes. the systematic assessment at admission consisted of full blood count, biochemistry analyses (creatinine, urea, bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, albumin, and venous lactate), urine analysis, pregnancy tests for women between and years of age, and chest x-rays. we also classified patients according to the number of severe criteria fulfilled as a proxy of higher severity, for which more specific and easier applicable criteria [ ] were used: severe anemia (hemoglobin < g/dl in adults and < g/dl in children); respiratory distress/ acute lung injury; circulatory shock (systolic blood pressure < mmhg refractory to fluid); acute renal failure; and cerebral malaria. a cut-off was decided to categorize cases as more severe if they presented three or more severe criteria. the performance of additional investigations for comorbidities was triggered either for specific manifestations and/or at the physician's discretion. these criteria included: i) severe anemia: hemoglobinopathies investigation and glucose- -phosphate dehydrogenase (g pd) assessments, and abdominal ultrasound; ii) respiratory distress: chest x-rays, blood gas, chest computerized tomography (ct) scan, and blood cultures; iii) alt. u/l: serology against hepatitis a, hepatitis e (only in india), and dengue; iv) creatinine > mg/dl: renal ultrasound, -h proteinuria measurement and creatinine clearance; v) cerebral malaria: ct scan and lumbar puncture (if not contraindicated); and vi) severe abdominal pain: abdominal ultrasound. hiv testing (serology) was conducted for all admitted patients. additionally, co-infection with dengue fever (by serology and pcr), and leptospirosis (serology) were systematically investigated in all admitted patients in manaus. blood cultures were performed in bikaner, although samples were collected after patients had been started on antibiotics, a practice which is routine among patients with severity criteria. in manaus, two blood culture samples were drawn for all admitted patients with severe criteria ( ml of blood). chronic co-morbidities were determined based on patients' provided information and assessment of medical records. for these analyses, patients admitted due to primaquine-induced hemolysis (only observed in manaus) were excluded, and the details concerning its presentation and outcomes will be presented in a separate publication (in preparation). all the data were double entered in forms designed in the open clinica w online platform, with the discordances and inconsistencies corrected according to a pre-established protocol. only hospitalized patients with pcr-confirmed p. vivax mono-infection were included for the analyses. the demographic and clinical characteristics of patients were described in terms of proportions and compared using the chi-square or fisher test as appropriate. unadjusted simple logistic regression analyses were also performed considering different outcomes, especially the fulfillment of who severe criteria for p. falaciparum [ ] and death. further description and analyses were performed for each of the main severe complications observed in order to provide a broader picture of the clinical spectrum of this infection. unadjusted linear regression was undertaken to explore the association between number of severe criteria and risk factors. multiple analyses were not performed, because the sample size did not offer sufficient power for that purpose. the diagnostic performance of laboratorial parameters for identifying severity or multiplicity of severity criteria was assessed by means of receiver operating characteristic (roc) curves. the analyses were performed using spss w version during the study period, and patients were admitted with vivax malaria in manaus and bikaner respectively ( figure and table ) with three and seven associated fatalities per site. among the patients with fatal outcome, there was a predominance of women (eight patients), four of them pregnant, with patients from manaus presenting higher age and number of comorbidities compared to bikaner. the characteristics of the patients with fatal outcome are presented in additional file : table s . only in manaus was p. falciparum/p. vivax co-infection seen in one patient with severe criteria. among patients without who criteria, no deaths were observed. on admission, patients had a negative tbs, all of them having initiated antimalarials in other health units, of which pcr was positive for p. vivax in of them. there were patients admitted in manaus due to primaquine-associated hemolysis and associated complications, all of them with g pd deficiency, with no patient being diagnosed with this condition in bikaner. regardless of the frequency of specific complications, in manaus more patients with co-morbidities were admitted, however with similar proportion of deaths (table ) . antibiotics were administered to patients in manaus, for treatment of pneumonia in patients, cellulitis in patients, amebiasis in , and enteritis in . although blood and urine cultures were obtained from all these patients prior to therapy, only in one patient was a microorganism identified (staphylococcus aureus associated with cellulitis). in bikaner, antibiotics were administered to patients (with . % of those with at least one severe criterion receiving them). additional investigations were performed, as aforementioned, at physicians' discretion or triggered by specific manifestations, limiting the estimation of its occurrence within the study population. the main chronic and acute co-morbidities diagnosed in these patients are described in table . dengue fever co-infection, due to its high occurrence and public health importance in manaus, has been described in another publication [ ] . patients presented a varied array of clinical complications associated with p. vivax mono-infection, including atypical complications seen only on imaging exams. anemia was the more frequent complication at both sites, followed by acute renal failure. respiratory distress, hyperlactatemia, hypoglycemia, and disseminated intravascular coagulation, although rare, were mostly seen in manaus (table ) . there was a higher proportion of patients presenting with three or more complications in bikaner compared to manaus ( . % versus . %, respectively; p = . ), with no further discrepancies observed between sites. for the outcome of presenting at least one of the who severe malaria criteria, there was association with female gender, first malarial infection, and pregnancy. for multiple severity criteria, the only variable showing evidence of association was the presence of chronic comorbidity, with borderline evidence for an association with both pregnancy status and female gender. there was evidence of association of female gender as a risk factor for death among p. vivax admitted patients, and although the proportions of individuals with chronic co-morbidities and non-pregnant women were higher among the patients who died, the differences were not meaningful and the lack of power needs to be taken into consideration (table ). similar findings resulted when the same analysis was performed per site (data not analysis restricted to women of reproductive age ( - years-old); *restricted to patients not in use of antimalarials at the initial assessment ( , parasites/mm was the lower limit of the highest quartile). shown). further characterization of specific manifestations is shown below. an additional linear regression analysis on the association with the number of severe criteria in each patient with the same investigated risk factors was also undertaken, with the only variables with significant association being female gender (coefficient = . ; p = . ), pregnancy status (coefficient = . ; p = . ), and the presence of any chronic co-morbidity (coefficient = . ; p = . ). severe anemia was the most common clinical complication at both sites, occurring among ( . %) of the admitted patients, with a higher proportion of females compared to males ( . % versus . %; p < . ), with more pregnant women presenting severe anemia ( . % versus . %; p = . ). surprisingly, age, chronic comorbidities, previous malaria history, and report of antimalarial use in the preceding days were not associated with severe anemia. the proportion of patients presenting with jaundice, splenomegaly, and hepatomegaly did not differ between patients with and without severe anemia. no hemoglobinopathies were detected among our cohort, reflecting the low prevalence in both study areas. blood transfusions were administered to patients, corresponding to . % of individuals fulfilling the severe anemia criteria, illustrating its effectiveness in identifying the most severe cases. six patients with severe anemia experienced fatal outcomes (fatality rate = . %). acute kidney injury was characterized in a total of patients from both sites, above the age of . a similar proportion of both genders was affected, with only two pregnant women presenting this complication. the mean creatinine at presentation for these patients was . mg/dl (sd = . ), with . % presenting abnormal renal ultrasound characterized by hyperechogenicity in the cortex, usually associated with interstitial nephritis. dialysis therapy was undertaken in ( . %) of these patients, with a total of nine patients being admitted to the icu and five patients with this complication dying (fatality rate = . %). respiratory distress in our series was observed with considerably higher frequency in manaus (table ) . major changes in chest x-rays were observed for eight patients ( . %), mainly characterized by bi-basal interstitial opacities. no children presented with acute respiratory distress syndrome (ards), and there was no association with gender or pregnancy status in its occurrence. there was, however, strong evidence of association of ards with having initiated antimalarials previously to admission. six of the patients presented respiratory distress upon admission, which was characterized as acute lung injury, and of these five had begun antimalarials within the preceding hours. two patients developed ards as part of a systemic inflammatory response syndrome with multi-organ dysfunction and subsequent death. one hundred nineteen patients arrived with the previous diagnosis of p. vivax infection and use of chloroquine (with or without primaquine) prescribed at other health services. considering the clinical presentation on admission, patients who used antimalarials in the preceding hours were more likely to present with respiratory distress (or = . ; % ci . - . ). four patients with ards died, resulting in a fatality rate of . %. cover image of a patient presenting ards post-chloroquine initiation. cerebral malaria was characterized, following the who guidelines, as impaired conscience or repeated convulsions. it was more common in india, affecting five patients, while only one was diagnosed in brazil (table ) . of the six patients with central nervous system syndromes, four were male, and their ages ranged from to years of age. all patients had impaired consciousness on admission, with one -year-old indian female patient also presenting with repeated seizures. lumbar puncture was performed on three patients without significant changes in any of them. in one male patient from manaus, varicella-zoster virus was identified in the cerebrospinal fluid (there were no changes in the cerebrospinal fluid analysis). ct scans were performed for three patients without pathological findings. besides the aforementioned severity criteria, patients also presented with hyperlactatemia, hypoglycemia, and disseminated intravascular coagulation (table ) . furthermore, clinical complications outside the who severe criteria definitions were also characterized among the admitted patients, such as mild hepatitis (alt > u/ml) in patients, acalculous cholecystitis in patients, and splenic rupture or infarction in patients. from the three cases with spleen-related complications, two were diagnosed with spleen rupture characterized by very low hemoglobin concentrations ( . mg/dl and . mg/dl) and spleen hematoma observed at the ct scan, while the patient with spleen infarction, as characterized by both abdominal ultrasound and ct scan, presented with intense upper right quadrant abdominal pain, with none of them presenting any other severe manifestation, such as circulatory shock. all of them were managed conservatively and recovered without further sequelae. all pregnant women were submitted to obstetric ultrasound and appropriate testing, and were followed up to determine the pregnancy outcome through a parallel ongoing study protocol. apart from one patient presenting subchorionic hematoma with subsequent abortion at weeks of pregnancy, no other pregnancy-associated complications were observed on admission. among the pregnant women with severe manifestations, the most common complications were severe anemia ( ), ards ( ), cerebral malaria ( ) and acute kidney injury ( ) . all four pregnant women who died presented with ards, with three of them also presenting with anemia and one of them also presenting with acute kidney injury and circulatory shock. although no autopsies were performed, no additional causes of death were suggested. the performance of laboratorial tests (hematology, biochemistry, and parasitemia) to discriminate severe cases, deaths, or cases with multiple severity criteria was assessed using roc curves. except for total serum bilirubin, which presented a reasonable discriminative performance (auc = . ; % ci = . - . ; p < . ), with values above . mg/d presenting a sensitivity of . % and a specificity of . %, resulting in an overall accuracy of . % (figure ) no other parameters presented good accuracy for any of the evaluated outcomes. parasite density among patients who had not received antimalarials prior to admission presented a very poor accuracy to discriminate patients with three or more severity criteria (auc = . ; % ci = . - . ; p > . ), as did platelet counts and alanine aminotransferase (auc = . and . , respectively), indicating that these parameters should not be used as criteria to identify patients with p. vivax-associated complications. this is, to our knowledge, the first multisite study conducted in two very distinct geographical areas, trying to comprehensively describe severe vivax malaria cases after an adequate diagnosis, with pcr confirmation of exclusive p. vivax mono-infection as an important strength. through additional investigations, we have been able to identify a high number of associated co-morbidities, although by not performing a systematic investigation in all admitted cases from both sites, there was an important limitation on estimating the prevalence of their occurrence and association with severe syndromes, an important issue to consider [ , ] . furthermore, although we have tried to ascertain the presence of previous chronic co-morbidities through medical interviews and patient record revisions, the possibility of underreporting and underdiagnosis must be considered. indeed, one of the main concerns of the protocol was to exclude misdiagnosis and co-infection with p. falciparum by applying validated and standardized molecular methods [ ] , as microscopy can frequently miss out or even misdiagnose a varied proportion of cases. our data provide yet again a robust confirmation of the potential of this species to cause significant morbidity and even mortality, a fact now widely recognized by the scientific community and by who in its recently published severe malaria monograph [ ] . indeed, the associated case fatality rate (cfr) among admitted patients to the study in the brazilian amazon ( . %) and indian rajasthan ( . %) is not negligible, and is comparable to cfrs previously described in papua new guinea [ ] and indonesia [ ] , and not too dissimilar to those for p. falciparum in africa [ ] . these findings must be taken cautiously, as the low incidence of p. falciparum in the study areas and the hospital-based design can limit comparisons and estimates of community cfrs. however, when compared the overall hospitalization and fatality rates, a striking difference could be observed between manaus and bikaner, as the latter presented much higher rates, up to -fold higher for fatality. conducting multisite studies allows for an active comparison of the different clinical complications and associated rates that would be expected by the very distinct demographic, socioeconomic characteristics, health systems features, and, especially, the local malaria transmission dynamics in the different p. vivax endemic areas. the influence of these factors could already be observed by comparing the descriptions of clinical epidemiology of complications associated with this infection from different sites, showing that in areas of higher transmission intensities, children are the most frequently affected population [ , , , ] , while in areas of moderate and low intensities, adults contribute more to the proportion of severe cases [ , , ] . our study highlighted many of these differences. for instance, when comparing patients hospitalized at both sites, there was evidence that the higher proportion of patients being admitted in india was secondary to a higher frequency of first malarial infections in that location, reflecting distinctive transmission dynamics, including a differential pattern of relapse rates that could contribute to some degree of clinical immunity among brazilian patients [ , ] . the spectrum of clinical complications in both sites was broadly similar, with severe anemia being by far the most frequent of the complications, as previously described in other p. vivax endemic settings [ , , , ] , and followed by acute renal failure, a complication that seems to be particularly frequent in the two countries where the study was conducted albeit rare elsewhere [ ] . the presence of three or more severity criteria was also frequent and common at both sites. the proportion of severe malaria cases with acute lung injury/respiratory distress was, however, significantly higher among brazilian patients. this particular difference could be due to a number of factors, including a higher proportion of indian patients being systematically treated with antibiotics, or differences in parasite virulence or host genetics, which could not be assessed in this study and should be considered in future studies. however, our data point to the beginning of antimalarial treatment as a triggering phenomenon of respiratory distress, which needs further investigation. there were only six episodes of cerebral malaria among our patients, with one of them presenting co-infection with varicella-zoster virus (vzv) isolated by pcr from the csf, in agreement with data from other settings showing low rates of occurrence [ ] . there were deaths among our admitted patients' series, and although there was low power for assessment of prognostic factors, there was evidence that female gender (probably confounded by the risk conferred by pregnancy) and chronic co-morbidities were associated with a higher risk of dying. one of the most striking findings in this study was the confirmation that pregnancy seems to be a clear risk factor for severe vivax malaria and even for death (despite being only borderline significant). it has been argued that, unlike p. falciparum, p. vivax rarely causes severe malaria in pregnant women [ , [ ] [ ] [ ] ; however, our series confirms a very high and almost identical proportion (above / in both sites) of pregnancies among the cases of severe malaria occurring in women of reproductive age, and four maternal deaths (all occurring in bikaner). pregnant women were systematically evaluated for obstetric complications, allowing us to diagnose an abortion occurring as a consequence of a subchorionic hematoma which we attributed to a malaria-related complication, leading us to hypothesize that further studies aimed at this population could properly detect and estimate the pregnancy-related burden of p. vivax infection. we were also able to detect the frequent occurrence of pregnancyrelated complications such as subchorionic hematoma. on the other hand, the histopathological evidence in the literature points to minor damage of p. vivax-infected placentas [ , ] . ongoing studies specifically targeting malaria in pregnancy in malaria endemic areas should help clarify the specific contribution of this parasite in causing maternal morbidity and death. the occurrence of co-morbidities has been associated with higher morbidity of malaria in different african locations, starting with hiv infection but also including other viral and bacterial co-infections [ ] [ ] [ ] [ ] , stressing the importance of investigating their occurrence and possibly promoting joint management strategies for common concurrent conditions in many tropical areas [ ] . bacterial systemic concurrent infections were rarely observed in manaus, which could be a potential reflection that among adult patients the concomitant occurrence of bacterial infection seems much rarer than that among p. falciparum-infected children [ ] . yet other studies have reported similar rates affecting both age groups [ ] , in which factors associated with each setting could be playing a higher role, a topic we could not explore due to the systematic use of antibiotics in bikaner. there were, however, important differences in the prevalence of co-morbidities in manaus and bikaner, with the former presenting considerably higher frequencies of both acute and chronic illnesses. the difference in the observed proportions of co-morbidities between malaria endemic areas is a reflection of the local epidemiology influenced by the demographic and socioeconomic structures, and also of the health systems' capacities to diagnose and detect concomitant illnesses. previous studies from the brazilian amazon region had already described the joint occurrence of malaria simultaneously with other health conditions, either acting as a contributing factor for severe manifestation or eventually being an incidental finding in patients with other severe diseases leading to critical illness or even fatal outcomes [ , , ] . in a scenario where many tropical regions are facing epidemiological transition, the occurrence of p. vivax infection in individuals with chronic diseases is likely to become an important problem in these areas [ ] [ ] [ ] , putting a great deal of stress on and requiring effective recognition and management by local health systems. we have been able to characterize a diverse range of clinical complications among the included patients, including a higher risk for death among the patients developing ards, which was more frequent in patients who had started antimalarials prior to hospitalization, similar to previously described cases [ , ] . other clinical syndromes were also observed to occur with considerable frequency, noteworthy anemia requiring transfusion and acute renal failure, with cerebral malaria remaining a rare and intriguing manifestation within this infection [ ] . the who severe malaria criteria were initially developed to identify individuals with p. falciparum infection at higher risk of death [ ] , and there have been discussions among experts on the need to define specific severity criteria to be applied for p. vivax infection. our study demonstrates that the application of the who criteria can reliably identify the patients at higher risk of complications, who therefore require more urgent and intensive care, which further agrees with previous pediatric data from the same research group [ ] . a comprehensive analysis of the array of complications observed among the patients in our study and in the published literature provides reassurance of these findings by demonstrating that the spectrum of clinical manifestations is broadly covered by these definitions [ , ] , with unusual manifestations being rarely reported. however, it seems important to highlight that severity derived from the use of primaquine among g pd-deficient individuals, or splenic rupture, two well-known complications mostly seen in vivax infections [ , ] , are not included in the current who definitions and should be carefully considered by clinicians working in vivax endemic areas. furthermore, one must consider that in primary and community healthcare units, the characterization of the fulfillment of all who criteria is not possible due to the unavailability of laboratory facilities. more easily applicable guidelines to identify severely ill patients regardless of etiology must be used by health professionals to assist with decisions on referral or more aggressive management. although it is not currently possible to reliably estimate the total parasite biomass in p. vivax infection due to the difficulty of assessing the extent of cytoadhesion [ ] and spleen sequestration [ ] , we were able to observe that parasite densities within the higher quartile were associated with higher risk of severity. among the clinical and laboratory markers, only total bilirubin presented a high discriminative performance to identify more than three criteria of severe disease, showing that although jaundice was justifiably excluded from the who severe malaria criteria, it still has an important prognostic value and should not be dismissed by health professionals in their initial assessment of p. vivaxinfected patients. intense abdominal pain and low hemoglobin levels should prompt health professionals to consider the diagnosis of spleen rupture or infarction and take the appropriate diagnostic and management procedures [ ] . our study has some clear limitations that need to be addressed. we decided to focus on providing a more comprehensive description of the clinical manifestations and complications associated with p. vivax infection in detriment to comparing disease expression between sites due to lack of adequate power and heterogeneity of procedures, undermining what could have been an important output from this study. the unrepresentativeness of children at both sites probably reflects the fact that neither of the sites is a reference center for pediatric populations, albeit publications from both locations have previously described severe manifestation among p. vivax-infected children [ , ] . the fact that the decisions to admit patients were made at the attending physician's discretion may have resulted in added selection bias, which we tried to minimize by applying the who severe malaria criteria and determining the occurrence of more than three criteria (as a surrogate for more severe disease). note also that there are important differences in the health system organization as well as particular disparities in the management of cases, such as for example the systematic use of antibiotics upon admission in india. ensuring that both sites followed the common protocol proved also to be challenging, and in some cases probably hinders some of the comparisons in this study, especially regarding the presence of comorbidities, such as malnutrition and other co-infections. also, by not systematically measuring some immune molecules that have been associated with clinical complications of this infection, such as superoxide dismutase- [ ] , an opportunity was missed to properly evaluate the prognostic value of some promising biomarkers that could be of potential utility for future case management. geneva: world health organization mortality and morbidity from malaria among children in a rural area of the gambia, west africa clinical features and pathogenesis of severe malaria eliminating malaria -all of them key gaps in the knowledge of plasmodium vivax, a neglected human malaria parasite the neglected burden of plasmodium vivax malaria plasmodium vivax hospitalizations in a monoendemic malaria region: severe vivax malaria? a long neglected world malaria map: plasmodium vivax endemicity in a research agenda to underpin malaria eradication shrinking the malaria map: progress and prospects vivax malaria: neglected and not benign evidence and implications of mortality associated with acute plasmodium vivax malaria defying malaria: fathoming severe plasmodium vivax disease severe plasmodium vivax malaria, brazilian amazon risk factors and characterization of plasmodium vivax-associated admissions to pediatric intensive care units in the brazilian amazon clinical features of children hospitalized with malaria -a study from bikaner, northwest india severe plasmodium vivax malaria: a report on serial cases from bikaner in northwestern india multidrug-resistant plasmodium vivax associated with severe and fatal malaria: a prospective study in papua differential patterns of infection and disease with p. falciparum and p. vivax in young papua new guinean children revised who treatment recommendations for malaria why is plasmodium vivax a neglected tropical disease? pernicious and threatening plasmodium vivax as reality uncomplicated plasmodium vivax malaria in pregnancy associated with mortality from acute respiratory distress syndrome the pathophysiology of vivax malaria understanding the clinical spectrum of complicated plasmodium vivax malaria: a systematic review on the contributions of the brazilian literature severe vivax malaria: newly recognised or rediscovered malaria in brazil: an overview introduction, transmission and aggravation of malaria in desert ecosystem of rajasthan, india guia prático de tratamento da malária no brasil. brasília, brasil: ministerio da saúde world health organization. guidelines for the treatment of malaria world health organization parasitological confirmation of malaria diagnosis world health organization. basic malaria microscopy simultaneous identification of the four human plasmodium species and quantification of plasmodium dna load in human blood by real-time polymerase chain reaction vivax malaria and dengue fever co-infection: a cross-sectional study in the brazilian amazon a hospital based serosurveillance study of dengue infection in jaipur (rajasthan), india clinical profile of concurrent dengue fever and plasmodium vivax malaria in the brazilian amazon: case series of hospitalized patients world health organization. severe malaria plasmodium vivax and mixed infections are associated with severe malaria in children: a prospective cohort study from papua new guinea vivax malaria: a major cause of morbidity in early infancy demographic risk factors for severe and fatal vivax and falciparum malaria among hospital admissions in northeastern indonesian papua plasmodium vivax malaria tafenoquine plus chloroquine for the treatment and relapse prevention of plasmodium vivax malaria (detective): a multicentre, double-blind, randomised, phase b dose-selection study geographical variation in plasmodium vivax relapse is anemia in plasmodium vivax malaria more frequent and severe than in plasmodium falciparum? coma associated with microscopy-diagnosed plasmodium vivax: a prospective study in papua effects of plasmodium vivax malaria in pregnancy adverse pregnancy outcomes in an area where multidrug-resistant plasmodium vivax and plasmodium falciparum infections are endemic malaria in pregnancy in the asia-pacific region placental malaria in colombia: histopathologic findings in plasmodium vivax and p. falciparum infections placental histopathological changes associated with plasmodium vivax infection during pregnancy the interaction between malaria and human immunodeficiency virus infection in severely anaemic malawian children: a prospective longitudinal study distinguishing malaria from severe pneumonia among hospitalized children who fulfilled integrated management of childhood illness criteria for both diseases: a hospital-based study in mozambique effect of acute plasmodium falciparum malaria on reactivation and shedding of the eight human herpes viruses hiv infection, malnutrition, and invasive bacterial infection among children with severe malaria vulnerability to malaria, tuberculosis, and hiv/aids infection and disease. part ii: determinants operating at environmental and institutional level bacteraemia in adult patients presenting with malaria in india vivax malaria and bacteraemia: a prospective study in kolkata postmortem characterization of patients with clinical diagnosis of plasmodium vivax malaria: to what extent does this parasite kill? non-communicable diseases in low-and middle-income countries: context, determinants and health policy ageing, lifestyle modifications, and cardiovascular disease in developing countries the double burden of communicable and non-communicable diseases in developing countries lung injury in vivax malaria: pathophysiological evidence for pulmonary vascular sequestration and posttreatment alveolar-capillary inflammation world health organization. social mobilization and training team: diagnosis and management of severe falciparum malaria. geneva: world health organization pathological rupture of the spleen in malaria: analysis of cases ( - ) on the cytoadhesion of plasmodium vivax-infected erythrocytes spleen rupture in a case of untreated plasmodium vivax infection plasma superoxide dismutase- as a surrogate marker of vivax malaria severity this study has provided robust evidence asserting the role of p. vivax as a cause of severe human disease and death. indeed, this infection commonly progresses with severe manifestations, and the development of severe symptomatology seems to be more frequent among females, pregnant women, individuals presenting with their first malarial infection, and those with acute or chronic co-morbidities. although the overall the overall fatality rates are in concordance with findings from other p. vivax endemic areas, we observed differences between sites on specific disease manifestations and outcomes, which still require further and more comprehensive studies to be conducted to better elucidate the mechanisms and factors influencing disease expression. only by understanding the underlying pathophysiological mechanisms by which this species initiates and modifies organ functions, ultimately leading to clinical disease, as well as the role of the socioeconomic and health systems, will we be able to start answering the many pending questions related to this never-to-be-called-again benign parasite. additional file : table s . demographic and clinical characteristics of patients admitted with p. vivax infection that presented fatal outcome. the authors declare that they have no competing interests. key: cord- -k hquon authors: cilloni, l.; fu, h.; vesga, j. f.; dowdy, d.; pretorius, c.; ahmedov, s.; nair, s. a.; mosneaga, a.; masini, e. o.; suvanand, s.; arinaminpathy, n. title: the potential impact of the covid- pandemic on tuberculosis: a modelling analysis date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: k hquon background routine services for tuberculosis (tb) are being disrupted by stringent lockdowns against the novel sars-cov- virus. we sought to estimate the potential long-term epidemiological impact of such disruptions on tb burden in high-burden countries, and how this negative impact could be mitigated. methods we adapted mathematical models of tb transmission in three high-burden countries (india, kenya and ukraine) to incorporate lockdown-associated disruptions in the tb care cascade. the anticipated level of disruption reflected consensus from a rapid expert consultation. we modelled the impact of these disruptions on tb incidence and mortality over the next five years, and also considered potential interventions to curtail this impact. results even temporary disruptions can cause long-term increases in tb incidence and mortality. we estimated that a -month lockdown, followed by months to restore normal tb services, would cause, over the next years, an additional . million tb cases (crl . - . ) and , tb deaths (cri - thousand) in india, , ( , - , ) tb cases and , deaths ( . - . thousand) in kenya, and , ( , - , ) cases and , deaths ( , - , ) in ukraine. however, any such negative impacts could be averted through supplementary 'catch-up' tb case detection and treatment, once restrictions are eased. interpretation lockdown-related disruptions can cause long-lasting increases in tb burden, but these negative effects can be mitigated with targeted interventions implemented rapidly once lockdowns are lifted. the emergence of the novel virus sars-cov- has caused morbidity, mortality and societal disruption on a global scale. in the absence of pharmaceutical interventions, many countries have resorted to population-wide lockdowns to slow the spread of the virus and to allow their health systems to cope . these lockdowns have had an important effect on sars-cov- transmission , . however, unintended consequences are inevitable with such sweeping measures. in low-and middle-income countries with health systems already under strain, even temporary disruptions in health services can have lasting impact on population health , . in the present study we focus on tuberculosis (tb) -globally, the leading cause of death due to an infectious disease . in recent decades tb incidence and mortality have been steadily declining, reflecting ongoing improvements in diagnosis, treatment and prevention . however, in march a rapid analysis conducted by the stop tb partnership brought attention to severe impacts of covid-related lockdowns on tb care in different countries . for example, in the weeks following the imposition of a nationwide lockdown on march , , india reported an % drop in daily notifications of tb relative to average pre-lockdown levels. such declines, likely reflecting reductions in access to diagnosis and treatment, could have a lasting impact on tb burden at a country-wide level. missed diagnoses would mean increased opportunities for transmission, while worsened treatment outcomes increase the risk of death from tb. therefore, while lockdowns are an important measure to mitigate the immediate impact of covid- , it is critical to anticipate (i) the potential long-term impact of these measures on tb and other diseases, and (ii) how this impact might be stemmed, in the short term, by appropriately targeted investment and effort. we therefore aimed to examine these questions using mathematical modelling of tb transmission dynamics. building on earlier modelling conducted for the lancet commission on tuberculosis , , we modelled the potential tbrelated impact of covid-related lockdowns -and mitigating effects of potential post-lockdown interventions -in three focal countries: india, the republic of kenya, and ukraine. for each country we drew from previously published models of tb transmission , which were designed to capture essential features of the tb care cascade. for the current analysis, this approach allowed us to model the impact of disruptions acting at multiple points in the care cascade. for india we incorporated the dominant role of the private healthcare sector in providing tb care ; for kenya, the role of hiv in driving tb dynamics ; and for ukraine, the burden of drug resistance . we calibrated each country model to the available data on tb burden, including who estimates of tb incidence and mortality , and on the burden of drug resistance. full details of each model are provided in the supporting information. calibration was performed using markov chain monte carlo (mcmc) simulation [ ] [ ] [ ] , whereby we allowed model parameters to vary over pre-specified prior distributions, using a likelihood function based on the calibration targets listed above to weight simulations according to their fit to the observed data. for each country, we drew samples from the weighted (posterior) density of simulations following burn-in and thinning as described in the supporting information. we then performed model projections on the basis of each of these samples, under the lockdown scenarios described below. for any model projection (for example, incidence over time), we estimated bayesian credible intervals as . th and . th percentiles, and central estimates as th percentiles, of the corresponding posterior density. disruptions to tb services can act at all stages of the tb care cascade. during a lockdown, movement restrictions would curtail opportunities for those experiencing tb symptoms to seek care. even once these people are able to visit a provider or health facility, the diagnostic and laboratory capacity needed to support tb diagnosis may be severely reduced -for example, with molecular diagnostic tools for tb being repurposed for covid- or tb laboratory staff being redirected to covid- efforts. national tb programmes are investing significant effort to continue supporting those already on tb treatment, but there are also concerns that lockdown conditions may interfere with the continued supply of drugs . to capture this range of possible disruptions, we performed a rapid consultation amongst experts at the stop tb partnership and the united states agency for international development (usaid). table lists those experts' consensus opinion as to the degree to which tb services could be disrupted by covid-related lockdowns, at each step of the care cascade. there is substantial uncertainty around these possible impacts, and as described below, we performed sensitivity analysis to identify which components of disruptions would have the greatest impact on overall tb burden. depending on its readiness, a country tb programme may take weeks or months to restore tb services to normal after a lockdown. this process may be delayed if, for example, laboratory capacity for diagnosis needs time to be reconstituted for tb, or indeed if there remains a reluctance to seek care amongst those with tb symptoms, as a consequence of fear and stigma caused by the covid pandemic. accordingly, to model the impact of the lockdown and its aftermath, we assumed two phases: a lockdown of given duration, during which all impacts listed in table are in full effect, followed by a 'restoration' period, during which tb services are gradually (for simplicity, linearly) restored to normal. we also assumed that tb transmission would revert to normal at the same time as lifting the lockdown, as a result of contact rates in the community rapidly being restored to normal (although see below for sensitivity analysis). this assumption may be appropriate in high-burden, low-income settings where physical distancing is less feasible than in high-income settings, but also where there are strong economic incentives to restore livelihoods as soon as possible. we present results for two scenarios: a 'moderate' scenario consisting of a -month lockdown followed by a -month . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint restoration period for tb services, and a 'severe' scenario consisting of a -month lockdown followed by a -month restoration period. in each scenario we simulated the excess tb cases and deaths that would arise, over the period from - , compared against a situation where tb services continue as normal over this period. in doing so, we ignore potential expansions in tb care, for example the scaleup of engagement with the private sector in india that was ongoing prior to the covid- pandemic . since our analysis does not include the benefits of continuing these expansions, our model projections should be conservative with respect to the excess tb burden arising from the lockdown. until further data become available (discussed below), we took the assumptions in table as plausible scenarios for disruption. we also analysed how the impact of lockdown may vary, under different conditions for the type and length of disruption. first, we examined model sensitivity to the duration l of the lockdown and r of the restoration period. for a fixed value of r, we simulated excess tb burden (cases or deaths) for a hypothetical range of l between and months. using the gradient of excess tb burden with respect to l, we estimated the additional tb burden that would result, between and , for every month of lockdown. likewise, we estimated the excess tb burden per month of restoration, by holding l fixed and estimating the gradient of excess burden with respect to r between and months. second, we conducted a 'leave-one-out' analysis, in which we simulated the impact of the lockdown, but in the absence of a single element in table (for example, a scenario where all impacts are in full effect with the exception of diagnosis, which remains at pre-lockdown levels). this analysis allows an assessment of how excess tb burden may vary under more limited disruptions than the full set of scenarios identified in table . in doing so, this analysis also helps to identify which types of disruption have the strongest contribution to excess tb burden. by performing a 'leave-one-out' simulation for each row of table in turn, we aimed to estimate the influence of each type of disruption. additionally, while many of the assumptions in table can be refined as further data become available, the effect of reduced contact rates in particular will be challenging to measure empirically. we therefore conducted additional simulations of excess tb burden with all disruptions in effect, but using an alternative assumption of % reduction (rather than %) in contact rates during the lockdown period. we additionally simulated a scenario where community contact rates revert to normal over a period of months (rather than immediately), independently of the time taken to restore normal tb services. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint role of the funding source sa is employed by usaid and san, am, em and ss are employed by the stop tb partnership. the funders otherwise had no role in the study, preparation of the report, or decision to submit the paper for publication. figures s -s in the supporting information show the model calibrations to each of the targets shown in table . on the basis of these calibrations, following a moderate lockdown we projected that between and , in india there would be an increase of , tb cases ( % bayesian credible interval (cri) - thousand) and , tb deaths ( % cri - thousand). likewise, in kenya there would be an additional , cases ( % cri , - , ) and , deaths ( % cri , - , ), and in ukraine an additional , cases ( % cri , - , ) and deaths ( % cri - ) (see figures and , and table ). overall, this excess burden translates to a - % increase across countries in tb incidence, and - % in tb deaths, between and . both estimates of adverse impact were projected to increase by three-to four-fold in the case of a severe, rather than moderate, lockdown ( table ). in terms of the monthly dynamics, figures and illustrate that increases in mortality would be greater proportionally than increases in incidence, but would also recover more rapidly than incidence upon restoration of normal tb services. increases in incidence lasted far beyond the period of disruption; for example, in india, incidence was projected to remain at least % higher than a "business-as-usual" baseline for a period of months, even in the moderate scenario of a two-month lockdown followed by two-month restoration ( figure s ). the five-year impact of covid-related lockdowns on tb burden is strongly affected by the durations of the lockdown and restoration periods (table ) . for example, in india each month of lockdown would give rise to an additional , tb cases ( % cri - thousand) and , tb deaths ( % cri . - . thousand) over the next years, while each month to restore normal tb services would give rise to an additional , tb cases ( % cri - thousand) and , tb deaths ( % cri . - . thousand). figure s in the supplementary information shows the analyses informing these results. in india, the four specific disruptions having the most effect on incidence and mortality are, in order: the probability of diagnosis per visit to a provider; the increase in the initial patient delay before first presenting to a provider; the drop in treatment initiation; and the drop in transmission rate ( figure ). likewise in kenya, the same four factors appear as most influential on the impact of the lockdown, on both tb incidence and mortality. in ukraine, a setting with a high burden of drug resistance, the drop in second-line treatment completion was far more influential on overall impact, though reductions in transmission rate, the drop in drug sensitivity testing, . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint and the drop in the probability of tb diagnosis per visit to a provider were also important considerations. the effect of disruptions in diagnosis, as well as in care-seeking and treatment initiation, is an expansion of the pool of individuals with undetected and untreated tb. figure shows how the size of this pool grows over time; the right-hand panel illustrates the potential impact of a twomonth campaign to reduce the prevalence of untreated tb in india through expanded case finding to reach an augmented monthly notification target, immediately upon easing of lockdown restrictions (i.e., implemented alongside the restoration of tb services). depending on lockdown severity and duration of restoration, such a two-month campaign could, preemptively, bring year incidence trends back to pre-lockdown levels. we also conducted analyses to test the sensitivity of model projections, to our assumptions for transmission. figure s shows simulations under alternative scenarios, namely transmission that is reduced by % (not %) during a lockdown, and taking several months (not immediately) to return to normal, once a lockdown is lifted. this additional analysis highlights that short-term increases in tb mortality are likely to occur whatever the effect of the lockdown on transmission, since these increases in mortality are driven by build-ups in undetected tb, rather than by transmission. on the other hand, long-term incidence can be affected by different scenarios for transmission. in particular, when assuming that transmission takes months to return to normal (right-hand panels of figure s ), a moderate lockdown scenario represents an example where tb services are restored more rapidly (i.e. within months) than tb transmission, and a severe scenario represents the converse (i.e. service restoration within months). figure s illustrates the implications of these scenarios: namely, that the risk of longterm elevations in incidence is greatest when community transmission rates return to normal more rapidly than the restoration of tb services. additional analyses, provided in the supporting information (section ), illustrate a simple approach for extrapolating from these three focal countries to the global level. this approach suggests, for example, that a severe lockdown scenario could lead to an additional , , tb cases, and an additional , , tb deaths worldwide between and . this modeling analysis in three key countries illustrates that even short covid-related lockdowns can generate long-lasting setbacks in tb control. our results suggest that, even in a moderate lockdown scenario, over the next five years tb deaths could see increases of - %, while tb incidence could see increases of - %, in the three countries studied here. this impact would increase roughly threefold under a severe lockdown scenario (figures and , and table ). our results also illustrate how these long-term dynamics depend strongly on the duration of the disruption: in the example of india, each additional month of restoration could cause an additional , cases and , deaths over the next five years (table ) . . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint the reason for these dynamics is illustrated by figure , which shows the accumulation in undetected and untreated tb during a lockdown, as a result of missed opportunities for diagnosis and treatment initiation. this expanded pool of undetected tb continues to seed new infections of latent tb, many of which would take years to manifest as incident tb disease. consequently, service disruptions give rise to a short-term escalation of tb mortality (figure ), followed by a prolonged increase in incidence that could take years to undo (figure ). it follows that this excess burden could be averted through focused efforts to address the problem of undetected tb, immediately upon lifting the lockdown (figure ). in practice, such supplementary measures could involve active case-finding , , including contact tracing with longitudinal followup . on the patient side, covid- and pulmonary tb are both associated with respiratory symptoms. if, during the current pandemic, covid- comes to be seen as a "tb-like" disease, public recognition of the importance of recognising tb symptoms may wane once covid- is thought to be under control. additional efforts may therefore be needed to address these misperceptions. an additional concern is that covid- may carry stigma in many communities, and this stigma may transfer to individuals with tb as well . conversely, there may be opportunities to leverage synergies between the two diseases; for example, integrated tb and covid- screening and testing algorithms or combined contact investigation strategies. any such strategies based on respiratory symptoms could use similar infrastructure and staff to mitigate both the direct impacts of sars-cov- transmission and the indirect effects of augmented m. tuberculosis transmission. in short, readiness to restore tb services as rapidly as possible, combined with focused efforts to 'catch up' on missed diagnoses, will be critical in limiting any long-term setback to tb care efforts as a result of the covid- response. one important uncertainty is the potential impact of the lockdown, on tb transmission. we have assumed that a lockdown would reduce transmission by %, and moreover that transmission would revert to normal as soon as a lockdown is lifted. these assumptions reflect expert opinion for the implementation of lockdowns in low-and middle-income settings, but carry substantial uncertainty. as illustrated by section in the supporting information, which tests both of these assumptions, it is likely that short-term increases in tb mortality would be unaffected by alternative scenarios. this is because both factors do little to address the problem of undetected tb, that accumulates during a lockdown. however, our estimates for long-term incidence trends may be affected by alternative scenarios for transmission. in general, the risk of long-term increases in incidence are greatest if community contact rates return to normal at a faster rate than tb services ( figure s ). overall, therefore, this sensitivity analysis underlines the practical implications of our analysis: that it is critical to restoring routine tb services as rapidly as possible, alongside 'catch-up' campaigns immediately upon lifting a lockdown. a key implication of our scenario analysis is the centrality of establishing surveillance and other data systems to inform the extent of lockdown-associated disruptions in tb care. for example, . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint tb notifications (e.g., ref ) can be monitored in real time at a national and subnational level, to evaluate the depth and duration of any reductions in tb diagnosis at different stages of any lockdown. if these indicators suggest persistent declines in notifications and/or falling levels of treatment success, targeted interventions (e.g., active case finding, treatment support, or expanded access) can be rapidly implemented. as contact investigation for tb is implemented, surveillance of infection and active tb can be established and time trends can be used to inform whether household transmission has increased and/or access to care has declined, again at the local, subnational, and national levels. in the longer term, community-based surveys (e.g., serial surveys of tb infection in young children , can be conducted to explore the impact of lockdowns on tb transmission more broadly. we note that the present analysis focuses only on the potential impact of lockdowns on the tb epidemic, and does not address the potential for direct interactions between tb and covid- (for example, increased risk of covid- mortality among individuals with tb). for this reason, our estimates for excess mortality in particular are likely to be conservative. for example, early evidence suggests that existing tb infection, whether latent or active, can be a strong risk factor for severe disease resulting from sars-cov- infection . moreover, through pre-existing lung damage , past tb infection might also predispose individuals to poorer outcomes from covid- . further evidence on both potential impacts would be invaluable for future work examining these potential pathogen-pathogen interactions. as with any modelling study, our analysis involves several simplifications. our models do not distinguish age structure, nor pulmonary versus extrapulmonary tb, instead taking an average over these distinctions. for our modelling of kenya, for simplicity we have only captured the transmission dynamics of tb, treating hiv incidence as pre-specified. our model therefore does not capture the potential tb implications of disruptions in hiv care, and for this reason may be conservative. lockdowns are likely to reduce community transmission but at the expense of intensifying and prolonging household and congregate setting exposure. faithfully capturing household contact structure is generally not feasible in compartmental models such as in the current analysis, and instead we have taken a simple approach of an assumed overall net reduction in transmission. as discussed above, practical implications of our analysis remain unchanged by uncertainties relating to transmission. in conclusion, our analysis illustrates how increases in tb burden can take months to manifest, but years to undo. even if a lockdown is a period of curtailed programmatic activity, our results also highlight how this period might be used by country programmes and international agencies to prepare for the timely restoration of tb control activities and even "catch-up" campaigns upon easing of restrictions, to prevent such long-term negative impacts from taking hold. the resilience of systems to end tb worldwide will depend critically on readiness to restore, supplement and monitor tb services as rapidly as possible. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint author contributions ss, sa and na conceived the study, and na, dd and cp designed the approach. sa, san, am, em, and ss provided expert input in constructing the model assumptions, and validated model findings. lc, hf, jfv and cp performed the analysis, and all authors contributed to the interpretation. lc, hf, na and dd wrote a first draft of the manuscript, and all authors contributed to the final version. we declare no conflict of interest. figure . the potential impact of a lockdown on tb incidence in india, kenya and ukraine. shown is monthly tb incidence in each country, in and , for two lockdown scenarios: (i) a 'moderate' scenario with a -month lockdown and a -month restoration (orange), and (ii) a 'severe' scenario with a -month lockdown and a -month restoration (red). bars labeled with "l" and "r" denote, respectively, the lockdown and restoration periods, with numbers giving the number of months in each period. as described in the main text, we assume that the disruptions in table are in full effect during the lockdown period, and that they are reduced to zero in a linear way over the restoration period. shaded intervals show % bayesian credible intervals, reflecting uncertainty in pre-lockdown model parameters. cumulative excess tb incidence over the period - is given in table . . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint figure . the potential impact of a lockdown on tb deaths in india, kenya and ukraine. as for figure , but showing monthly tb deaths in each country. as in figure , bars labeled with "l" and "r" denote, respectively, the lockdown and restoration periods, with numbers giving the number of months in each period. shaded intervals show % bayesian credible intervals, reflecting uncertainty in pre-lockdown model parameters. excess tb deaths over the period - are listed in table . . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . table in effect, with the exception of one (given by the label to the left). bars in the figures show the excess tb burden between and arising from this scenario, relative to the scenario where all disruptions are in effect. vertical lines mark median excess tb cases and deaths in the 'full-impact' scenario. the largest bars therefore indicate those types of disruption that are most influential, for excess tb burden. left-hand panels show results in terms of excess tb incidence, and right-hand panels show excess tb deaths. error bars show % credible intervals, calculated by iterating this process over posterior samples for each country. abbreviations: dst: drug susceptibility test, fl: first-line, hiv: human immunodeficiency virus, ipt: isoniazid preventive therapy, sl: second-line, tx: treatment. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the left-hand panel shows, in the example of india, the growth in the prevalence of undetected and untreated tb during the lockdown period, taking the example of a -month lockdown followed by a -month restoration. as described in the text, this expanded pool of prevalent tb is a source of short-term increase in tb mortality, as well as seeding new infections of latent tb that manifest as incident tb disease over the subsequent months and years. the right-hand panel shows the effect of 'supplementary measures' that are instigated immediately upon lifting the lockdown, and that operate over a two-month period to reach these missed cases and initiate them on treatment as rapidly as possible. in practical terms, such efforts could be guided by notification targets. shown in the figure is the example of a moderate lockdown scenario, followed by supplementary measures that aim to reach a peak target of ( %cri - ) monthly notifications per , population. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . footnotes: scenarios were constructed through a rapid consultation with experts in the stop tb partnership and usaid, the former using information from a rapid survey of national tb programmes . . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint the scenarios listed here are not predictive, but illustrative on the basis of current information: they offer a basis for examining the potential impact of different types of disruption. for the initial levels of these parameters in each country, see tables s -s (entries highlighted in yellow) in the supporting information. lockdowns would have the effect of reducing transmission in the community level, but also intensifying and prolonging exposure at the household level. as our models do not incorporate household vs community structure, these scenarios instead aim to capture the net effect of changes in household vs community transmission. in urban slums in particular, where tb transmission is strongest, overcrowding may tend to reduce the effect of any lockdown on community transmission. in section in the supporting information, we present corresponding sensitivity analyses to these assumptions. the initial patient delay is an assumed interval of active, infectious tb, prior to a patient's first presentation for care. it is calibrated to match epidemiological data (see table s for data, and tables s -s for parameter estimates). for simplicity, only the kenya model incorporates the role of hiv/tb coinfection, which is estimated to account for % of incident tb. however, we note that ukraine has a high burden of hiv as well; in the present study, our focus in ukraine is on the role of drug-resistant tb. abbreviations: covid- : coronavirus disease , dr: drug-resistant (i.e. rifampicin-resistant), ds: drug-susceptible, dst: drug susceptibility test, hiv: human immunodeficiency virus, ipt: isoniazid preventive therapy, plhiv: people living with hiv, tb: tuberculosis . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint how will country-based mitigation measures influence the course of the covid- epidemic? estimating the number of infections and the impact of non-pharmaceutical interventions on covid- in european countries the effect of control strategies to reduce social mixing on outcomes of the covid- epidemic in wuhan, china: a modelling study malaria morbidity and mortality in ebola-affected countries caused by decreased health-care capacity, and the potential effect of mitigation strategies: a modelling analysis health in financial crises: economic recession and tuberculosis in central and eastern europe world health organization. global tuberculosis report . world health organization tuberculosis : burden, challenges and strategy for control and elimination we did a rapid assessment: the tb response is heavily impacted by the covid- pandemic building a tuberculosis-free world: the lancet commission on tuberculosis assessing tuberculosis control priorities in highburden settings: a modelling approach the number of privately treated tuberculosis cases in india: an estimation from drug sales data kenya tuberculosis prevalence survey : challenges and opportunities of ending tb in kenya alarming levels of multidrug-resistant tuberculosis in ukraine: results from the first national survey inference for deterministic simulation models: the bayesian melding approach bayesian melding for estimating uncertainty in national hiv prevalence estimates population health impact and cost-effectiveness of tuberculosis diagnosis with xpert mtb/rif: a dynamic simulation and economic evaluation tuberculosis and hiv responses threatened by covid- joint effort for elimination of tuberculosis turning off the tap: stopping tuberculosis transmission through active case-finding and prompt effective treatment how much is tuberculosis screening worth? estimating the value of active case finding for tuberculosis in south africa, china, and indi household-contact investigation for detection of tuberculosis in vietnam world health organization. social stigma associated with covid- central tb division india. nikshay dashboard decreasing household contribution to tb transmission with age: a retrospective geographic analysis of young people in a south african township active or latent tuberculosis increases susceptibility to covid- and disease severity tuberculosis and lung damage: from epidemiology to pathophysiology to the beginning of . percentages show increases in cases and deaths relative to a baseline of no lockdown conditions see figure s , supporting information, for further details. abbreviations: cri-credible interval we gratefully acknowledge support from sara gonzalez andino and shinichi takenaka from stop tb partnership, in the process of development of modelling assumptions. key: cord- -e dq t v authors: chand, raj; asmil, sadiyah h.; chico, michelle title: letter to the editor in response to the article: “increase in the risk of type diabetes during lockdown for the covid pandemic in india: a cohort analysis” (ghoshal et al.) date: - - journal: diabetes metab syndr doi: . /j.dsx. . . sha: doc_id: cord_uid: e dq t v nan letter to the editor in response to the article: "increase in the risk of type diabetes during lockdown for the covid pandemic in india: a cohort analysis" ( this is a pdf file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. this version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. letter to the editor in response to the article: "increase in the risk of type diabetes during lockdown for the covid pandemic in india: a cohort analysis" (ghoshal et al.) we read the article by samit ghosal et al. [ ] with great interest and appreciate the findings of weight gain in non-diabetic individuals during the covid- lockdown period. however, the weight gain following days of lockdown can be brought about by either fluid retention or increased calorie intake [ ] . fluid retention is routinely noticed in hypertension and pathologies of the heart, liver, and kidneys. this change in weight is generally short-lived as they tend to get resolved with the use of diuretics. ever since the covid- pandemic lockdown, many patients are denied access to health care and medications [ ] . this leads to fluid retention and weight gain in such patients with previously controlled by medications. thus, it becomes crucial to exclude this set of patients from the study as they gain weight due to loss of access to medications rather than due to a sedentary lifestyle because of the covid- lockdown. it is unclear in this study if inquiries were made to exclude such patients. according to the authors, there is an increased risk of developing diabetes based on the validated american diabetes association (ada) risk score. as indicated by the table that is marked as in this study, the change in ada risk score post-lockdown appears to be . %. but we did not find the p-value to learn if the change in ada risk score post-lockdown is statistically significant or not [ ] . suppose ada risk score after days of lockdown is statistically significant, it is unclear how there is an increased risk of developing type diabetes mellitus (t d) in the population without the disease. ada scoring is primarily used to decide if an individual with certain risk factors would benefit from screening for t d. the increased ada risk score if found in a certain population during post-lockdown would simply mean that this group of the population qualifies to be screened for t d. we thank the authors for sharing their findings, but for now, it remains unclear if the lockdown during the covid- pandemic in india would lead to an increase in risk for developing type diabetes. in the future, large well-designed cohorts are crucial to better understand the effects of covid- lockdown on the risk factors associated with t d. the study must provide important parameters like p-value, confidence interval, and relative risk to substantiate as evidence for conclusions of the study. anoop misra: increase in the risk of type diabetes during lockdown for the covid pandemic in india: a cohort analysis clinical methods: the history, physical, and laboratory examinations healthcare delivery in india amid the covid- pandemic: challenges and opportunities the p value and statistical significance: misunderstandings, explanations, challenges, and alternatives malaysia corresponding author: raj chand key: cord- -ao p ra authors: paul, suman; bhattacharya, subhasis; mandal, buddhadev; haldar, subrata; mandal, somnath; kundu, sanjit; biswas, anupam title: dynamics and risk assessment of sars-cov- in urban areas: a geographical assessment on kolkata municipal corporation, india date: - - journal: spat doi: . /s - - - sha: doc_id: cord_uid: ao p ra sars-cov- has been transmitted and outbreak took place in india during the last week before nationwide st lockdown took place. urban areas found more vulnerable and reported nearly % of cases during every phase of lockdown. mumbai, among four metropolitan cities found huge number of containment zones with nearly % of sars-cov- cases indicating clustering of cases. most of the containment zones of sars-cov- cases in kolkata municipal corporation found a significant relation with slum areas. the study primarily tries considering the nature of sars-cov- cases in different urban centres with the help of cartographic techniques. ahp method has been used to determine the factors responsible for such concentration of sars-cov- cases with vulnerability assessment (exposure, sensitivity and resilience) and risks. before nationwide lockdown starts, the share of urban centres found % which has been transformed into nearly % at the end of (rd) phase of lockdown. growth rate of sars-cov- cases found very high for chennai and thane with less number of doubling time to nation. slum concentration and containment density shows a higher degree of correlation in kolkata municipal corporation. risk map also shows the concentration of cases in central and north kolkata with higher degree of diseases exposure and sensitivity. control measures must be taken by the central and state government to minimise the transmission rate of sars-cov- mainly urban areas. as urban area contributing a higher share of sars-cov- cases, a proper management plan must be enforce. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. in the present day context urbanisation becomes a major driver of demographic change of an area. according to united nations report, world's population living in the urban areas has grown from to % during to [ , ] . by , it has been estimated that the world's % population will be reside in urban areas. this kind of urban growth and population concentration leads to sprawling and shanty development outside and within the city respectively. high population density, low per capita spacing, concentration of urban poor make significant impact on the epidemiology of the infectious diseases electronic supplementary material the online version of this article (https://doi.org/ . /s - - - ) contains supplementary material, which is available to authorized users. [ , ] . association between urban poor and risk of pathogen transmission is very high in this scenario. high human to human propagation can easily be spike with such vulnerable condition [ ] . presently, more than million populations in the world are living in slums whereas the figure of india is nearly million [ ] . in , worldwide figure of slum populations were nearly million which has been booming to million in next years i.e. in [ ] . in the current worldwide pandemic situation of sars-cov- , growth pattern, transmission nature and driving factors are the key aspects need to study. december , an outbreak of covid- (as known earlier) has been reported from wuhan city of hubei province in mainland china and rapidly spread into the other provinces of china along with countries within end of january, [ ] . wuhan city has been under full lockdown (travel ban and closure of everything except essential services) from january [ ] . but the decision has been taken by the government was too late as the by novel coronavirus (ncov- ) infections has already transmitted in different parts of mainland china and also in the different countries of the world. this episode is highly correlated with the chinese great migration during the january-february when near about million people are moving towards mainland china (within the country and from outside the country) to celebrate their lunar new year. from mid-february countries of european continent, u.s.a, australia facing a terrible spike of sars-cov- cases which has been not affected india at a large till the end of march, . nearly . million populations has been affected by sars-cov- and the fatality has reached into . million (as on - - ). several countries like united states, russia, brazil, italy, france, united kingdom, germany, turkey, iran has faced a major setback due the this pandemic [ , ] . india has also reached the mark of , confirmed sars-cov- cases after days of first case found. though the time taken by india to reach one lack infected cases much higher than the other countries, but the exponential triggering has been noticed during last week of rd phase of nationwide lockdown (from may, to may, ). nearly % cases are reported from major cities of india and most interestingly, mumbai, delhi, ahmedabad, chennai, thane, pune, kolkata become the most contributing urban centres to sars-cov- cases (as on may, ). high population density and higher concentration of slum population make an interruption for maintaining the social distancing and lockdown effectively [ ] [ ] [ ] . considering such backdrop the nature of spreading of sars-cov- cases in the indian cities need to be analysed. further an attempt has also been made to quantify and assess the hotspot zones along with risks of the concentrated areas of kolkata (one of the metro city) for proper understanding of transmission of diseases in the congested and unhealthy places as a case study [ , , ] . india has only cases of sars-cov- up to march , but all cases has transmitted and grow in a slow but steady in different areas of india especially in urban centres. except kasaragode, a rural base area in kerala, urban areas of maharashtra, delhi, gujarat and rajasthan have shown a large number of sars-cov- positive cases. in this regard, the mumbai, ahmedabad, chennai, pune, thane, indore, delhi, jaipur, kolkata, surat urban centres have been considered for initial analysis as these urban centres contribute more than % of sars-cov- cases during nationwide lockdown periods. from the analysis of urban centres contribution of sars-cov- cases, four megacities of india (i.e. mumbai, ncr delhi, kolkata and chennai) has been further chosen ( fig. ) to find out the nature of relationship between containment zones and sars-cov- cases. as urban centres with high population density and high concentration of slum population faced a risk of rapid transmission of sars-cov- , a risk analysis have also been assessed on kolkata municipal corporation for the better understanding of driving factors of transmission of sars-cov- . the sars-cov- data set has been obtained from indian council for medical research (icmr) and health website which provide the real time data set on the outbreak of this pandemic. another good source of data has been found from 'how india lives'. this website provides different health infrastructure dataset at district level and uploading the real time covid- cases for each day at district and city level. containment zones cities which is a very important source of information to identify the sars-cov- hotspot has been taken from health bulletin, govt. of west bengal. major cities of india are taken for primary level study with duration of before lockdown situation to present day ( - - ) scenario. the slum data set has been taken from unpublished baseline survey report of by the department of bustee services, kolkata municipal corporation. as most of the dataset of slum related indicators found from census of india, dataset, we have to take baseline survey report of kmc. this data base has helped to identify the nature of exposure, sensitivity and resilience of world wise slam households which can assess the nature of risk among the slums. to depict the nature of sars-cov- spatial association, local moran's i statistic has been used to identify the cluster and spatial outlier in the neighborhood for - - dataset [ ] [ ] [ ] [ ] . moran's i highlights the location based cluster form high to low infection and calculated as follows: where zi the number of sars-cov- containment zones at a spatial unit i (ward as an areal unit), z is the overall containment zones in the study area (kmc as a whole) and n is the number of spatial unit which are (no. of wards in kmc) and v is the rate of the variance of sars-cov- containment zones in different wards which is computed as below: this method represents high (positive) and low (negative) values. high-high cluster values show the results cluster up of similar values with q-value range from . to . ( . for %, . for % and . for % of confidence level) and low-low cluster shows the clustering of dissimilar values with same q-values. higher the q-values with lower the z-score value shows the perfect significance of the method applied for study the nature of clustering pattern. the p value is a value of probability. for the pattern study, it is the probability which create spatial pattern using some random process. the small p-value value suggests that the observed spatial pattern is an outcome of random process; hence null hypothesis can be rejected. analytical hierarchical process has been developed by satty [ ] to facilitate priority setting and decision making. ahp now broadly applied in social science research and specifically in hazard and risk analysis. in this method a pairwise matrix has been developed among the set of scale of choices (table ) on the given alternatives [ ] . ahp methods also deliver to judge the nature of consistency of preferences given by the report using consistency ratio when the value has . (cr c . ). the consistency ratio is defined as: where cr is consistency ratio, ri represent random number (table) and ci represent consistency ratio is expressed by for the present work, consistency ratio has been found as . , consistency index as . and the value of random number for n = has been determined . . based on socio-economic data of slum of kolkata municipal corporation and containment zone data and containment zone data from different web sources we have selected the following indicators for quantity exposure, sensitivity and resilience for assessing the risk [ ] infector disease like sars-cov- (see table ). the study considered the following as exposure indicators, number of sars-cov- containment zones/ population (e ), percentage share of slum population to total world population (e ), number of containment zones sq.km (e ), number of slum located in the ward (e ), and percentage slum area to total area of the ward (e ). the study considered the following as sensitivity indicators, hhs size (s ), percentage of hhs size with persons and above (s ), no. of persons in the slum, used community toilet, no. of persons/tube well used (s ), population density (s ) and household density (s ). the study considered the following as resilience indicators, percentage of hhs access to drinking water facility within premise (r ), percentage of hhs access drinking water from treated source (r ), percentage of literate population (r ), average per capita income of the slum located in the ward (r ) and work participation rate (r ). number of containment zones/ population in one of the most important indicators affecting the exposure of sars-cov- cases. according to icmr, the sars-cov- cases are taken the epicenter of this containment zone [ ] . on the basis of data, we have divided the whole data set into categories having high risk factor to low risk factor (above . / population, . - . / population . - . / population, . - . / population and below . / population). share of slum population is another prime indicator to explain the exposure of such infections dieses h h pattern. so the shanty and confected household are very much exposed to such dieses. here, we also divide the whole set of data into categories on the basis of risk factor. density of containment zones in another good indicator for assessing the nature of exposure. as the density is increasing, the exposure of sars-cov- to other persons source: computed by the authors becomes very high. slum area to total area is another crucial factor as areal coverage increase, the congestion pattern of living, unhygienic situation are very much exposed. thus higher the percentage signifies higher risk factor. each of the indicators has been categories under five classes of risk factor and weightage of these indicators have been assigned using ahp method. the exposure index of sar-cov- has been determined using following formula. exposure index ei ð Þ : where e c denote the ward data lies or which class [class [ ] [ ] [ ] [ ] [ ] as mentioned in table and e w is weightage assessed using ahp model. here, in this study purpose identifies the factors which can trigger the intensity and probability of spiking up of sars-cov- cases. household size undoubtedly increases the extent of severity of such h h infectious disease. population belonging in a household also led the situation more badly. when social distancing is addressed nationwide, the poor people of the slums cannot maintain such as due to shortage of space in the households. community toilet and tube well use is also promoting the chances of mass gathering in the slams. many people are living under such shanty places and also depend upon these facilities which can aggravate and spread such infectious disease in the community level. sensitivity index can be expressed in the following manner: where s c denote the ward data lies or which class [class [ ] [ ] [ ] [ ] [ ] and s w is weightage assessed using ahp model. resilience can be defined as reduction and prevention approach to risk any vulnerability for making an area more socio-economically stronghold [ ] . drinking water facility with premises and from treated source, level of literate population are the important indicators for resilience study. on the other hand per capita income and work participation rate is the potential indicator to increase the resilience of the any households. resilience index can be determined as: where r c denote the ward data lies or which class [class [ ] [ ] [ ] [ ] [ ] and r w is weightage assessed using ahp model. on the basis of assessed results from exposure index (ei), sensitivity index (si) and resilience index (ri), risk of the selected wards have been estimated using following methodology as prescribed by ipcc [ ] framework: where ei w is the exposure index, w e weightage of exposure, si w is the sensitivity index, w s weightage of sensitivity, ri w is the resilience index, w r weightage of resilience. results and discussion outbreak of novel corona virus (earlier it is termed as -ncov and later renamed as sars-cov- during the preparation of this manuscript) leading to lockdown (which means entire closure of all services except frontline services and essential services, i.e., banking, fire service etc.) of entire country which took place on and from th april, midnight. till date of the preparation of this manuscript, india already gone through three phases of lockdown (which will end on th may, ) and during these phases, urban centres have been found the most threating situation contributing nearly % of total affected cases of sars-cov- from most popular cities of india. nearly it was may , when india experienced , confirmed sars-cov- cases with death and entered into the list of top fifteen countries of the world. it is only . % sars-cov- cases to rest of the world but it was only . % ( cases) when nationwide lockdown started. the surge of sars-cov- cases as seen by usa, italy, france, germany, brazil, russia was not same in india till may, . cases are found to be doubled in every days at that time. but after may, a large spike has been found till june, which put india in the same bracket as brazil and russia in terms of upward trend in the infected cases and fatalities. the fact that despite of four lockdown imposed by central and state governments combine, the stringent index has been found to fall from (on - - ) to . ( - - ) which make a straightway relation of surging the sars-cov- cases in the different parts of india (fig. ) . another issue is the return back of stranded labour from mainly southern and western states to the eastern portion make this spread to rural areas also. based on the dataset and fig. of sars-cov- of major urban centres, mumbai has been found most cases with one-fifth ( . %) to total country's cases up to th may, when the lockdown starts on th march, it was only . % of whole country with a rapid growth of . , . and . during st phase, nd phase and rd phase of lockdown respectively. doubling rate of cases is . times (mumbai doubled the cases in . days as on . . ) to country doubling time ( . days). ncr delhi also contributes a larger extent of sars-cov- cases with . % which was only . % just before lockdown. a single event at nizamuddin marcus (a religions congregation) makes the situation worse during first phase of lockdown [ ] . a sharp rise or cases (nearly . % to country's total cases) has been experienced during this time which has been slow down gradually. stringent actions have been taken by the respective state governments which reflect in the higher rate of doubling time ( . days) to country's data. after ncr delhi, ahmedabad from state of gujarat originate as a big area of concern for the country which contributing . % of total country's cases at the end lapse of rd phase of lockdown but it was only . % at the starting of st phase of lockdown. during nd phase of lockdown a tremendous spike in the cases of sars-cov- has been experienced by this urban centre. during these phase, most of the cases (nearly %) are related to travel within the country and related to delhi's religious congregation took place is end of march, [ ]. through having higher value of doubling rate ( . days to double) from country's perspective and having decreasing growth rate. number of containment zones gives a clear picture of clustering of cases which signifies the nature of community spreading which is a matter of uneasiness. chennai shows an alarming situation with . % of cases during the end period of rd phase of lockdown which was just . % on . . (just before the lockdown). though the growth rate is decreasing (from . % at st phase of the lockdown and . % at nearly end of rd phase of lockdown) but the doubling time of cases is . days which signifies a great risk. among all the urban centres under study (which are combine contribute : % of cases), chennai has the lowest doubling time which is a matter of concern. on th may , nearly sars-cov- have been outlined to a wholesale vegetable market named koyambedu and authorities have acknowledged it as a coronavirus hotspot [ ] . after cases being reported from the popular market of on the other hand kolkata shows a steady but consistency in growth and spreading of sars-cov- cases. almost in all the lockdown phases, kolkata shows much below transmission of sars-cov- and contributing least to country's tota. doubling rate gives a clear picture of this scenario with almost . days which is a good indication with a population of nearly . million and having nearly . % of slum population lived in this region (census, ). pune ( . %), thane ( . %), indore ( . %), jaipur ( . %) and surat ( . %) contribute nearly . % of the cases to country's total. growth rates of sars-cov- in these urban centres are constantly decreasing which is a good pictogram of action taken by the government of those states as well as social awareness with following social distancing. among all the urban centres, thane shows an alarming situation in doubling rate which is . days and thus thane can be an emerging hot spot like mumbai and chennai if proper action not taken at the earliest. two days before the second phase of lockdown started, india has charted identification of red, orange and green zones which is a strategic approach for defining the area of operation, applying perimeter control, delineating containment and buffer zones. meanwhile ministry of health and family welfare, govt. of india declared districts as 'hotspots' and districts as 'non-hotspots'. ministry also categorises hotspots in two way-(a) clusters-increase in the incidence of sars-cov- with less than cases and there must be epidemiologically linked and (b) large outbreak-when more than cases have been found from a defined geographical area and these cases may not be epidemiologically linked. to combat with this pandemic, state governments have begun to experiment the idea of containment zones to deal with sars-cov- . mechanism of the containment zones is very straight forward, clusters or large outbreak which shown rise of cases and shown rapid transmission either in family or in community must be seated. movement in these zones are very limited which is only for foot line workers and residential movement is completely ban. when large number of cases are found in a smaller number of containment area it may a reflection of large outbreak (ratio is very high) but when large amount of cases with larger number of containment area (the ratio is low) suggest the clustering of disease took place. in case of comparison of confirmed new cases on daily data initiated from the period of first lockdown for four cities is smoothen using five year weighted moving average method. the study considers the weights as defined by using the rule the weighted value of moving average can be calculated from p i¼ x i w i for the corresponding five values of the series. the study deals with the three types of lock down considering them as phase-i (consist of days starting from . . ), phase-ii (consist of days starting from . . ), and the phase-iii (consist of days starting from . . ). the smoothing data set of new cases of ncovid- syndrome is depicted in fig. . the nature of the new cases shows that situation of kolkata is relatively best in compare to other three cities [ ] . whatever be the ways the explosion of new cases are found with some controlled behaviour and even with rare fluctuations. the situations of chennai showing some controlled behaviour up to . . i.e. in the middle of phase-iii lockdown but as the relaxation in the lockdown started the outbreak increases with huge rate. similar path also observable for delhi ncr like chennai, but it includes massive fluctuations. as time precedes the frequencies of fluctuations in case of delhi also increases. the situation of mumbai is worse among the all four cities. the periodic up and downs of the new cases puzzle the governance to control it. the linear trend line for cities shows that the line is steepest for mumbai, and it is more than double of delhi. four metro cities shows different pattern of transmission during end ward of st phase of lockdown to present time. delhi shows a higher ratio between number of sars-cov- cases and containment zones suggesting the larger outbreak for the region. on the other hand mumbai, chennai and kolkata show a clustering scenario of these cases during this time setting. higher number of cases with lower ratio also suggests the expansion of the sars-cov- cases in the new areas in faster rate. in may , mumbai and chennai show nearly same value ( . and . respectively) but with the sars-cov- cases nearly . times to chennai. mumbai city shows a huge spreading along different places in this period of time. during this period, delhi shows a much higher rate fluctuating from . to . (having a highest ratio of . ) and pinpointing the large out break as stated earlier. during this period, kolkata shows a steady pattern having a ratio of . - . . the containment zones caused trouble to the citizens, by restricting the mobility almost entirely and have to depend on government officials and selected venders for maintaining the essential services. this methodology of curtailment of rights is temporary for the containing and stops the spreading of disease. but slums in the urban area cannot fully follow the thumb rules of such containment zone. as these people lives in a shanty, unhygienic environment, and using community toilet with large dependency on tube well for water accessibility are very much susceptible for these h h transmission. mumbai and delhi shows the perfect example of such transmission. dharavi, the world famous slum has been hardly heated by this pandemic. kolkata face a challenge to combat with the spreading of sars-cov- cases in the densely slums concentrated areas [ ] . most of the wards in kmc having more than containment zones where a large percentage of population living in the slums. increasing number containment zones along with number of cases has proven the spatial dispersal of sars-cov- cases in kmc which is needed to be studied further. in kolkata municipal corporation figure shows the time series pattern of the confirmed cases of sars-cov- from st case detected on th march, to th may, when cumulative number were and for kmc and state of west bengal respectively. as kolkata has experienced st case of sars-cov- , here we have taken ward wise containment zone to find out the nature of hot spots located in the municipal area. as per icmr, containment zone confirms the epicentre of cases and due to unavailability of sars-cov- ward wise data; we used number of containment zones as proxy indicator [ ] . figure also confirms that, up to st week of april kolkata municipal corporation (cmc) contributes a huge percentage share to state's total which has been decreasing afterwards. this scenario again found from starting of fourth week of april when kolkata share nearly % of state's total. a huge population of nearly lakh (census of india, ) with a high percentage share of slum population ( . %) is very much vulnerable for transmitting this h h virus where population density, slum density, using per capita community latrine and tube well are high [ ] . figure shows the hot spots for covid- using satscan on the basis of two different dates dataset on containment zones result which identifies two primary clusters and three secondary clusters with high confidence value (p-values are found less than . ) in kmc. the primary clusters are located covering (a) kareya, tiljala, topsia, tansra, survey park region and (b) jorabagan, burtola, girish park area. secondary clusters have been identified to designate more cases likely to aggregate from kmc which are extent from northern portion to south-western portion. these secondary clusters have also the significance values less than . (p-value). the highly decentralized nature of incidence of this disease clearly showed limited hotspots within the city of kolkata. ward no. (tiljala/topsia area) has been found a large number of containment zones in a smaller area and it has increasing very sharp. this area has fallen the primary cluster of central kolkata when ward no. and (banstala, girish park region) are fallen under another primary cluster. the sars-cov- views caused tremendous pressure situation in the wards in kolkata municipal corporation out of wards (fig. a) . containment zones have been found on those wards on - - which has been increased into numbers located in wards. the distribution pattern of containment zones in two different dates has shown a clear increase in spatiality among the wards of kmc. the highest number of zones has been found in the wards located in central kolkata, east suburban and port area and some portion of north kolkata. huge numbers of slums (registered and unregistered) are found in those areas which may play a role of catalyst to spread and transmitted this pandemic [ ]. highest concentrations of containment zones have been found in tiljala, kareya, beliaghata, phoolbgan, razabazar, tala, burtola, jorabagan, girish park, bowbazar, entally, muchipara, and survey park area. total number of containment zones in this area have been covered nearly % of the total containment zones (fig. b) . wards with high containment zones are falling in those wards which have a higher degree of slum population as well as the number. most of the areas under slums are very old and developed before independence [ ] . old shanty dwelling slots with higher family size, higher dependency on community toilet/latrine with water availability source as tube well make the area more risky and vulnerable to this sars-cov- [ ] . as it is already known to everyone that this infection can transmit h h pattern and ro of . , it is really need to assess the scenario of those slums for better approach to stop the transmission and break the chain of this infection. here need the assessment of the risk of those hotspot areas to make a proper evaluation of vulnerability and steps to be taken in coming days. municipal corporation (kmc) here where ew is weightage of exposure, ei w is the ward-wise exposure index, sw is weightage of sensitivity, si w is the ward-wise sensitivity index, rw is weightage of resilience and ri w is the ward-wise resilience index. on the resulted dataset, risk zones have been categorised into classes from very high risk zone to very low risk zone. of the total selected wards under study ( ), are very highly exposed to sars-cov- followed by highly exposed wards ( ), moderately exposed ( ), low exposed ( ) and very low exposed ( ) categories. the exposure index is composed of sars-cov- containment zones density with population, share of slum population and density of slums with areal coverage to ward area made the wards located in north and central kolkata more exposed as these areas are very old and the slums in these wards have an age of more than years. old drainage system, located behind the rail lines and nullas (old sewerage lines) make the situation more worsen. overall the area under gardenreach, metiaburuz ( % of very high exposed wards from this area) with a high percentage of muslim population face the higher degree of exposed of such infections (fig. a) . on the initial stage reluctant situation from government end and non-maintaining the social distancing norm during nation-wide lockdown period make this areas face a terrible trouble and have experienced a number of sars-cov- cases with a large number of containment zones. sensitivity index analysis showing that of the total wards very high sensitivity has been found among wards followed by wards in high sensitive index, moderately sensitivity found among wards when and wards are found in low to very low sensitivity values respectively. high sensitive wards are mostly lies in the north kolkata and partly in central kolkata (fig. b) where population density, household density, latrine and tube well dependency among the slum dwellers are very high which clearly gives the results of very high sensitive zones. these zones settled are much before of independence which has a migration legacy ( , ) . resilience capability among the selected wards of kmc found to be high as more than % of the total wards are characterised by very poor to moderate level of resilience. the wards are very much lagging behind in facilities which can protect them from such infections and the nature of infrastructural development are also found low in nature. figure c shows that the most vulnerable wards (high to very high) located in central and eastern portion of the study area. drinking water facilities, per-capita income and work participation rate are very low in these wards. eastern portion wards of the study area are joined with kmc much later during onwards which shows the less unavailability of facilities in respect to others ( , ) . risk analysis revealed that very high vulnerability has been observed in wards followed by high risk areas with wards (nearly % to total wards under study). as a whole high to very high wards coved nearly % of the studied area (fig. d) this indicates a disquieting situation for such infectious disease. most of the wards located in central and some portion of north kolkata. four wards also most of the containment zones, high slum population share and density with excessive dependency on community toilet and tube well are the driving forces behind this high risk factor in these areas [ ] [ ] [ ] . on the other hand low working population, low per-capita income, high household density in topsia, tiljala, gardenreach, rajabazar, beliaghata, burabazar, jorabagan area make more hazard prone. earlier evidences of dengue fever also found the same type of hotspots in the past years. unhygienic and close spacing of settlements, not maintaining social distancing and very low per-capita space availability (nearly - persons in an - sq. feet room) make the region hotspots and rightly most of the sars-cov- cases found from these places. the spatiality of sars-cov- has wide-ranging expressively from april to may , and it has exhibited consistency in northern and central part of kmc. a grouping of irregular and epidemic patterns of human-to-human exposure has been observed during this period [ ] . by contrast, the distribution curve for cities in india, mumbai has been experienced largest outbreak in india where kolkata has constrains its spike. purely temporal cluster analyses of sars-cov- infection illustrated significant clusters in april and may of . this finding is consistent with previous studies of eifan [ ] , which showed significant peaks in mers-cov incidence between march and may in saudi arabia in . in this study, sars-cov- was observed during mass gatherings in different part of india, which are inconsistent with previous studies [ ] . this indicates another knowledge gap regarding the mode of transmission that needs further investigation. though the transmission and outbreak has not a sudden one, major urban centres have been found more vulnerable to transmit this h h virus. high population density, concentration of high amount of slum population with high household density with low per-capita income shows the main driving factors for such outbreak. the people of those places are compel to break the said social distancing, as the people have a little, very little space for stay in household (in some cases they lived in sq. feet area with - persons), they used to go and use community toilet, tube well sharing with other hundreds of population make the situation more grave ( , , ) . quick preparation and execution of the containment plan, deployment of adequate human resources (mainly from health workers) at ward level, active surveillance in the well-defined geographical area and higher test (rapid antibody test) can minimise the chance of transmission in community level. as the spacing of households is very congested, such actions 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institutional affiliations acknowledgements the authors acknowledge the department of bustee service, kmc, hogg buildings ( rd floor), kolkata for providing data support for the study.authors' contributions sp and sb designed the study; sh, ab and bm contributed to data acquisition; sk and sm carried out the statistical analysis; sp and sb drafted the manuscript. all authors contributed to the interpretation of data and revision of the manuscript. all authors read and approved the final manuscript.funding this work has not been supported by any state or central government funding agencies. key: cord- - iee jc authors: roy, s. title: spread of covid- in india: a simple algebraic study date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: iee jc the number of patients, infected with covid- , began to increase very rapidly in india from march . the country was put under lockdown from march . the present study is aimed at providing a simple algebraic analysis of the trend that is evident in the spread of the disease in this part of the world. the purpose of this algebraic approach is to simplify the calculation sufficiently by deviating from the standard techniques that are conventionally used to construct mathematical models of epidemics. the predictions, obtained from this algebraic study, are found to be in reasonable agreement with the recorded data. using this mathematical formulation we have determined the time variation of the number of asymptomatic patients, who are believed to play a major role in spreading the disease. we have discussed the effect of lockdown in reducing the rate of transmission of the disease. on the basis of the proposed models, predictions have been made regarding the possible trend of the rise in the number of cases beyond the withdrawal of lockdown. all these things have been calculated by using very simple mathematical expressions which can be easily understood and used by those who have a rudimentary knowledge of algebra. in early december , a cluster of cases of pneumonia had been reported in wuhan, hubei province of china. a few days later, the health authorities of that country declared that this cluster was associated with a newly discovered coronavirus (sars-cov- ) and the infectious disease caused by it was named coronavirus disease (covid- ) by the world health organization (who) [ , ] . this outbreak of novel coronavirus pneumonia has been declared a public health emergency of international concern by who. as of : pm cest, may , there have been , , confirmed cases of covid- , including , deaths, reported to who globally [ ] . according to who, no pharmaceutical products have yet been shown to be safe and effective for the treatment of covid- . invitro studies have shown that chloroquine, an immune-modulant drug, which has been traditionally used for the treatment of malaria, is effective in reducing viral replication in infections including the sars-associated coronavirus (cov) and mers-cov [ , ] . it has been revealed by the current studies that respiratory symptoms of covid- such as fever, dry cough and dyspnea are the most common manifestations, quite similar to severe acute respiratory syndrome (sars) in and middle east respiratory syndrome in (mers), which firmly indicates the droplet transmission and contact transmission of the virus. apart from the typical respiratory disorder, there are less common features like diarrhea, nausea, vomiting, and abdominal discomfort that have been found significantly in different degrees among different study populations [ ] . recent evidences have revealed that covid- virus is transmitted between people through respiratory droplets and contact routes [ ] [ ] [ ] [ ] [ ] . transmission through droplets takes place when a person is in close contact (within metre) with another person, who has developed respiratory symptoms (coughing or sneezing) due to covid- infection, and is thereby at risk of having his/her mucosae (mouth and nose) or conjunctiva (eyes) exposed to potentially infective respiratory droplets (which are generally known to be greater than - μm in diameter). droplet transmission can also occur through fomites in the immediate vicinity around the infected person [ ] . thus, the transmission of the virus that causes covid- can occur by direct contact with an infected person and indirect contact with surfaces in his/her immediate environment or with the objects that have been used on the infected person (e.g. stethoscope or thermometer). airborne transmission of the virus is not the same as droplet transmission. it is caused by the microbes within droplet nuclei, which are generally like particles less than μm in diameter, and which are released by the evaporation of larger droplets or exist within dust particles. these particles may remain in the air for long periods of time and they can be transmitted to persons over distances greater than metre [ ] . the first case of covid- infection was reported in india on january . as of : am ist, may , a total of , cumulative cases of infection including , active cases, , recoveries and , deaths in the country have been confirmed by the ministry of health and family welfare [ ] . so far, the government has issued necessary guidelines and taken several measures to spread awareness regarding covid- and also to enforce social distancing of its citizens to break the chain of transmission of the disease. on march , a nationwide lockdown was announced for a period from march to april . on april , this lockdown was extended till may . on may it was further extended till may . chatterjee et al. have carried out a detailed study to accumulate evidence that can guide research activities towards the prevention and control such a pandemic spreading so rapidly in india [ ] . in another study, agarwal et al have elaborately discussed the necessity for a proper medical infrastructure to be built up in india to tackle the flow of patients and to ensure the safety of the healthcare workers [ ] . through a detailed mathematical analysis, mandal et al have discussed the policies to be implemented to prevent the spread of the virus by community transmission [ ] . some other mathematical models, based on several standard theories, have been constructed to predict the number of infections of covid- in india with sufficient accuracy [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . these models are expected to serve as efficient tools which would certainly help the policy makers of the country, at different levels, to make proper plans to prevent the spread of this disease. in a previously published article, based on a mathematical model, we showed the effect of imposition of lockdown in reducing the rate of rise in the number of infections [ ] . it was a dynamical model which was based on a differential equation that was formulated to find the time variation of the number of asymptomatic patients, from which, the number of symptomatic cases was estimated. in the present study, we have constructed the entire mathematical structure upon a simple algebraic equation. the purpose of choosing this method is to make the article comprehensible to the policy makers of the country who come from various educational backgrounds. the models that are based on calculus lead to very accurate results or predictions but they are sometimes very difficult to understand for those who are not sufficiently trained in mathematics. in most of the cases, the conventional models do not lead to mathematical expressions from which predictions can be made. one needs to do numerical calculations (rather than analytical) to arrive at a prediction. in view of the severity and urgency of the crisis caused by covid- outbreak, mathematical models should be created in a simple way so that the can be easily understood, amended or modified if necessary and applied extensively by the persons who are responsible for decision making regarding infrastructural arrangements and also the formulation and implementation of rules to be imposed upon the society to ensure social distancing. the calculations involved in the present study are extremely simple in comparison to the ones where one needs to solve a set of coupled differential equations keeping under consideration various factors connected to the society and the constraints of the actual situations caused by the pandemic and the measures to control it. in the present article, we have discussed the step by step construction of an algebraic structure that allows one to derive an expression representing the time evolution of the number of asymptomatic patients in the country. like our previously published article, which was based on calculus, this model has an underlying assumption that, due to the lack of tests in sufficient numbers, the statistics regarding the number of patients infected, as declared by the government, are actually about the number of symptomatic patients. after detection, most of them are put under isolation, during which they are not much capable of spreading the disease to other persons. therefore, the asymptomatic carriers can be regarded as the main agents of transmission of the virus in the society. the present study is based on three models whose unknown parameters have been determined by fitting these models to the actual data of covid- infections in india. for this purpose we have used the statistics of the number of infected persons in india, during the period from march to may , obtained from the government sources [ ] . using these three models we have determined the time evolution of the number of infected persons over this period. we have graphically shown the positive impact of the imposition of lockdown throughout the country. the present study makes predictions regarding the number of infected cases beyond may , the date up to which the lockdown will continue as per the last announcement made on may . these models show very clearly that a high degree of social distancing has to be maintained to slow down or prevent the transmission of the disease in the country. let and be the numbers of asymptomatic patients on the first and the second days of the span of time under consideration. we propose to express in terms of in the following way. ( ) in equation ( ), is the average number of persons who become infected with covid- , after coming in close contact with each of these carriers of the disease, on the first day. here denotes the fraction of who have undergone a transformation from asymptomatic to symptomatic modes on the first day. it is assumed in the present model that a patient, after being identified as symptomatic, is put into absolute isolation from the society. it prevents the patient completely from playing any role in the transmission of the disease. it is also assumed that no new asymptomatic or symptomatic carrier has entered the geographical region under consideration, during the entire span of time for which this study has been conducted. the subscript of is connected to the serial number of the day concerned. when a lockdown is imposed, the social mixing pattern changes significantly, resulting in a change in the number of persons coming in contact with an asymptomatic carrier. let us consider a combination of three consecutive periods, of , & days respectively, during which we . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint have no-lockdown, lockdown and again no-lockdown situations successively in a country. the time dependence of (i.e. dependence upon n), under such situations, can be expressed as, here, the value of each of these three functions, ( ), ( ) and ( ), is unity over the periods of , & days respectively, and zero otherwise. thus, the values of would be equal to the constants , and again , respectively, during these three periods. we have for , for and for . here and can be regarded, respectively, as the measures of social distancing during lockdown and no-lockdown periods. they decrease as social distancing increases. like , the subscript of corresponds to the serial number of the day under consideration. its time dependence is due to an assumption that the number of asymptomatic patients may increase at such a rate that, the fraction of them turning into symptomatic ones on a certain day, cannot have a constant value. one of the three forms of , introduced in the present paper, has been assumed to have a constant value (denoted by in section . ), which might be regarded as a kind of time-average of that fraction. a generalized version of equation ( ) can be expressed as, for , one obtains equation ( ) from equation ( ). putting in equation ( ), one gets, substituting for in equation ( ) from equation ( ), one obtains, continuing in this fashion, equation ( ) can be written as, the number of cases ( ) that become symptomatic from the asymptomatic type, on the day, is then given by, therefore, the total number of symptomatic cases recorded till the day is given by, in equations ( ), ( ) and ( ) ( ) ( ) ( ) , as per equation ( ). if the third phase is absent we have ( ) ( ) . there can be many such phases coming one after another. for a process, with l number of such phases, is given by, . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . here for the odd values of m and for the even values of m. equation ( ) actually gives us the value that needs to be compared with the number that is declared by the government as the total number of confirmed covid- cases registered in the country till the n th day. it is the cumulative count of asymptomatic cases till that day. without any imposition of lockdown, over the entire period under study, we must have , according to equation ( ) . equation ( ) will then have the following form. relative proportions of the symptomatic and asymptomatic patients, denoted by ( ) and ( ) respectively, are given by the following two expressions. ( ) and ( ) can be expressed in percentages by multiplying their expressions with . as an average estimate one can say that, for each symptomatic case there are or ( ) ( ) number of asymptomatic cases, which remain mostly undetected in india due to lack of testing facilities. combining the numbers of symptomatic and asymptomatic cases, one gets the total number of cumulative infections in the country. dividing this value by the present population of india (n), one can get the fraction of the population infected with covid- . this fraction, denoted by here, is given by, can be expressed in percentages by multiplying its expressions with . . for the present article, we have assumed three functional forms of described in the following three models. here we assume the following relation for . , ( )- in equation ( ) , and are constants. the parameter determines how fast changes for any change of j. substituting this into equations ( ), ( ) and ( ), respectively, we get, . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . here we assume the following relation for . in equation ( ), and are constants. the parameter determines how fast changes for any change of j. substituting this into equations ( ), ( ) and ( ), respectively, we get, here we consider the following form for . in equation ( ), is a constant. substituting this into equations ( ), ( ) and ( ), respectively, we get, for the present study we have used the following expressions for ( ), ( ) and ( ) respectively, which are required for equations ( ) and ( ). according to the definitions of ( ), ( ) and ( ), discussed previously, they must behave like rectangular pulses of unit heights. for this purpose, one must choose the value of the constant to be sufficiently large in comparison to the values of , and . . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . graphical interpretation figure shows the time variation of the number of symptomatic patients ( ). the black circles represent the data regarding the confirmed covid- cases registered in india from march (i.e. n = ) to may (i.e. n = ), as obtained from the government sources [ ] . the red circles represent the values predicted by model- of the present study. the predictions from the model are in reasonable agreement with the recorded data for a certain set of parameter values which are, , , , and . these values have been used in the present study for model- . (fig. ) . lockdown was in effect from march . the impact of lockdown is evident from the reduction of slope of both curves. figure shows the time variation of the number of asymptomatic and symptomatic cases, over the period from march (i.e. n = ) to may (i.e. n = ), based on model- , using the parameter values obtained by fitting this model to the actual data (fig. ) . lockdown was in effect from march . the impact of lockdown is evident from the reduction of slope of both curves. figure depicts the time evolution of the number of asymptomatic and symptomatic cases, over the period from march (i.e. n = ) to may (i.e. n = ), based on model- , using the parameter values obtained by fitting this model to the actual data (fig. ) . lockdown was in effect from march . the impact of lockdown is evident from the reduction of slope of both curves. figure shows the variation of the number of symptomatic patients as a function of time, with and without the imposition of lockdown, over the period from march (i.e. n = ) to may (i.e. n = ), from model- , using the parameter values obtained by fitting the model to the actual data (fig. ) . for the case of no lockdown imposition, we have taken . as per prediction of this model, the number ( ) would have been nearly . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint times larger than its recorded value, on the th day, if the lockdown had not been in effect from the th day onwards. figure shows the variation of the number of symptomatic patients as a function of time, with and without the imposition of lockdown, over the period from march (i.e. n = ) to may (i.e. n = ), from model- , using the parameter values obtained by fitting the model to the actual data (fig. ) . for the case of no lockdown imposition, we have taken . as per prediction of this model, the number ( ) would have been nearly times larger than its recorded value, on the th day, if the lockdown had not been in effect from the th day onwards. figure shows the variation of the number of symptomatic patients as a function of time, with and without the imposition of lockdown, over the period from march (i.e. n = ) to may (i.e. n = ), from model- , using the parameter values obtained by fitting the model to the actual data (fig. ) . for the case of no lockdown imposition, we have taken . as per prediction of this model, the number ( ) would have been nearly times larger than its recorded value, on the th day, if the lockdown had not been in effect from the th day onwards. figure shows the time variation of the number of symptomatic patients, in three phases: ) pre lockdown, ) during lockdown, ) post lockdown, from model- , where the lockdown continues till may (as per the announcement made on may ), using the parameter values obtained by fitting the model to the actual data (fig. ) . it has been assumed here that lockdown won't continue beyond may . here for march . figure shows the time variation of the number of symptomatic patients, in three phases: ) pre lockdown, ) during lockdown, ) post lockdown, from model- , where the lockdown continues till may (as per the announcement made on may ), using the parameter values obtained by fitting the model to the actual data (fig. ) . it has been assumed here that lockdown won't continue beyond may . here for march . figure shows the time variation of the number of symptomatic patients, in three phases: ) pre lockdown, ) during lockdown, ) post lockdown, from model- , where the lockdown continues till may (as per the announcement made on may ), using the parameter values obtained by fitting the model to the actual data (fig. ). it has been assumed here that lockdown won't continue beyond may . here for march . figure shows the time evolution of the number of asymptomatic patients from model- , for three values of the parameter b, over a period of days, where lockdown continues from the th day onwards. these three values of b are smaller than the value obtained by fitting this model to the recorded data (fig. ) . a smaller value of b means greater degree of strictness in enforcing the lockdown. this figure shows that, for a sufficiently small value of b, starts decreasing just after the imposition of lockdown. figure shows the time evolution of the number of symptomatic patients from model- , for three values of the parameter b, over a period of days, where lockdown continues from the th day onwards. these three values of b are smaller than the value obtained by fitting this model to the recorded data (fig. ) . a smaller value of b means a greater degree of social distancing in the lockdown. this figure shows that, for a sufficiently small value of b, the slope of starts decreasing just after the imposition of lockdown, approaching gradually a . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . figure shows the time evolution of the number of asymptomatic patients from model- , for three values of the parameter b, over a period of days, where lockdown continues from the th day onwards. these three values of b are smaller than the value obtained by fitting this model to the recorded data (fig. ) . a smaller value of b means a greater degree of social distancing in the lockdown. this figure shows that, for a sufficiently small value of b, starts decreasing just after the imposition of lockdown. ), assuming the lockdown to continue till may (as per the announcement made on may ) and not beyond. the smallest value of the ratio of a/s is / . due to lack of tests in sufficient numbers, the asymptomatic cases mostly remain undetected. therefore, we may conclude that for every two confirmed cases there are at least three undetected cases in india. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint the present study is based on an assumption that a symptomatic patient is put into complete isolation and thereby he/she is prevented completely from spreading the disease. this cannot be entirely true under the present circumstances. the infection in the body of a person, who has developed some symptoms, can remain undiagnosed mainly due to two reasons. one of the reasons is that some of the symptoms are very much similar to those of other diseases (caused by influenza viruses). the other reason is obviously the lack of testing facilities in the country. this method of algebraic study or prediction can be improved by taking into consideration the role played by the symptomatic patients in the transmission of the disease. another aspect, which has a plenty of scope for modification, is the functional form of of equation ( ) . apart from the three choices, in this regard, described in the sections . - . , there can be many other functions that can represent the time dependence of this parameter. we have chosen the simplest ones. a limitation of this calculation is that the values of the parameters a and b, have been assumed to remain constant over the normal (i.e. pre/postlockdown) period and the lockdown period respectively. in reality, the social mixing or distancing patterns may vary frequently with time during a pandemic. in spite of such limitations, the predictions from these models are in reasonable agreement with the actual records, for a certain set of parameter values. based on this set, the most important finding of the present study is actually a message that social distancing has to be maintained as stringently as possible, which is quite evident from the figures - . the value of the parameter b, which is an indicator of social distancing during lockdown, needs to be sufficiently decreased, to cause to fall with time and also to get a flat curve for . the continuing -ncov epidemic threat of novel coronaviruses to global health -the latest novel coronavirus outbreak in wuhan prevalence of comorbidities and its effects in patients infected with sars-cov- : a systematic review and meta-analysis website of the world health organization (who) effects of chloroquine on viral infections: an old drug against today's diseases? the lancet infectious diseases chloroquine for the novel coronavirus sars-cov- covid- : gastrointestinal manifestations and potential fecal-oral transmission community transmission of severe acute respiratory syndrome coronavirus a familial cluster of pneumonia associated with the novel coronavirus indicating person-to-person transmission: a study of a family cluster early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia clinical features of patients infected with novel coronavirus in wuhan active monitoring of persons exposed to patients with confirmed covid- -united states surface environmental, and personal protective equipment contamination by severe acute respiratory syndrome coronavirus (sars-cov- ) from a symptomatic patient title: modes of transmission of virus causing covid- : implications for ipc precaution recommendations website of the ministry of health and family welfare, government of india the novel coronavirus disease (covid- ) pandemic: a review of the current evidence guidance for building a dedicated health facility to contain the spread of the novel coronavirus outbreak prudent public health intervention strategies to control the coronavirus disease transmission in india: a mathematical model-based approach analyzing covid- pandemic with a new growth model for population ecology modeling and predictions for covid spread in india anticipating the novel coronavirus disease (covid- ) pandemic. (a preprint from www estimation of undetected covid- infections in india. (a preprint from www covid- prediction for india from the existing data and sir(d) model study. (a preprint from www predictions for covid- outbreak in india using epidemiological models. (a preprint from www predictive model with analysis of the initial spread of covid- in india. (a preprint from www covid- : mathematical modeling and predictions. (a preprint from www.researchgate.net) spread of covid- in india: a mathematical model there is no conflict of interest associated with this article. no financial assistance has been received for this research. key: cord- -r lv us authors: asad, ali; srivastava, siddharth; verma, mahendra k. title: evolution of covid- pandemic in india date: - - journal: trans indian natl doi: . /s - - -y sha: doc_id: cord_uid: r lv us a mathematical analysis of patterns for the evolution of covid- cases is key to the development of reliable and robust predictive models potentially leading to efficient and effective governance against covid- . towards this objective, we study and analyze the temporal growth pattern of covid- infection and death counts in various states of india. our analysis up to august , , shows that several states (namely maharashtra, tamil nadu, west bengal) have reached [formula: see text] power-law growth, while gujarat and madhya pradesh exhibit linear growth. delhi has reached [formula: see text] phase and may flatten in the coming days. however, some states have deviated from the universal pattern of the epidemic curve. uttar pradesh and rajasthan show a gradual rise in the power-law regime, which is not the usual trend. also, bihar, karnataka, and kerala are exhibiting a second wave. in addition, we report that initially, the death counts show similar behavior as the infection counts. later, however, the death growth rate declines as compared to the infection growth due to better handling of critical cases and increased immunity of the population. these observations indicate that except delhi, most of the indian states are far from flattening their epidemic curves. covid- pandemic has been impacting the life and economy across the globe since december and has caused major disruptions (walker et al. ) . as of august , covid- has infected nearly million people across the globe with countries in community transmission stage (world health organization) leading to significant efforts towards control (rawaf et al. ) , modelling (barkur and vibha ; chatterjee et al. a; giordano et al. ) , search for a cure (le et al. ) for covid- across the world and india (chatterjee et al. b; singhal ) . keeping this in mind, in this paper, we analyze the evolution of covid- cases and deaths in various indian states. specifically, we study and model the temporal evolution of infection and death counts for various time intervals and analyze their variations. at the onset of the covid- pandemic, india imposed the world's strictest nationwide lockdown beginning from march , (lancet ). however, preparedness and impact of the lockdown varied across states depending upon past experiences such as the nipah virus in kerala or odisha's disaster response due to recent natural disasters (lancet ; dore ). therefore, attempts have been made to study the impact of covid- in india. sardar et al. ( ) mathematically assessed the impact of the first days of the lockdown in terms of the total number of cases. tomar and gupta ( ) employed deep learning to provide a day forecast of the death cases and recovered cases. chatterjee et al. ( a) provided estimates on the growth of infections using nonpharmacological interventions such as social distancing and lockdown. network-based epidemic growth models have also been evolved for modeling covid- pandemic (marathe and vullikanti ) . epidemiological models, e.g., seir model, are being evolved to suit the national conditions (bjørnstad ; daley and gani ; labadin and hong ; lópez and rodo ; peng et al. ) . a model based on delaydifferential equations considers the effects of past events (shayak and rand ) . ranjan ( ) studied the effects of various factors in the dynamics of epidemic spread. due to lack of ample historical data ,many models for studying covid- are appearing everyday (chauhan et al. ; bhardwaj ; tiwari ; sharma and nigam ) . however, none of them is able to model the epidemic pattern to sufficient accuracy (holmdahl and buckee ) . furthermore, predictive models are based on the underlying patterns of covid- data (petropoulos and makridakis ; verma et al. ) . note however that the patterns of covid- cases vary due to the extent of government measures (hale et al. a, b) . consequently, forecasting covid- is quite complex. verma et al. ( ) and chatterjee et al. ( c) analyzed infection counts of leading countries. they observed the emergence of power-laws after an initial exponential phase. they showed that china and south korea followed powerlaw regimes-t , t, √ t-before flattening their epidemic curves. also, the infection data for european countries (spain, france, italy, and germany), usa, and japan followed a power-law regime ( t n , ≤ n ≤ ). they attributed these characteristics to long-distance travel and asymptomatic carriers. they concluded that √ t regime is a common feature among all infection curves that exhibit saturation. in this paper, we extend the works of verma et al. ( ) and chatterjee et al. ( c) to the severely affected indian states. we observe that some states exhibit t and t growth phases, while some others have linear or √ t growths. bihar, karnataka, and kerala appear to have second waves of infections. these findings will be useful to the epidemic control panel. we discuss our results in "analysis and results" section and conclude in "discussions and conclusions" in this paper, we analyze the covid- infection and death counts in nineteen indian states: maharashtra, tamil nadu, delhi, gujarat, uttar pradesh, rajasthan, madhya pradesh, west bengal, karnataka, bihar, and kerela. we combine the data of all the north-eastern (ne) states (arunachal pradesh, assam, manipur, meghalaya, mizoram, nagaland, sikkim, and tripura) because the counts for each of them is rather small for any statistical analysis. as of august , , the above states constitute about % ( . × ∕ . × ) of the total covid- infections in india. for our analysis, we employed the real-time data available at the website of ministry of health and family welfare, government of india. we have consolidated the data using the application programming interface (apis) from covid- india tracker. for our analysis, we consider data till august , . first, we perform a temporal evolution analysis of infection count, which is denoted by i(t), where t is time in days. in fig. , we plot the time series of i(t) and its derivative ̇i (t) in semi-logy (the y-axis has logarithmic scale, while the x-axis has linear scale) format using red and blue curves respectively. the starting date, listed in table , is chosen from the day the infection began to increase in the respective states. similarly, we studied the evolution of total death cases for six states (maharashtra, delhi, gujarat, tamil nadu, west bengal, and uttar pradesh) that have reported a large number of deaths. the cumulative death cases are denoted by d(t). the time series of d(t) and its derivative Ḋ (t) are plotted in fig. in semi-logy using red and blue curves respectively. also, the starting date (see table ) is considered from the day death counts begin to increase. the starting dates for the infection plots and the death plots are not the same. this is because the death cases peaks after a delay from the infection peak due to the incubation period. we employ exponential and polynomial functions to compute best-fit curves on different regions of i(t) and d(t) data. the time series for both i(t) and d(t) follow exponential regimes during the early phases of the pandemic and subsequently transition to power-law regimes. this is in accordance with the earlier work of verma et al. ( ) and chatterjee et al. ( c) . the best-fit functions along with their relative errors are listed in tables and for the infected and death cases respectively. the error for a given fit is calculated using the mean of the absolute difference between the best-fit curve and the corresponding actual curve. in table , we report rel. error = (| i fit − i actual | × )∕i actual . the epidemic curves transition to power-law regimes after the exponential phase. we employ python's polyfit function to calculate the best-fit polynomials for these regions. the polyfit function employs regression via minimization of error and provides best-fit curves. verma et al. ( ) and chatterjee et al. ( c) showed that the epidemic curves of many countries pass through a series of polynomials, t , t , t, √ t , before saturation. the intermediate power-law regimes are believed to appear due to lockdown and social restrictions. as shown in fig. , many states deviate from the above patterns, which are possibly due to unlocking in india on june . note that the unlocking of various states occurred at a later date. in the following discussion, we describe how the i(t) curves for various states behave. the infection curves of maharashtra, tamil nadu, and west bengal, as well as the combined ne-states, exhibit a t regime followed by a t phase. whereas, gujarat and madhya pradesh have reached a linear growth after going through a t regime. the i(t) curve of delhi follows t and linear regimes before reaching a √ t growth. this trend indicates that delhi is close to saturating its epidemic curve. it is worth noting that the states mentioned above follow the universal pattern of the epidemic curve (chatterjee et al. c ). unfortunately, the power-law regime of some states does not follow the universal trend. for instance, uttar pradesh reached a t phase after passing through t and t regimes. also, the infection curve of rajasthan reached t after following t and linear regimes. these states observed a gradual growth in daily cases as their i(t) curves pass through the power-law regime. however, this growth is still not exponential and hence does not amount to a second wave. note that such deviations from the universal pattern are indicators for authorities to take suitable action. the infection curves of bihar, kerela, and karnataka exhibit a rise which is preceded by a region of a linear regime or a nearly flattened curve. also, this growth of the i(t) curve is exponential indicating a second wave for the epidemic (de castro ). the emergence of this phase corresponds with relaxation in lockdowns and an increase in testing intensity. in bihar, such a surge may have resulted from the influx of migrant workers and students from different parts of the country. the best-fit curves for the second wave are functions of t , where t = t − t . here, t corresponds to the day from which the daily count shows an unprecedented rise after a region of decline. similar to the i(t) curves, the d(t) curves begin with exponential regimes ( d(t) = a d exp( d (t)) ), and then transition to fig. semi-logy plots of total infection count (i(t)) vs. time (t) (red thin curves) and ̇i (t) vs. t (blue thick curves) for the eleven states individually and consolidated for north-eastern indian states. the dotted curves represent the best-fit curves. refer table for the best-fit functions power-law regimes ( t , t , t). interestingly, for many states, the power-laws for both i(t) and d(t) curves are qualitatively similar. for example, both i(t) and d(t) curves for gujarat exhibit a t region followed by a linear phase (t). this further substantiates the claims of chatterjee et al. ( c) that d(t) is proportional to i(t) statistically. this is because a fraction of the infected population is susceptible to death. note that the growth of d(t) curve has declined in many states with respect to their i(t) curves. this may be attributed to immunity developed in the community, better handling of critical cases, plasma therapy, etc. the values of i and d represent the growth rates of infected and death cases, respectively. it must be noted that i and d depend on various factors such as immunity level, the average age of the population, population density, local policy decisions (lockdowns, testing intensity, social distancing, healthcare facilities), etc. in figs. and , we also plot daily infection and death counts, which are represented by ̇i (t) and Ḋ (t) , respectively. we calculate the derivative using python's gradient function and take a -day moving average in order to smoothen the ̇i (t) and Ḋ (t) curves. we observe that in the exponential regimes, the daily counts are proportional to the cumulative number of infected and death cases i.e. ̇i ≈ i i and Ḋ ≈ d d . verma et al. ( ) show that power-law regime can be approximated as i(t) ∼ at n , and hence, ̇i ∼ i − ∕n . similarly, it can be shown that for power-laws Ḋ ∼ d − ∕n . this shows that the daily counts are suppressed in the power-law region compared to the exponential phase. note that in the linear growth regime, ̇i ≈Ḋ ≈ constant, implying a constant daily count. the daily count is expected to decrease after a linear regime (see delhi in fig. ) , however, this may not be the case when a second wave emerges. an interesting question is whether the indian states with lower covid- cases are closer to saturation. to investigate this issue, we compute the infection time series for india without the three worst affected states, which are maharashtra, tamil nadu, and delhi. we denote this time series as Ī (t) , and it is computed as Ī (t) = i(t) ind − {i(t) mh + i(t) tn + i(t) dl } . in fig. , we plot Ī (t) and ̇Ī (t) , and compare them with the total i(t) and ̇i (t) . from the plots it is evident that both the plots exhibit exponential and power-law regimes (see table ), and that Ī (t) and i(t) are proportional to each other. although these states comprise of almost % ( × ∕ × ) of the total infection count in india, their removal from total i(t) does not cause any behavioural change in the Ī (t) curve. based on these observations we conclude that almost all the affected states shown in fig. are following similar epidemic evolution. in fig. , we plot i(t) vs. t curve in log-log (both x-axis and y-axis has a logarithmic scale) format for both cases shown in fig. . in the power-law region, we fit a power-law ( i(t) = at n ) instead of a polynomial curve. the exponential n of power-law fit ( n = ) differs from that calculated using polynomial fit ( n = , ). this analysis indicates that for a epidemic curve, the power-law exponent is typically larger than the highest power of the fig. semi-logy plots of total death cases (d(t)) vs. time (t) (red thin curves) and Ḋ (t) vs. t (blue thick curves) for six states of india. the dotted curves represent the best-fit curves (see table ) ( ) . t − t + t − (± . %) ( ) t − t + × (± . %) ( ) . e . t (± . %) (march ) ( ) . e . t (± . %) ( ) . t − . t + t − (± . %) ( ) . t − t + (± . %) ( ) . t + t − (± . %) ( ) t − (± . %) ( ) t − t + × (± . %) ( ) . e . t (± . %) (march ) ( ) . t − t + (± . %) ( ) . t − t + t − (± . %) ( ) t − t + (± . %) ( ) . e . t (± . %) (march ) ( ) . t + . t − (± . %) ( ) . e . t (± . %) ( ) . t − . t + t − (± . %) ( ) . t + (± . %) ( ) e . t (± . %) ( ) . t + t − (± . %) ( ) . t − t − t + (± . %) the order of the functions for respective states correspond to the bestfit curves marked on i(t) of fig. table best-fit functions for the death cases and corresponding relative errors for major indian states the order of the functions for respective states correspond to the bestfit curves on d(t) of fig. states (start date) best-fit functions with errors ( ) . e . t (± . %) (april ) ( ) . t − . t + . t + (± . %) ( ) . t − t + (± . %) ( ) t − (± . %) west bengal ( ) . e . t (± . %) (march ) ( ) . t − t + (± . %) uttar pradesh ( ) . e . t (± . %) (april ) ( ) . t − . t + . t − (± . %) ( ) . t − t + (± . %) north east ( ) e . t (± . %) (march ) ( ) e . t (± . %) corresponding polynomials (the best-fit curve). still, highorder polynomials will lead to larger power-law exponent. we can summarize the findings of the state-wise epidemic study as follows. most of the indian states exhibit rise in the growth of infected cases. some have reached up to t part of the epidemic evolution, while others have reached the linear regime ( i(t) ∼ t ). unfortunately, uttar pradesh and rajasthan show an increasing trend in the power-law phase. while bihar, kerala, and karnataka are observing a second wave of the epidemic. however, delhi exhibits a decrease in daily cases and is closer to saturation. the overall count in india has shifted from t to t . these observations indicate that we are far from saturation or flattening of the epidemic curve. we conclude in the next section. in this paper, we analyzed the cumulative infection and death counts of the covid- epidemic in the worstaffected states of india. the respective time series, i(t) and d(t) , exhibit exponential and power-law growth in the epidemic. maharashtra, tamil nadu, and west bengal and combined ne-states have reached t growth. while gujarat and madhya pradesh have reached linear phase. the infection rate in delhi exhibits a √ t regime which indicates that it is close to flattening its curve. all these states follow the universal trend of the epidemic curve. however, uttar pradesh and rajasthan, as well as states exhibiting a second wave (bihar, kerela, and karnataka) deviate from the universal pattern. we remark that such deviations are indicators for the authorities to take suitable action. the epidemic in india has grown alarmingly after the lockdown restrictions were lifted. note that the lifting of lockdown is expected to increase the social contacts, and hence the epidemic growth. regarding the death count, among the six states we analysed, west bengal and uttar pradesh exhibit t growth, while tamil nadu and maharashtra show linear growth. delhi and gujarat have reached √ t regime. these observations indicate that the death rate exhibits a decline as compared to the growth rate of the infected cases. this may be attributed to immunity developed in the population (tay et al. ; kwok et al. ) and better treatment of critical cases (plasma therapy, more ventilators, early detection, etc.). at the initial stage, the death rate and infection rate are nearly proportional to each other, consistent with the earlier observation of chatterjee et al. ( c) . we also observe that at present, the infection count in the whole country is increasing as t . these observations indicate that we are far from the flattening of the epidemic curve. the present work is based on data analytics, rather than focussing on specific epidemic models which are being constantly revised in order to successfully forecast the epidemic evolution (peng et al. ; lópez and rodo ; mandal et al. ) . note, however, that the epidemic models involve many free parameters that lead to ambiguities and difficulties in the forecasting of the epidemic evolution. our focus on data analytics is due to the latter reason. our work shows that the power laws in the epidemic curves indicate the stage of the epidemic evolution. this feature helps us table ). both i(t) (green curve) and Ī (t) (magenta curve) curves follow a power-law, i.e., i(t) = at , where a = . . the thick blue and brown curves in the plot depict the derivatives of i(t) and Ī (t) respectively table best-fit functions for cumulative cases and the respective relative errors for various stages of evolution shown in fig. cases best-fit functions and errors india: case-i ( ) e . t (± . %) ( ) t − t + × (± . %) ( ) . t − t + t − × (± . %) india: case-ii ( ) e . t (± . %) ( ) t − t + (± . %) ( ) . t − t + × t − × (± . %) in contrasting the evolution of the covid- epidemic in various states of india. sentiment analysis of nationwide lockdown due to covid outbreak: evidence from india a predictive model for the evolution of covid- epidemics: models and data using r healthcare impact of covid- epidemic in india: a stochastic mathematical model the novel coronavirus disease (covid- ) pandemic: a review of the current evidence evolution of covid- pandemic: power-law growth and saturation regression analysis of covid- spread in india and its different states cambridge university press, cambridge de castro f ( ) modelling of the second (and subsequent) waves of the coronavirus epidemic. spain and germany as case studies covid- : collateral damage of lockdown in india modelling the covid- epidemic and implementation of population-wide interventions in italy variation in government responses to covid- oxford covid- government response tracker wrong but useful-what covid- epidemiologic models can and cannot tell us herd immunity-estimating the level required to halt the covid- epidemics in affected countries transmission dynamics of -ncov in malaysia lancet t ( ) india under covid- lockdown the covid- vaccine development landscape a modified seir model to predict the covid- outbreak in spain and italy: simulating control scenarios and multi-scale epidemics prudent public health intervention strategies to control the coronavirus disease transmission in india: a mathematical model-based approach computational epidemiology ministry of health and family welfare ( ) govt. of india epidemic analysis of covid- in china by dynamical modeling forecasting the novel coronavirus covid- temporal dynamics of covid- outbreak and future projections: a data-driven approach unlocking towns and cities: covid- exit strategy assessment of days lockdown effect in some states and overall india: a predictive mathematical study on covid- outbreak covid- predictions using a gauss model modeling and forecasting for covid- growth curve in india self-burnout -a new path to the end of covid- a review of coronavirus disease- (covid- ) the trinity of covid- : immunity, inflammation and intervention modelling and analysis of covid- epidemic in india prediction for the spread of covid- in india and effectiveness of preventive measures covid- pandemic: power law spread and flattening of the curve report the global impact of covid- and strategies for mitigation and suppression situation report as on th the authors thank soumyadeep chatterjee and shashwat bhattacharya for their help in early works. we also thank shayak bhattacharya, prateek sharma, and anurag gupta for useful discussions. this project is supported by a serb matrics project serb/f/ / - . ali asad is supported by indo-french (cefipra) project - . key: cord- - c g hqx authors: das, sourish title: prediction of covid- disease progression in india : under the effect of national lockdown date: - - journal: nan doi: nan sha: doc_id: cord_uid: c g hqx in this policy paper, we implement the epidemiological sir to estimate the basic reproduction number $mathcal{r}_ $ at national and state level. we also developed the statistical machine learning model to predict the cases ahead of time. our analysis indicates that the situation of punjab ($mathcal{r}_ approx $) is not good. it requires immediate aggressive attention. we see the $mathcal{r}_ $ for madhya pradesh ( . ) , maharastra ( . ) and tamil nadu ( . ) are more than . the $mathcal{r}_ $ of andhra pradesh ( . ), delhi ( . ) and west bengal ( . ) is more than the india's $mathcal{r}_ = . $, as of march, . india's $mathcal{r}_ = . $ (as of march, ) is very much comparable to hubei/china at the early disease progression stage. our analysis indicates that the early disease progression of india is that of similar to china. therefore, with lockdown in place, india should expect as many as cases if not more like china. if lockdown works, we should expect less than , cases by may , . all data and texttt{r} code for this paper is available from url{https://github.com/sourish-cmi/covid } the world health organization (who) declared the outbreak of the novel coronavirus, covid- , as a pandemic. it will take twelve to eighteen months to develop the vaccine for the covid- , [ ] . the absence of a vaccine makes the situation worse for the already overstretched indian health care system. for example, the number of hospital beds, per population, is less than one, [ ] -it is just one indicator to cite the miserable situation of india's health care system. in the absence of a vaccine, the 'social distancing' is the optimal strategy to control the spread of novel coronavirus, [ ] . other than social distancing, broad base rapid test and cluster tests are essential to identify those who are infected and isolate them. however, india did not have enough testing capacity as it is reported widely in media, [ ] . though, indian scientists recently developed the affordable testing kit for covid- , [ ] ; india needed a complete overhaul of its health care system in a war footing. in such a situation, india's prime minister narendra modi announced an unprecedented three-weeks nationwide lockdown on the th march . the purpose of the lockdown is to slow down the spread of the novel coronavirus; so that the govt can take a multi-prong strategy to add more beds in its network of hospitals, scale up the production of the testing kit of the covid- and personal protection equipment (ppe) for the health workers. in such a grim scenario, the important question for indian health officials is how many new confirmed cases will be seen and by what time; with the hope that the national lockdown will slow down the spread of the virus; which will buy them time to overhaul of the health care system. however, is lockdown going to provide the necessary slow down of the virus spread? even if the lockdown helps india to control the spread of the virus, it is not economically sustainable to continue the lockdown further, as large the workforce in india employed in the informal sector as a daily wage laborer. therefore, in this policy paper, we try to estimate the effect of lockdown and set up a track following which we will know if the lockdown is working! in this paper, we develop the epidemiological sir model and statistical machine learning model to predict disease progression in india. we implemented the sir model to estimate the basic reproduction number r at the national and state level. so that we identify which states require more attention. then we implement the machine learning model to predict the number of cases ahead of time so indian administration can be better prepared ahead of time. in section ( ), we introduce the database, from where the data is downloaded and model is built. in section ( ), we present the methodology to analyze and predict the data. in section ( ) we present our analysis and prediction of the covid- disease progression in india. section ( ) concludes the paper with some policy recommendations. in this paper, we used the following major databases. legendary statistician prof george box, once said "all models are wrong, but some are useful", see [ ] . keeping this in our mind, here in this paper, we take a model agnostic two-prong approach. one is to understand the severity of the ground situation; and the second is the prediction, which will help the health officials to make the plans accordingly. the epidemic models for infectious disease yield insights into the dynamic behavior of the disease spread. with new insights, health officials can develop more effective disease intervention strategies. besides, such epidemic models are also used to forecast the course of the epidemic. in addition to epidemic models, we consider the statistical machine learning (sml) models, which are extremely good for prediction. often, the interpretability of sml models is questioned. however, as we take a model agnostic approach; we can use the epidemic models to understand the ground reality while adopting the sml to achieve better prediction accuracy. the popular epidemic models for an infectious disease is the susceptible, infected, recovered (sir) model. the model considers a closed population. to start with, a few infected people are added to the population. it assumes that the mixing pattern is homogeneous. during the period of the sickness, the contagious people each infect on average r other people, who each then go on to infect r others, who are susceptible. the r is popularly known as the basic reproduction number. the r is the fundamental quantity of the disease progression, and higher r means, more people will tend to be infected in the course of the epidemic. the major advantage of the sir model is it gives a number r , which can be used to benchmark and compare the ground situation of different states and resource allocations can be made to those states which are hard hit. the sir model can be described as, where s, i, and r are the number of people in the population that are susceptible, infected and recovered. the β is the transmission rate. each susceptible person contacts β people per day; a fraction i n of which are infectious. therefore β si n move out of the susceptible group and goes into the infected group. the transmission rate is the average rate of contacts a susceptible person makes that is sufficient to transmit the infection. the parameter γ is the recovery rate, and γi is the flow out of the infected crowd and goes into the recovered group. the average duration a person spends in the infected group is γ days. for covid- , γ is around days, see [ ] . in this paper, we follow the sir implementation methodology as described in [ ] . given r , β and γ, the implementation of sir model is fairly straight forward via desolve package, a solvers for initial value problems of differential equations, see [ ] . it is known that r = β γ , see [ ] . we considered γ as , from [ ] . however, we need some good estimates of the r , so that we can implement the sir model and predict the disease progression in india. in order to estimate the r , we use the r-package called, 'r ', a toolbox to estimate r , see [ ] . the time between the infection of a primary case and one of its secondary cases is called a generation time, see [ ] . the 'r ' package assumes generation time of infection is known and should be provided as input. the mean generation time for the wuhan has been reported as . days, [ ] . in this paper, we assume the generation time follows gamma distribution and we estimated the mean and shape parameter of the gamma distribution using data. our estimated mean generation time for hubei province turns out to be . , presented in the table . on the recovery from infection, we assume the individuals are assumed to be immune to re-infection in the short term. this assumption is same as [ ] . currently, we are deploying a grid search method over the mean and shape of the gamma distribution for the time generation process. for a particular choice of the mean (µ) and shape (κ) parameter, we generate the time and then given that as input we estimate the r using the 'r ' package in r. then for an estimated r and γ (assumed to be / ), we simulate the disease progression, for the period, for which we observed the new incidences. then we calculate the mean square error (mse) in the following way: whereÎ(t) is the new incidence estimated from sir model described in ( ) at time point t, and i obs (t) is the actual incidence observed in the data at time point t. we estimate the mean parameter µ and shape parameter κ for which the mse in ( ) is minimum. the, for estimated mean and shape parameter, r is estimated using the 'r ' package. the infection rate of a typical epidemic reaches its peak and then it slows down. the sir model predicts when that peak will be reached very well because it captures the inherent dynamism of the epidemic. however, the sir model is not helpful for short and medium-term predictions. we also need short and medium-term prediction, to predict the cases as quickly as possible so that the health officials can take the appropriate decision. the statistical machine learning (sml) models are most popular for its prediction accuracy from short to medium term, [ ] . consequently, sml and sir models complement each other. note that the sml does not do well in long term prediction, particularly it cannot predict when it will reach the peak. under this understanding, we develop traditional sml models and not deep learning models. we refrain to develop deep learning type models because we need a lot of data. however, in epidemiology, we do not have such kind of big data. in addition, the literature on how to adopt deep-learning for small data is not sufficient yet. therefore we refrain from developing deep learning models and we develop the traditional regression type sml model, for short to medium type prediction. as different countries or provinces population levels are different; we consider the our variable to analyze as cases per , (aka., rate), × , . the we model the rate as a function of time, country and time-country interaction in the following way: where rate it is the rate of the i th country at the t th time point, α i is the effect of i th country, α i t is the linear effect of time on the rate of the i th country, α i t is the quadratic effect of time on the rate of the i th country. we considered the following countries in our model: ( ) on march , , india announced the national lockdown of the nation. to measure the effectiveness of the lockdown, we used all data up to march , , to train the model and learn the parameters of the model. based on the trained model, we predict the disease progression path. since the incubation period of the covid- is about days, it is likely that for days from the beginning of the lockdown, the disease will follow the predicted path and then, it will deviate down from the predicted path. if the new confirmed cases come below the predicted path then we will know that is due to the effect of lockdown. on the other hand, if the disease progression stays on the predicted path then we will know the lockdown did not work. if the disease progression comes above the predicted path then we can say that the ground situation worsen during the lockdown. exploratory data analysis (eda) is important to develop good predictive models. in the figure ( ) , we plot the case per , (aka., rate) for us, eu and iran. the worst-hit us, eu and iran's rates are in the range of and . on the other hand, disease progression among asian countries is very different, see figure ( ). the disease progression for both india and japan are similar. we see the exponential rise in india and japan but at a very lower rate than the western nations. china has able to flatten the curve and south korea was able to curb the rise from exponential to linear. however, so far south korea experienced the worst rate among the major four asian countries. table ( ), we present the actual prediction till may , . if lockdown works then actual confirmed cases for india should stay below , by may , . a comparison of r between india and china : in the table ( ) , r with a % confidence interval for hubei province and china is around . during the first days from the starting of the lockdown. india's r with a % confidence interval computed using two different starting points as breakout. one from -mar- , because the number of cases in india started rising from that day. the r for india for the first days till the lockdown is around . , like china. however, if we use the data, till -apr- , then the r value is around . . it indicates since the lockdown the situation has worsen. it is also clear from the figure ( ) . in the second approach, we consider india's breakout from -jan- . in that situation, if we consider the data till -mar- , the r with % confidence is almost . and if we consider data till -apr- , the r is nearly . . it means if we use the data earlier to -mar- the india's r looks better. in the figure ( ) , we compare the incidences of hubei and india in figure ( :a) and ( :b) . we consider the date range for hubei from -jan- to -feb- , i.e., during the first days of hubei lockdown. on the other hand, we considered the data for india, from the -jan- to -jan- , till the lockdown. on the -jan- , hubei had confirmed cases and overall china had confirmed cases. on -jan- , india had only confirmed cases, whereas on the day of lockdown, i.e., on -jan- , india had confirmed cases. so on the day, when the lockdown starts both india and hubei and/or china had a comparable number of cases. perhaps, we should consider india's r as around . similar to that of the early stage covid- disease progression of china. even with the lockdown, china experienced more than , cases. perhaps, we should prepare for at least that many cases if not more in india. stat wise r : in table ( ), we present the state wise basic reproduction number, r , as of march, . we see the punjab's r is worst in the country. punjab's high r ≈ is likely due to a super spreader, who ignored advice to self quarantine after returning from a trip to italy and germany, see [ ] . the situation is punjab is really complicated and serious intervention is required. in figure ( ) , we present the cases in punjab over time. since march , the number of confirmed cases increased at an unprecedented rate. from table ( ), we see the r for madhya pradesh ( . ) , maharastra ( . ) and tamil nadu ( . ) are more than . clearly the situations are complicated in these three states. the r of andhra pradesh ( . ), delhi ( . ) and west bengal ( . ) is more than the india's r which is . . these seven states should need special attention as their r is more than that of india ( . ). these numbers are as of apr, . for the following states, we either do not have enough data to make inference for r ; or the algorithm fail to converge: ( ) andaman and nicobar islands; ( ) arunachal pradesh; here we present a point by point discussion of our analysis and prediction. . situation of punjab (r ≈ ) is bad. it requires immediate aggressive attention. . we see the r for madhya pradesh ( . ) , maharastra ( . ) and tamil nadu ( . ) are more than . aggressive intervention is needed. table : r with a % confidence interval for hubei province and china is around . during the first days from the starting of the lockdown. india's r with a % confidence interval using two different starting points. one from -mar- , because the number of cases in india started rising from that day. the r for india for the first days till the lockdown is around . , like china. however, if we use the data, till -apr- , then the r value is around . . in the second approach, we consider india's breakout from -jan- . in that situation, if we consider the data till -mar- , the r with % confidence is almost . and if we consider data till -apr- , the r is nearly . . . we consider the date range for hubei from -jan- to -feb- , i.e., during the first days of hubei lockdown. on the other hand, we considered the data for india, from the -jan- to -jan- , before the lockdown. on the -jan- , hubei had confirmed cases and overall china had confirmed cases. on -jan- , india had only confirmed cases, whereas on the day of lockdown, i.e., on -jan- , india had confirmed cases. punjab's high r is likely due to a super spreader ignored advice to self quarantine after returning from a trip to italy and germany, see [ ] . the high r is likely due to a super spreader ignored advice to self quarantine after returning from a trip to italy and germany, see [ ] . coronavirus: india 'super spreader' quarantines , people. bbc news coronavirus: why is india testing so little? bbc news science and statistics mathematical epidemiology impact of non-pharmaceutical interventions (npis) toto reduce covid- mortality and healthcare demand. london: imperial college covid- response team early transmission dynamics in wuhan, china, of novel corona virus-infected pneumonia the r package: a toolbox to estimate reproduction numbers for epidemic outbreaks coronavirus: the woman behind india's first testing kit a bayesian perspective of statistical machine learning for big data desolve: solvers for initial value problems of differential equations a note on generation times in epidemic models epidemic modelling with compartmental models using r hospital beds (per , people) here due to space constraint, we present only days interval and recent out of sample values at the daily level key: cord- -o ru nr authors: tewari, a. title: temporal analysis of covid- peak outbreak date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: o ru nr intent of this research is to explore how a specific class of mathematical models namely susceptible-infected-removed model can be utilized to forecast peak outbreak timelines of covid- epidemic amongst a population of interest starting from the date of first reported case. till the time of this research, there was no effective and universally accepted vaccine to control transmission and spread of this infection. covid- primarily spreads in population through respiratory droplets from an infected person cough and sneeze which infects people who are in proximity. covid- is spreading contagiously across the world. if health policy makers and medical experts could get early and timely insights into when peak infection rate would occur after first reported case, they could plan and optimize medical personnel, ventilators supply, and other medical resources without over-taxing the infrastructure. the predictions may also help policymakers devise strategies to control the epidemic, potentially saving many lives. thus, it can aid in critical decision-making process by providing actionable insights into covid- outbreak by leveraging available data. coronavirus is a large family of viruses causing illness in both animals and/or humans. over last decade or so, several other coronaviruses are known to cause respiratory infections in humans, ranging from the common cold to more severe diseases such as middle east respiratory syndrome (mers) and severe acute respiratory syndrome (sars). the recently discovered coronavirus causes coronavirus disease covid- . today covid- is causing a global pandemic affecting almost all countries [ ] . data from health organizations indicate that asymptomatic individuals can transmit the virus without themselves showing any signs of infection. disease control organizations across the globe are investing in research on this topic and how often this happens. recovery from novel coronavirus usually takes days [ ] . about %- % of patients with covid- infection require intensive care surveillance and ventilator support [ ] . this poses a challenge for health planners and administrators as to how to optimally plan and allocate medical staff and other resources such as ventilators etc. in a large sized country such as india. according to a joint report [ ] by princeton university and the center for disease dynamics, economics & policy (cddep), most of the beds and ventilators in india are concentrated in seven states only. the report also mentioned that bed capacity was saturated at hospitals and any spike in covid- cases would require drastic expansion of hospital beds and ventilators. this problem represents crux of the issue that the current research is trying to address by using mathematical modeling to predict peak covid- outbreak timeline in various states across india. many previous researches and studies have attempted to employ mathematical models to provide insights into spread of influenza epidemics and pandemics [ ] [ ] [ ] . many studies have investigated historical pandemics of the th century [ ] [ ] [ ] . modeling techniques have also been used to understand the influence of interventions in mitigating pandemics [ ] . a category of mathematical models is agent-based models (abm) which represent a relatively recent approach to model complexities in a system composed of agents whose actions are described using simple rules. it is different from classical sir mathematical models (which assume homogeneous population), as agent-based models try to simulate individuals with distinct characteristics and in theory can provide more realistic results. a recent study used agent-based model to evaluate covid- transmission risks in facilities [ ] . however, there are several difficulties associated with creating abms such as integration with too many features, choice of model parameters, model results being either trivial or too complex [ ] . the spread of covid- in india has been investigated in many researches including [ ] [ ] [ ] [ ], but they laid little emphasis on post-model validation for peak covid- timeline forecast. with this in mind, sir model is explored in current research to forecast peak covid- outbreak over a large population in india. the sir model was chosen because of its simplicity as well as minimalist compute and data requirements as compared to agent-based models. for the purpose of this research, compartmental class of mathematical models is used in modelling covid- . specifically, kermack-mckendrick susceptible-infected-removed (sir) model [ ] is employed which distributes . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint the copyright holder for this this version posted september , . . population in compartments with labels -s, i, or r at any point of time. s is the number of susceptible individuals, i is the number of individuals infected, r is the number of individuals who have recovered and developed immunity to the infection. the number of s, i and r individuals may vary over time, but total population remains constant. model computes the predicted number of people infected with a contagious illness in a closed population over time. the model assumes fixed size homogeneous population with no social or spatial structure. an individual with covid- is infectious for approximately days [ ]. let's assume during these weeks period, they can potentially pass covid- to approximately people. these parameters determine the model inputs viz γ, the recovery rate (= days) and β, rate of infection (= / = . ). using these parameters, the time to reach peak covid- outbreak starting from first reported case is predicted by solving below system of three linked nonlinear ordinary differential equations in python [ ] : data covid- statistics data till -august- used in this research has been sourced from ndtv [ ]. population figures for the largest states in india have been taken from statistics times [ ] . together these states constitute more than % of total population in india. . . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this this version posted september , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this this version posted september , . . https://doi.org/ . / . . . doi: medrxiv preprint v. discussion this research was conducted to evaluate the feasibility of application of sir model to predict peak covid- outbreak timeline from the date of first reported case for the largest states in india which together constitute more than % or almost / th of total population in india. the broader goal is to analyze and evaluate sir model to provide early insights to public health agencies which in turn can expedite optimum response to covid- epidemic. the research results indicate that for out of these states, sir model could predict peak covid- outbreak timeline from the date of first reported case with error of +/- days or less, standard deviation (sd) in error = . days and mean absolute deviation (mad) in error = . days. aim of this research paper was to predict covid- peak timeline in various indian states using sir model. for out of largest states in india included in the research, chosen sir model could predict peak outbreak timeline from the date of the first reported case with error of +/- days or less and standard deviation (sd) in error = . day. these states constitute over % of total population of india. the model results present a potential opportunity for health policy makers and medical experts to gain early and timely insights into covid- peak outbreak timelines for a large proportion of population in india. they could use these insights to plan and optimize medical personnel and equipment or to devise strategies to control the epidemic, well before it hits its peak. while sir models have been extensively used, there is little research on validating their predictions. this research provided pragmatic validation of sir models over a large population. compartmental models are in many ways favorable to other exotic models due to their simplicity and minimal computational requirements. however, sir models assume several assumptions [ ] that do not exist in real world epidemic conditions. the sir model assumes that there is homogeneous mixing of the infected and susceptible individuals and that the total population is constant in time. in the classic sir model, the susceptible population decreases monotonically towards zero. however, these assumptions are not strictly valid in the case of covid- outbreak, since new hot-spots spike at different times. also, the effect of enforcing social distancing measures by respective government and health agencies has not been considered. this research does not attempts to perform an exhaustive study because of lack of suitable data as well as uncertainty in different factors, namely, the degree of home isolation, restrictions in social contact, the initial number of infected and exposed individuals, variations in incubation and infectious periods, and the fatality rate. population density, geographic area, demographics such as age and effect of social isolation etc. are possibly some parameters to consider and include in building more advanced epidemiology models for predicting peak epidemic outbreak timeline. disease spread models can also be used to predict number of infected individuals to better manage epidemics. the author would like to thank the editor and the reviewers for their helpful comments and review that contributed to improve the manuscript. ventilation of covid- patients in intensive care units the center for disease dynamics a contribution to the mathematical theory of epidemics statisticstimes seasonal influenza in the united states, france and australia:transmission and prospects for control the effect of public health measures on the influenza pandemicin us cities transmission dynamics of the great influenzapandemic of in geneva, switzerland: assessing the effects of hypothetical interventions transmissibility of pandemic influenza analyses of the (asian) influenza pandemic in the united kingdomand the impact of school closures predicting the global spread of new infec-tious agents estimating the impact ofschool closure on influenza transmission from sentinel data global stability of an sir epidemic model with time delays an agent-based model to evaluate the covid- transmission risks in fa-cilities communicating social simulation models to sceptical minds forecasting covid- impact in india using pandemic waves nonlinear growthmodels.medrxiv a minimal and adaptive prediction strategy for critical resource planning in apandemic.medrxiv possibilities of exponential or sigmoid growth of covid data in different states ofindia.medrxiv recent update on covid- in india: is locking down the country enough?medrxiv key: cord- -gqekw si authors: samanta, indranil; joardar, siddhartha n.; das, pradip k. title: chapter biosecurity strategies for backyard poultry: a controlled way for safe food production date: - - journal: food control and biosecurity doi: . /b - - - - . - sha: doc_id: cord_uid: gqekw si abstract the people of rural and periurban india depend on backyard farming system for poultry meat and eggs. it is used by weaker sections of society, such as marginal farmers as insurance against crop failure, for ready cash and to ensure basic economic returns and the empowerment of women and children. however, backyard farming does not appear to be a promising strategy to achieve the poverty reduction until the production level is increased. the major constraint in increasing the production in backyard birds is microbial infection due to lack of biosecurity knowledge among the farmers. the mitigation of the microbial infection depends on the detection of the infection route and its prevention. the source of microbial infection (salmonella, escherichia coli) and their dissemination through the eggs in backyard flocks kept in different agroclimatic zones of west bengal, a major egg producing state in india, was identified. the pattern of virulence gene specially associated with urinary tract infection and antibiotic resistance genes, such as extended spectrum β lactamase (esbl) genes of the isolates was studied. the chapter will elaborate the backyard farming including breeds reared, housing, feeding with special emphasis on suggested biosecurity strategies and consequence of the adapted strategy. the food and agricultural organization of the united nations (fao) classified poultry production system into four sectors based on the level of biosecurity and marketing of birds and their products (fao, ) . apart from commercial poultry maintained in integrated farming systems with moderate to high levels of biosecurity (sector - ), there is a "backyard" or "village level" poultry sector with minimal biosecurity (sector ). in this backyard sector, native birds or locally available breeds are maintained, and the birds or their products are mostly consumed locally. the concept of backyard farming is as old as civilization. many families in the villages of the rural world keep a small chicken flock of various ages. the majority of these birds are kept in free-range systems, in which the birds scavenge around the house or in the backyard during daytime. the term backyard farming is originated from it. a primitive type of poultry house is offered to the birds during night. the feed consists of household wastes or kitchen scraps like raw vegetables, cooked rice, insects, larvae, seeds, and so on (samanta et al., ) . the world organisation for animal health (oie) considered the backyard system as the most familiar system of poultry rearing throughout the world because the system is highly adaptable to local climate, and it requires less capital and other inputs to establish (fao, a) . in the economy of developing countries this kind of poultry plays a major role by means of income generation and household food security. it is an important component of small farmers' livelihoods and a tool for poverty alleviation (sambo et al., ) . it can provide meat and eggs throughout the year and ready cash in times of hardship or emergency, which may make the difference between life and death. the ready cash is also used for school expenditure, daily household need, buying of other domestic animals, etc. (fao, a) . the supply of eggs and meat can be maintained by backyard farming to meet the rising demand. sometimes the products are consumed by the owners or used as gifts to the friends and relatives during festival and as sacrificial offer to traditional deity (hamilton-west et al., ) . in bhutan, backyard products also act as a source of protein for the female members of the household during pregnancy and postparturition period (tashi and dorji, ) . backyard chicken eggs are popular among urban and educated consumers due to their higher nutritional quality. these eggs contain higher concentration of vitamins, omega- fatty acids, and β-carotene (long and alterman, ) . the backyard farming reduces environmental pollution by the conversion of kitchen scraps into proteins (meat and eggs), and the use of chicken manure as garden fertilizer. moreover, production of meats and eggs locally reduces the transport of the items from distant places and thus reduces carbon emission (fukumoto, ). besides rural backyard farming, in the urban area of developed countries, also, there is a growing trend for keeping chickens in backyards. this rearing system is known as "hobby/ peridomestic/fancy poultry" or "urban backyard farming." in urban backyard farming, the birds are primarily kept for a homemade source of food, for fun, or as a hobby or companion pet to improve psychological health of the owners. this last purpose is usually a family tradition, exposing children to the food production process and general affection for birds, and functioning as insect control (usda, ) . this kind of farming is not associated with economical benefit because their rearing costs are often higher than the production (pollock et al., ) . in urban united states, keeping backyard poultry flocks have been steadily increasing in popularity. the study in the united states detected that . % of urban and . % of suburban residents prefer to keep backyard poultry (elkhorabi et al., ) . even a number of cities in the united states, such as columbia, missouri, ann arbor, michigan, denver, colorado, and auburn, alabama have passed regulations allowing chickens to be kept at residences (bartling, ) . the trend of keeping urban backyard poultry is also detected in the greater london area in the united kingdom (karabozhilova et al., ) , canada (burns et al., ) , and new zealand (lockhart et al., ) . in british columbia (canada), an authorized person may keep up to egg-producing hens and may produce up to kg of chicken meat per year (british columbia farm review board, ). backyard poultry farming is considered as an integral part of livelihood for many rural families throughout the world. in ethiopia (africa), chicken constitutes the largest share among the farm animal species (mammo et al., ) and % of the chicken population is maintained under a scavenging system (yemane et al., ) . similarly, in asian countries, such as in vietnam, thailand, and bangladesh, % of rural households rear poultry in their backyard and it makes a contribution to the monthly income of rural families and to the national economy (chakma, ; chantong and kaneene, ; edmunds et al., ) . in india, the majority of families ( %- %) in west bengal, tripura, and assam practiced backyard poultry production (nsso, ) . in pakistan, after textiles, the poultry industry is the biggest commercial sector in the country and it contributes considerably to the national economy. pakistan also maintains a large backyard poultry sector and it is observed that every rural family and every fifth urban family breed poultry at home (sadiq, ) . in developing countries, this kind of farming system also offers women empowerment, because women directly control the farming and the income generated from the sale of chickens and chicken products. studies in ethiopia and other african countries showed that this is the only source of independent income for women due to scarcity of resources (wilson, ) . in rural bangladesh, poultry rearing is an occupation of % of women (sultana et al., a) . no literature is currently available regarding the economic importance of this means women empowerment through backyard farming. in developed country, such as in chile, %- % of the studied farms were maintained by men alone or jointly with women (hamilton-west et al., ) . in bangladesh, % of the total egg production is contributed by backyard sector with an annual egg production of . billion from this sector itself (dolberg, ) . in india, this rural poultry sector contributes % of the total national egg production (ngullie and sharma, ) and the income per bird per annum ranges between us$ . - . (indian rupees - per bird/month) (ahuja et al., ) . this contribution is considerably low for a rural livelihood, but it can be increased by expanding the egg production level. the major constraint in increasing the egg production in backyard birds is microbial infection due to lack of biosecurity practices followed by the farmers (conan et al., ) . similarly, in developed countries, such as chile, the farmers mostly sell their products to their neighbors during any occasion or to the tourists who occasionally visit the farms (hamilton-west et al., ) . thus, the income is not sustainable and considerably low. chicken (gallus sp.) is the most common species kept in backyard farming throughout the world. for example, the majority of the backyard farmers in chile, new zealand (north island) and egypt prefer to rear domestic chicken (abdelwhab and hafez, ; hamilton-west et al., ; zheng et al., ) . in ethiopia, however, cattle are the most common species reared by backyard farmers, which is followed by chickens (sambo et al., ) . other species of birds, such as turkeys (meleagris gallopavo), geese (aseranser), ducks (anas sp.), muscovy ducks (cairina sp.), quail (coturnix sp.), pigeons (columbidae sp.), and guinea fowl (numididae sp.) are also reared in some countries and sometimes housed together. ducks are the second predominant species after chicken kept by backyard farming in southeast asian countries (e.g., thailand). in thailand, ducks are raised on rice fields after the harvest to feed on leftover rice grains. the ducks are moved by truck or other vehicle from one rice field to another during the postharvest season ( - months out of the year) (gilbert et al., ) . the ducks are also reared on ponds or channels with or without fish/ pig farming on the same site. rearing pigs in an enclosure within the backyard farm was also observed in new zealand (zheng et al., ) . in some countries (e.g., india), fighting cocks are reared for income generation in places where cock fighting is a traditional recreation among villagers. cockerels (male chickens less than year of age) are reared for cultural and religious purposes in some places (fao, a) . a small number of people (e.g., % of studied population in chile and some people of thailand) prefer to keep wild birds, such as austral thrush (turdus falcklandii), shiny cowbird (molothrus bonariensis), austral blackbird (curaeus curaeus) and common diuca finch (diuca diuca), and ostrich (struthio camelus) as backyard pets (gilbert et al., ; hamilton-west et al., ) . selection of livestock or poultry breeds is an age-old practice that depends on the folk traditions, needs, agroclimatic zone of the country, and availability of the breeds (banerjee et al., ) . among the domestic chicken breeds, indigenous or native or nondescript breeds are preferred for backyard farming due to easy availability, higher adaptability to the local environment, resistance to some diseases, good egg and meat flavor, hard eggshell, high fertility and hatchability, and high dressing percentage (abdelqader et al., ) . in west bengal (india), common indigenous breeds that are maintained in backyard farming are native feathered chickens (desi), naked neck chickens (galakata murgi), frizzled fowls (sojaru murgi), muffed/bearded fowl (dariwala murgi), creeper chickens (bete murgi), crested fowls (khopa murgi), rumpless fowl (bocha murgi), and feathered shank fowl (aseel, haringhata black/black haringhata) (figs. . and . ) (banerjee, ; samanta et al., ) . similarly in bangladesh, indigenous or nondescript breeds of chickens are the preferable choice for rearing. sometimes, the farmers keep fayoumiand sonali (cross-breed of rhode island red and fayoumi) chickens in a semiscavenging system (biswas et al., ) . in bhutan, native breeds, such as seim (sm), phulom (pl), yuebjha narp (yn), and khuilay (kl) are ideal breeds for backyard farming (tashi and dorji, ) . the most common backyard chicken breeds in thailand are native and mixed breed chickens (e.g., three-bloodbreed). three types of duck breeds are reared in thailand-namely, egg-laying ducks (khaki campbell), crossbreed of khaki campbell and native laying ducks, and a small number of meat type ducks (pekin, white cherry valley) (gilbert et al., ) . in sudan and ethiopia (africa), large beladi (lb), bare neck (bn), betwil (bt) dwarf, naked neck, and gasgie and gugut breeds of chickens are kept in backyard farms (getu et al., ; wani et al., ) . some temperate/artificial breeds of poultry were introduced in tropical countries, such as in india and ethiopia for better production and up gradation of native breeds, which altered the traditional husbandry systems. in india and ethiopia, the rhode island red (rir) breed was introduced through government-sponsored developmental schemes, such as rastriyo krishi vikas yojana (rkvy), a self-help group developmental program in india and poultry extension package in ethiopia (dinka et al., ; samanta et al., ) . the better egg production ( eggs per bird/annum) of rir chicken than the native breeds ( - eggs/bird/annum) was observed in west bengal (india) when the birds were provided with supplemented feed along with scavenging . in ethiopia, rir breeds of chicken showed poor tolerance to the local climate. moreover, supply of rir hen's eggs, pullets, and cocks in the localities reduced the brooding capacity of the native breeds and their adaptation to the local feeding system (dinka et al., ) . moreover, a synthetic breed (kuroiler) developed by a private organization was introduced in india for backyard rearing. kuroiler is a dual type bird having higher production capacity than the indigenous (desi) chickens with some features of native birds, such as feather color and alertness ( fig. . ) (ahuja et al., ) . in urban backyard farming, chickens are the most preferred species in the united states. layer breeds of chickens producing colored eggs, such as rir, plymouth rock, ameraucana, orpington, and wyandotte are preferred (elkhorabi et al., ) , although in minnesota (usa), meat-type chickens are also reared (yendell et al., ) . other birds, such as turkeys, ducks, pigeons, doves, game birds, and guinea fowl are also reared (beam et al., ) . in some countries, raptors (hunting birds) are reared in the backyard (fao, b) . the management practices for keeping backyard birds vary between the countries throughout the world. in chile, the birds are kept in three types of systems-namely, permanent confinement, free-range, and a mixed confinement. in mixed confinement, the birds scavenge freely in the courtyard of the farmer's house during daytime, and at night they are kept in an indigenous pen. among these three systems, the mixed confinement is the most common one (hamilton-west et al., ) . the indigenous pens are mostly made of bamboo with or without an asbestos shade in asian countries (samanta et al., ) . in thailand and sudan, at night the birds are kept under a bamboo basket also (chantong and kaneene, ; wani et al., ) . on the north island of new zealand, most of the farms ( %) allow free movement of chickens and ducks in nearby pastures, including access to waterways, such as ponds, streams, rivers, and drains (zheng et al., ) . in bangladesh, most of the farmers ( %) keep the birds within their houses, and others keep them in a coop in the front yard. the coop is made of soil or wood and it has a tin shade (alam et al., ; sultana et al., a) . the majority of the farmers prefer to keep the birds on a wooden perch constructed inside their own houses in ethiopia (yemane et al., ) . resting of the birds on treetops at night was observed in south pacific island countries (ajuyah, ) . development of brick houses for the poultry is rarely observed ( %) in india (west bengal) (banerjee, ) . during crisis periods, such as flooding the farmers keep the chickens in a cage and hang the cage inside the room as observed in bangladesh (sultana et al., a) . the average flock size of the birds in rural backyard farming is variable. in ethiopia and sudan, the average flock size per household was . and . , respectively (wani et al., ; yemane et al., ) . in another study in ethiopia, a lower average flock size ( . ) was detected (sambo et al., ) . in other countries, such as in bangladesh and belgium, the mean flock size of small holdings of poultry was observed to be less than (alam et al., ; van steenwinkel et al., ) . in a study in some districts of west bengal (india), such as jalpaiguri, dinajpur, west medinipur, howrah, and south parganas, the average flock size was observed as - (samanta et al., b) . scavenging in yards, animal sheds, bushes, neighbouring houses and the nearest grain field is the major source of feed for the backyard birds. mostly small worms, insects, snails, rice, fallen cereal brans, kitchen wastes, household vegetables, and green grasses are taken by the birds during the scavenging period and are considered as scavenging feed resource base (sfrb). in asian countries, such as in india, bangladesh, and thailand, women also offer the supplementary feed and drinking water from local ponds to the birds once or twice in a day (chantong and kaneene, ; sultana et al., a; samanta et al., ) . in developed countries, such as in new zealand (north island), however, the birds were mostly provided with drinking water collected from bore ( %), rivers, and streams ( %). only a few people ( %) use ponds or dams as a source of drinking water for their birds (zheng et al., ) . the birds are mostly bred within the flock to increase the flock size. the breeding activity of the birds is conducted by the women of the family, as observed in ethiopia and chile (aklilu et al., ; hamilton-west et al., ) . in new zealand, chickens were usually homebred ( %) (zheng et al., ) . in bangladesh, the women of the family select a space within their bedroom or on the windowsill for the chickens to lay and brood eggs. however, ducks prefer to lay the eggs where they stay at night (sultana et al., a) . the farmers utilize other sources of birds to introduce new birds in the existing flocks. examples of other sources include neighbors, local markets, commercial farms, breeders, shows/auctions, and government supported developmental schemes. in chile, % of the studied population used the other sources to purchase new birds (hamilton-west et al., ) . in new zealand, % of the owners obtained the chickens privately, and a few people ( %) bought the chicken from local commercial dealers (zheng et al., ) . in ethiopia, an average of . chickens were added to a flock annually (yemane et al., ) . during the introduction of new birds, no quarantine or other preventive measures to reduce the transmission of infections are followed. urban backyard farming is a little different than the rural farming. most of the persons keeping the birds have high income, higher education, and in the united states only % people were associated with agriculture. the flock size is almost the same as it is in rural backyard farming. in the united states, most of the people rear - birds (elkhorabi et al., ) . in new zealand too, small flock size (median, ; range, - ) was detected (lockhart et al., ) . however, higher flock size ( - ) was detected in minnesota (usa) (yendell et al., ) . the age range of chickens in the flocks surveyed in the united states was - years with predominantly female chickens. among the studied flocks, % of flocks had no rooster, % had , and % more than rooster in a flock (elkhorabi et al., ) . most of the bird keepers in the united states prefer to keep the birds indoor in a shed/coop. some of them ( %) provided enclosed run space along with the coop, % of them provided free-range during daytime and a small proportion of keepers ( %) preferred both of them (elkhorabi et al., ; yendell et al., ) . very few bird keepers used portable housing or cages for rearing the birds. in a us-based study, perches ( %) and nest boxes ( %) were mostly used as roosting and egg-laying space, respectively (elkhorabi et al., ) . similarly, in new zealand, the majority of the bird keepers rear the birds by free-range within the boundaries of the property during daytime (lockhart et al., ) . the women even with high educational background mostly take care of the birds like rural backyard farming. in the united states, the birds ( %) mostly receive a mixed ration of feed (purchased and kitchen scraps). although a small fraction of keepers ( . %) did not offer any supplementary feed to the birds in expectation that the birds will collect their feeds from free range. similarly, majority of the keepers ( %) provide fresh water to the birds and only . % of the keepers allowed the birds to obtain the drinking water from natural sources. the bird keepers ( %) also used supplemental grit and calcium for their birds, especially for the laying hens (elkhorabi et al., ) . in new zealand, the majority of the keepers use purchased feeds (lockhart et al., ) . in the european union, countries feeding kitchen scraps (except raw vegetables from the garden) to the food-producing animals, including chickens kept as pets, is banned since to prevent the transmission of zoonotic infections. access of poultry to the compost mass containing kitchen waste is also restricted (whitehead and roberts, ) . in developing countries, the backyard poultry sector mostly suffers from two infectious diseases, such as avian influenza (ai) and newcastle disease (nd) due to lack of biosecurity and proper vaccination (alexander, ) . surveillance of infectious diseases (such as ai) in backyard and free-grazing poultry is challenging due to the reluctance of the farmers to report outbreaks (kanamori and jimba, ) . avian influenza virus (aiv) infection is reported from poultry and wild birds in asia, africa, and europe (oie, ). the transmission of zoonotic aiv has so far (january ) generated human cases with deaths (who, .). among different subtypes of aiv, h and h are considered as pathogenic and are frequently isolated from chicken, turkeys, quails, and pheasants (suarez et al., ) . ducks and shorebirds mostly carry h , h , h , h , h , and h sybtypes of aiv (suarez and schultz-cherry, ) . genetic reassortment between avian and swine influenza can occur and generate a new subtype. h n is an example of a reassorted subtype that was detected in backyard birds and swine in ohio (killian, among the african countries, egypt is considered as endemic for aiv in spite of several attempts to eradicate the virus. in , backyard flocks accounted for % of the ai outbreaks in poultry. the infection was further confirmed in human patients having exposure to the backyard flocks (kandeel et al., ) . moreover, higher infection rates of aiv (h and h ) were observed in backyard birds and birds from local bird markets in comparison to birds from commercial farms in egypt (osman et al., ) . furthermore, a higher prevalence of aiv was reported in backyard flocks that had mixed populations of chickens and waterfowls together (el-zoghby et al., ) . two clades of hpai-h n are circulating in egypt, known as classic . . and variant . . strains (hafez et al., ) . the classic strain originated from ducks (saad et al., ) and currently is maintained in backyard birds. the variant strain has been circulating in commercial poultry since late (hafez et al., ) . the phylogenetic analysis of hpai strains from egypt revealed close relationship with the h n viruses circulating in gaza and israel, suggesting a common virus progenitor (el bakrey et al., ) . similarly in libya, hpai-h n belonged to . . lineage having similarities with egyptian isolates. it was detected in backyard flocks (kammon et al., ) . (chaka et al., ) . furthermore, in central africa (cameroon, central african republic, congo-brazzaville, gabon), evidence of aiv was detected in chickens, ducks, songbirds, and kingfishers (fuller et al., ) . in mali (west africa), ai seroprevalence was significantly higher in backyard birds than the commercial farms (molia et al., ) . severe h n outbreaks were detected in all kinds of poultry in thailand (asia) during - , which was later controlled, and in , toie declared thailand as free of h n infection (oie, ) . the study with the scenario of the tree modeling approach in backyard flocks in thailand also revealed the high probability to be free from h n infection (goutarda et al., ) . however, the backyard flocks in other asian countries possess the aiv. evidence of h n aiv was observed in a village backyard flock in kandal province in cambodia (theary et al., ) . in pakistan, two highly pathogenic subtypes (h n and h n ) caused a sporadic ai outbreak in poultry in . vaccination was done in poultry against h , h , and h subtypes to control the infection. as a consequence of reassortment with vaccine strains a more virulent subtype (h n ) of the virus appeared, which crossed the species barrier and further infected human. this reassorted subtype (h n ) possessed a nonstructural gene segment of h n , which increased the capacity of the virus to adapt to new hosts (due to ifn-β inhibitory activity) and environments (munir et al., ) . currently the existence of h n subtype is also detected in apparently healthy backyard flocks in pakistan. so, the backyard flocks in pakistan act as asymptomatic carrier of h n with increased possibility of human transmission (munir et al., ) . the h n virus circulating in pakistan belonged to the g lineage of virus (qa/hk/g / ), which was also common in hong kong (iqbal et al., ) . h n originated in turkeys in (homme and easterday, ) . since then it has been considered as a low pathogenic strain (lpai) and is panzootic in multiple avian species in asia, middle east, africa, and europe (capua and alexander, ) . the property of cross species transmission to human was first detected in in hong kong and china, which also originated from poultry (peiris et al., ; butt et al., ) . in bangladesh (asia), h n subtype of lpai is frequently detected in commercial poultry and backyard flocks that are phylogenetically related to south asian and middle east isolates (parvin et al., ) . moreover, h n isolates of bangladesh also possessed the evidence of reassortment between h n and h n subtypes like their counterparts in pakistan (parvin et al., ) . a low proportion ( %) of backyard birds in bangladesh die every day due to hpai infection. clinical study showed that cyanotic comb and wattle are frequently observed in both commercially farmed and backyard poultry (p = . ), but edema of the head and face, drowsiness, and huddling were more common in backyard farms (p = . ; p = . ) (biswas et al., a,b) . furthermore, full genome analysis of hpai viruses (h n ) isolated from poultry including backyard flocks in bangladesh revealed the evidence of reassortment between two circulating clades of viruses ( . . . and . . . ) and also between hpai (h n ) and lpai (h n ) strains (gerloff et al., ) . the virus clade . . . was introduced in bangladesh after and the strain spread into different places and species (chickens, crows) in the country (islam et al., ) . the aiv belonged to similar lineage with bangladeshi isolates were also detected in nepal suggesting the transboundary transmission either through trade or wild birds (nagarajan et al., ) . similarly in india (neighbouring country of bangladesh) the existence of hpai-h n clade . . . was observed in poultry since (nagarajan et al., ) . until , the clade . dominated in indian poultry (chakrabarti et al., ; pattnaik et al., ) . in europe, ai virus belonging to clade . was most prevalent among poultry and wild birds (brown, ). however, in romania, hpai h n virus of clade . . was detected in backyard flocks (reid et al., ) . in italy, eight hpai outbreaks in backyard poultry flocks infected with h n virus were reported in - (alexander, ) , while chickens raised for recreational purposes in the urban localities in the netherlands acted as major risk factors for a hpai outbreak in (slingenbergh et al., ) . in maryland (united states), low seroprevalence ( . %) of aiv was detected in backyard birds. no evidence of subtypes h , h , and h was observed. the seroprevalence was positively correlated (not statistically significant) with exposure to waterfowl, pest control, and location (madsen et al., ) . in new zealand also, low seroprevalence ( . %) of hpai was detected in backyard chickens and no influenza a virus was detected by molecular technique (zheng et al., ) . newcastle disease virus (ndv) belonged to the genus avulavirus and family paramyxoviridae (niewiesk and oglesbee, ) . all the ndvs come under a single serotype but based on phylogenetic analysis it is divided into two classes: class i and class ii. class i strains are mostly apathogenic for chicken except one isolated from waterfowl and shore birds. all the pathogenic strains belonged to class ii, and this class is further divided into genotypes (i-xi). among them, i, ii, iii, iv, and ix genotypes are considered as "early/old" (appeared between and ) and the genotypes appeared after are considered as late/recent (v, vi, vii, viii, x, xi) (kim et al., ) . backyard flocks throughout the world, especially in asian and african countries suffer or carry the ndv infection (permin and pedersen, ) . pakistan (asia) is considered as endemic for ndv infection in poultry. both commercial and backyard flocks can carry the infection, and all the virus isolates from both of the sectors belonged to genotype vii. the backyard flocks, however, do not show any syndrome of nd, but the virus isolated from the backyard flocks possessed a typical motif in f-protein associated with virulence. frequent contact with commercial poultry might be responsible for the transmission of virulent ndv into the backyard flocks and the virus was later adapted in the backyard flocks (munir et al., ) . however, in nepal, nd was detected to be responsible for % mortality in backyard flocks during (alexander, ) . in iran (bushehr province), % seroprevalence of ndv antibody was detected in unvaccinated backyard chickens (saadat et al., ) . in africa, studies revealed an average nd serological prevalence of . [ % (ci) . - . ] in poultry, which is more prevalent in the area with low altitudes, high humidity, and high human and poultry population densities. these predisposing factors are also favorable for persistence of ndv in backyard flocks because high humidity enhances virus survival and further transmission through the oral route. comparison of the ndv transmission rate within the flocks revealed more rapid transmission in the commercial sector than in the backyard flocks (miguel et al., ) . in a study in ethiopia, overall seroprevalence of the ndv antibody in backyard flocks was detected as . %- % in different seasons, which is higher than the average ndv seroprevalence ( . %) in africa . the backyard farmers also identified nd as the most prevalent infection among the birds in ethiopia (sambo et al., ) . moreover, in mali, among unvaccinated backyard birds, nd seroprevalence was . %, and the seropositivity was more associated with adult, female chickens than the ducks (molia et al., ) . in the middle-east countries, ndv has been circulating in poultry populations since the last century. in oman, high seroprevalence ( %) of ndv was detected in backyard flocks with mild or no symptoms. the management practices, such as introduction of new birds into existing flocks, direct contact with neighboring poultry and feeding of uncooked poultry waste were correlated with this high seroprevalence (al . the seroprevalence data of ndv in backyard flocks in other countries is variable. in new zealand, . %- % of the studied backyard chickens were seropositive for ndv antibody. all the chickens reared with ducks were found seropostive (dunowska et al., ) . in the periurban area of madagascar, a study showed that ndv was responsible for % of annual mortality in local backyard chickens (maminiaina et al., ) . in brazil, higher seroprevalence of ndv was detected in backyard flocks in which the farmers introduced their own poultry to restock the flock. this replacement caused the continuous presence of virus in the flock. further, proximity to water bodies (estuary) provided direct contact with other infected birds and favored the transmission of ndv (marks et al., ) . the ectoparasites were the most commonly reported health problem in backyard flocks in developed countries, such as in united states and canada (garber et al., ; burns et al., ) . in a study in california (united states), % of the backyard premises were observed to be infested with ectoparasites. the permanent ectoparasites detected in the study were six species of chicken louse, such as menacanthus stramineus ( %), goniocotes gallinae ( %), lipeurus caponis ( %), menopon gallinae ( %), menacanthus cornutus ( %), and cuclotoasterheterographus ( %). among the chicken mites, three species were most prevalent [ornithonyssus sylviarum ( %), knemidocoptes mutans ( %), dermanyssus gallinae ( %)]. it is noteworthy to mention that these parasites were exclusively detected in backyard flocks, not in commercial layers in california (murillo and mullens, ) . backyard flocks kept in and around the mississippi river delta suffered from black fly (simulium spp.) infestations. the external signs, such as cutaneous hemorrhagic lesions and a huge numbers of black flies within the digestive tract of the birds (after post mortem) were found. black flies can also transmit some blood protozoa (leucocytozoon spp., haemoproteus spp.), which cause further infection in the affected poultry. moderate occurrence ( %) of leucocytozoon spp. was detected in black fly infested backyard flocks (jones et al., ) . in the united states, toxoplasma was detected in %- % of backyard chickens although clinical cases of toxoplasmosis are rarely reported in poultry (dubey and jones, ) . in tropical countries, humid climatic conditions favor the growth of helminths, which reduce the egg and meat production of backyard poultry. in a study in india (jammu and kashmir), % of the backyard flocks were determined infested with gastrointestinal helminths. in the studied state of india, ascaridia galli was the most prevalent helminth ( . %) among the flocks. other helminths, such as heterakis gallinarum, raillietina cesticillus, and raillietina echinobothrida were also detected. the backyard chickens of the studied area take various insects as feed present in the soil, which may act as intermediate hosts for helminths ( fig. . ) (katoch et al., ) . similarly, in other tropical countries, such as in ethiopia (africa), % of the backyard flocks were infected with several cestode and nematodes (hussen et al., ) . low occurrence ( %) of histomonas meleagridis, a blood protozoon, was detected in backyard flocks in vietnam (nguyen et al., ) . triatoma dimidiata, a vector of trypanosoma cruzi causing chagas disease in humans was identified in the chicken coops in mexico (koyoc-cardeña et al., ) . in australia, the study showed that % of the backyard flocks suffer from coccidiosis (eimeria). the weather of australia, such as ambient temperatures around °c and high humidity (> %), favors the growth of eimeria and three species, such as e. mitis, otu-y, and e. acervulina were most prevalent (godwin and morgan, ) . meat and poultry products are recognized as the major sources for transmission of salmonella spp.(a gram-negative zoonotic bacterium) to human with % of the clinical cases attributed to the consumption of egg and poultry products (sanchez et al., ) . nontyphoidal salmonella spp. is reported to cause . million sufferings, including , people admitted to hospitals and deaths in a year in the united states (scallan et al., ) . sometimes, poultry birds, although infected with salmonella spp. and appearing healthy, can shed the bacteria through the faeces (behravesh et al., ) . human outbreaks of salmonellosis, especially between the caretaker and children associated with backyard poultry, are a global concern nowadays (cdc, ). moreover, many serovars of salmonella spp. can produce serious diseases and deaths in chickens too, especially at a young age (samanta, ) . the seroprevalence rate of salmonella in backyard chicken was moderate ( %) in argentina (xavier et al., ) . however, a lower isolation rate was reported by (jafari et al., , namata et al., and leotta et al., who found . , , and . % as salmonella prevalence in backyard chicken flock in iran, belgium, and paraguay, respectively. in a study in backyard birds (rir breed) in india (west bengal), the isolation rate of salmonella was %. salmonella isolates were also obtained from feed ( %), drinking water ( %), and eggs ( %) of the studied backyard flocks. no salmonella was detected from utensil swabs, litter, swab from the wall of the poultry house, dried manure under the house, and soil collected from all the studied agroclimatic zones. salmonella isolation rate was significantly correlated (p < . ) with a higher-age group of the backyard birds ( - weeks) as compared to the middle-or lower-age group. further, none of the salmonella isolates possessed extended spectrum β lactamase (esbl) genes probably due to a lack of antibiotic exposure (samanta et al., a) . transmission of antimicrobial-resistance genes into the commensal flora may take place in the intestinal tract of animals, including birds (gustafson and bowen, ) . specifically, the esbl enzymes are increasingly expressed by many strains of bacteria with a potential for dissemination. these esbls diminish the activity of wide-spectrum antibiotics, creating major therapeutic difficulties in treatment of the patients (samanta et al., a) . e. coli are present as commensal microflora of the intestinal tract of mammals including poultry and their environment. among several pathotypes, avian pathogenic e. coli (apec) are able to cause colibacillosis due to possession of specific virulence factors (samanta, ) . in california, e. coli were the most commonly diagnosed infectious diseases among backyard birds (mete et al., ) . e. coli are also classified under several phylogenetic groups. the phylogenetic group b strains are commonly found in mammals and are often associated with extraintestinal infection in humans, pets, and avian species. the group b strains are more commonly associated with ectotherms, birds, and environment (blyton et al., ) . sometimes, e. coli present in avian (apec) and humans (uropathogenic e. coli, upec) share common virulence factors, such as iucc, tsh, papc (rodriguez-siek et al., ) . in india, e. coli isolated from backyard flocks (rir breed) did not possess the virulence genes (iucc, tsh, papc) associated with upec (samanta et al., b) . similarly, virulence gene (papc) was not detected in any of the e. coli isolates from free-range healthy layers in australia (obeng et al., ) . further, none of the e. coli isolates from backyard flocks in india (west bengal) was found to possess extended-spectrum β-lactamases (bla tem , bla shv , bla ctx-m ) or quinolone resistance gene (qnra) due to a lack of antibiotic exposure (samanta et al., b) . thus, the studied backyard birds in india can be considered as safe food in relation to virulent and antibiotic resistant commensal bacteria. similarly, no esbl-producing e. coli were detected in backyard flocks in finland (pohjola et al., ; miranda et al., ) , which also reported lower levels of antibiotic resistance in e. coli isolates from organic poultry meat. in contrast, tetracycline resistance was most common in e. coli isolates from backyard poultry ( %) than in-care birds ( %) and wild birds ( %) in australia due to the use of tetracycline for treatment of the birds (blyton et al., ) . fowlpox virus belongs to the genus avipoxvirus and family poxviridae. it can infect the poultry throughout the world. most of the infections in backyard birds are reported from asia. in a study in india (west bengal), fowlpox virus was detected in a backyard flock with pock lesions in comb, eyelid, beak, and wattle. sequence analysis revealed the presence of nearly full-length reticuloendotheliosis provirus within the genome of fowlpox virus (biswas et al., a,b) . a number of fowlpox outbreaks without reticuloendotheliosis virus have also been reported from backyard poultry at different regions of india and iran (dana et al., ; das et al., ; gholami-ahangaran et al., ; roy et al., ; saha, ) . further study detected immunodominant b-cell and t-cell antigens in the fowlpox virus isolates from backyard birds, which will be useful for vaccine production (roy et al., ) . . it seems that backyard poultry and free-ranging birds act as a center for ibv transmission currently (promkuntod, ) . in canterbury, new zealand, revealed the presence of campylobacter spp. in % of the studied backyard chicken flocks (anderson et al., ) . campylobacter jejuni alone, campylobacter coli alone and both c. jejuni and c. coli were detected in ( %), ( %), and ( %) of the flocks, respectively. pfge analysis and comparison of the genotypes with the pulsenetaotearoa campylobacter database showed the similarity of the isolates with the isolates from human and commercial chickens indicating the possibility of crosstransmission. in finland, backyard chickens were also detected as a reservoir of c. jejuni strains (pohjola et al., ) . clinical listeriosis is rare in birds. however, recently an outbreak of listeria monocytogenes was observed in backyard flocks in seattle (united states). depression, lack of appetite, labored breathing, and increased mortality were noted in several affected birds. the pathologic changes in the internal organs of infected birds included severe myocarditis, pericarditis, pneumonia, hepatitis, and splenitis. no lesions were noted in the brain (crespo et al., ) . in finland too, backyard chickens were observed to possess l. monocytogenes, although their role as a primary reservoir is questionable (pohjola et al., ) . in europe, seroprevalence studies in backyard and fancy-breed poultry flocks revealed the presence of mycoplasma gallisepticum, ornithobacterium rhinotracheale, and avian metapneumovirus antibodies (haesendonck et al., ) . in another study in oman, backyard flocks were positive for avian metapneumovirus subtype b (al- . pasteurella multocida causing fowl cholera was detected in . % backyard birds in egypt. most of the p. multocida isolates belonged to a: serotype (mohamed et al., ) . among noninfectious conditions, fatty liver hemorrhagic syndrome (flhs) and reproductive tract adenocarcinoma were the leading causes of mortality in backyard flocks in california (mete et al., ) . necropsy findings in flhs include abundant coelomic fat and an enlarged, tan to yellow, friable liver with hemorrhages. another study revealed absence of hepatocellular lipidosis in % of the flhs cases and mild hepatocellular lipidosis in % of the flhs cases in the backyard birds (trott et al., ) . lead toxicosis was detected in backyard flocks in california and the flaking paint from a wooden structure in the chicken coop was identified as the source of toxicosis. no clinical signs in the birds were detected. however, the birds were excreting the lead through the eggs. the edible portion of the eggs contained lead levels as high as . µg/g (bautista et al., ) . in urban backyard flocks in the united states, ectoparasites, diarrhea, injuries, prolapsed vent, sour crop, and vices (feather pecking, cannibalism, piling, aggression) are most common menaces. mortality due to diseases or vices is uncommon. the predation is the major cause of mortality in urban backyard flocks both in the united states and the united kingdom (elkhorabi et al., ; karabozhilova et al., ) . in minnesota, lameness was the most commonly observed symptom followed by nasal or eye discharge, coughing, sneezing, and swollen sinuses in urban backyard flocks (yendell et al., ) . vaccinations are an important tool for disease prevention in all poultry flocks throughout the world. the vaccines against ndv infection are available for decades, but in most of the countries they are sold in large vials of more than doses, which are expensive for small-scale backyard farmers. the reconstituted vaccine should be used within a short period of time to avoid the loss of potency (merck animal health, ) . further, in remote villages, accessibility of the vaccines, proper diluents, cold chain, and, moreover, qualified paraveterinarians are limited. in some countries, such as in ethiopia, the vaccines are produced locally, which also creates challenges, such as irregular supply of specific pathogen-free (spf) eggs, required for sustainable vaccine production (sambo et al., ) . consequently, production and supply of vaccine is often hampered. because of all these factors, conventional vaccination is not usually performed in most of the backyard flocks each year to prevent the outbreaks. in the literature, very few examples are present regarding successful vaccination in backyard flocks. in java (indonesia), a large-scale mass vaccination was carried out to control outbreaks of hpai in backyard flocks, and positive titer to h was detected in %- % of poultry sampled in the mass vaccination area. in the hpai-nd combined vaccination group, %- % of the population had positive nd titers, compared to %- % in the areas without nd vaccination . in another study in indonesia, the results suggested that the hpai-nd combined vaccination significantly reduced the incidence of hpai in backyard poultry (bett et al., ) . several types of inactivated h n and h n vaccines were also used in egypt to control hpai outbreaks (abdelwhab and hafez, ) . however, use of live vaccine against hpai is a controversial issue, and it is presumed that such vaccination against hpai in china helped in the evolution of more virulent virus strain (smith et al., ) . in pakistan, too, it is speculated that import of live poultry and extensive use of live vaccines can pose a huge risk for the emergence of new ndv strain (munir et al., ) . in most of the endemic countries, such as in india, vaccination is not practiced to control the hpai infection in poultry. culling or stamping out birds in a - km declared infected area is the official policy to control the outbreak in india (dadf, ). the metapopulation dynamic study of a poultry population in the united states demonstrated the effectiveness of culling in reducing the number of outbreaks in large poultry populations (hosseini et al., ) . besides conventional vaccines, a novel approach in the form of fast-dissolving tablets (fdt) against nd virus was also produced. the virus (lasota strain) was freeze-dried into tablets containing a small number of doses, which is economically feasible for backyard farmers. the vaccine tablet can be diluted in water and administered either in drinking water of birds or by intraocular and/or intranasal route. the compact packaging of the fdts will also provide cost savings in storing and distributing the vaccine in the cold chain (lal et al., ) . treatment of diseases in backyard flocks is also limited. the backyard poultry farmers in india (west bengal) are reluctant to call for the assistance of local veterinarians or paraveterinarians due to lack of awareness, time, and motivation. in addition, doorstep services are also unavailable, especially in the remote villages (debnath et al., ) . the landless or marginal farmers also could not afford the treatment or vaccine costs (indian rupees or us$ . per bird/year) (sapplpp, ) . this is the probable reason the backyard birds reared in this part of india are not exposed to the antimicrobials and thus the commensal (e. coli, salmonella spp.) present in the birds do not possess major antibiotic resistance genes (samanta et al., b) . in bangladesh, sometimes the farmers prefer to collect the medicines and suggestions from the local medicine shops. the farmers also avoid the government animal health centers due to lack of proper diagnosis and availability of poultry medicines (sultana et al., b) . the reluctance of owners to seek veterinary attention was also noted even in developed countries, such as the united states ( . % farmers use veterinary service), the united kingdom, and chile (garber et al., ; hamilton-west et al., ; karabozhilova et al., ) . the urban backyard farmers in the united states mostly use dewormers (coccidiostats) and antibiotics in larger flocks (< ) of birds (elkhorabi et al., ) . in chile, the backyard birds were sometimes treated with the drugs approved for human use, which could be responsible for presence of drug residues in the poultry products (greenlees, ) . the animals and animal products (examination for residues and maximum residue limits) regulations, , control residues of medicines in food animals, including poultry, in european union countries. these regulations divide medicinal substances into three categories: allowed, prohibited, and unlisted. use of prohibited/unlisted medicines in poultry (commercial and backyard) is illegal (table . ) (whitehead and roberts, ) . occasionally, elderly farmers offered ethnoveterinary medicines, such as sour fruits, chili, and warm water to their backyard flocks (sultana et al., a) . similarly, in ethiopia, tobacco leaf, "melia" plant, pepper, garlic, lemon juice, and table oil is administrated with drinking water to the sick birds (sambo et al., ; yemane et al., ) . in brazil, ash is applied on the body of backyard birds to prevent parasite infestation. in nigeria, the ashes after burning of nicotiana rustica, n. tabacum, or carica papaya leaves are used. this is rubbed into the plumage to protect against parasitic infestation. shea butter is used as a curative method against bird scabies. palm oil is used especially against fleas and mites. tobacco leaves (nicotiana tabacum) provide protection for approximately month against sarcoptes, psoroptes, and demodex (salifou et al., ) . in bangladesh, indonesia and china, the sick birds are slaughtered and consumed when the treatment fails (padmawatia and nichterb, ; sultana et al., b; zhang and pan, ) . addition of an indigenous homemade probiotic (axone/akhuni) in diet (at % w/w) significantly improved the growth rate, egg production, and egg weight of backyard poultry in india (vanraja variety). microbiological analysis of the probiotic (axone) revealed the presence of bacillus coagulans, a well-known beneficial bacterium (singh and singh, ) . the zoonotic pathogens, such as hpai are transmitted to humans from the backyard birds through direct or indirect contact. the direct contact takes place while walking through the flocks and handling sick poultry and while slaughtering poultry personally without appropriate protection (burns et al., ; liao et al., ). at the time of slaughter, the most commonly identified risk factors were direct contact with infected blood or other body fluids (van kerkhove et al., ) . associated risk factors related to environmental exposure include cleaning poultry areas, removal of feces, using poultry waste as fertilizer, inhalation, ingestion, and intranasal inoculation of contaminated water (van kerkhove et al., ) . indirect contact is more frequent and takes place when backyard farmers are exposed to apparently healthy poultry without any precautions (rabinowitz et al., ) and when the farmers meet with each other (burns et al., ) . backyard poultry acted as greater source of hpai transmission than the commercial birds due to the absence of biosecurity measures. it is also estimated that average daily contact rate of humans was higher with the backyard flocks than with commercial poultry ( . or contacts per year) (patyka et al., ) . rural people are at higher risk of hpai transmission than their urban counterparts due to greater amount rearing of these backyard birds. besides from being an essential component of rural livelihood, poultry rearing is also an important sector of the agricultural ecosystems. the droppings of chickens are used to feed aquatic animals and as soil fertilizers, which facilitates pathogen transmission (liao et al., ) . moreover, asian rural people prefer to take freshly slaughtered poultry than the packaged and processed meat. in a study in southeast asia, it was observed that almost all vietnamese and more than half of the thai people slaughtered the birds by themselves at home. this kind of practice also increases the possibility of disease transmission (liao et al., ) . cock fighting (a traditional recreation in rural asia) with backyard birds may also play a role in disease transmission. the owners transport their birds long distances to participate in bouts and sometimes they lick the wounds on their fighting cocks (edmunds et al., ) . more hazardous practices, such as keeping birds inside the bedroom, scavenging of birds around the places where food is cooked, using the same water source where villagers bath or wash their utensils for the birds' drinking were observed in bangladesh (sultana et al., b) . the hpai virus belonged to clade . . and was prevalent in backyard and commercial poultry in india and bangladesh before (who, ) . during that period ( ), an hpai outbreak in humans was detected, which was also followed by two subsequent human cases. in all these cases, the etiological virus belonged to clade . . with other similar genetic characteristics indicating the cross-transmission from the poultry (brooks et al., ) . in vietnam, most of the human exposure ( %) to hpai occurred from the backyard poultry (fielding et al., ) . in thailand, during - , confirmed h n cases in humans were detected of which persons died (who, ) . the history of direct contact to the backyard chickens and free-grazing ducks appeared to be related to h n infections in humans in thailand (chantong and kaneene, ) . in china, a total of h n infections were identified in the zhejiang province in humans during . all the live poultry markets were closed and backyard poultry were slaughtered to control the outbreak in the locality (gong et al., ) . in beijing (china), farmers who reared ducks in their backyards possessed antibody against avian influenza, but they never vaccinated, indicating the means for possible transmission . using logistic regression, it was shown that backyard poultry could act as a source of campylobacter jejuni infection to children (el-tras et al., ) . lpai is also transmitted from poultry to humans causing influenza-like syndrome (cdc, ) . antibodies against h and h avian influenza virus were detected in a small locality in lebanon among the backyard farmers (kayali et al., ) . there is serologic evidence that waterfowl hunters, wildlife professionals, and veterinarians are at higher risk of infection with lpai (gill et al., ; myers et al., ) . urban backyard flocks also pose a major risk for transmission of zoonotic pathogens, such as salmonella spp. in young and elderly persons handling the birds (pollock et al., ) . centres for disease control and prevention (cdc) had warned about handling of poultry by people below years of age (cdc, ) . other than transmission of zoonotic pathogens, eggs of the backyard birds are also detected to be contaminated with dioxins (lin et al., ) . during scavenging, the birds get access to the source of dioxins, such as soil, feeds, plants, insects, building materials containing fly ashes, debris, etc. (solorzano-ochoa et al., ) . dioxins enter the body through ingestion and mostly accumulate in the liver, ovarian follicles, and the adipose tissue (piskorska-pliszczynska et al., ) . the vicious cycle of hpai virus transmission from the reservoir ducks into the backyard flocks was detected. in south asia, domestic ducks were the major risk factor for hpai persistence and transmission into the backyard poultry (gilbert and pfeiffer, ) . in madagascar, the high density of ducks (palmipeds) and prevalent rice paddies were associated with ai infection in backyard birds (andriamanivo et al., ) . the water bodies and their banks or rice paddies are contaminated with the virus excreted by the reservoir ducks. the virus survives in the lower temperature of the water. the backyard flocks are exposed to the contaminated water and the virus is transmitted through oral route. so the presence of water bodies adjacent to the backyard farm is considered a major risk factor for the transmission of pathogens. other than ducks, wild birds found around the water bodies, such as teals (anas chlorotis), swans (cygnus atratus), shags (phalocrocorax carbo), seagull (larus novaehollandiae scopulinus), pheasant (phasianus colchicus), turkeys (meleagris gallopavo), and hawks (circus approximans) also play an important role in transmission of hpai in backyard flocks (zheng et al., ) . sparrows (passer domesticus) and starlings (sturnus vulgaris) most commonly visit the place where the backyard flocks are kept. both sparrows and starlings are susceptible to experimental hpai infection (boon et al. ) and thus may act as a source of infection for the backyard birds. moreover, in a metapopulation dynamics study, it was observed that movement of ai virus between commercial and backyard poultry may contribute to the maintenance of outbreaks in an area, but direction of the viral transmission cannot be predicted (farnsworth et al., ) . in bangladesh, the poultry purchased from the market are slaughtered at home and the remnants are offered to their backyard flocks. this malpractice is considered as the strongest risk factor for transmission of hpai in backyard flocks in bangladesh (biswas et al., ) . in egypt, significant correlation exists between disposal of poultry carcass and feces in the environment and hpai infection in poultry (f = . , p < . ) (sheta et al., ) . in ethiopia, scavenging behavior of backyard chickens and chicken dealers were considered a major risk factor for infecting the backyard flocks. a number of farmers identified dogs bringing infected carcasses home to be an additional risk factor for transmission of infection (sambo et al., ) . female backyard birds were found to be more susceptible to ndv infection than male chickens due to extensive roaming throughout the village with a greater possibility of exposure to infected birds (molia et al., ) . biosecurityis in practical terms a mindset or philosophythat must be developed by the producers to prevent the entry of disease into the flock. it is an approach with a focus on maintaining or improving the health status of the birds and preventing the introduction of new pathogens by assessing all the possible risks (permin and detmer, ) . in rural backyard farming specially in developing countries, biosecurity measures are not practiced due to a lack of awareness and high cost of the measures (samanta et al., c) . for example, the cost of a hen house in cambodia (southeast asia) is us$ , whereas, the average monthly income of a cambodian family is us$ (conan et al., ) . a study conducted in a broiler farm in finland detected . euro cents (us$ . ) per bird as an average biosecurity cost (siekkinen et al., ) . in bangladesh, although government circulated -point biosecurity measures to prevent aiv transmission, the backyard farmers ignored these recommendations because they were unable to identify the infection and measure the transmission risk. most of the farmers considered the disease as fate or god's will or due to exposure to evil gas and air (sultana et al., b) . after confirmation of human h n infections in anhui province (china), the provincial government decreed that all backyard poultry must be kept in cages but the authority failed to implement the law (kaufman, ) . similarly, poultry farmers of indonesia (java) and china (haining) ignored the biosecurity practices due to lack of knowledge regarding zoonotic potentiality of avian influenza (padmawatia and nichterb, ; zhang and pan, ) . in literatures, there are very few examples of the biosecurity practices being followed in the rural backyard farms in the developing countries. in ethiopia, removal of manure and bedding from the chicken coops was occasionally performed to sell the objects directly as fertilizer. the materials used to build the chicken sheds, such as mud and cow dung made it difficult for sufficient cleaning with chemical disinfectants (sambo et al., ) . in ghana, general biosecurity practices, such as hand washing after handling poultry, was low in the farmers (odoom et al., ) . in bangladesh, the farmers who kept the birds in the sheds, cleaned the sheds every - days. the dried poultry feces and other debris were collected in a basket and directly used as fertilizer. the sick birds were mostly slaughtered for consumption. hand washing with soap after slaughter, cleaning up the slaughter place in the yard with detergent was rarely practiced. the offals and visceras after slaughter were thrown into the nearest water bodies and bushes (sultana et al., b) . similarly in india (west bengal), a low level of biosecurity awareness was observed among the backyard farmers, such as preparation of feed with boiled water (only % of the cohort), cleaning of feeding utensils and the drinking trough once in a month ( %), frequency of change of drinking water in the trough in days interval ( %), frequency of change of litter in days ( %), and storage of eggs at room temperature ( %). majority of the farmers ( %) did not wash their hands before providing feed to the birds and before entry or exit of the poultry houses (table . ) (samanta et al., c) . in developed countries, a moderate level of biosecurity awareness among the backyard farmers was observed probably due to higher education and socioeconomic conditions. in chile, dead or sick backyard birds were neither consumed nor sold (hamilton-west et al., ) . in european union countries, consumption of birds kept for the purpose samanta, i., joardar, s.n., ganguli, d., das, p.k., sarkar, u., b . evaluation of egg production after adoption of biosecurity strategies by backyard poultry farmers in west bengal. vet. world , [ ] [ ] [ ] [ ] [ ] [ ] of showing or as pets is prohibited (whitehead and roberts, ) . in new zealand, poultry waste was composted prior to use as fertilizer on pastures or gardens to reduce the possibility of disease transmission (zheng et al., ) . in canada (british columbia), the biosecurity measures, such as limiting human visitors to the flock, isolation of new and sick birds, use of footbaths during entry or exit of the shed, changing clothes when returning home, designing pens to decrease risk of wild bird contact, and not sharing equipments were observed (burns et al., ; yendell et al., ) . in the united states, the keepers of the backyard flocks followed similar kind of biosecurity measures, especially hand washing after handling the birds (beam et al., ) . however, majority of them did not use separate clothes to enter the coops and allowed visitors in the coop area. feed and water of their birds were accessible to wild birds and rodents. the keepers were mostly unaware about the disease transmission possibility associated with the presence of wild birds or rodents (elkhorabi et al., ) . lack of knowledge regarding the sources of infection and transmission pathways is still deficient among bird keepers, even in developed countries (beam et al., ; burns et al., ; garber et al., ; karabozhilova et al., ; lockhart et al., ) . cdc played a major role by publishing educational documents on the risk of zoonotic pathogens from contact with live poultry, especially for inexperienced flock owners (cdc, ) . the guideline is also framed for urban backyard poultry owners to reduce the risk of pathogen transmission. the guideline stressed limited flock size, composting of manure before using as fertilizer, prohibition of slaughter, required veterinary care to sick birds, and appropriate disposal of dead birds (tobin et al., ) . the fao had issued several guidelines for the farmers on how to increase biosecurity in backyard flocks, but a significant proportion of villagers continue their at-risk practices as observed in several countries (fao, (fao, , . this discrepancy was explained by the fact that measures were often costly and may not be correlated with the economic benefits of the farmers (aini, ) . in bangladesh, the biosecurity recommendation issued by the government to decrease the transmission of ai was not followed by the farmers because change in practices caused financial losses (sultana et al., b) . in india (west bengal), a cost-effective, agroclimatic zone-specific biosecurity strategy was developed for backyard farmers. the strategy stressed daily cleaning of the utensils with ash, offering potable drinking water to the birds, preparation of feed with boiled water, daily change of drinking water in the trough, sprinkling of detergent water left after washing of clothes in the scavenging area, disposal of carcasses by garden burial, washing of the eggs, storage of the eggs in cold temperature maintained by indigenous structures, and so forth. the strategy was moderately well adopted among the farmers due to its cost-effective nature and the ease of administration. adoption of such strategies caused change in practices (table . ) and as a consequence, the egg production level in the studied village increased (samanta et al., c) . the chapter elaborated the backyard farming including breeds reared, housing, feeding, with special emphasis on suggested biosecurity strategies and consequence of the adapted strategy. other than chicken as the primary species, turkeys, geese, ducks, muscovy ducks, quail, pigeons, and guinea fowl are reared by backyard farming throughout the world. the birds are kept by permanent confinement, free-range, and mixed confinement. in developing countries, the backyard poultry sector mostly suffers from two infectious diseases, such as ai and nd due to lack of 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flocks in two regions of new zealand influence of different rearing systems on natural immune parameters in broiler turkeys a cross-sectional survey of influenza a infection, and management practices in small rural backyard poultry flocks in two regions of new zealand estimates of enteric illness attributable to contact with animals and their environments in the united states avian fatty liver hemorrhagic syndrome: a comparative review avian and pandemic human influenza policy in south-east asia: the interface between economic and public health imperatives university of hawaii at manoa, college of tropical agriculture and human resources key: cord- -rzrfkkci authors: dua, pami title: monetary policy framework in india date: - - journal: indian econ rev doi: . /s - - - sha: doc_id: cord_uid: rzrfkkci in , the monetary policy framework moved towards flexible inflation targeting and a six member monetary policy committee (mpc) was constituted for setting the policy rate. with this step towards modernization of the monetary policy process, india joined the set of countries that have adopted inflation targeting as their monetary policy framework. the consumer price index (cpi combined) inflation target was set by the government of india at % with ± % tolerance band for the period from august , to march , . in this backdrop, the paper reviews the evolution of monetary policy frameworks in india since the mid- s. it also describes the monetary policy transmission process and its limitations in terms of lags and rigidities. it highlights the importance of unconventional monetary policy measures in supplementing conventional tools especially during the easing cycle. further, it examines the voting pattern of the mpc in india and compares this with that of various developed and emerging economies. the synchronization of cuts in the policy rate by mpcs of various countries during the global slowdown in and the covid- pandemic in the early s is also analysed. the monetary policy framework in india has evolved over the past few decades in response to financial developments and changing macroeconomic conditions. the operational framework of monetary policy has also gone through significant changes with respect to instruments and targeting mechanisms. the preamble of the reserve bank of india (rbi) act, was also amended in , which now clearly provides the mandate of the rbi. it reads as follows: "to regulate the issue of bank notes and keeping of reserves with a view to securing monetary stability in india and generally to operate the currency and credit system of the country to its advantage; to have a modern monetary policy framework to meet the challenge of an increasingly complex economy; to maintain price stability while keeping in mind the objective of growth." the aim of monetary policy in the initial years of inception of rbi was mainly to maintain the sterling parity, with exchange rate being the nominal anchor of monetary policy. liquidity was regulated through open market operations (omos), bank rate and cash reserve ratio (crr). soon after independence and through the late s, the role of the central bank was aligned with the planned development process of the nation in accordance with the -year plans. thus, it played a major role in regulating credit availability, employing omos, bank rate, and reserve requirement towards this end. with the nationalization of major banks in , the main objective of monetary policy through the s till the mid- s was the regulation of credit in accordance with the developmental needs of the country. this period was marked by monetization of fiscal deficit while inflationary consequences of high public expenditure necessitated frequent recourse to crr. in , on the recommendation of the committee set up to review the working of the monetary system (chairman: dr. sukhamoy chakravarty), a new monetary policy framework, monetary targeting with feedback was implemented based on empirical evidence of a stable demand for money function. however, financial innovations in the s implied that demand for money may be affected by factors other than income. further, interest rates were deregulated in the mid- s and the indian economy was getting increasingly integrated with the global economy. therefore, the rbi began to deemphasize the role of monetary aggregates and implemented a multiple indicator approach (mia) to monetary policy in encompassing all economic and financial variables that influence the major objectives outlined in the preamble of the rbi act. this was done in two phases-initially mia and later augmented mia (amia) which included forward looking variables and time series models. based on rbi's report of the expert committee to revise and strengthen the monetary policy framework ( , chairman: dr urjit r patel), a formal transition was made in towards flexible inflation targeting and a six member monetary policy committee (mpc) was constituted for setting the policy repo rate. the monetary policy framework agreement (mpfa) was signed between the government of india and the rbi in february to formally adopt the flexible inflation targeting (fit) framework. this was followed up with the amendment to the rbi act, in may to provide a statutory basis for the implementation of the fit framework. with this step towards modernization of the monetary policy process, india joined the set of countries that adopted inflation targeting, starting from by new zealand, as their monetary policy framework. the central government notified in the official gazette dated august , , that the consumer price index (cpi) inflation target would be % with ± % tolerance band for the period from august , to march , . at the time of writing (april ), this period is drawing to a close in less than a year. in this backdrop, this paper discusses the evolution of the monetary policy framework in india and describes the workings of the current framework. the paper is divided into the following sections. section presents a schematic representation of the main components of a general monetary policy framework and describes its key features. section describes the genesis of the monetary policy framework in india since covering the monetary targeting framework, multiple indicator approach and flexible inflation targeting. the main recommendations of rbi's report of the expert committee to revise and strengthen the monetary policy framework ( , chairman: dr urjit r patel) are also discussed. composition, workings and voting pattern of the monetary policy committee from october to march are also provided. further, a comparison of voting patterns with various countries across the globe is undertaken. section discusses a general framework for monetary policy transmission and applies the framework to india. it also describes interest rate linkages at the global level. section examines unconventional monetary policy measures adopted in late and early . section concludes the paper. the specification of the monetary policy framework facilitates the conduct of monetary policy. the general framework comprises well-defined objectives/goals of monetary policy along with instruments, operating targets and intermediate targets that aid in the implementation of monetary policy and achievement of the ultimate objectives. a schematic representation of a monetary policy framework is shown in fig. (laurens et al. ; mishkin ) . instruments are tools that the central bank has control over and are used to achieve the operational target. examples of instruments include open market operations, reserve requirements, discount policy, lending to banks, policy rate. operational targets are the financial variables that can be controlled by the central bank to a large extent through the monetary policy instruments and guide the day-to-day operations of the central bank. these can impact the intermediate target and thus help in the delivery of the final goal of monetary policy. examples of operational targets include reserve money and short-term money market interest rates. intermediate targets are variables that are closely related with the final goals of monetary policy and can be affected by monetary policy. intermediate targets may include monetary aggregates and short-term and long-term interest rates. goals refer to the final policy objectives. these may include price stability, economic growth, financial stability and exchange rate stability. this general framework is applied to the monetary targeting framework with feedback that prevailed from to and to the inflation targeting framework that exists from onwards. the multiple indicator approach that was operational from to was based on a number of financial and economic variables and was not exactly specified on the basis of this framework although broad money was treated as an intermediate target and the goals of monetary policy are the same across the various frameworks. in the s through the mid- s, monetization of the fiscal deficit exerted a dominant influence on monetary policy with inflationary consequences of high public expenditure necessitating frequent recourse to crr. against this backdrop, in , on the recommendation of the committee set up to review the working of the monetary system (rbi ; chairman: dr. sukhamoy chakravarty), a new monetary policy framework, monetary targeting with feedback was implemented based on empirical evidence of a stable demand for money function. the recommendation of the committee was to control inflation within acceptable levels with desired output growth. further, instead of following a fixed target for money supply growth, a range was followed which was subject to mid-year adjustments. this framework was termed "monetary targeting with feedback" as it was flexible enough to accommodate changes in output growth. this operational framework is depicted in fig. . (definitions of variables shown in fig. are given in appendix ). the main instruments in this framework were cash reserve ratio (crr), open market operations (omos), refinance facilities and foreign exchange operations. broad money (m ) was chosen as the intermediate target while reserve money (m ) was the main operating target. however, an analysis of money growth outcomes during the monetary targeting framework reveals that targets were rarely met (rbi (rbi - . even with increases in crr, money supply growth remained high and fuelled inflation. further, financial innovations in the s implied that demand for money may be affected by factors other than income. since the mid- s, with global integration, factors such as swings in capital flows, volatility in the exchange rate and global growth also impacted the economy. moreover, interest rates were deregulated allowing for changing interest rates and a market determined management system of exchange rates was also adopted. ( ) primary objective of monetary policy in india is to maintain price stability, while keeping in mind the objective of growth. ( ) definitions of variables are given in appendix against the backdrop of changing domestic and global dynamics, rbi implemented a multiple indicator approach (mia) to monetary policy in encompassing various economic and financial variables based on the recommendations of rbi's working group on money supply (rbi ; chairman: dr yv reddy). these variables included several quantity variables such as money, credit, output, trade, capital flows, fiscal indicators as well as rate variables such as interest rates, inflation rate and the exchange rate. the information on these variables provided a broad-based monetary policy formulation, which not only encompassed a diverse set of information, but also accorded flexibility to the conduct of monetary management. the mia was conceptualized when dr bimal jalan was governor and was implemented in two stages-mia and later augmented mia, by including forward looking variables and a panel of time series models, in addition to the economic and financial variables (mohanty ; reddy ) . forward looking indicators were drawn from rbi's industrial outlook survey, capacity utilization survey, inflation expectations survey and professional forecasters' survey. all the variables together with time series models provided the projection of growth and inflation while rbi provided the projection for broad money (m ) and treated this as the intermediate target. the operational framework of amia is illustrated in fig. . compared to the monetary targeting framework, the goals of monetary policy remained the same and broad money continued to serve as the intermediate target while the underlying operating mechanism of mia evolved over time. in may , the weighted average call money rate (wacr) was explicitly recognized as the operating target of monetary policy while the repo rate was made the only one independently varying policy rate. these measures improved the implementation and transmission of monetary policy along with enhancing the accuracy of signaling of monetary policy stance (mohanty ) . the importance of focusing on inflation was first highlighted in the report of the committee on financial sector reforms (government of india ; chairman: dr. raghuram rajan) constituted by the government of india. the report recommended that rbi can best serve the cause of growth by focusing on controlling inflation and intervening in currency markets only to limit excessive volatility. the report pointed out that the cause of inclusion can also be best served by maintaining this focus because the poorer sections are least hedged against inflation. further, the report recommended that there should be a single objective of staying close to a low inflation number, or within a range, in the medium term, moving steadily to a single instrument, the short-term interest rate to achieve it. former environment. the committee was also required to review the organizational structure, operating framework and instruments of monetary policy, liquidity management framework, to ensure compatibility with macroeconomic and financial stability, as well as market development. the impediments to monetary policy transmission were to be identified and measures along with institutional pre-conditions to improve transmission across financial markets and real economy were to be suggested. some issues central to the report were selecting the nominal anchor for monetary policy, defining the inflation metric and specifying the inflation target. a nominal anchor is central to a credible monetary policy framework as it ties down the price level or the change in the price level to attain the final goal of monetary policy. it is a numerical objective that is defined for a nominal variable to signal the commitment of monetary policy towards price stability. generally five types of nominal anchors have been used, namely, monetary aggregates, exchange rate, inflation rate, national income and price level. the expert committee recommended inflation to be the nominal anchor of the monetary policy framework in india as flexible inflation targeting recognizes the existence of growthinflation trade-off in the short-run and stabilizing and anchoring inflation expectations is critical for ensuring price stability on an enduring basis. further, low and stable inflation is a necessary precondition for sustainable high growth and inflation is also easily understood by the public. regarding the inflation metric, the committee recommended that rbi should adopt the all india cpi (combined) inflation as the measure of the nominal anchor. this is to be defined in terms of headline cpi inflation, which closely reflects the cost of living and influences inflation expectations relative to other available metrics. cpi is also easily understood as it is used as a reference in wage contracts and negotiations. headline inflation was preferred against core inflation (headline inflation excluding food and fuel inflation) since food and fuel comprise more than % of the consumption basket and cannot be discarded. the committee recommended the target level of inflation at % with a band of ± % around it. the tolerance band was formulated in the light of the vulnerability of the indian economy to supply and external shocks and the relatively large weight of food in the cpi basket. the expert committee also recommended that decision-making should be vested in a monetary policy committee (mpc). with the signing of the monetary policy framework agreement (mpfa) between the government of india and the rbi on feb , , flexible inflation targeting (fit) was formally adopted in india. in may , the reserve bank of india (rbi) act, was amended to provide a statutory basis for the implementation of the fit framework. the amended rbi act, also provided that the central government shall, in consultation with the bank, determine the inflation target in terms of the consumer price index, once in every years. accordingly, the central government has notified in the official gazette % consumer price index (cpi) inflation as the target for the period from august , to march , with the upper tolerance limit of % and the lower tolerance limit of %. the amended rbi act, also provides that rbi shall be seen to have failed to meet the target if inflation remains above % or below % for three consecutive quarters. in such circumstances, rbi is required to provide the reasons for the failure, and propose remedial measures and the expected time to return inflation to the target. in , india thus joined several developed and emerging market economies that have implemented inflation targeting. figure shows the timeline for implementation of inflation targeting for countries in this category, starting in . the amended rbi act, provides for a statutory and institutionalized framework for a six-member monetary policy committee (mpc) to be constituted by the central government by notification in the official gazette. the central government in september thus constituted the mpc with three members from rbi including the governor as chairperson and three external members as per gazette notification dated september , . (details of the composition of mpc are given in appendix ). the committee is required to meet at least four times a year although it has been meeting on a bi-monthly basis since october . each member of the mpc has one vote, and in the event of equality of votes, the governor has a second or casting vote. the resolution adopted by the mpc is published after conclusion of every meeting of the mpc. on the th day, the minutes of the proceedings of the mpc are published which includes the resolution adopted by the mpc, the vote of each member on the resolution, and the statement of each member on the resolution. it may be noted that before the constitution of the mpc, a technical advisory committee (tac) on monetary policy was set up in which consisted of external experts from monetary economics, central banking, financial markets and public finance. the role of this committee was to enhance the consultative process of monetary policy by reviewing the macroeconomic and monetary developments in the economy and advising rbi on the stance of monetary policy. with the formation of mpc, the tac on monetary policy ceased to exist. the mpc is entrusted with the task of fixing the benchmark policy rate (repo rate) required to contain inflation within the specified tolerance band. the framework entails setting the policy rate on the basis of current and evolving macroeconomic conditions. once the repo rate is announced, the operating framework looks at liquidity management on a day-to-day basis with the aim to anchor the operating target-the weighted average call rate (wacr)-around the repo rate. this is illustrated in fig. , where the intermediate targets are the short-term and long-term interest rates and the goals of price stability and economic growth are aligned with the primary objective of monetary policy to maintain price stability, keeping in mind the objective of growth. in addition to the repo rate, the instruments include liquidity facility, crr, omos, lending to banks and foreign exchange operations (rbi ). ( ) ( ) primary objective of monetary policy in india is to maintain price stability, while keeping in mind the objective of growth. ( ) definitions of variables are given in appendix it is imperative here to note some of the key elements of the revised framework for liquidity management (rbi ) that are particularly relevant for the operating framework shown in fig. . as noted in the rbi monetary policy report, . • liquidity management remains the operating procedure of monetary policy; the weighted average call rate (wacr) continues to be its operating target. • the liquidity management corridor is retained, with the marginal standing facility (msf) rate as its upper bound (ceiling) and the fixed reverse repo rate as the lower bound (floor), with the policy repo rate in the middle of the corridor. • the width of the corridor is retained at basis points-the reverse repo rate being basis points below the repo rate and the msf rate basis points above the repo rate. (the corridor width was asymmetrically widened on march and april , .) • instruments of liquidity management continue to include fixed and variable rate repo/reverse repo auctions, outright open market operations, forex swaps and other instruments as may be deployed from time to time to ensure that the system has adequate liquidity at all times. • the current requirement of maintaining a minimum of % of the prescribed crr on a daily basis will continue. (this was reduced to % on march , .) the first meeting of the mpc was held in october . between october and march , the mpc has met times. table shows the voting patterns for each meeting with respect to the direction of change in the policy rate, magnitude of change and the stance of monetary policy. table , on the other hand, provides an overall summary of the voting of all the meetings. it is interesting to note in table , that with respect to direction of change/status quo of the policy rate, consensus was achieved in meetings out of . of these meetings, there were three meetings where there were differences in the magnitude of the change voted for although there was consensus regarding the direction of change. the diversity in voting of the mpc members reflects the differences in the assessment and expectations of individual members as well as their policy preferences. to examine if this diversity exists in mpcs of other countries as well, we analyse the voting patterns of countries across the globe during october to march in table . for many countries, we find dissents in some of the meetings, similar to the lack of consensus in some of the meetings of the indian mpc. it merits mention that the committee approach towards the conduct of monetary policy has gained prominence across globe. the advantages of this approach include confluence of specialized knowledge and expertise on the subject domain, bringing together different stakeholders and diverse opinions, improving representativeness and collective wisdom, thus making the whole greater than the sum of parts (blinder and morgan ; maier ). further, rajan ( ) notes that mpc would bring more minds to bear on policy setting, preserve continuity in case a member has to quit or retire, and be less subject to political pressures. maintain neutral - august reduce bps . to . bps reduce bps [ ] maintain . bps [ ] maintain neutral - october maintain . bps reduce bps [ ] maintain neutral - december maintain . bps reduce bps [ ] maintain neutral - february maintain . bps increase bps [ ] maintain neutral - april maintain . bps increase bps [ ] maintain neutral - june increase bps . to . bps maintain neutral - august increase bps . to . maintain . bps [ ] maintain neutral - october maintain . bps increase bps [ ] change to calibrated tightening - december maintain . bps maintain calibrated tightening - reduce bps . to . bps maintain . bps [ ] change to neutral - april reduce bps . to . bps maintain . bps [ ] maintain this section presents a stylized representation of a framework for monetary policy transmission and also applies this framework to india. monetary policy transmission is the process through which changes in monetary policy affect economic activity in general as well as the price level. with note: the decided rates are in bold, the minority votes are italicized, the meetings with changes in stance are underlined developments in financial systems, the world over, and growing sophistication of financial markets, most central banks use the short-term interest rate as the policy instrument for the conduct of monetary policy. monetary policy transmission is thus the process through which a change in the policy rate is transmitted first to the shortterm money market rate and then to the entire maturity spectrum of interest rates covering the money and bond markets as well as banks' deposit and lending rates. these impulses, in turn, impact consumption (private and government), investment and net exports, which affect aggregate demand and hence output and inflation. there are five channels of monetary transmission-interest rate channel; exchange rate channel; asset price channel; credit channel and expectations channel. the interest rate channel is described above. monetary transmission takes place through the exchange rate channel when changes in monetary policy impact the interest rate differential between domestic and foreign rates leading to capital flows (inflow or outflow) which in turn affects the exchange rate and hence the relative demand for exports and imports. transmission through the asset price channel occurs when changes in monetary policy influence the price of assets such as equity and real estate that lead to changes in consumption and investment. a change in prices of assets can lead to a change in consumption spending due to the associated wealth effect. for example, if interest rates fall, people may consider purchasing assets that are non-interest bearing such as real estate and equity. a rise in demand for these assets may result in higher prices, a positive wealth effect and thus higher consumption. further if equity prices rise, firms may increase investment spending. transmission through the credit channel happens if monetary policy influences the quantity of available credit. this may happen if the willingness of financial institutions to lend changes due to a change in monetary policy. further, debt obligations of businesses may also change due to a change in the interest rate. for instance, if the policy rate falls, debt obligations of firms may decrease, strengthening their balance sheets. as a result, financial institutions may be more willing to lend to businesses, thus increasing investment spending. monetary policy changes can impact public's expectations of output and inflation and accordingly, aggregate demand can be impacted via the expectations channel. for instance, expected future changes in the policy rate can impact medium-term and long-term expected interest rates through market expectations and thus affect aggregate demand. further, if inflation expectations are firmly anchored by the central bank, this would imply price stability. a stylized representation of the monetary policy transmission framework of a change in the policy rate is shown in fig. . figure depicts the monetary transmission through the interest rate channel with specific reference to india. (definitions of all variables shown in fig. are given in appendix .) this shows that a change in the policy rate (repo rate) first impacts the call money rate (weighted average call money rate-wacr) and in turn all other money market rates as well as bond market rates including the repo market, certificates of deposit (cd) and commercial paper (cp) markets, treasury bill (t-bill) market, government securities (g-sec) market and the bond market. the lending rate of banks also changes as depicted by the marginal cost of funds based lending rate (mclr). this further impacts consumption and investment decisions as well as net exports and through these, aggregate demand and ultimately the goals of monetary policy. details of the monetary transmission process are given in rbi ( c). the transmission mechanism is beset with lags. as explained in simple terms in rangarajan ( ) , there are two components of the transmission mechanism. the first is how far the signals sent out by the central bank are picked by the banks and the second is how far the signals sent out by the banking system impact the real economy. rangarajan ( ) labels the first component as "inner leg" and the second as "outer leg". to illustrate monetary transmission of the first kind, we examine the impact of a cumulative reduction in the policy repo rate by basis points between february and january . during this period, transmission to various money and bond markets ranged from basis points in the overnight call money market to basis points in the market for -year government securities to basis points in the market for -year government securities. transmission to the credit market was also modest with the -year median marginal cost of funds-based lending rate (mclr) declining by basis points during february and january . the weighted average lending rate (walr) on fresh rupee loans sanctioned by banks fell by basis points while the walr on outstanding rupee loans declined by basis points during february to december . monetary transmission increased somewhat after the introduction of the external benchmark system in october whereby most banks have linked their lending rates to the policy repo rate of the reserve bank. during october to december , the walrs of domestic banks on fresh rupee loans fell by basis points for housing loans, basis points for vehicle loans and basis points for loans to micro, small and medium enterprises (msmes). monetary transmission in various markets is depicted in figs. , and . figure shows the policy corridor with the msf rate as the ceiling and the reverse repo rate as the floor for the daily movement in the weighted average call money rate. the figure shows that the wacr moved closely in tandem with the policy rate (repo rate). figure shows that the g-sec market rates followed the movements in the policy rate. figure shows that the direction of change of mclr was more or less in synchronization with that of the repo rate. the walr for fresh rupee loans tracked the repo rate much more than the walr on outstanding loans. figure shows the % target inflation rate with the ± % tolerance band along with the headline inflation rate. this shows that the headline inflation generally stayed within the band. the average inflation rate from august to march was . % and up to december , it was . %, i.e. close to %. the average gdp growth between q : - and q : - was . % (fig. ). an interesting phenomena, world-wide is the synchronization in the movements in interest rates across the globe. table shows that mpcs in various countries have voted for a cut in their policy rate in at a time when many countries were simultaneously experiencing a slowdown. due to covid- pandemic, in early , some countries have cut the policy rate sharply. this pattern of rate cuts in up to march is almost perfectly aligned with the movements in the repo rate (policy rate) in india. these global patterns are illustrated in figs. and . figure shows that the policy rates for the brics nations moved in tandem from to . figure indicates a similar pattern amongst policy rates of us, ecb, uk and japan. we have so far discussed conventional monetary policy. as already described, monetary transmission of conventional monetary policy entails a change in the policy rate impacting financial markets from short-term interest rates to longer-term bonds and bank funding and lending rates. a change in the policy rate is thus expected to permeate through the entire spectrum of rates that further translates into affecting interest sensitive spending and thus economic activity. however, if there are problems in the monetary policy transmission mechanism or if additional monetary stimulus is required in the circumstances that the policy rate cannot be reduced further (or in addition to a change in the policy rate), then the central banks may employ unconventional monetary policy tools. unconventional monetary measures target financial variables other than the short-term interest rate such as term spreads (e.g., interest rates on risk free bonds), liquidity, credit spreads (e.g. interest rates on risky assets) and asset prices. the objective of unconventional tools is to supplement the conventional monetary policy tools especially in the easing cycle to boost economic growth. in the recent past, rbi has utilized various unconventional tools in addition to conventional monetary policy measures. to better understand the use of accommodative: interest rates stay the same or decrease; tightening: interest rates stay the same or increase: neutral: interest rates can decrease, increase or stay the same table . . large scale asset purchases (also referred to as quantitative easing) by a central bank involve purchase of long-term government securities financed by crediting reserve accounts that commercial banks hold at the central bank. this purchase would lower government bond yields and serve as a signal that the policy rate will stay at a lower level for a longer period. sellers of government bonds may, in turn, change their investment portfolios and invest in more risky assets (e.g., corporate bonds) leading to a decrease in the relevant interest rate and higher asset price and thus boost economic growth. central banks can also purchase assets from the private sector. . lending operations entail provision of liquidity to financial institutions by the central bank through the creation of new or extension of existing lending facilities. this mechanism is different from conventional lending since this is undertaken at looser or specific conditions, e.g., expanding the set of eligible collateral, extending maturity of the loan, providing funding at lower cost and channel/target lending to desired areas or activities with explicit conditions on loans. this lending increases the credit flows to the private sector and helps to restart flow of credit to credit-starved sectors. it can also lead to lower borrowing costs for the financial and real economy sectors. . forward guidance involves central banks communicating future policy intentions and commitments regarding the policy rate to influence policy expectations. forward guidance is given routinely by most central banks. its use as an unconventional tool implies that a central bank uses this to signal that it is open to undertaking extraordinary policy actions for a longer duration. forward guidance can be 'time specific' or 'state specific'. under the former, the central bank makes a commitment to keep interest rates low for a specified period. under the latter, the central bank maintains low rates until specific economic conditions are met. . the rationale of a negative interest rate is that if an interest rate is charged on the reserves that commercial banks hold at the central bank, the banks may be induced to reduce their excess reserves by increasing lending. the first three of these have been applied to india and are reported in table . these include operations twist in december and january as well as april , long-term repo operation (ltro) in february , targeted long-term repo operations (tltro) in march and april , and special refinance facilities to national bank for agriculture and rural development (nabard), small industries development bank of india (sidbi) and national housing bank (nhb) in april . the application of these unconventional monetary tools was necessitated, first by the slowdown in the indian economy in , and second, by the impact of covid- pandemic due to which economic activity and financial markets, the world over, came under severe stress. it was thus necessary for the reserve bank to employ measures to mitigate the impact of covid- , revive growth and preserve financial stability. thus the unconventional monetary policy tools supplemented the conventional monetary policy measures to stimulate growth in the economy. this paper reviews the evolution of monetary policy frameworks in india since the mid- s. it also describes the monetary policy transmission process and its limitations in terms of lags in transmission as well as the rigidities in the process. it also highlights the importance of unconventional monetary policy measures in supplementing conventional tools especially during the easing cycle. at the time of writing (april ), three and a half years have passed since the implementation of the flexible inflation targeting framework and the constitution of the monetary policy committee. with the implementation of fit, india joined the group of various developed, emerging and developing countries that have implemented inflation targeting since . the inflation target specified by the central government was % for the consumer price index (cpi) inflation for the period from august , to march , with the upper tolerance limit of % and the lower tolerance bound of %. as shown in fig. , from august through march , the headline inflation generally stayed within the tolerance band with the average inflation rate slightly less than % during this period. there were episodes of high/unusual inflation due to supply shocks (food inflation, oil prices) but these were suitably integrated in the policy decisions. the monetary policy committee has also been in existence since october . the mandate of the mpc is to set the policy repo rate while taking cognizance of the primary objective of monetary policy-to maintain price stability while keeping in mind the objective of growth-as well as the target inflation rate within the tolerance band. once the policy repo rate is set, the monetary transmission process facilitates the percolation of the change in the policy rate to all financial markets (money and bond markets) as well as the banking sector which further impacts interest sensitive spending in the economy and eventually increases aggregate demand and output growth. in practice, however, there are rigidities as well as lags in the transmission process that impede the speed and magnitude of the transmission and thus question the efficacy of monetary policy with respect to the policy repo rate. nevertheless, the external benchmarking system introduced by rbi from october , whereby all new floating rate personal or retail loans (housing, auto etc.) and floating rate loans to micro and small enterprises extended by banks were benchmarked to an external rate, strengthened the monetary transmission process with several banks benchmarking their lending rate to the policy repo rate. this requirement of an external benchmark system was further expanded to cover new floating loans to medium enterprises extended by banks with effect from april , . this is expected to further improve the transmission process. of course, the policy repo rate is not a panacea for all ills but serves well as a signaling rate. the rbi routinely brings out the statement on developmental and regulatory policies that is released simultaneously with the resolution of the mpc. rbi has also taken recourse to unconventional measures to supplement the conventional tools to boost economic growth. more recently, with the slowdown in followed by the extraordinary slump in economic activity due to covid- pandemic, rbi has been compelled to use rather innovative and unconventional tools starting in december as discussed in table . needless to say, in the unprecedented times of the global pandemic (and, in general, in periods of severe crises), a multi-pronged approach comprising monetary, fiscal and other policy measures is required to protect economic activity and minimize the negative impact of the pandemic (crisis) on economic growth. the importance of monetary-fiscal coordination is highlighted in the resolution of the monetary policy committee dated march , (available on the rbi website) that states the following: "strong fiscal measures are critical to deal with the situation." thus, in addition to monetary policy, fiscal policy has a major role in combating the economic effects of the covid- pandemic. in response to the need of the hour, the government of india has implemented various fiscal measures to provide a boost to the economy. while central banks across the globe have responded to the global pandemic with monetary and regulatory measures, various governments have reinforced the monetary measures by deploying massive fiscal measures to shield economic activity from the effect of the covid- pandemic. a few words about the workings of the mpc are also warranted. as discussed in the paper, the voting pattern of the indian mpc is comparable to international standards, reflecting the healthy diversity in the assessment of the members. the workings of the mpc are transparent with the resolution being made available soon after the end of the meetings. furthermore, each member of the committee has to submit a statement that is made available in the public domain on the th day after the meeting. thus, each member is individually accountable, making the process perhaps more stringent than that of mpcs in other countries. the governor of the bank-chairperson deputy governor of the bank, in charge of monetary policy-member one officer of the bank to be nominated by the central board-member professor, indian statistical institute (isi)-member professor pami dua, director, delhi school of economics (dse)-member; and the three external members have served on the committee since its inception and continue to serve. there have been some changes in the rbi members as follows urjit patel chaired the committee from former deputy governor attended the viral acharya, former deputy governor in charge of monetary policy attended the meetings from deputy governor attended the meetings from michael patra attended all the meetings, first as executive director till december and continues to attend meetings as deputy governor in charge of monetary policy janak raj has attended meetings since february as executive director. references bank for international settlements a hundred small steps: report of the committee on financial sector reforms (chairman: raghuram rajan) state of the art of inflation targeting. handbooks, centre for central banking studies the evolution of inflation expectations in japan. bank of international settlements working papers breaking monetary policy rules in russia the journey of inflation targeting: easier said than done the case for transitional arrangements along the road how central banks take decisions: an analysis of monetary policy meetings the economics of money, banking, and financial markets. pearson: columbia university monetary policy framework in india: experience with multiple-indicators approach changing contours of monetary policy in india. mumbai: reserve bank of india bulletin i do what i do the new monetary policy framework-what it means monetary policy operating procedures in emerging market economies report of the committee to review the working of the monetary system (chairman: dr. sukhamoy chakravarty) report on currency and finance - : fiscal-monetary co-ordination report of the expert committee to revise and strengthen the monetary policy framework (chairman: dr. urjit patel) report of the internal study group to review the working of the marginal cost of funds based lending rate system (chairman: dr. janak raj) forex market operations and liquidity management (by-janak raj, sitikantha pattanaik, indranil bhattacharya and abhilasha) report of the internal working group to review the liquidity management framework governor's statement, sixth bi-monthly monetary policy statement governor's statement, seventh bi-monthly monetary policy statement monetary policy transmission in india-recent trends and impediments (by-arghya kusum mitra and sadhan kumar chattopadhyay). reserve bank of india bulletin monetary policy report, april. mumbai. reserve bank of india. ( e) reflections on analytical issues in monetary policy: the indian economic realities publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations acknowledgements i am grateful to michael patra and janak raj, deputy governor and executive director respectively, reserve bank of india for useful and constructive suggestions. i also gratefully acknowledge help and support from hema kapur, deepika goel and neha verma, teachers in colleges of the university of delhi, who also motivated me to write in a student-friendly manner. special thanks are due to naina prasad for competent and diligent research assistance. i am grateful to the editors of the indian economic review for inviting me to contribute to the newly instituted section on policy review. earlier versions of this paper were presented as a public lecture at the delhi school of economics in march and as a keynote address at the annual conference of the indian econometric society at madurai kamaraj university in january . i am grateful to the participants of these events for their feedback. repo rate is the (fixed) interest rate at which the rbi provides overnight liquidity to banks against the collateral of government and other approved securities under the liquidity adjustment facility (laf) reverse repo rate is the (fixed) interest rate at which the rbi absorbs liquidity, on an overnight basis, from banks against the collateral of eligible government securities under the laf liquidity adjustment facility (laf) enables the rbi to modulate short-term liquidity under varied financial market conditions to ensure stable conditions in the overnight (call) money market. the laf operates through daily repo and reverse repo auctions thereby setting a corridor for the short-term interest rate consistent with policy objectives corridor is determined by the msf rate as ceiling and reverse repo rate as the floor of the corridor for the daily movement in the weighted average call money rate marginal standing facility (msf) is the facility under which scheduled commercial banks can borrow additional amount of overnight money from the rbi at a penal rate against eligible securities. banks are allowed to dip into their statutory liquidity ratio (slr) portfolio to borrow funds under this facility up to a limit decided by the rbi. this provides a safety valve against unanticipated liquidity shocks to the banking system bank rate is the standard rate at which the rbi is prepared to buy or rediscount bills of exchange or other commercial papers eligible for purchase under the reserve bank of india act, cash reserve ratio (crr) is the minimum cash balance that a scheduled commercial bank is required to maintain with the rbi as a certain percentage of its net demand and time liabilities (ndtl) relating to the second preceding fortnight. it is prescribed by rbi from time to time statutory liquidity ratio (slr) is the share of ndtl that the scheduled commercial banks are required to maintain on a daily basis in safe and liquid assets, such as unencumbered government securities and other approved securities, cash and gold open market operations (omos) are conducted by the rbi by way of sale/ purchase of government securities to/ from the market with an objective to adjust the rupee liquidity conditions in the market on a durable basis market stabilization scheme (mss) was introduced as an instrument for monetary management in april . surplus liquidity of a more enduring nature arising from large capital inflows is absorbed through sale of short-dated government securities and treasury bills. the cash so mobilized is held in a separate government account with the rbi monetary base (reserve money/m ) = currency in circulation + bankers' deposits with the rbi + 'other' deposits with the rbi m = currency with the public + demand deposits with the banking system + 'other' deposits with the rbi m = m + saving deposits of post office saving banks call money rate is the rate at which overnight money are lent and borrowed in the money market weighted average call money rate (wacr) is volume weighted average of rates at which overnight money or money at short notice (up to a period of days) are lent and borrowed in the money market. this weighted average rate can be computed for any period such as, daily, weekly, yearlyrefinance facility under monetary targeting framework was provided by rbi as an additional source of reserves. the two types of refinance facility provided to banks include export credit refinance (extended against bank's outstanding export credit eligible for refinance) and general refinance (provided to banks to tide over their temporary liquidity shortages) (excluding rrbs, payment banks and small finance banks) on the outstanding rupee loans and fresh rupee loans sanctioned by the banks. it is based on lending rates to different sectors with weights based on credit extended to different sectors money market: market for lending and borrowing of short-term funds which are highly liquid. it covers money and financial assets that are close substitutes for money including call money, repo, tri-party repo, t-bills, cash management bills, commercial paper and certificate of deposit call money market: instrument: overnight money and money at short notice (up to a period of days) is lent and borrowed without collateral. call money is liquid and can be turned into money quickly at low cost and provides an avenue for equilibrating the short-term surplus funds of lenders and the requirements of borrowers borrowers: scheduled commercial banks (excluding rrbs), co-operative banks (other than land development banks), and primary dealers (pds) lenders: same as borrowers market repo: instruments: repurchase agreement (repo) which is used for borrowing funds by selling securities with an agreement to repurchase the said securities on a mutually agreed future date at an agreed price which includes interest for the funds borrowed. government securities, cps, cds, units of debt etfs, listed corporate bonds and debentures are eligible securities for repo. repo against corporate bonds are called repo in corporate bond participants: banks, pds, mutual funds, listed corporates, all india financial institutions, any other entity approved by the rbi tri-party repo market: instrument: tri-party repo, a repo contract where a third entity (apart from the borrower and lender), called a tri-party agent, acts as an intermediary between the two parties to the repo to facilitate services like collateral selection, payment and settlement, custody and management during the life of the transaction participants scheduled commercial banks, recognized stock exchanges and clearing corporations of stock exchanges or clearing corporations authorized under pss act and any other entity regulated by rbi or sebi are eligible subject to certain criterion. all the repo market eligible entities are permitted to participate in tri-party repo market instrument: short-term debt instruments issued by the goi and sold by rbi on an auction basis. treasury bills are zero coupon securities that pay no interest, issued at a discount and redeemed at the face value at maturity. they are currently issued in three tenors, namely, days, days and days. they are also traded in the secondary market investors: any person resident of india, including firms, companies, corporate bodies, institutions and trusts along with non-resident indians and foreign investors (subject to approval by government) can invest through a competitive route certificate of deposits market: instrument: a negotiable money market instrument issued in dematerialized form or as a usance promissory note against funds deposited at a bank or other eligible financial institution for a specified time period. maturity ranges from days to years. cds can be traded in the secondary market issuers: banks and financial institutions investors: individuals, corporations, companies (including banks and pds), trusts, funds, associations and non-resident indians (but only on non-repatriable basis) commercial paper market: instrument: an unsecured money market instrument issued in the form of a promissory note. they are issued for the maturities between a minimum of days and a maximum of up to year from the date of issue (given that the credit rating of the issuer is valid in the period). cps can be traded in the secondary market issuers: corporates, pds and all india financial institutions (fis) investors: individuals, banks, other corporate bodies (registered and incorporated in india), non-resident indians, bond market: instrument: a debt instrument whereby an investor loans money to an entity (typically corporate or government) which borrows the funds for a defined period of time at a variable or fixed interest rate. bonds are used by companies, municipalities, states and sovereign governments to raise money to finance a variety of projects and activities issuers: government or corporates investors: banks, mutual funds, foreign institutional investors, provident funds, pension funds government securities market: instrument: a tradable instrument issued by the central or the state governments. it acknowledges the government's debt obligation. securities issued by state governments in india are known as state development loan (sdl). the short-term g-secs (treasury bills) have original maturities of less than year while long-term g-secs (government bonds or dated securities) have original maturity of year or more. there is an active secondary market in g-secs participants: commercial banks, pds, institutional investors like insurance companies, other banks including cooperative banks, regional rural banks, mutual funds, provident and pension funds, foreign portfolio investors (allowed with quantitative limits prescribed from time to time), and corporates instrument: debt securities issued by private and public corporations. companies issue corporate bonds to raise money for a variety of purposes, such as building a new plant, purchasing equipment, or growing the business. the stock exchanges have a dedicated debt segment in their trading platforms to facilitate the needs of retail investors. a corporate bond is generally priced on the basis of price of g-sec of comparable tenure with a spread added to it. they are also traded in secondary market participants: corporates, banks, retail investors and institutional investors including insurance companies and mutual funds, foreign investors the gazette notification of the ministry of finance dated september , notes the following. "in exercise of the powers conferred by section zb of the reserve bank of india act, act, ( of , the central government hereby constitutes the monetary policy committee of the reserve bank of india, consisting of the following, namely: key: cord- -zyzwrm p authors: golechha, mahaveer; panigrahy, rabindra k title: covid- and heatwaves: a double whammy for indian cities date: - - journal: lancet planet health doi: . /s - ( ) - sha: doc_id: cord_uid: zyzwrm p nan the world urgently needs a planetary health perspective to properly address the challenge posed by covid- . the covid- pandemic and extreme heat events are already coinciding, further threatening community health in many cities across the globe. the onset of the hot season presents individuals and local decision makers with new challenges on the optimal ways to stay safe from both heat stress and covid- . the india meteorological department has predicted that heatwave conditions are likely to be severe in . in india, heatwaves typically occur between march and july. by may, the temperature had already started soaring in india, and some cities had already reported maximum temperatures of more than °c. effective public health interventions for the prevention of heat-related illnesses and mortality during heatwaves-such as leaving home for cooler public spaces, shopping malls, or gardens, seeking ambulatory medical care, and checking on vulnerable people might be impossible or in contradiction to public health advice on social distancing and the stringent lockdown measures for containing the transmission of covid- . in india, extreme heatwave conditions might exacerbate and introduce additional challenges for individuals, health workers, health facilities, and communities in the management of covid- , considering india's health inequalities, marked economic and social disparities, and distinct cultural values and geographical conditions. severe heat waves in indian cities could endanger the lives and health of people living in poorly ventilated, hot, crowded homes, low-income urban slum dwellers, people with poor options for self-quarantine or for maintaining the requisite hygiene levels. furthermore, many of the people who are most vulnerable to covid- are also vulnerable to extreme heat, including older people, those with pre-existing medical conditions (such as cardiovascular disease, respiratory illness, or diabetes), homeless people, and outdoor workers. india's historically hot summers are being intensified by climate change, with deadly consequences. in , the city of ahmedabad in gujarat state suffered a recordbreaking heat wave that killed more than people. in the wake of this silent disaster, the ahmedabad municipal corporation collaborated with public health and policy experts to develop and implement a heat action plan. ahmedabad's plan was the first heat action plan and early warning system in south asia. the ahmedabad heat action plan aims to provide a framework for the implementation, coordination, and evaluation of extreme heat response activities. important activities under the heat action plan include public awareness and community outreach to communicate the risks of heatwaves, an early warning system and inter-agency coordination, and building the capacity of medical officers and frontline health workers for the prevention and management of heatrelated illnesses. according to a study, this was associated with a reduced death rate on hot days, with more than deaths avoided each year after it was implemented. it is now widely recognised that many heat-related risks are manageable through timely warnings about an impending event and adoption of a heat action plan. public health services and government machinery at all levels are embroiled in the battle to contain the spread of the covid- pandemic, but cities also need to be ready to deal with the adverse effects of severe heatwaves. indian state and local city administrations should update their heat action plans as required by the national disaster management authority and should implement various activities for the prevention and management of heat-related illness. for example, the personal protective equipment (ppe) used by frontline workers makes it more difficult to lose body heat. to optimise endurance and cognitive performance while wearing ppe, workers should seek to lower their body's core temperature at the onset of work and attenuate it during work, and cooling down, hydrating, and recovering between shifts should be advised, because heat stress can increase with consecutive days of exposure. in the present situation, outreach and communication about heat stress is even more important. city administrations should emphasise remote services such as telehealth, community phone trees, and telephone hotlines, which check in on vulnerable people on a regular basis during the heatwave and can be lifesaving. the ambulatory and medical staff should be alert to recognising potential hyperthermia cases and facilitating correct testing, diagnosis, and treatment. in the face of the compounded risks from rising heat and covid- , communities should be prepared through effective awareness raising and early warning. the local city administration and state government needs to implement appropriate policies for enhancing community and health system resilience. it is also important to coordinate with government and nongovernmental social services to reach out to those who are most vulnerable to both risks. indian cities should treat heatwaves with the same urgency as the covid- pandemic; a heat action plan, along with other essential measures, will enable better management of the complex and intersecting health risks of covid- during periods of excessive heat and heatwaves. e . national disaster management authority, ministry of home affairs, government of india. national guidelines for preparation of action planprevention and management of heat wave indian meteorological department, government of india. daily heat wave bulletin heat-related deaths during the july heat wave in chicago heat-related mortality in india: excess all-cause mortality associated with the ahmedabad heat wave development and implementation of south asia's first heat-health action plan in ahmedabad building resilience to climate change: pilot evaluation of the impact of india's first heat action plan on all-cause mortality efficacy of heat mitigation strategies on core temperature and endurance exercise: a meta-analysis key: cord- -dx itceo authors: bhat, m mohsin alam title: hate crimes in india date: - - journal: jindal global law review doi: . /s - - - sha: doc_id: cord_uid: dx itceo nan . https ://www.washi ngton post.com/world /asia_pacif c/amusli m-and-a-hindu -thoug ht-they-could -be-a-coupl e-then-came-the-love-jihad -hit-list/ / / / be- d b- e - dc - b e b _story .html. accessed july ; rahul bhatia, 'the year of love jihad in india' (the new yorker, december ). https ://www.newyo rker.com/cultu re/ -inrevie w/the-year-of-love-jihad -in-india . accessed july . often accompanied sectarian mobilisation in the context of elections. the most striking problem throughout this history has been state complicity in violence, and impunity of state and non-state actors. while there is a need for more research, contemporary incidents of hate violence appear to follow these patterns. most of the reported incidents have involved targeting of individuals rather than mass violence. but they continue to ft into, and often serve, a political ecosystem. incidents of violence have often preceded and followed political hate speech. and as is the case with sectarian mass violence, the report on legal accountability here remains dismal. this special issue seeks to make three contributions. first, it reckons with the contemporary. what are the historical antecedents of contemporary hate violence in india? in what ways is the present moment a continuation from the past? what new challenges for the law does it pose? second, it seeks to advance the conversation around hate violence by taking legal categories seriously. what categories are best attuned to capture the personal and social harm of violence? how should we best interpret these legal categories to advance the ends of justice? third, the issue takes the role of institutions seriously. how should we evaluate the role of criminal justice institutions in addressing -or maintaining -impunity? what are the best institutional strategies to address violence? this issue self-consciously situates itself in the current moment. on april , a mob of self-styled gau rakshaks (cow protectors) attacked and killed pehlu khan only a few kilometres from delhi. pehlu, a -year-old dairy farmer, was transporting cows he had recently purchased from a cattle fair across the border in the state of rajasthan. the video of the gruesome act that was soon circulating online generated both outrage and alarm. this, unfortunately, was not an isolated incident. over the next many months, a series of violent incidents -with dalit and muslim victims -came to dominate the public discourse. in july , the former chief justice of the supreme court, deepak misra, warned against india turning into a 'mobocracy'. these incidents of vigilantism and mob lynching were a reminder of the deep social cleavages in our society. they also soon exposed the limitations in the criminal justice system. commentators and activists noted the failure of the police to rein in the perpetrators. they also noted the tremendous costs of this violence for the victims and survivors, as well as for the social fabric. while this special issue was being fnalised, delhi was on fre. from december , there were unprecedented protests against the citizenship amendment act, . the legislation introduced a religious test for citizenship for a country that many have always seen to be founded on secularism. the inspiring mobilisation adopted the constitutional language of equality and inclusion in the face of tremendous political opposition. just as the protests were dealing with the impact of covid- , shocking violence broke out in delhi on february . the violence, initially directed at the protestors, spread like wildfre, resulting in more than casualties and hundreds of displaced citizens. the sectarian violence was a reminder that this special issue must foreground its immediate context even as it sought to intervene academically. this context made the intervention urgent and signifcant. the interviews with harsh mander and teesta setalvad -two of the foremost activists in the feld -keep this issue grounded in the concrete realities of violence, impunity, and accountability. both mander and setalvad chart the histories of sectarian violence in india -from the partition violence, the various episodes of mass communal violence, to the recent spate of more localised incidents of lynching. they draw from their extensive experience of legal activism to explore the entrenched institutional problems that have inhibited legal accountability. they also offer the political causes and stakes of battling hate violence. signifcantly, their experiments with legal interventions offer important resources to scholars and researchers interested in constructing social solidarities and litigation strategies. nikhil roshan's photo-essay further grounds this special issue. it highlights both the context as well as the ethical stakes involved. through images and text, roshan explores the horrors of the recent delhi violence. he presents a vivid portrayal of what we may often miss in our study of hate violence. we do see the loss of life. but we may fail to see how everyday poverty and segregation enable violence. his contribution reminds us that overt violence breaks out from intractable -and often invisible -marginalisation. the political and legal category that is conventionally used to describe sectarian violence in india is 'communal riot'. as setalvad points out in this issue, the use of the word 'riot' potentially mischaracterises the nature of the violence, which is often targeted against minorities and accompanied by state complicity. she argues that the category of 'pogrom' is better suited to describe the nature and impact of sectarian violence in the indian context. the supreme court's july order, which acknowledged the harms of hate violence, laid down a series of guidelines to counter it. the court framed its intervention in terms of the category of 'lynching'. in their contribution to the issue, bhat, bajaj, and kumar point out how -despite the court's extensive guidelines -police personnel have often operated with an interpretation of the category that runs counter to the stated objectives of the judicial order. this discussion illuminates the value of paying close attention to the words we use to describe violence within and outside legal discourse. joanna perry's contribution to the issue is a strong expression of this keen attention on how legal categories visibilise violence, create spaces of institutional redress, and travel transnationally. perry argues in favour of adopting the hate crime framework in india, which in her view invites institutions to focus on protection for marginalised groups facing violence, rather than treating them as the problem. the core of her contribution offers an institutional and contextual account of how the hate crime concept has travelled into local national contexts. she notes that this can be best understood as a vernacularisation of the concept: national state and non-state actors adopt the concept creatively by often formulating 'partner concepts' that suit the local contexts. she thus advocates creative, strategic, and hybrid ways of battling hate crime by evolving local techniques, defnitions, and institutional modes. she argues that 'vigilantism' can be such a partner concept in india, which can incorporate the normative and institutional goals of the hate crime concept while being responsive to the specifc challenges in the country. while perry focuses on vigilantism as a potential partner concept in india, vandita khanna's contribution develops the concept of 'targeted violence'. using the delhi high court's judgment in the hashimpura massacre case as a springboard, she develops the normative contours of targeted violence. specifcally, she shows the concept's potential for making the autonomy and dignity harms of violence legally legible. this focus on legal categories -rather novel in the indian context -can generate a more searching academic conversation about how various manifestations of hate crime are connected. there is now an important feld of scholarship on castebased violence or atrocities. how is the category of caste atrocities conceptually, legally, and normatively related to that of hate crime based on other identities like religion, race, ethnicity, disability, or sexual orientation? does thinking of them within the rubric of hate crime enhance our understanding of violence and generate more compelling solidarities? or will we lose out on nuance and specifcity? we hope the special issue generates this dialogue. the third theme of this special issue is the promise and limitations of legal institutions. in her contribution, perry quotes legal anthropologist sally engle merry on one of the most profound challenges of law. while the state is often the major violator of human rights, merry writes, 'ironically it is also the agent for carrying out human rights reforms.' the nuances of this central dilemma are apparent in the interview with mander. he describes the long legal battle for legal justice in cases of sectarian violence. the debate on the prevention of communal and targeted violence (access to justice and reparations) bill, is of particular relevance. as he notes, the specifc challenge in india has been not to proliferate criminal law, but to strengthen institutional accountability. his account perhaps reveals the need for a constant acknowledgment -on the part of advocates, lawyers, and activists -of the law's entrenched limitations to counter violence. this is also the core of bhat, bajaj, and kumar's contribution. they provide a sobering account of the supreme court's celebrated judgment against mob lynching. their detailed interviews with police officials, and the account of one police investigation in a lynching case, show that the fate of court orders and criminal legislation remains precariously subject to the quotidian exercise of police discretion. this exercise is shaped by and channels entrenched police culture and institutional bias. the conversation about legal reform, thus, must also integrate the systemic questions of prejudice, power, and democracy. the production of hindu-muslim violence in contemporary india votes and violence: electoral competition and ethnic riots in india on their watch: mass violence and state apathy in india, examining the record (three essays collective lynching and trolling: why political parties can't absolve themselves of responsibility' (the economic times the modi years: what has fuelled rising mob violence in india?' (scroll under modi government, vip hate speech skyrockets -by %' (ndtv fear of law has evaporated as cases of lynching have become regular and brazen' (outlook key: cord- -qp k fz authors: goswamy, tushar; parmar, naishadh; gupta, ayush; tandon, vatsalya; shah, raunak; goyal, varun; gupta, sanyog; laud, karishma; gupta, shivam; mishra, sudhanshu; modi, ashutosh title: ai-based monitoring and response system for hospital preparedness towards covid- in southeast asia date: - - journal: nan doi: nan sha: doc_id: cord_uid: qp k fz this research paper proposes a covid- monitoring and response system to identify the surge in the volume of patients at hospitals and shortage of critical equipment like ventilators in south-east asian countries, to understand the burden on health facilities. this can help authorities in these regions with resource planning measures to redirect resources to the regions identified by the model. due to the lack of publicly available data on the influx of patients in hospitals, or the shortage of equipment, icu units or hospital beds that regions in these countries might be facing, we leverage twitter data for gleaning this information. the approach has yielded accurate results for states in india, and we are working on validating the model for the remaining countries so that it can serve as a reliable tool for authorities to monitor the burden on hospitals. social media websites like twitter and facebook encourage frequent user expressions of their thoughts, opinions, and random details of their lives. india has the th largest user base of twitter in the world, with . million users and growing, followed by indonesia with . million users [statista, ] . this highlights the potential for gaining useful insights from the tweets posted by millions of users in these countries. tweets and status updates range from significant events to inane comments. most messages contain little informational value, but the aggregation of millions of messages can generate valuable knowledge. twitter users often publicly express personal experience about overcrowding at hospitals, difficulties faced due to a shortage of equipment by them or their relatives and other issues arising due to the pandemic, which can help understand the ground reality of the situation. previous research has studied the correlation between twitter trends and influenza rates using tweets about the symptoms [paul and dredze, ] . statistical techniques have been used to forecast flu rates using twitter data [santillana et al., ] . influenza rates have been monitored at the * contact author local level in the usa during the influenza epidemic of [broniatowski et al., ] . similarly, signorini et al [signorini et al., ] have studied the correlation between twitter data and h n cases for tracking of the infection. in this study, we are using the twitter data of users to study the surge in hospitalization volumes due to the covid- pandemic. we have focused our work on india, indonesia, and bangladesh for the scope of this study, with plans to extend this approach to other geographies in south-east asia. our research aims to identify incidents of overcrowding at hospitals, shortage of critical equipment like ventilators, and lack of available icu units. this system can help understand the medical preparedness levels of the health facilities in these countries and the burden on their hospitals as the pandemic spreads. the system pipeline includes scraping historical tweets at a granular level to obtain a corpus, processing the corpus using natural language processing tools, calculating signals from the processed data, and finally evaluating the results by comparing ground reports and bulletins. we have deployed neural translation models to account for the usage of regional language. our primary contribution to the ai community through this research is to demonstrate the application of an nlp-based twitter model to monitor the burden on health facilities due to the covid- pandemic. to the best of our knowledge, this is the first and the only approach of its kind, which can detect the trends in the worst-hit regions accurately based on twitter data. we are closely working with members from who's regional office for south-east asia (who-searo) to study and monitor our model's signals, and it is intended to help them with monitoring the situation in these countries and in identifying regions which are facing a resource crunch due to the pandemic. our model can thus be used by public health organisations to recommend appropriate actions to the authorities in the regions which the model has identified. data extraction and pre-processing . natural language processing for tweets historical tweet extraction we used the getoldtweets api [mottl, updated ] to scrape and extract historical tweets from the twitter website. unfortunately, twitter has some restrictions due to which we are unable to access all the tweets beyond seven days from the date of scraping. this leads to a misleading spike in the data (fig. ) . to address this, we scaled the tweets using the factor of change across the peak. to eliminate noise in the data and extract the important information, we performed the following operations on the tweet corpus: • removing website links: to prevent the same information from being captured twice. • removing non-ascii characters: to eliminate noise and focus on relevant keywords only • removing stopwords: removed words like 'is', 'an', 'the' to focus on hospital-related words in the frequency analysis • tokenisation: we utilized the nltk tweettokenizer api [loper and bird, ] to tokenize tweets. this was done to aid the keyword calculation process in subsequent steps. • lemmatisation: implemented lemmatization on the tokens obtained for each tweet to convert the higher form of each word to their base forms. we observed that the indonesian tweets were heavily codemixed as indonesian bahasa and english. thus we implemented a modified version of the pipeline described by barik et al. [barik et al., ] to normalize and process the indonesian tweets before calculating the scores. for tweets from bangladesh, the majority of the tweets were not codemixed and were either in the roman english script or in the bengali script. thus, we processed the english tweets using the same set of operations mentioned above and implemented tokenization and normalization for the bangla tweets. to shortlist keywords which are most relevant to our analysis and can yield accurate signals for the trend, we first created a corpus of common words related to the study like 'hospital', 'icu', etc. this was followed by applying topic modelling using latent dirichlet allocation [blei et al., ] , to find words under similar category as our initial corpus. topic modelling provides clusters of similar words based on their usage, as well as their weight to indicate how closely the words of a cluster are related. we also performed an n-gram analysis to find the frequency of these keywords in our corpus. this was followed by finding the most similar words to these keywords using word vec [mikolov et al., ] . it allowed us to create vector representations for all the words in the vocabulary by taking into account the lexical as well as semantic features of the word. the context of all the keywords was studied to minimise noise in our corpus by avoiding irrelevant words/phrases, and at the same time ensuring that the critical signals are captured. finally, based on the approaches outlined above, we shortlisted the following keywords for india, indonesia and bangladesh: • india: 'hospital', 'medical college', 'beds', 'icu', 'shortage' we experimented with different combinations of scores for the model, and finally shortlisted the following based on the requirements of public health agencies who will use this model: we obtain the twitter word count/day plot by calculating the daily count of the shortlisted keywords for a region. it is aimed at capturing incidents of overcrowding of hospitals as well as the shortage of beds and critical equipment. the twitter volume/day score is calculated as the count of all the words in the filtered tweets. this indicates the trend in the volume of tweets related to the covid- pandemic in that region. data adjustment . adjusting the peak we discovered an abrupt peak in both the plots mentioned in the previous section. after a thorough analysis and observing the trend by re-scraping the data for a week, we found that the peak shifts by a day, if we scrape the data again, and always occurs at the th historical day from the date of scraping. this can be attributed to a possible restriction imposed by twitter on accessing historical tweets. to overcome this issue, we normalised the historical tweets older than days using the ratio of values across the peak. this was done since the full volume of tweets are scraped for the most recent days, and the issue only arises for the tweets which are older than days from out date of scraping. the original and adjusted plots for delhi can be seen in fig. when we directly plot the data, it picks up the noise in the data, and this is visible as random fluctuations. this can be misleading in the analysis, and thus we 'smooth' the data by statistical techniques. we experimented with the following smoothing techniques and shortlisted the approach which gave the highest correlation with the positive cases data: • moving averages: we successively plot the average of n -days (which is the window size) to get a smoother curve which captures the overall trend better. different includes two smoothing constants, one for the level and one for the trend. two equations, one for an estimate of the local level, and the local trend's estimate are applied iteratively to each point, that apply exponential smoothing [nau, updated ] . we compared the pearson correlation coefficient from the results of these techniques with the positive cases data and found the -day moving average to give the highest correlation and thus, the best results. since social media data is sensitive to political events, we marked the major political events of each country on the plots and studied the peaks which did not overlap with any major national events. we analyzed the trends for the worst-hit states and provinces, studied the tweets corresponding to the peaks, and compared them with news reports and bulletins to validate our results. a detailed analysis of maharashtra (fig. ) , delhi (fig. )(worst-affected states in india) and kerala (fig. ) (state in india where the cases have started falling, and it did not witness any overcrowding or shortage incidences at hospitals) has been provided below. for indonesia and bangladesh, we are monitoring the trends and finetuning the model to capture the signals accurately. these two countries' results have not been included in this paper as the work is still in progress. we observe major peaks near th april and th may, as seen in fig. . we studied the tweets corresponding to these timestamps to understand the rise in the usage of the selected figure : twitter word count/day plot for maharashtra, with major political events marked as vertical lines keywords like 'hospital' and 'overcrowding'. we found that majority of the tweets were indicative of the rise in hospitalisation numbers, as well as the increase in the incidences of overcrowding at hospitals in cities like mumbai which is the financial capital of india and the most populated city of maharashtra. some sample tweets can be seen in fig. and . we validated this information using official news reports about these incidents [tare, ] . the overall trend is also increasing and the moving average is at a higher level compared to march, which is in agreement with ground reports that the situation in hospitals is worse now compared to march [staf, ] . we observed peaks in delhi at earlier dates compared to maharashtra, which was verified by news reports confirming overcrowding and shortage of beds at major hospitals in delhi like lnjp, deen dayal hospital, etc. peaks near th march, th april, th april, th may, th may, st june and a rising trend thereafter can be seen in fig. . similar to maharashtra, we found that most of the tweets corresponding to these peaks were indicative of the increasing burden [sibtain, ] , [jha, ] and [dutt, ] confirm the incidences reported by the tweets and observed as peaks on the plots. also, the moving average is at a higher level compared to march and continues to increase. this is in agreement with news reports about the worse condition of delhi now as compared to march [lalwani, ] . we obtained similar results for the states of tamil nadu, gujarat and west bengal which are the next worst-hit states in india. kerala provides an interesting counter-case study to the examples we have provided above. kerala was the first state in india to identify a confirmed case of covid- [rawat, ] , and has tackled the situation well. it is observing a declining curve for the number of active cases, while the rest of the country continues to witness a surge in numbers. the state was able to ensure that the health facilities do not face shortage of critical equipment [roy and babu, ] , and kept checks on overcrowding at hospitals [biswas, ] . the state performed better compared to other states in the country like maharashtra and delhi and its model to combat the covid- pandemic is being studied as a case study [faleiro, ] . kerala has also reported a low death toll of only deaths , which indicates that the health facilities weren't burdened to the extent other states are suffering. this trend is reflected in our model's plot as the values have remained low since the beginning of the study, and has stagnated at a level https://www.mohfw.gov.in/ close to since th april (fig. ) . the plot, corresponding tweets and news articles validate our claim that the model is successfully able to capture that the state has remained free of any incidences of overcrowding or shortage of critical equipment. from the literature review and results obtained, we can conclude that information obtained from twitter data can provide useful insights about disease spread and its impact on the healthcare system. twitter can provide trends about the ground reality of the burden on medical facilities, which might not be captured in the official government reports. we found increasing signals and spikes, which were in accordance with the increase in the number of covid- cases, as well as the incidences of overcrowding at hospitals as confirmed by the news reports. thus, researchers and epidemiologists can expand their range of methods used for monitoring of the covid- pandemic by using the twitter data model, as described in this paper. however, twitter cannot provide all answers, and it may not be reliable for certain types of information. a significant limitation of the model is that social media is a platform where users can freely post anything, and thus, there is no way to verify the claims of any individual tweet. therefore, we are relying on the assumption that if thousands of people are tweeting an incident, it is real and worth reporting. however, these need to be verified by trustable sources such as verified news articles to establish the claims reported by the twitter data. soutik biswas. coronavirus: how india's kerala state 'flattened the curve'. bbc news national and local influenza surveillance through twitter: an analysis of the - influenza epidemic anonna dutt. % beds in private hospitals to be reserved for covid- surge. hindustan times what the world can learn from kerala about how to fight covid- . mit technology review durgesh jha. covid beds running out in delhi private hospitals. times of india please help': as coronavirus cases soar in delhi, patients are struggling to find hospital beds. scroll india efficient estimation of word representations in vector space statistical forecasting: notes on regression and time series analysis you are what you tweet: analyzing twitter for public health coronavirus in india: tracking country's first covid- cases; what numbers tell. india today combining search, social media, and traditional data sources to improve influenza surveillance the use of twitter to track levels of disease activity and public concern in the u.s. during the influenza a h n pandemic mumbai runs out of hospital beds for suspected covid- patients, starts a 'waitlist'. the wire mumbai: viral video shows bodies of coronavirus victims lying next to patients at sion hospital. india today key: cord- -tpqsjjet authors: nan title: section ii: poster sessions date: - - journal: j urban health doi: . /jurban/jti sha: doc_id: cord_uid: tpqsjjet nan food and nutrition programs in large urban areas have not traditionally followed a systems approach towards mitigating food related health issues, and instead have relied upon specific issue interventions char deal with downstream indicators of illness and disease. in june of , the san francisco food alliance, a group of city agencies, community based organizations and residents, initiated a collahorarive indicator project called rhe san francisco food and agriculture assessment. in order to attend to root causes of food related illnesses and diseases, the purpose of the assessment is to provide a holistic, systemic view of san francisco\'s food system with a focus on three main areas that have a profound affect on urban public health: food assistance, urban agriculture, and food retailing. using participatory, consensus methods, the san francisco food alliance jointly developed a sec of indicators to assess the state of the local food system and co set benchmarks for future analysis. members collected data from various city and stare departments as well as community based organizations. through the use of geographic information systems software, a series of maps were created to illustrate the assets and limitations within the food system in different neighborhoods and throughout the city as a whole. this participatory assessment process illustrates how to more effectively attend to structural food systems issues in large urban areas by ( t) focusing on prevention rather than crisis management, ( ) emphasizing collaboration to ensure institutional and structural changes, and ( ) aptly translating data into meaningful community driven prevention activities. to ~xplore the strategies to overcome barriers to population sample, we examined the data from three rapid surveys conducted at los angeles county (lac). the surveys were community-based partic· patory surveys utilizing a modified two-stage cluster survey method. the field modifications of the method resulted in better design effect than conventional cluster sample survey (design effect dose to that if the survey was done as simple random sample survey of the same size). the surveys were con· ducte~ among parents of hispanic and african american children in lac. geographic area was selected and d .v ded int.o small c~usters. in the first stage, clusters were selected with probability proportionate to estimated size of children from the census data. these clusters were enumerated to identify and develop a list of households with eligible children from where a random sample was withdrawn. data collectmn for consented respondents involved - minutes in-home interview and abstraction of infor· ma~ion from vaccine record card. the survey staff had implemented community outreach activities designed to fost~r an~ maintain community trust and cooperation. the successful strategies included: developing re.lat on .w. th local community organizations; recruitment of community personnel and pro· vide them with training to conduct the enumeration and interview; teaming the trained community introduction: though much research has been done on the health and social benefits of pet ownership for many groups, there have been no explorations of what pet ownership can mean to adults who are marginalized, living on fixed incomes or on the street in canada. we are a community group of researchers from downtown toronto. made up of front line staff and community members, we believe that community research is important so that our concerns, visions, views and values are presented by us. we also believe that research can and should lead to social change. method: using qualitative and exploratory methods, we have investigated how pet ownership enriched and challenged the lives of homeless and transitionally housed people. our research team photographed and conducted one-on-one interviews with pet owners who have experienced home· lessncss and live on fixed incomes. we had community participation in the research through a partnership with the fred vicror centre camera club. many of the fred victor centre camera club members have experienced homelessness and being marginalized because of poverty. the members of the dub took the photos and assisted in developing the photos. they also participated in the presenta· tion of our project. results: we found that pet ownership brings important health and social benefits to our partici· pants. in one of the most poignant statements, one participant said that pet ownership " ... stops you from being invisible." another commented that "well, he taught me to slow down, cut down the heavy drugs .. " we also found that pet ownership brings challenges that can at times be difficult when one is liv· ing on a fixed income. we found that the most difficult thing for most of the pet owners was finding affordable vet care for their animals. conclusion: as a group, we decided that research should only be done if we try to make some cha.nges about what we have learned. we continue the project through exploring means of affecting social change--for example, ~eti.tions and informing others about the result of our project. we would like to present our ~mdmgs and experience with community-based participatory action resea.rch m an oral. presentarton at yo~r conference in october. our presentation will include com· mumty representation ~f. both front-hne staff and people with lived experience of marginalization and homdessness. if this is not accepted as an oral presentation, we are willing to present the project m poster format. introduction the concept of a healthy city was adopted by the world health organization some time ago and it includes strong support for local involvement in problem solving and implementation of solutions. while aimed at improving social, economic or environmental conditions in a given community, more significantly the process is considered to be a building block for poliq reform and larger scale 'hange, i.e. "acting locally while thinking globally." neighbourhood planning can he the entry point for citizens to hegin engaging with neighbours on issues of the greater common good. methods: this presentation will outline how two community driven projects have unfolded to address air pollution. the first was an uphill push to create bike lanes where car lanes previously existed and the second is an ongoing, multi-sectoral round table focused on pollution and planning. both dt•monstrate the importance of having support with the process and a health focus. borrowing from traditions of "technical aid"• and community development the health promoter /planner has incorporated a range of "determinants of health" into neighbourhood planning discussions. as in most urban conditions the physical environment is linked to a range of health stressors such as social isolation, crowding, noise, lack of open space /recreation, mobility and safety. however typical planning processes do not hring in a health perspective. health as a focus for neighbourhood planning is a powerful starti_ng point when discussing transportation planning or changing land-uses. by raising awareness on determmants of health, citizens can begin to better understand how to engage in a process and affect change. often local level politics are involved and citizens witness policy change in action. the environmental liaison committee and the dundas east hike lanes project resulted from local level initiatives aimed at finding solutions to air pollution -a priority identified hy the community. srchc supported the process with facilitation and technical aid. _the processs had tangible results that ultimately improve living conditions and health. •tn the united kmgdom plannm in the 's established "technical aid" offices much like our present day legal aid system to provide professional support and advocacy for communities undergoing change. p - (c) integrating community based research: the experience of street health, a community service agency i.aura cowan and jacqueline wood street health began offering services to homeless men and women in east downtown ~oronto in . nursing stations at drop-in centres and shelters were fo~lowed by hiv/aids prevent ~, harm reduction and mental health outreach, hepatitis c support, sleeping bag exchange, and personal tdennfication replacement and storage programs. as street health's progi;ams expanded, so to~ did the agency:s recognition that more nee~ed t~ be done to. address the underl~ing causes of, th~ soct~l and economic exclusion experienced by its clients. knowing t.h~t. a~voca~y ts. helped by . evtd~nce , street he.alt~ embarked on a community-based research (cbr) initiative to dent fy commumty-dnven research priorities within the homeless and underhoused population. methods: five focus groups were conducted with homeless people, asking participants to identify positive and negative forces in their lives, and which topics were important to take action on and learn more about. findings were validated through a validation meeting with participants. results: participants identified several important positive and negative forces in their lives. key positive forces included caring and respectful service delivery, hopefulness and peer networks. key negative forces included lack of access to adequate housing and income security, poor service delivery and negative perceptions of homeless people. five topics for future research emerged from the process, focusing on funding to address homelessness and housing; use of community services for homeless people; the daily survival needs of homeless people and barriers to transitioning out of homelessness; new approaches to service delivery that foster empowerment; and policy makers' understanding of poverty and homelessness. conclusions: although participants expressed numerous issues and provided much valuable insight, definitive research ideas and action areas were not clearly identified by participants. however, engagement in a cbr process led to some important lessons and benefits for street health. we learned that the community involvement of homeless people and front-line staff is critical to ensuring relevance and validity for a research project; that existing strong relationships with community parmers are essential to the successful implementation of a project involving marginalized groups; and that an action approach focusing on positive change can make research relevant to directly affected people and community agency staff. street health benefited from using a cbr approach, as the research process facilitated capacity building among staff and within the organization as a whole. p - (c) a collaborative process to achieve access to primary health care for black women and women of colour: a model of community based participartory research notisha massaquoi, charmaine williams, amoaba gooden, and tulika agerwal in the current healthcare environment, a significant number of black women and women of color face barriers to accessing effective, high quality services. research has identified several issues that contribute to decreased access to primary health care for this population however racism has emerged as an overarching determinant of health and healthcare access. this is further amplified by simultaneous membership in multiple groups that experience discrimination and barriers to healthcare for example those affected by sexism, homelessness, poverty, homophobia and heterosexism, disability and hiv infection. the collaborative process to achieve access to primary health care for black women and women of colour project was developed with the university of toronto faculty of social work and five community partners using a collaborative methodology to address a pressing need within the community ro increase access to primary health care for black women and women of colour. women's health in women's hands community health centre, sistering, parkdale community health centre, rexdale community health centre and planed parenthood of toronto developed this community-based participatory-action research project to collaboratively barriers affecting these women, and to develop a model of care that will increase their access to health services. this framework was developed using a process which ensured that community members from the target population and service providers working in multiculrural clinical settings, were a part of the research process. they were given the opportunity to shape the course of action, from the design of the project to the evaluation and dissemination phase. empowerment is a goal of the participatory action process, therefore, the research process has deliberately prioritized _ro enabling women to increase control over their health and well-being. in this session, the presenters will explore community-based participatory research and how such a model can be useful for understanding and contextualizing the experiences of black women and women of colour. they will address. the development and use of community parmerships, design and implementation of the research prorect, challenges encountered, lessons learnt and action outcomes. they will examine how the results from a collaborative community-based research project can be used as an action strategy to poster sessions v address che social determinants of women health. finally the session will provide tools for service providers and researchers to explore ways to increase partnerships and to integrate strategies to meet the needs of che target population who face multiple barriers to accessing services. lynn scruby and rachel rapaport beck the purpose of this project was ro bring traditionally disenfranchised winnipeg and surrounding area women into decision-making roles. the researchers have built upon the relationships and information gachered from a pilot project and enhanced the role of input from participants on their policy prioriries. the project is guided by an advisory committee consisting of program providers and community representatives, as well as the researchers. participants included program users at four family resource cencres, two in winnipeg and two located rurally, where they participated in focus groups. the participants answered a series of questions relating to their contact with government services and then provided inpuc as to their perceptions for needed changes within government policy. following data analysis, the researchers will return to the four centres to share the information and continue che discussion on methods for advocating for change. recommendations for program planning and policy development and implementation will be discussed and have relevance to all participants in the research program. women's health vera lefranc, louise hara, denise darrell, sonya boyce, and colleen reid women's experiences with paid and unpaid work, and with the formal and informal economies, have shifted over the last years. in british columbia, women's employability is affected by government legislation, federal and provincial policy changes, and local practices. two years ago we formed the coalition ior women's economic advancement to explore ways of dealing with women's worsening economic situations. since the formation of the coalition we have discussed the need for research into women's employabilicy and how women were coping and surviving. we also identified how the need to document the nature of women's employability and reliance on the informal economy bore significanc mechodological and ethical challenges. inherent in our approach is a social model of women's health that recognizes health as containing social, economic, and environmental determinants. we aim to examine the social contexc of women's healch by exploring and legitimizing women's own experiences, challenging medical dominance in understandings of health, and explaining women's health in terms of their subordination and marginalizacion. through using a feminist action research (far) methodology we will explore the relationship between women's employability and health in communities that represent bricish columbia's social, economic, cultural/ethnic, and geographic diversities: skidegate, fort st . .john, lumhy, and surrey. over the course of our year project, in each community we will establish and work with advisory committees, hire and train local researchers, conduct far (including a range of qualitative methods), and support action and advocacy. since the selected communities are diverse, the ways that the research unfolds will ·ary between communities. expected outcomes, such as the provision of a written report and resources, the establishment of a website for networking among the communities, and a video do.:umentary, are aimed at supporting the research participants, coalition members, and advisory conuniuces in their action efforts. p t (c) health & housing: assessing the impact of transitional housing for people living with hiv i aids currently, there is a dearth of available literature which examines supporrive housing for phas in the canadian context. using qualitative, one-on-one interviews we investigace the impact of transitional housing for phaswho have lived in the up to nine month long hastings program. our post<'r pr<·senta-t on will highlight research findings, as well as an examination of transitional housing and th<· imp;kt it has on the everyday lives of phas in canada. this research is one of two ground breaking undertakings within the province of ontario in which fife house is involved. p - (c) eating our way to justice: widening grassroots approaches to food security, the stop community food centre as a working model charles l.evkoe food hanks in north america have come co play a central role as the widespread response to growing rates of hunger. originally thought to be a short term-solution, over the last years, they have v poster sessions be · · · · d wi'thi'n society by filling the gaps in the social safety net while relieving govemcome mst tut ona ze . . . t f the ir responsibilities. dependent on corporate donations and sngmauzmg to users, food banks men so th' . · i i . are incapable of addressing the structural cause~ of ~u~ger. s pres~ntation w e~~ ore a ternanve approaches to addressing urban food security while bmldmg more sustamabl.e c~mmumt es. i:nrough the f t h st p community food centre, a toronto-based grassroots orgamzanon, a model is presented case e h'l k' b 'id · b that both responds to the emergency food needs of communities w e wor mg to. u ~ sustama le and just food system. termed, the community food centre model. (cfc), ~he s~op is worki?g to widen its approach to issues of food insecurity by combining respectful ~ rect service wit~ com~~mty ~evelop ment, social justice and environmental sustainability. through this approach, various critical discourses around hunger converge with different strategic and varied implications for a~ion. as a plac~-based organization, the stop is rooted within a geographical space and connected directly to a neighbourhood. through working to increase access to healthy food, it is active in maintaining people's dignity, building a strong and democratic community and educating for social change. connected to coalitions and alliances, the stop is also active in organizing across scales in connection with the global food justice movement. inner city shelter vicky stergiopoulos, carolyn dewa, katherine rouleau, shawn yoder, and lorne tugg introduction: in the city of toronto there are more than , hostel users each year, many with mental health and addiction issues. although shelters have responded in various ways to the health needs of their clients, evidence on the effectiveness of programs delivering mental health services to the home· less in canada has been scant. the objective of this community based research was to provide a forma· tive evaluation of a multi-agency collaborative care team providing comprehensive care for high needs clients at toronto's largest shelter for homeless men. methods: a logic model provided the framework for analysis. a chart review of clients referred over a nine month period was completed. demographic data were collected, and process and outcome indicators were identified for which data was obtained and analyzed. the two main outcome measures were mental status and housing status months after referral to the program. improvement or lack of improvement in mental status was established by chart review and team consensus. housing outcomes were determined by chart review and the hostel databases. results: of the clients referred % were single and % were unemployed. forty four percent had a psychiatric hospitalization within the previous two years. the prevalence of severe and persistent men· tal illness, alcohol and substance use disorders were %, % and % respectively. six months after referral to the program % of clients had improved mental status and % were housed. logistic regression controlling for the number of general practitioner and psychiatrist visits, presence of person· ality or substance use disorder and treatment non adherence identified two variables significantly associ· ated mental status improvement: the number of psychiatric visits (or, . ; % ci, . - . ) and treatment non adherence (or, . ; % ci, . - . ). the same two variables were associated with housing outcomes. history of forensic involvement, the presence of a personality or substance use disorder and the number of visits with a family physician were not significantly associated with either outcome. conclusions: despite the limitations in sample sire and study design, this study can yield useful informa· tion to program planners. our results suggest that strategies to improve treatment adherence and access to mental health specialists can improve outcomes for this population. although within primary care teams the appropriate collaborative care model for this population remains to be established, access to psychiatric follow up, in addition to psychiatric assessment services, may be an important component of a successful program. mount sinai hospital (msh) has become one of the pre-eminent hospitals in the world by contributing to the development of innovative approaches to effective health care and disease prevention. recently, the hospital has dedicated resources towards the development of a strategy aimed at enhancing the hospital's integration with its community partners. this approach will better serve the hospital in the current health care environment where local health integration networks have been struck to enhance and support local capacity to plan, coordinate and integrate service delivery. msh has had early success with developing partnerships. these alliances have been linked to programs serving key target populations with _estabhshe~. points of access to msh. recognizing the need to build upon these achievements to remain compe~mve, the hospital has developed a community integration strategy. at the forefront of this strategy is c.a.r.e (community advisory reference engine): the hospital's compendium of poster sessions v community partners. as a single point of access to community partner information, c.a.r.e. is more than a database. c.a.r.e. serves as the foundation for community-focused forecasting and a vehicle for inter and intra-organizational knowledge transfer. information gleaned from the catalog of community parmers can be used to prepare strategic, long-term partnership plans aimed at ensuring that a comprehensive array of services can be provided to the hospital community. c.a.r.e. also houses a permanent record of the hospital's alliances. this prevents administrative duplication and facilitates the formation of new alliances that best serve both the patient and the hospital. c.a.r.e. is not a stand-alone tool and is most powerful when combined with other aspects of the hospital's community integration strategy. it iscxpected that data from the hospital's community advisory committees and performance measurement department will also be stored alongside stakeholder details. this information can then be used to drive discussions at senior management and the board, ensuring congruence between stakeholder, patient and hospital objectives. the patient stands to benefit from this strategy. the unique, distinct point of reference to a wide array of community services provides case managers and discharge planners with the information they need to connect patients with appropriate community services. creating these linkages enhances the patient's capacity to convalesce in their homes or places of residence and fosters long-term connections to neighborhood supports. these connections can be used to assist with identifying patients' ongoing health care needs and potentially prevent readmission to hospital. introduction: recruiting high-risk drug users and sex workers for hiv-prevention research has often been hampered by limited access to hard to reach, socially stigmatized individuals. our recruitment effom have deployed ethnographic methodology to identify and target risk pockets. in particular, ethnographers have modeled their research on a street-outreach model, walking around with hiv-prevention materials and engaging in informal and structured conversations with local residents, and service providers, as well as self-identified drug users and sex workers. while such a methodology identifies people who feel comfortable engaging with outreach workers, it risks missing key connections with those who occupy the margins of even this marginal culture. methods: ethnographers formed a women's laundry group at a laundromat that had a central role as community switchboard and had previously functioned as a party location for the target population. the new manager helped the ethnographers invite women at high risk for hiv back into the space, this time as customers. during weekly laundry sessions, women initiated discussions about hiv-prevention, sexual health, and eventually, the vaccine research for which the center would be recruiting women. ra.its: the benefits of the group included reintroducing women to a familiar locale, this time as customers rather than unwelcome intruders; creating a span of time (wash and dry) to discuss issues important to me women and to gather data for future recruitment efforts; creating a location to meet women encountered during more traditional outreach research; establishing the site as a place for potential retention efforts; and supporting a local business. women who participated in the group completed a necessary household task while learning information that they could then bring back to the community, empowering them to be experts on hiv-prevention and vaccine research. some of these women now assist recruitment efforts. the challenges included keeping the group women-only, especially after lunch was provided, keeping the membership of the group focused on women at risk for hiv, and keeping the women in the group while they did their laundry. conclusion: public health educators and researchers can benefit from identifying alternate congregation sites within risk pockets to provide a comfortable space to discuss hiv prevention issues with high-risk community members. in our presentation, we will describe the context necessary for similar research, document the method's pitfalls and successes, and argue that the laundry group constitutes an ethical, respectful, community-based method for recruitment in an hiv-prevention vaccine trial. p - t (c) upgrading inner city infrastructure and services for improved environmental hygiene and health: a case of mirzapur in u.p. india madhusree mazumdar in urgency for agricultural and industrial progress to promote economic d.evelopment follo_wing independence, the government of india had neglected health promotion and given less emphasis on infrastructure to promote public health for enhanced human pro uct v_ity. ong wit r~p m astrucrure development, which has become essential if citie~ are to. act ~s harbmger.s of econ~nuc ~owth, especially after the adoption of the economic liberalization policy, importance _is a_lso ~emg g ve.n to foster environmental hygiene for preventive healthcare. the world health orga~ sat ~ is also trj:' ! g to help the government to build a lobby at the local level for the purpose by off~rmg to mrroduce_ its heal.thy city concept to improve public health conditions, so as to reduce th_e disease burden. this pape~ s a report of the efforts being made towards such a goal: the paper descr~bes ~ c~se study ?f ~ small city of india called mirzapur, located on the banks of the nver ganga, a ma or lifeline of india, m the eastern part of the state of uttar pradesh, where action for improvement began by building better sanitation and environmental infrastructure as per the ganga action plan, but continued with an effort to promote pre· ventive healthcare for overall social development through community participation in and around the city. asthma physician visits in toronto, canada tara burra, rahim moineddin, mohammad agha, and richard glazier introduction: air pollution and socio-economic status are both known to be associated with asthma in concentrated urban settings but little is known about the relationship between these factors. this study investigates socio-economic variation in ambulatory physician consultations for asthma and assesses possible effect modification of socio-economic status on the association between physician visits and ambient air pollution levels for children aged to and adults aged to in toronto, canada between and . methods: generalized additive models were used to estimate the adjusted relative risk of asthma physician visits associated with an interquartile range increase in sulphur dioxide, nitrogen dioxide, pm . , and ozone, respectively. results: a consistent socio-economic gradient in the number of physician visits was observed among children and adults and both sexes. positive associations between ambient concentrations of sul· phur dioxide, nitrogen dioxide and pm . and physician visits were observed across age and sex strata, whereas the associations with ozone were negative. the relative risk estimates for the low socio-«onomic group were not significantly greater than those for the high socio-economic group. conclusions: these findings suggest that increased ambulatory physician visits represent another component of the public health impact of exposure to urban air pollution. further, these results did not identify an age, sex, or socio-economic subgroup in which the association between physician visits and air pollution was significantly stronger than in any other population subgroup. eco-life-center (ela) in albania supports a holistic approach to justice, recognizing the environ· mental justice, social justice and economic justice depend upon and support each other. low income cit· izens and minorities suffer disproportionately from environmental hazards in the workplace, at home, and in their communities. inadequate laws, lax enforcement of existing environmental regulations, and ~ea.k penalties for infractions undermine environmental protection. in the last decade, the environmental ust ce m~ve~ent in tirana metropolis has provided a framework for identifying and exposing the links ~tween irrational development practices, disproportionate siting of toxic facilities, economic depres· s on, and a diminished quality of life in low-income communities and communities of color. the envi· ~onmental justice agenda has always been rooted in economic, racial, and social justice. tirana and the issues su.rroun~ing brow~fields redevelopment are crucial points of advocacy and activism for creating ~ubstantia~ social chan~~ m low-income communities and communities of color. we engaging intensively m prevcnnng co'.' mumnes, especially low income or minority communities, from being coerced by gov· ernmenta~ age_nc es or companies into siting hazardous materials, or accepting environmentally hazard· ous_ practices m order to create jobs. although environmental regulations do now exist to address the environmental, health, and social impacts of undesirable land uses, these regulations are difficult to poster sessions v enforce because many of these sites have been toxic-ridden for many years and investigation and cleanup of these sites can be expensive. removing health risks must be the main priority of all brown fields action plans. environmental health hazards are disproportionately concentrated in low-income communities of color. policy requirements and enforcement mechanisms to safeguard environmental health should be strengthened for all brownfields projects located in these communities. if sites are potentially endangering the health of the community, all efforts should be made for site remediation to be carried out to the highest cleanup standards possible towards the removal of this risk. the assurance of the health of the community should take precedence over any other benefits, economic or otherwise, expected to result from brownfields redevelopment. it's important to require from companies to observe a "good neighbor" policy that includes on-site visitations by a community watchdog committee, and the appointment of a neighborhood environmentalist to their board of directors in accordance with the environmental principles. vancouver - michael buzzelli, jason su, and nhu le this is the second paper of research programme concerned with the geographical patterning of environmental and population health at the urban neighbourhood scale. based on the vancouver metropolitan region, the aim is to better understand the role of neighbourhoods as epidemiological spaces where environmental and social characteristics combine as health processes and outcomes at the community and individual levels. this paper builds a cohort of commensurate neighbourhoods across all six censuses periods from to , assembles neighbourhood air pollution data (several criterion/health effects pollutants), and providing an analysis to demonstrate how air pollution systematically and consistently maps onto neighbourhood socioeconomic markers, in this case low education and lone-parent families. we conclude with a discussion of how the neighbourhood cohort can be further developed to address emergent priorities in the population and environmental health literatures, namely the need for temporally matched data, a lifecourse approach, and analyses that control for spatial scale effects. solid waste management and environment in mumbai (india) by uttam jakoji sonkamble and bairam paswan abstract: mumbi is the individual financial capital of india. the population of greater mumbai is , , and sq. km. area. the density of population , per sq. km. the dayto-day administration and rendering of public services within gr. mumbai is provided by the brihan mumbai mahanagar palika (mumbai corporation of gr. mumbai) that is a body of elected councilors on a -year team. mumcial corporation provides varies conservancy services such as street sweeping, collection of solid waste, removal and transportation, disposal of solid waste, disposal of dead bodies of animals, construction, maintance and cleaning of urinals and public sanitary conveniences. the solid waste becoming complicated due to increase in unplanned urbanization and industrialization, the environment has deteriorated significantly due to inter, intra and international migration stream to mumbai. the volume of inter state migration to mumbai is considerably high i.e. . lakh and international migrant . lakh have migrated to mumbai. present paper gives the view on solid waste management and its implications to environment and health. pollution from a wide varity of emission, such as from automobiles and industrial activities, has reached critical level in mumbai, causing respiratory, ocular, water born diseases and other health problems. sources of generation of waste are -household waste, commercial waste, institutional waste, street sweeping, silt removed from drain/nallah/cleanings. disposal of solid waste in gr. mumbai done under incineration . processing to produce organic manure. . vermi-composting . landfill the study shows that the quantity of waste disposal of through processing and conversion to organic ~anure is about - m.t. per day. the processing is done by a private agency m/s excel industries ltd. who had set up a plant at the chincholi dumping ground in western mumbai for this purpose. the corporation is also disposal a plant of its waste mainly market waste through the environment friendly, natural pro-ces~ known as vermi-composing about m.t. of market waste is disposed of in this manner at the various sites. there are four land fill sites are available and percent of the waste matter generated m mumbai is disposed of through landfill. continuous flow of migrant and increa~e in slum population is a complex barrier in the solid waste management whenever community pamc pat on work strongly than only we can achieved eco-friendly environment in mumbai. persons exposed to residential craffic have elevated races of respiratory morbidity an~ ~ortality. since poverty is an important determinant of ill-health, some h~ve argued that t~es~ assoc at ons may relate to che lower socioeconomic status of those living along ma or roads. our ob ect ve was to evaluate the association between traffic intensity at home and hospital admissions for respiratory diagnoses among montreal residents older than years. morning peak traffic estimates from the emmej montreal traffic model (motrem ) were used as an indicator of exposure to road traffic outside the homes of those hospitalised. the influence of socioeconomic status on the relationship between traffic intensity and hospital admissions for respiratory diagnoses was explored through assessment of confounding by lodging value, expressed as the dollar average over road segments. this indicator of socioeconomic status, as calculated from the montreal property assessment database, is available at a finer geographic scale than socioeconomic information accessible from the canadian census. there was an inverse relationship between traffic intensity estimates and lodging values for those hospitalised (rho - . , p vehicles during che hour morning peak), even after adjustment for lodging value (crude or . , cl % . - . ; adjusted or . , cl % . - . ). in montreal, elderly persons living along major roads are at higher risk of being hospitalised for respiratory illnesses, which appears not simply to reflect the fact that those living along major roads are at relative economic disadvantage. the paper argues that human beings ought to be at the centre of the concern for sustainable development. while acknowledging the importance of protecting natural resources and the ecosystem in order to secure long term global sustainability, the paper maintain that the proper starting point in the quest for urban sustainability in africa is the 'brown agenda' to improve che living and working environment of che people, especially che urban poor who face a more immediate environmental threat to their health and well-being. as the un-habitat has rightly observed, it is absolutely essential "to ensure that all people have a sufficient stake in the present to motivate them to take part in the struggle to secure the future for humanity.~ the human development approach calls for rethinking and broadening the narrow technical focus of conventional town planning and urban management in order to incorporate the emerging new ideas and principles of urban health and sustainability. i will examine how cities in sub-saharan africa have developed over the last fifty years; the extent to which government policies and programmes have facilitated or constrained urban growth, and the strategies needed to achieve better functioning, safer and more inclusive cities. in this regard i will explore insights from the united nations conferences of the s, especially local agenda of the rio summit, and the istanbul declaration/habitat agenda, paying particular attention to the principles of enablement, decentralization and partnership canvassed by these movements. also, i will consider the contributions of the various global initiatives especially the cities alliance for cities without slums sponsored by the world bank and other partners; che sustainable cities programme, the global campaigns for good governance and for secure tenure canvassed by unhabit at, the healthy cities programme promoted by who, and so on. the concluding section will reflect on the future of the african city; what form it will take, and how to bring about the changes needed to make the cities healthier, more productive and equitable, and better able to meet people's needs. heather jones-otazo, john clarke, donald cole, and miriam diamond urban areas, as centers of population and resource consumption, have elevated emissions and concentrations of a wide range of chemical contaminants. we have developed a modeling framework in which we first ~stimate the emissions and transport of contaminants in a city and second, use these estimates along with measured contaminant concentrations in food, to estimate the potential health risk posed by these che.micals. the latter is accomplished using risk assessment. we applied our modeling framework to consider two groups of chemical contaminants, polycyclic aromatic hydrocarbons (pah) a.nd the flame re~ardants polybrominated diphenyl ethers (pbde). pah originate from vehicles and stationary combustion sources. ~veral pah are potent carcinogens and some compounds also cause noncancer effects. pbdes are additive flame retardants used in polyurethane foams (e.g., car seats, furniture) fer sessions v and cl~ equipm~nt (e.g., compute~~· televisio~s). two out of three pbdes formulations are being voluntarily phased by mdustry due to rmng levels m human tissues and their world-wide distribution. pbdes have been .related to adv.erse neurological, developmental and reproductive effects in laboratory ijlimals. we apphed our modelmg framework to the city of toronto where we considered the southcattral area of by km that has a population of . million. for pah, local vehicle traffic and area sources contribute at least half of total pah in toronto. local contributions to pbdes range from - %, depending on the assumptions made. air concentrations of both compounds are about times higher downtown than km north of toronto. although measured pah concentrations in food date to the s, we estimate that the greatest exposure and contribution to lifetime cancer risk comes from ingestion of infant formula, which is consistent with toxicological evidence. the next greatest exposure and cancer risk are attributable to eating animal products (e.g. milk, eggs, fish). breathing downtown air contributes an additional percent to one's lifetime cancer risk. eating vegetables from a home garden localed downtown contributes negligibly to exposure and risk. for pbdes, the greatest lifetime exposure comes through breast milk (we did not have data for infant formula), followed by ingestion of dust by the toddler and infant. these results suggest strategies to mitigate exposure and health risk. p - (a) immigration and socioeconomic inequalities in cervical cancer screening in toronto, canada aisha lofters, rahim moineddin, maria creatore, mohammad agha, and richard glazier llltroduction: pap smears are recommended for cervical cancer screening from the onset of sexual activity to age . socioeconomic and ethnoracial gradients in self-reported cervical cancer screening have been documented in north america but there have been few direct measures of pap smear use among immigrants or other socially disadvantaged groups. our purpose was to investigate whether immigration and socioeconomic factors are related to cervical cancer screening in toronto, canada. methods: pap smears were identified using fee codes and laboratory codes in ontario physician service claims (ohip) for three years starting in for women age - and - . all women with any health system contact during the three years were used as the denominator. social and economic factors were derived from the canadian census for census tracts and divided into quintiles of roughly equal population. recent registrants, over % of whom are expected to be recent immigrants to canada, were identified as women who first registered for health coverage in ontario after january , . results: among , women age - and , women age - , . % and . %, rtspcctively, had pap smears within three years. low income, low education, recent immigration, visible minority and non-english language were all associated with lower rates (least advantaged quintile:most advantaged quintile rate ratios were . , . , . , . , . , respectively, p < . for all). similar gradients were found in both age groups. recent registrants comprised . % of women and had mm;h lower pap smear rates than non-recent registrants ( . % versus . % for women age - and . % versus . % for women age - ). conclnsions: pap smear rates in toronto fall well below those dictated by evidence-based practice. at the area level, immigration, visible minority, language and socioeconomic characteristics are associated with pap smear rates. recent registrants, representing a largely immigrant group, have particularly low rates. efforts to improve coverage of cervical cancer screening need to be directed to all ~omen, their providers and the health system but with special emphasis on women who recently arrived m ontario and those with social and economic disadvantage. challeges faced: a) most of the resources are now being ~pent in ~reventing the sprea.d of hiv/ aids and maintaining the lives of those already affected. b) skilled medical ~rs~nal are dymg under· mining the capacity to provide the required health care services. ~) th.e comphcat o~s of hiv/aids has complicated the treatment of other diseases e.g. tbs d) the ep dem c has led. to mcrease number of h n requiring care and support. this has further stretched the resources available for health care. orp a s d db . . i methods used on our research: . a simple community survey con ucte y our orgamzat on vo · unteers in three urban centres members of the community, workers and health care prov~ders were interviewed ... . meeting/discussions were organized in hospitals, commun.ity centre a~d with government officials ... . written questionnaires to health workers, doctors and pohcy makers m th.e health sectors. lessors learning: • the biggest-health bigger-go towards hiv/aids prevention • aids are spreading faster in those families which are poor and without education. •women are the most affected. •all health facilities are usually overcrowded with hiv/aids patients. actions needed:• community education oh how to prevent the spread of hiv/aids • hiv/aids testing need to be encouraged to detect early infections for proper medical cover. • people to eat healthy • people should avoid drugs. implications of our research: community members and civic society-introduction of home based care programs to take care of the sick who cannot get a space in the overcrowded public hospitals. prl-v a te sector private sector has established programs to support and care for the staff already affected. government provision of support to care-givers, in terms of resources and finances. training more health workers. introduction: australian prisons contain in excess of , prisoners. as in most other western countries, reliance on 'deprivation of liberty' is increasing. prisoner numbers are increasing at % per annum; incarceration of women has doubled in the last ten years. the impacts on the community are great - % of children have a parent in custody before their th birthday. for aboriginal communities, the harm is greater -aboriginal and/or torres strait islanders are incarcerated at a rate ten times higher than other australians. % of their children have a parent in custody before their th birthday. australian prisons operate under state and territory jurisdictions, there being no federal prison system. eight independent health systems, supporting the eight custodial systems, have evolved. this variability provides an unique opportunity to assess the capacity of these health providers in addressing the very high service needs of prisoners. results: five models of health service provision are identified -four of which operate in one form or another in australia: • provided by the custodial authority (queensland and western australia)• pro· vided by the health ministry through a secondary agent (south australia, the australian capital territory and tasmania) • provided through tendered contract by a private organization (victoria and northern territory) • provided by an independent health authority (new south wales) • (provided by medics as an integral component of the custodial enterprise) since the model of the independent health authority has developed in new south wales. the health needs of the prisoner population have been quantified, and attempts are being made to quantify specific health risks /benefits of incarceration. specific enquiry has been conducted into prisoner attitudes to their health care, including issues such as client information confidentiality and access to health services. specific reference will be made to: • two inmate health surveys • two inmate access surveys, and • two service demand studies. conclusions: the model of care provision, with legislative, ethical, funding and operational independence would seem provide the best opportunity to define and then respond to the health needs of prisoners. this model is being adopted in the united kingdom. better health outcomes in this high-risk group, could translate into healthier families and their communities. p - (a) lnregrated ethnic-specific health care systems: their development and role in increasing access to and quality of care for marginalized ethnic minorities joshua yang introduction: changing demographics in urban areas globally have resulted in urban health systems that are racially and ethnically homogenous relative to the patient populations they aim to serve. the resultant disparities in access to and quality of health care experienced by ethnic minority groups have been addressed by short-term, instirutional level strategies. noticeably absent, however, have been structural approaches to reducing culturally-rooted disparities in health care. the development of ethnic-specific h~alth car~ systems i~ a structural, long-term approach to reducing barriers to quality health care for eth· me mmonty populations. methods: this work is based on a qualitative study on the health care experiences of san francisco chinatown in the united states, an ethnic community with a model ethnic-specific health care infrastrucrure. using snowball sampling, interviews were conducted with key stakeholders and archival research was conducted to trace and model the developmental process that led to the current ethnic-specific health care system available to the chinese in san francisco. grounded theory was the methodology ijltd to analysis of qualitative data. the result of the study is four-stage developmental model of ethnic-specific health infrastrueture development that emerged from the data. the first stage of development is the creation of the human capital resources needed for an ethnic-specific health infrastructure, with emphasis on a bilingual and bicultural health care workforce. the second stage is the effective organization of health care resources for maximal access by constituents. the third is the strengthening and stability of those institutional forms through increased organizational capacity. integration of the ethnic-specific health care system into the mainstream health care infrastructure is the final stage of development for an ethnic-specific infrastructure. conclusion: integrated ethnic-specific health care systems are an effective, long-term strategy to address the linguistic and cultural barriers that are being faced by the spectrum of ethnic populations in urban areas, acting as culturally appropriate points of access to the mainstream health care system. the model presented is a roadmap to empower ethnic communities to act on the constraints of their health and political environments to improve their health care experiences. at a policy level, ethnic-specific health care organizations are an effective long-term strategy to increase access to care and improve qualiiy of care for marginalized ethnic groups. each stage of the model serves as a target area for policy interventions to address the access and care issues faced by culturally and linguistically diverse populations. users in baltimore md: - noya galai, gregory lucas, peter o'driscoll, david celentano, david vlahov, gregory kirk, and shruti mehta introduction: frequent use of emergency rooms (er) and hospitalizations among injection drug users (idus) has been reported and has often been attributed to lack of access to primary health care. however, there is little longitudinal data which examine health care utilization over individual drug use careers. we examined factors associated with hospitalizations, er and outpatient (op) visits among idus over years of follow-up. methods: idus were recruited through community outreach into the aids link to lntravenous experience (alive) study and followed semi-annually. , who had at least follow-up visits were included in this analysis. outcomes were self-reported episodes of hospitalizations and er/op visits in the prior six months. poisson regression was used accounting for intra-person correlation with generalized estimation equations. hits: at enrollment, % were male, % were african-american, % were hiv positive, median age was years, and median duration of drug use was years. over a total of , visits, mean individual rates of utilization were per person years (py) for hospitalizations and per py for er/op visits. adjusting for age and duration of drug use, factors significantly associated with higher rates of hospitalization included hiv infection (relative incidence [ri(, . ), female gender (ri, . ), homelessness (ri, . ), as well as not being employed, injecting at least daily, snorting heroin, havmg a regular source of health care, having health insurance and being in methadone mainte.nance treatment (mmt). similar associations were observed for er/op visits except for mmt which was not associated with er/op visits. additional factors associated with lower er/op visits were use of alcohol, crack, injecting at least daily and trading sex for drugs. % of the cohort accounted for % of total er/op visits, while % of the cohort never reported an op visit during follow-up. . . . lgbt) populations. we hypothesized that prov dmg .appomtments .for p~t ~nts w thm hours would ensure timely care, increase patient satisfaction, and improve practice eff c ency. further, we anticipated that the greatest change would occur amongst our homeless patients.. . methods: we tested an experimental introduction of advanced access scheduling (usmg a hour rule) in the primary care medical clinic. we tracked variables inclu~ing waiting ti~e fo~ next available appointment; number of patients seen; and no-show rates, for an eight week penod pnor to and post introduction of the new scheduling system. both patient and provider satisfaction were assessed using a brief survey ( questions rated on a -pt scale). results and conclusion: preliminary analyses demonstrated shorter waiting times for appointments across the clinic, decreased no-show rates, and increased clinic capacity. introduction of the advanced access scheduling also increased both patient and provider satisfaction. the new scheduling was initiated in july . quantitative analyses to measure initial and sustained changes, and to look at differential responses across populations within our clinic, are currently underway. introduction: there are three recognized approaches to linking socio-economic factors and health: use of census data, gis-based measures of accessibility/availability, and resident self-reported opinion on neighborhood conditions. this research project is primarily concerned with residents' views about their neighborhoods, identifying problems, and proposing policy changes to address them. the other two techniques will be used in future research to build a more comprehensive image of neighborhood depri· vation and health. methods: a telephone survey of london, ontario residents is currently being conducted to assess: a) community resource availability, quality, access and use, b) participation in neighborhood activities, c) perceived quality of neighborhood, d) neighborhood problems, and e) neighborhood cohesion. the survey instrument is composed of indices and scales previously validated and adapted to reflect london specifically. thirty city planning districts are used to define neighborhoods. the sample size for each neighborhood reflects the size of the planning district. responses will be compared within and across neighborhoods. data will be linked with census information to study variation across socio-eco· nomic and demographic groups. linear and gis-based methods will be used for analysis. preliminary results: the survey follows a qualitative study providing a first look at how experts involved in community resource planning and administration and city residents perceive the availability, accessibility, and quality of community resources linked to neighborhood health and wellbeing, and what are the most immediate needs that should be addressed. key-informant interviews and focus groups were used. the survey was pre-tested to ensure that the language and content reflects real experiences of city residents. the qualitative research confirmed our hypothesis that planning districts are an acceptable surrogate for neighborhood, and that the language and content of the survey is appropriate for imple· mentation in london. scales and indices showed good to excellent reliability and validity during the pre· test (cronbach's alpha from . - . ). preliminary results of the survey will be detailed at the conference. conclusions: this study will help assess where community resources are lacking or need improve· ment, thus contributing to a more effective allocation of public funds. it is also hypothesized that engaged neighborhoods with a well-developed sense of community are more likely to respond to health programs and interventions. it is hoped that this study will allow london residents to better understand the needs and problems of their neighborhoods and provide a research foundation to support local understandmg of community improvement with the goal of promoting healthy neighborhoods. p - (a) hiv positive in new york city and no outpatient care: who and why? hannah wolfe and victoria sharp introduction: there are approximately million hiv positive individuals living in the united sta!es. about. % of these know their hiy status and are enrolled in outpatient care. of the remaining yo, approx~mately half do not know their status; the other group frequently know their status but are not enrolled m any .sys~em of outpatient care. this group primarily accesses care through emergency departments. when md cated, they are admitted to hospitals, receive acute care services and then, upon poster sessions v di 'harge, disappear from the health care system until a new crisis occurs, when they return to the emergency department. as a large urban hiv center, caring for over individuals with hiv we have an active inpatient service ".'ith appr~xi~.ately discharges annually. we decided to survey our inpatients to better charactenze those md v duals who were not enrolled in any system of outpatient care. results: % of inpatients were not enrolled in regular outpatient care: % at roosevelt hospital and % at st.luke\'s hospital. substance abuse and homelessness were highly prevalent in the cohort of patients not enrolled in regular outpatient care. % of patients not in care (vs. % of those in care) were deemed in need of substance use treatment by the inpatient social worker. % of those not in care were homeless (vs. % of those in care.) patients not in care did not differ significantly from those in me in terms of age, race, or gender. patients not in care were asked "why not:" the two most frequent responses were: "i haven't really been sick before" and "i'd rather not think about my health. conclusions: this study suggests that there is an opportunity to engage these patients during their stay on the inpatient units and attempt to enroll them in outpatient care. simple referral to an hiv clinic is insufficient, particularly given the burden of homelessness and substance use in this population. efforts are currently underway to design an intervention to focus efforts on this group of patients. p .q (a) healthcare availability and accessibility in an urban area: the case of ibadan city, nigeria in oder to cater for the healthcare need of the populace, for many years after nigeria's politicl independence, empphasis was laid on the construction of teaching, general, and specialist hospital all of which were located in the urban centres. the realisation of the inadequacies of this approach in adequately meeting the healthcare needs of the people made the country to change and adopt the primary health care (phc) system in . the primary health care system which is in line with the alma ata declaration of of , wsa aimed at making health care available to as many people as possible on the basis of of equity and social justice. thus, close to two decades, nigeria has operated primary health care system as a strategy for providing health care for rural and urban dwellers. this study focusing on urban area, examimes the availabilty and accessibility of health care in one of nigeria's urban centre, ibadan city to be specific. this is done within the contest of the country's national heath policy of which pimary health care is the main thrust. the study also offers necessary suggestion for policy consideration. in spite of the accessibility to services provided by educated and trained midwifes in many parts of fars province (iran) there are still some deliveries conducted by untrained traditional birth attendants in rural parts of the province. as a result, a considerable proportion of deliveries are conducted under a higher risk due to unauthorised and uneducated attendants. this study has conducted to reveal the pro· portion of deliveries with un-authorized attendants and some spatial and social factors affecting the selection of delivery attendants. method: this study using a case control design compared some potentially effective parameters indud· ing: spatial, social and educational factors of mothers with deliveries attended by traditional midwifes (n= ) with those assisted by educated and trained midwifes (n= ). the mothers interviewed in our study were selected from rural areas using a cluster sampling method considering each village as a cluster. results: more than % of deliveries in the rural area were assisted by traditional midwifes. there are significant direct relationship between asking a traditional birth attendant for delivery and mother age, the number of previous deliveries and distance to a health facility provided for delivery. significant inverse relationships were found between mother's education and ability to use a vehicle to get to the facilities. conclusion: despite the accessibility of mothers to educated birth attendants and health facilities (according to the government health standards), some mothers still tend to ask traditional birth attendants for help. this is partly because of unrealistic definition of accessibility. the other considerable point is the preference of the traditional attendants for older and less educated mothers showing the necessity of changing theirs knowledge and attitude to understand the risks of deliveries attended by traditional and un-educated midwifes. p - (a) identification and optimization of service patterns provided by assertive community treatment teams in a major urban setting: preliminary findings &om toronto, canada jonathan weyman, peter gozdyra, margaret gehrs, daniela sota, and richard glazier objective: assertive community treatment (act) teams are financed by the ontario ministry of health and long-term care (mohltc) and are mandated to provide treatment, rehabilitation and support services in the community to people with severe and persistent mental illness. there are such teams located in various regions across the city of toronto conducting home visits - times per week to each of their approximately respective clients. each team consists of multidisciplinary health professionals who assist clients to identify their needs, establish goals and work toward them. due to complex referral patterns, the need for service continuity and the locations of supportive housing, clients of any one team are often found scattered across the city which increases home visit travel times and decreases efficiency of service provision. this project examines the locations of clients in relation to the home bases of all act teams and identifies options for overcoming the geographical challenges which arise in a large urban setting. methods: using geographic information systems (gis) we geocoded all client and act agency addresses and depicted them on location maps. at a later stage using spatial methods of network analysis we plan to calculate average travel rimes for each act team, propose optimization of catchment areas and assess potential travel time savings. resnlts: initial results show a substantial scattering of clients from several act teams and substan· rial overlap of visit travel routes for most teams. conclusions: reallocation of catchment areas and optimization of act teams' travel patterns should lead to substantial savings in travel times, increased service efficiency and better utilization of resourc_~· ~e l'<!tenri~i modifications to catchment areas must be conducted with appropriate attention to specific clients servtce needs, service continuity and applicable regulations by the mohl tc. venice lido is a popular island within and outside italy because it hosts the international cinema festival yearly. only few people remember the island for its hospital, which, in the fifties, was one of the most important hospitals in italy and in europe, being a modern center for wind-, sun-and thermal-therapy. since the sixties, its fame became to drop away, since its structure was no longer adequate for the evolving medicine science. at the end of the seventies all the wards were moved into a new big building in the same area. at present the hospital is made up by about forty 'pavilions' (mostly partially used or empty) and a big building, disseminated in a hectares area, on the sea front, on the m long beach. the aim of my research is to suggest a realistic solution, sustainable on the functional use of the area according to basic local needs and economically realizable. i used a philological and multi-disciplinary method, more in detail: -from historical documents, i found what was the very first call of the property and how it adapted to the needs of the demographic development and the sanitary supply over time; -by contacting some operators from different fields, i realized which functions were suitable to the buildings in existence, to the population's needs and to the present sanitary supply. moreover the planning idea considers: -the debate going on between local people who strongly want to preserve the property, and die ones who want to renew it by different new opportunities; and -the regional sanitary politics, aiming at rationalizing the regional hospitals dislocation, and the budget needs. this plan analyzes and proposes some new alternative solutions to satisfy different needs. the different activities will be dealt out and the environmental fall will be limited as much as possible. after having analyzed its basic call, considered its environmental peculiarities and its position, verified the emerging needs of the local population, the plan proposes different activities: the hospital; the social-rehabilitation center; the elderly house; the thermal center; the residential center; and other activities. such a plan wants to share in the solution of a basic problem by giving architectonic and functional dignity to an historical completely degraded area and by starting again a social-economical broken off process, by bringing in venice lido some fresh necessary elements for its so wished new throw. p - (c) dilemma of free health care in spokane, wa david bunting introduction: the paper reports on the activities of project access spokane [pas], a physician sponsored initiative to provide uncompensated health care to low income, uninsured residents of spokane county wa. program providers included all county hospitals, over physicians, other medical professionals, and specialized clinics. each prescription requires only a $ co-payment. sponsored and administered by the county medical society, pas is funded by local and national foundations, private corporations, municipalities, civic organizations and individuals. method: the paper is based on a first year assessment report funded by pas, using hcfa [health care financing administration] insurance claim data documenting utilization rates, disease categories and donated charge information and patient cares [centralized applications, referrals and enrollment status) data. results: while essentially free for enrollees, the program involved real costs. an administrative organization to refer over patients to any of over providers had to be developed and staffed, using both paid and unpaid personnel. methods to identify potential patients and veri.fy eligibility. had to ~devised. patient appointments and transportation had to be scheduled and monitored. pu~hc relanons, provider solicitations and fundraising activities were continuous. information requirements regarding program operation were also significant. data reporting the volume. ~nd value of dona~ed medical services were necessary to demonstrate accomplishments and attr~ct addmon~l support. providers required assurances their contributions were both significant and eqmtable. funding sources sought evidence that their support had important consequences. however, generating this ~~ta proved difficult. many providers failed to submit appropriate insurance claims forms because .of a~dmonal donated effort and administrative cost, thereby not only reducing their own apparent conmbut ons but also the overall significance of the program. conclusions: during its initial year, the estimated cost to deliver free health care was ~bout per enrollee. the lesson is that without an elaborate administrative structure and record keeping s.yst~~· efforts to provide free health care probably will fail. eligible enrollees c~n not be ~parated from in~hgi ble ones, care will not be accessed or delivered in an efficient manner, neither fundmg nor ~upport "". be offered without evidence of tangible benefits, and providers will withdraw if they perceive mequ table tteannent. v p - s (c) mobility in prostitution and the impact of health therese van der helm and henk sulman poster sessions introduction: many of the estimated . commer~ial ~ex wor~ers (c~w)in a'.' ~terdam ~~me from developing countries and eastern europe. to gain ins~ght mto their workmg and_ hvmg condinons the intermediary project (ip) at the municipal health serv ~e _contacts these women via ?utreach work on regular basis. since the new brothel law in october s ~troduc~d, ~sw ~rom outside the eu and who have no dutch residence permit are not allowed to work m prost tut n. smee then, many of these csw therefore have gone "underground." the consequences of the new law in the netherlands will be discussed with regard to the accessibility of csw and their risk for stl/hiv acquisition and unplanned pregnancies. methods: topics during outreach work are the interventions to increase the knowledge of safe sex and birth control for csw. written information is handed out in relevant languages and with addresses of health and social services. in conversations with the women, it appeared that many are not aware of these services. to provide easier access to health care for women, staff of the ip carries out free sti control csw working places, in windows brothels and sex houses. also, women are offered vaccination against hepatitis b (hbv). results: from january till july we approached csw for first contact. one third was dutch; others were from developing countries, other eu countries and eastern europe. sti consul· rations were done among non-iv drug using sex workers, of whom % was dutch. of these, % was diagnosed with syphilis, % with gonorrhea, and % with chlamydia. of women tested for hiv, none were infected. due to the high turnover of csw in .brothels, most wnmen were tested only once. among csw tested for hbv -of whom one third is dutch - % had antibodies for hbv, were carrier of hbv, most of whom came from hbv endemic areas. conclusions: sti control and hbv vaccination in brothels is an important support in health care. our findings suggest that csw do not play an important role in the transmission of sti. many csw are highly mobile and often not aware of the existing health and social services. continuous outreach is important to remain in contact with this mobile population. regulations in the new brothel law should not hamper contacts with (illegal) csw. heart disease (cho) is projected to become the leading cause of death. studies conducted in europe and the united states have proven a higher rate of cho in south asians who have migrated from south asia, most notably india, pakistan and bangladesh. approximately % of all heart attacks among south asian men occur under the age of ; % of them occur under the age of -unheard of in any other population. associated risk factors such as diabetes, high blood pressure and cholesterol are also com· mon in this group. the population of south asians residing in nyc has more than doubled over the past decade to over , , the majority being young, working-class and with limited health care access. many south asian men are employed as taxi drivers ( out of nyc taxi drivers are from south asial, working daily hour plus shifts. methods: acknowledging that this vulnerable, at-risk group was unavailable for outreach through conventional venues, three of the hospitals of the new york city health and hospital corporation, (elmhurst, queens and bellevue) conducted a one day outreach effort at nyc's jfk international air· ~rt's taxi holdin~ ar~a, ~here over one thousand taxis regularly assemble. bringing an outreach event directly to the taxi dnvers workplace, a tent was set up where cardiovascular-related health screenings, in~luding bl~ pressure, sugar, cholesterol, body mass index (bmi), were provided. results were shared with and explamed to the drivers and each participant received a south asian health education brochure. a total of taxi drivers who identified as south asian were involved. rau/ts: participants were all male, ranging from to years; mean age, . . screenings revealed % hypertensive; % had cholesterols over ; % blood glucose over ; % had a bmi greater than . conc~on: a unique outreach activity, adapting to logistical, occupational limitations, is pre· se~ted. on-site f~back and explanation of results, reiterating and reinforcing the concern that south asia~. men are at mcreased danger for early coronary heart disease, and the dissemination of a culturally sensmve and r~levant brochure, may heighten awareness of prevailing cardiac risk factors in this immi· grant community. p - (c) the community-hospital integration program framework: community-hospital panoenhips to improve the population's health john stevenson, richard blickstead, ann-marie marcolin, and sandi kendal v introduction: st. josephs health centre is a catholic community teaching hospital located in the heart of southwest toronto. st. joseph\'s was founded from a community-expressed need for hospital services, and since then has stayed committed to fostering a healthy community through collaboration and parmership. st. joseph's has developed an innovative model, the community-hospital integration program (chip), to strengthen st. joseph's partnerships with community stakeholders, and facilitates the building of links between community needs, service provision, and public policy outcomes to improve the health and wellness of the diverse neighbourhoods they together serve. methods: development of the chip framework st. joseph's health centre developed the chip framework through a multidisciplinary approach that included extensive international literature reviews, consultations, and key informant interviews with community service agencies and academics. to ensure active community voice, st. joseph's has hosted a number of community consultations including a community outreach forum attended by over ninety representatives from community partners. results: the chip framework the chip framework aims to improve the health and wellness of the urban communities served by st. josephs health centre through four intersecting pillars: • raising community voices provides an infrastructure and process that supports community stakeholder input into health care service planning, decision-making, and delivery by the hospital and across the continuum of care; • sharing reciprocal capacity promotes healthy communities through the sharing of our intellectual and physical capacity with our community partners; • cultivating integration initiatives facilitates vertical, horizontal, and intersectoral integration initiatives in support of community-identified needs and gaps; and • facilitating healthy exchange develops best practices in community integration through community-based research, and facilitates community voice in informing public policy. the chip framework drives the complex inter-relationships between community-hospital engagement, reciprocal capacity-building, integration initiatives, and community-based research and evaluation, to create an interconnected network of health care services. the fluidity and simplicity of this framework, and its dedication to balancing community needs and hospital mandate, posits the st. josephs health centre's chip model as an integral component in building healthy and thriving communities. p - (c) home based care promotion: improving acess to quality services and livelihood in the face of aids home based care is a service provided to persons affected/living with hiv/aids, a menu of care/support services at home/community. it is a prominent alternative approach. in uganda, hospital bed ocupacny is high, patient health care worker ratio deteriorating. empowering communities offers solutions to the problems; adressing cost, effectiveness of care. hiv/aids demands changes in attitudes, behaviour, approaches which is enhanced in home/community settings. for example art requires high levels of adherecnce, which medical workers have vety little opportunity to enforce. it also demands other support mechanisims in terms of nutrition, personal displine, etc which work best in stigma free environments. hence the relevance of home based care. this paper highlights the gaps that call for increased action in terms of home based care, examples of whre it has worked key challenges and recommendations for the future. p - (c) health care for one ... health care for alli katharina kovacs burns introduction: at the surface, it appears that every person in canada _has. ~ccess to a publicly funded health care system. those living in urban centers should have the best ava l~b hty, chmce, and access to a variety of health care services because of the distribution of health care services, fac lmes, and health professionals in concentrated in urban centers. this is not true for everyone -people with low income or who are homeless experience the challenges of social exclusion and being marginalized: there are many factors at play making it difficult for the latter group of people to access health care. service they need,.when they need them. health care is not as accessible or inclusive as intended. the quesuon to be explore.cl ~: if health care is available and accessible to one person, what makes it not available to all people? the ~ gmfic~nce of having marginalized people accessing health care and other services includes e~hanced quality of hfe and decreased risks associated with being homeless, and cost savings in ion~ ter~ w rh acute health care. methodology: community-based participatory research is applied m a case study on health care access and challenges experienced by low income and homeless people in one urban centre, edmonton, edmonton, and their challenges. the data is being gathered and ana_lyzed usmg basic m x~d methods. results: the results will focus on how services can be more mtegrated and accessible to all people with low income and who are homeless. there will also be discussion about specific perceptions of not only the service providers but also of people with low income an~ who are homeless~ and vario~s decision makers. the results will be compared to the literature regardmg health care services access mother urban centers in canada and elsewhere. conclusions: recommendations will need to address social exclusion and other factors which can make health care and other services more available to all people in the community. the implications for health care will also be discussed. additional information will be gathered in the next phases of the study to develop a community services access model. p - (c) availability and access exemplified: a case study beth hayhoe and ruth ewert introduction: access to health care in canada requires either the correct documentation or money. street youth have neither. in addition, health services in canada are designed by adults for adults. youth in general are often wary of having trust in adults with respect to their health concerns and frequently feel misunderstood. street youth are even more mistrustful of adults and public organizations, making their contact with health care professionals minimal. this combined with their risky behaviours and dangerous environment creates a population at risk for numerous health issues but with no place to have them investi· gated. at our non-government, not for profit health service designed specifically to provide a broad range of health care to street youth, professional services are provided almost entirely by volunteers. methods: using a retrospective analysis of the years of data gathered from this organization and reviewing the initial reasons gathered from youth about their needs, the success of the health centre was examined. results: all the things youth had listed as being important in a health centre have been implemented, and even more things have been added to improve the breadth and quality of services offered. the use of the health centre has increased by more than six times since its opening in . in addition, tens of thousands of visits have been paid to the health centre, costing the government and taxpayers nothing. as far as we know there is nothing else in canada that offers so many diverse and innovative services to youth in need. conclusion: it is clear from this case, that health care targeted at the needs of specific disadvan· taged populations can successfully provide them with appropriate health care. a model of accessible health care for marginalized populations can easily be developed for high impact and low cost from this successful case. toronto is one of the most ethno-racially diverse cities in the world of the estimated , , toronto residents, % ( , ) live in scarborough population growth in scarborough is faster than toronto. scarborough's population increased by % from to while toronto increased only by %. toronto's population is projected to increase by % ( ) in while scarbor· ough's will increase by %. (census canada ) low income, pove;ty, seniors, hidden homeless, new~omers to canada, the uninsured, are just a few of the issues concerning health care in our community. health care needs in scarborough are greatly impacted by diversity of ethnic and racial groups, poverty and settlement issues. this paper will share how the scarborough hospital (tsh) an urb~n communir_y hospital cares f~~ it~ community. tsh recognizes: •the changing community• b_arriers t~ accessing care • lnequalmes m health care the hospital in caring for its community pro· v ~es services that '!'e~e cu~turally, racially, and linguistically sensitive to our community. the paper will share the hospitals unique program on access and equity. the paper will share the needs in scar· borough and tsh's response to these needs: working in partnership with the local health committee, i:ne scarborough homeless co.mminee, the scarborough network of immigrant services organiza· nons a~d others. :' e paper will also share the many initiatives this urban community hospital has taken viz. community and home programs in service areas such as mental health, haemodialysis day care, t~~ home oxyg~n program, the palliative at-home program, and above all support for the volunteer clinic for the uninsured. j"'" tllu:lion: in canada's universal health care system it is generally assumed that everyone has equal access to health care. however, some immigrant groups in canada have historically been uninswed. these groups include failed refugee claimants, those overstaying their visas, and new immigrants in transition who are waiting to become eligible for health insurance. some estimates have suggested that at the present time there may be as many as one hundred thousand undocumented and thus uninsured immigrants in toronto alone. understandably, information on the characteristics of this marginalized population is very limited, since undocumented immigrants tend to have little contact with formal institutions. knowledge of the demographic characteristics of this population may aid in the development of health and social programs to better identify and meet the needs of undocumented immigrants in toronto. we conducted a review of all undocumented, uninsured patients, years of age or older at access alliance multicultural community health centre (aamchc) between and . demographic information such as age, gender, preferred language, length of time living in canada, selfreported education level and household income were recorded. rmdts: % of all adult patients at access alliance were undocumented and uninsured. % were under years of age (with a median age of years), % were women and only % spoke english. this group lived in canada for an average period of . years before they were first seen at aamchc. % of undocumented clients reported having completed at least a secondary or post-secondary education. % had self-reported household incomes of less than , $/year, while % of households reported earning less than $ , /year. the mean income per person in an average household was $/month. conchuions: uninsured individuals at aamchc were predominantly young females with limited knowledge of the english language. despite having attained a high level of education most were living well below the poverty line. recognition of these characteristics may assist in the development of health and social programs that are better adapted to meet the needs of undocumented immigrants. p - (c) sharing expertise: a role for the hospital lactation consultant in the community. badrgrmuul: st. michael's hospital is a tertiary care hospital that serves a large inner city population in downtown toronto. in order to provide care to this population, the hospital has developed a number of unique outreach roles. one such role was developed to work with pregnant and breastfeeding women living in regent park, a social housing complex located near the hospital. the population of regent park includes new immigrants, refugees and the socially disadvantaged. approach: the outreach lactation consultant provides care, as part of the canada prenatal nutrition program, in the community prenatally, in the hospital during their inpatient stay and postnatally when they return to the community. the continuity of care enhances the probability of long term successful breastfeeding. aside from the health benefits of breastmilk, breastfeeding is especially important for women who are financially needy and must depend on food banks for formula. . . lason learned: aher two years of partnership, the relationship between the an-hospital ~stpar tum experience for breastfeeding mothers and the community postpartum support, the breastfeeding rate ~thin this community is high. the professional support and visibility of the : ctation consultant, both m the hospital and in the community, contributes to the support of breastfee~m~.. . in light of ongoing funding constraints, this ha son between hospital and community could be at risk and discontinued. in light of the benefits to the mother/baby dyad, the lactation consultant as a community partner in the canada prenatal nutrition program should be safeguarded. . lldpodiu:tion: although the importance of adequate health care in pregna~cy is well recognised, ethnic disparities in utilization of prenatal care still exist in many western coun~~es. a fun~amental factor in these disparities may be language proficiency, as it influences women's ab hty. to ob~m and understand health information, to find the way in the health care system and to communicate with health care v poster sessions providers. we investigated the role of language proficiency in use and knowledge of folic acid as aspect of prenatal care in an urban multi-ethnic pregnancy c?hort. . . design: prospective cohort study. setting and parnc pants: amsterdam ~regnant women attending obstetric care providers for their first antenatal visit (n= ). country of birth defined ethnicity: the netherlands, surinam, antilles, turkey, morocco, ghana, other non-~est~m (nw) and other western (w) country. main outcome measures: knowledge about and use of.fohc a~d (fa) supplements in pregnancy, and determinants of these in diffe~~t ethnic ~~ups. deterrrunants mcl~ded age, ed~ tion, parity, pregnancy intention and dutch prof c ency. stansncs: ~ to co~p~re e~c groups, stranfied logistic regression (forward stepwise method) to explore determmants "'.'thm ethmc groups .. use of fa supplements was significantly lower among ghanaian, moroccan, turkish and other nw women ( %to %) than among dutch ( %) or other w women ( %). use amongsurinames and antillean women was intermediate ( %and %). ethnic differences in fa knowledge were similar. knowledge was the strongest determinant of use in all ethnic groups, with odds ratios (ors) ranging from . to . . language proficiency was the strongest determi~a~t of kno~ledge in ethnic groups with a mother tongue different from dutch (ors good vs. low proficiency ranging from . ro . ). educational level had a modifying role, as shown by an interaction effect between education and language proficiency in the nw group. here, the odds of having fa knowledge given a high education and good dutch proficiency was times the odds given a good proficiency but low education. conclusions: appropriate periconceptional use of folic acid supplements in non-western ethnic groups is low, reflecting an absence of knowledge that is largely determined by the inability to speak and understand the language of the habitual country. tailored interventions using communication channels most likely to address (pregnant) women from ethnic minority groups are necessary. apan from specific interventions, our results are in support of strong incentives on language education despite current political debate. introduction: recent research suggests living in an economically disadvantaged neighborhood is asso· ciated with decreased likelihood of undergoing mammography and increased risk of late-stage breast can· cer diagnosis. long distances and travel times to facilities offering low-or no-cost mammography may be imponant barriers to adherence to mammography screening recommendations for residents of economically disadvantaged neighborhoods. the purpose of this study was to examine whether facilities providing low-and no-cost screening mammography were less spatially accessible in low-income neighborhoods in chicago, and the extent to which the relationship between neighborhood income and the spatial accessibility of facilities varied by the proponion of african-american residents in the neighborhood. methods: the sample consisted of chicago neighborhoods. for each neighborhood, we con· structed three measures of the spatial accessibility of facilities: street network distance to the nearest facility, public transportation travel time to the nearest facility, and shortest automobile travel time to a facility. using decennial census data, we characterized the neighborhoods according to proportion of residents with incomes below the poverty line, proportion of residents in each of four raciavethnic groups (african-american, latino, white, and other), and population density. we used ordinary least squares (ols) and spatial exogenous lag regression to examine relationships. model estimated the relationship between neighborhood poverty and the spatial accessibility of facilities, adjusting for raciaveth· nic composition and population density. model added a multiplicative interaction term between neighborhood poverty and african-american. restllts: we identified deven facilities that provided low-or no-cost screening mammography to chicago residents in . we found that the distance and travel times via automobile and public trans· portation to facilities generally decreased as neighborhood poveny increased. however, we also found that the ~egative associations between neighborhood poverty and two of the spatial accessibility mea· sures -distance and public transportation travel time -were less strong in neighborhoods with the highest proponions of african-american residents. among neighborhoods in the highest tertile for poveny, th~ mean distance and mean public transportation travel time to facilities were over twice as long in neighborhoods in the highest tertile than in those in the lowest tenile of african-american residents. . ~ persistent socioeconomic and racial/ethnic disparities in breast cancer stage at diagno-s ~nd su~ val suggest that ensuring an equitable distribution of affordable mammography is a worth-w~e policy .goal. the ~~dy sugges~ that ~ture investigations should consider both neighborhood soc oecono d c charactensbes and rac avethmc composition when examining the spatial distribution of health resources. , ) . epidemiological data suggest tha~ hiv prevalence among msm is over % in some metropolitan cities, such .as beijing (ibid.). due to widespread homophobia in chinese society, however, this population remains invisible within current health/social services. lack of research on sexuality, specifically homosexuality, has impaired our understanding of health and health practices of chinese msm. focusing on the illness experiences of chinese msm with hiv/aids, this paper explores the socio-cultural impacts of hiv/ aids on this group. the data used for this paper were collected through semi-constructed in-depth face-toiace interviews with adult plwhas (including msm) in beijing, china. with the permission of the participants, the interviews were audio-taped or recorded in notes. the transcribed interviews and interview notes were analyzed by using n-vivo, a software program for qualitative data analysis. this phenomenological study aimed to understand the experiences chinese plwhas (including msm) from their own perspectives. results: it is found that the illness experiences of chinese msm with hiv/aids are profoundly shaped by the socio-cultural meanings of homosexuality, which are further complicated by the dominant discourses on hiv/aids in china. at a macro level, homophobia in the larger society has decreased the capability of this group to respond to this epidemic in a more efficient way. at a meso level, aids-phobia within the chinese msm circuits has prevented this group from openly confronting this disease and offering support to those who are already affected by it. at a micro level, however, these hiv-infected/ affected msm have tried their best to locate spaces to live and to construct hope for their future lives despite various barriers within family, community, and the larger society. this study suggests that facilitating chinese msm's response to the aids crisis urgently requires bridging awareness, commitment, knowledge and resources both within and without this group. it also illustrates the importance of understanding homosexuality in the local context of hiv i aids, which will be helpful for developing culturally sensitive hiv/aids programs for this population on the community, national and international levels. introduction: having a regular family doctor (rfd) is known to be positively correlated with a good medical follow up, including access to preventive and/or chronic care. inversely, a lack of primary care may lead to high rates of avoidable hospitalizations, especially among poor people and/or in underserved neighbourhoods. in such a matter, a recent comparative study showed that paris was better ranged than other cities, such as nyc, tokyo or london. nevertheless, despite a quasi universal health insurance and a high density of general practitioners, a noticeable fraction of the paris population does not have any regular physician and we aimed to understand who they are and for what reasons rhey don't have any rfd. mdbods: cross sectional population survey among a random sample of households in ~nderpriv ileged neighbourhoods in paris inner city, performed in , using a face-to-face quest nna re collecr- ng more than social and health characteristics. ruults: a quarter ( . %) of rhe study popularion did not have any rfd. this proporrion was iignificantly higher among male (or= . , %ci = [ . - . ), younger (e.g. or - /> .s l _= ._oo, " .ci = ( . - . )), and/or unemployed (or = . , %ci = ij . - . _ people. in multtvanate analysis, after a full adjustment on gender, age, health status, health insura~ce, income, occupat n and tducation level, we observed significant associations between having no rfd and: ~arrtal and_ pare~t hood status (e.g. or single no kids/in couple+kids = . , %ci = ( . - . ()~ quality of relattonsh ps with neighbours (or bad/good= . , %ci = [ . - . )), and length of residence m the neighbourhood (with a dose/effect statistical relationship). . co clusion: gender, age, employment status, mariral and parenthood stat~s as well as ~e gh bourhood anchorage seem to be major predictors of having a rfd, even when um.versa! health i~sur ance has reduced most of financial barriers. in urban contexts, where residential migrattons and single lift (or family ruptures) are frequent, specific information may be conducted to encourage people to ket rfd. :tu~y tries to assess the health effects and costs and also analyse the availability and accessibility to health care for poor. . methods: data for this study was collected by a survey on households of the local community living near the factories and households where radiation hazard w~s n?~ present. ~~art from mor· bidity status and health expenditure, data was collected ~n access, a~ail~b .hty and eff c ency of healrh care. a discriminant analysis was done to identify the vanables that d scnmmate between the study and control group households in terms of health care pattern. a contingent valuation survey was also undertaken among the study group to find out the factors affecting their willingness to pay for health insurance and was analysed using logit model. results: the health costs and indebtedness in families of the study group was high as compared to control group households and this was mainly due to high health expenditure. the discriminant analysis showed that expenditure incurred by private hospital inpatient and outpatient expenditure were significant variables, which discriminated between the two types of households. the logit analysis showed !hat variables like indebtedness of households, better health care and presence of radiation induced illnesses were significant factors influencing willingness to pay for health insurance. the study showed that study group households were dependent on private sector to get better health care and there were problems with access and availability at the public sector. conclusion: the study found out that the quality of life of the local community is poor due to health effects of radiation and the burden of radiation induced illnesses are so high for them. there is an urgent need for government intervention in this matter. there is also a need for the public sector to be efficient to cater to the needs of the poor. a health insurance or other forms of support to these households will improve the quality for health care services, better and fast access to health care facilities and reduces the financial burden of the local fishing community. the prevalence of substance abuse is an increasing problem among low-income urban women in puerto rico. latina access to treatment may play an important role in remission from substance abuse. little is known, however, about latinas' access to drug treatment. further, the role of social capital in substance abuse treatment utilization is unknown. this study examines the relative roles of social capital and other factors in obtaining substance abuse treatment, in a three-wave longitudinal study of women ages - living in high-risk urban areas of puerto rico, the inner city latina drug using study (icldus). social capital is measured at the individual level and includes variables from social support and networks, familism, physical environment, and religion instruments of the icdus. the study also elucidates the role of treatment received during the study in bringing about changes in social capital. the theoretical framework used in exploring the utilization of substance abuse treatment is the social support approach to social capital. the research addresses three main questions: ( t) does social capital predict parti~ipating in treatment programs? ( ) does participation in drug treatment programs increase social capital?, and ( ) is there a significant difference among treatment modalities in affecting change in ~ial capital? the findings revealed no significant association between levels of social capital and gettmg treatment. also, women who received drug treatment did not increase their levels of social capital. the findings, however, revealed a number of significant predictors of social capital and receiving drug ~buse treatment. predictors of social capital at wave iii include employment status, total monthly mcoi:rie, and baseline social capital. predictors of receiving drug abuse treatment include perception of physical health and total amount of money spent on drugs. other different variables were associated to treatment receipt prior to the icldus study. no significant difference in changes of social capital was found among users of different treatment modalities. this research represents an initial attempt to elucidate the two-way relationship between social capital and substance abuse treatment. more work is necessary to unden~nd. ~e role of political forces that promote social inequalities in creating drug abuse problems and ava lab hty of treatment; the relationship between the benefits provided by current treatment poster sessions v sctrings and treatment-seeking behaviors; the paths of recovery; and the efficacy and effectiveness of the trtaanent. and alejandro jadad health professionals in urban centres must meet the challenge of providing equitable care to a population with diverse needs and abilities to access and use available services. within the canadian health care system, providers are time-pressured and ill-equipped to deal with patients who face barriers of poverty, literacy, language, culture and social isolation. directing patients to needed supportive care services is even more difficult than providing them with appropriate technical care. a large proportion of the population do not have equitable access to services and face major problems navigating complex systems. new approaches are needed to bridge across diverse populations and reach out to underserved patients most in need. the objective of this project was to develop an innovative program to help underserved cancer patients access, understand and use needed health and social services. it implemented and evaluated, a pilot intervention employing trained 'personal health coaches' to assist underserved patients from a variety of ethno-linguistic, socio economic and educational backgrounds to meet their supportive cancer care needs. the intervention was tested with a group of underserved cancer patients at the princess margaret hospital, toronto. personal coaches helped patients identify needs, access information, and use supportive care services. triangulation was used to compare and contrast multiple sources of quantitative and qualitative evaluation data provided by patients, personal health coaches, and health care providers to assess needs, barriers and the effectiveness of the coach program. many patients faced multiple barriers and had complex unmet needs. barriers of poverty and language were the easiest to detect. a formal, systematic method to identify and meet supportive care needs was not in place at the hospital. however, when patients were referred to the program, an overwhelming majority of participants were highly satisfied with the intervention. the service also appeared to have important implications for improved technical health care by ensuring attendance at appointments, arranging transportation and translation services, encouraging adherence to therapy and mitigating financial hardship -using existing community services. this intervention identified a new approach that was effective in helping very needy patients navigate health and social services systems. such programs hold potential to improve both emotional and physical health out· comes. since assistance from a coach at the right time can prevent crises, it can create efficiencies in the health system. the successful use of individuals who were not licensed health professionals for this purpose has implications for health manpower planning. needle exchange programs (neps) have been distributing harm reduction materials in toronto since . counterfit harm reduction program is a small project operated out of a community health centre in south-east toronto. the project is operated by a single full-time coordinator, one pan-rime mobile outreach worker and two peers who work a few hours each week. all of counterfit's staff, peers, and volunteers identify themselves as active illicit drug users. yet the program dis~rib utes more needles and safer crack using kits and serves more illicit drug u~rs t~an the comb ~e~ number of all neps in toronto. this presentation will discuss the reasons behind this success, .s~ f cally the extended hours of operation, delivery models, and the inclusion of an. extremely marg ~ahzed community in all aspects of program design, implementation and eva.luat ?n. ~ounterfit was recently evaluated by drs. peggy milson and carol strike, two leading ep dem olog st and researchers in the hiv and nep fields in toronto and below are some of their findings: "the program has experienced considerable success in delivering a high quality, accessible and well-used program .... the pro· gram has allowed (service users) to become active participants in providing. services to others and has resulted in true community development in the best sense. " ... counterf t has ~~n verr succe~sful attracting and retaining clients, developing an effective peer-based model an.d assisting chen~s ~ th a vast range of issues .... the program has become a model for harm red~ctmn progr~ms withm the province of ontario and beyond." in june , the association of ?ntano co~mumty heal~~ <:en· ires recognized counterfit's acheivements with the excellence m community health initiatives award. in kenya, health outcomes and the performance of government health service~ have det~riorated since the late s, trends which coincide with a period of severe resource constramts necessitated by macro-economic stabilization measures after the extreme neo-liberalism of the s. when the govern· ment withdrew from direct service provision as reform trends and donor advocacy suggested, how does it perform its new indirect role of managing relations with new direct health services providers in terms of regulating, enabling, and managing relations with these health services providers? in this paper therefore, we seek to investigate how healthcare access and availability in the slums of nairobi has been impacted upon by the government's withdrawal from direct health care provision. the methodology involved col· leering primary data by conducting field visits to health institutions located in the slum areas of kibera and korogocho in nairobi. purposive random sampling was utilized in this study because this sampling technique allowed the researcher(s) to select those health care seekers and providers who had the required information with respect to the objectives of the study. in-depth interviews using a semi-structured ques· tionnaire were administered ro key informants in health care institutions. this sought to explore ways in which the government and the private sector had responded and addressed in practical terms to new demands of health care provision following the structural adjustment programmes of the s. this was complemented by secondary literature review of publications and records of key governmental, bilateral and multilateral development partners in nairobi. the study notes a number of weaknesses especially of kenya's ministry of health to perform its expected roles such as managing user fee revenue and financial sustainability of health insurance systems. this changing face of health services provision in kenya there· fore creates a complex situation, which demands greater understanding of the roles of competition and choice, regulatory structures and models of financing in shaving the evolution of health services. we rec· ommend that the introduction of user fees, decentralization of service provision and contracting-out of non-clinical to private and voluntary agencies require a new management culture, and new and clear insri· tutional relationships. experience with private sector involvement in health projects underlines the need not only for innovative financial structures to deal with a multitude of contractual, political, market and risks, but also building credible structures to ensure that health services projects are environmentally responsive, socially sensitive, economically viable, and politically feasible. purpose: the purpose of this study is to examine the status of mammography screening utilization and its predictors among muslim women living in southern california. methods: we conducted a cross-sectional study that included women aged ::!: years. we col· leered data using a questionnaire in the primary language of the subjects. the questionnaire included questions on demography; practices of breast self-examination (bse) and clinical breast examination (cbe); utilization of mammography; and family history of breast cancer. bivariate and multiple logistic regression analyses were performed to estimate the odds ratios of mammography use as a function of demographic and other predictor variables. . results: among the women, % were married, % were - years old, and % had family h story of breast cancer. thirty-two percent of the participating women never practiced bse and % had not undergone cbe during the past two years. the data indicated that % of the women did not have mammography in the last two years. logistic regression analysis showed that age ( r= . , % confi· dcnc~ interval (cl)=l. - . ), having clinical breast examination ( r= . , % cl= . - . ), and practtce of self-breast examination ( r= . , % cl= . - . ), were strong predictors of mammography use . . conclusions: the data point to the need for intervention targeting muslim women to inform and motivate th.cm a~ut practices for early detection of breast cancer and screening. further studies are needed to investigate the factors associated with low utilization of mammography among muslim women population in california. we conducted a review of the scientific literature and° government documents to describe ditnational health care program "barrio adentro" (inside the neighborhood). we also conducted qualiurivt interviews with members of the local health committees in urban settings to descrihe the comm unity participation component of the program. rtsmlts: until recently, the venezuelan public health system was characterized by a lack or limited access w health care ( % of the population) and long waiting lists that amounted to denial of service. moit than half of the mds worked in the five wealthiest metropolitan areas of the country. jn the spring oi , a pilot program hired cuban mds to live in the slums of caracas to provide health care to piople who had previously been marginalized from social programs. the program underwent a massive expansion and in only two years , cuban and , venezuelan health care providers were working acmss the country. they provide a daily average of - medical consultations and home visits, c lly out neighborhood rounds, and deliver health prevention initiatives, including immunization programs. they also provide generic medicines at no cost to patients, which treat % of presenting ill-ij!m, barrio adentro aims to build , clinics (primary care), , diagnostic and rehabilitation ctnrres (secondary care), and upgrade the current hospital infrastructure (tertiary care). local health committees survey the community to identify needs and organize a variety of lobby groups to improve dit material conditions of the community. last year, barrio adentro conducted . times the medical visits conducted by the ministry of health. the philosophy of care follows an integrated approach where btalrh is related to housing, education, employment, sports, environment, and food security. conclusions: barrio adentro is a unique collaboration between low-middle income countries to provide health care to people who have been traditionally excluded from social programs. this program shows that it is possible to develop an effective international collaboration based on participatory democracy. low-income americans are at the greatest risk of being uninsured and often face multiple health concerns. this evaluation of the neighborhood health initiative (nh!), an organization which uses multiple programmatic approaches to meet the multiple health needs of clients, reflected the program's many activities and the clients' many service needs. nh! serves low-income, underserved, and hard-to-reach residents in the des moines enterprise community. multiple approaches (fourth-generation evaluation, grounded theory, strengths-and needs-based) and methods (staff and client interviews, concept mapping, observations, qualitative and quantitative analysis) were used to achieve that reflection. results indicate good targeting of residents in the zip code and positive findings in the way of health insurance coverage and reported unmet health needs of clients. program activities were found to match client nttds, validating the organization\'s assessment of clients. important components of nhi were the staff composition and that the organization had become part of both the formal and informal networks. nhi positioned as a link between the target population and local health and social sc:rvice agencies, working to connect residents with services and information as well as aid local agencies in reaching this underserved population. p - (c) welfare: definition by new york city maribeth gregory for an individual who resides in new york city, to obtain health insurance under the medicaid policy one must fall under certain criteria .. (new york city's welfare programs ) if the individual _is on ssi or earns equal to or less than $ per month, he is entitled to receive no more than $ , m resources. a family the size of two would need to earn less than $ per month to qualify for no greater than ss, worth of medicaid benefits. a family of three would qualify for $ , is they earned less than $ per month and so on. introduction: the vancouver gay communiry has a significant number of asian descendan!l. because of their double minority status of being gay and asian, many asian men who have sex with men (msm) are struggling with unique issues. dealing with racism in both mainstream society and the gay communiry, cultural differences, traditional family relations, and language challenges can be some of their everyday srruggles. however, culturally, sexually, and linguistically specific services for asian msm are very limited. a lack of availability and accessibiliry of culturally appropriate sexual health services isolates asian msm from mainstream society, the gay community, and their own cultural communities, deprives them of self-esteem, and endangers their sexual well-being. this research focuses on the qualita· tive narrative voices of asian msm who express their issues related to their sexualiry and the challenges of asking for help. by listening to their voices, practitioners can get ideas of what we are missing and how we need to intervene in order to reach asian msm and ensure their sexual health. methods: since many asian msm are very discreet, it is crucial to build up trust relationships between the researcher and asian msm in order to collect qualitative data. for this reason, a community based participatory research model was adopted by forming a six week discussion group for asian msm. in each group session, the researcher tape recorded the discussion, observed interactions among the participants, and analyzed the data by focusing on participants' personal thoughts, experiences, and emotions for given discussion topics. ra lts: many asian msm share challenges such as coping with a language barrier, cultural differ· ences for interpreting issues and problems, and westerncentrism when they approach existing sexual health services. moreover, because of their fear of being disclosed in their small ethnic communities, a lot of asian msm feel insecure about seeking sexual health services when their issues are related to their sexual orientation. conclflsion: sexual health services should contain multilingual and multicultural capacities to meet minority clients' needs. for asian msm, outreach may be a more effective way to provide them with accessible sexual health services since many asian msm are closeted and are therefore reluctant to approach the services. building a communiry for asian msm is also a significant step toward including them in healthcare services. a communiry-based panicipatory approach can help to build a community for asian msm since it creates a rrust relationship between a worker and clients. p - (c) identifying key techniques to sustain interpretation services for assisting newcomers isolated by linguistic and cultural barriers from accessing health services s. gopi krishna lntrodaetion: the greater toronto area (gta) is home to many newcomer immigrants and other vulnerable groups who can't access health resources due to linguistic, cultural and systemic barriers. linguistic and cultural issues are of special concern to suburbs like scarborough, which is home to thousands of newcomer immigrants and refugees lacking fluency in english. multilingual community ~nterpreter. service~ (mcis) is a non-profit social service organization mandated to provide high quality mterpretanon services. to help newcomers access health services, mcis partnered with the scarborough network of immigrant serving organizations (sniso) to recruit and train volunteer interpreters to accompany clienrs lacking fluency in english and interpret for them to access health services at various locati?ns, incl~~ing communiry ~c:-lth centres/social service agencies and hospitals. the model envisioned agencies recruin~ and mcis ~.mm.g and creating an online database of pooled interpreter resources. this da.tabase, acces& bl~ to all pama~~g ?rganization is to be maintained through administrative/member · ship fees to. be ~ d by each parnapanng organization. this paper analyzes the results of the project, defines and identifies suc:cases before providing a detailed analysis for the reasons for the success . . methods:. this ~per~ q~ntitative (i.e. client numben) and qualitative analysis (i.e. results of key •~ormant m~rv ews with semce ~sers and interpreters) to analyze the project development, training and mplementanon phases of the project. it then identifies the successes and failures through the afore· mentioned analysis. poster sessions vss resljts: the results of the analysis can be summarized as: • the program saw modest success both ia l?lllls of numbers of clients served as well as sustainability at various locations, except in the hospital iririog. o the success of the program rests strongly on the commitment of not just the volunteer interprmr, but on service users acknowledgments through providing transponation allowance, small honororia, letter of reference etc. • the hospital sustained the program better at the hospital due to the iolume and nature of the need, as well as innate capacity for managing and acknowledging volunceers. collc/llsion: it is possible to facilitate and sustain vulnerable newcomer immigrants access to health !ul'ices through the training and commitment of an interpreter volunteer core. acknowledging volunteer commitment is key to the sustenance of the project. this finding is important to immigration and health policy given the significant numbers of newcomer immigrants arriving in canada's urban communities. nity program was established in to provide support to people dying at home, especially those who were waiting for admission to the resi<lential hospice. with the advent of haart and corresponding challenges for people living with hiv/aids in the community, the community program has developed a unique case management approach. this model features an interdisciplinary team providing a clientdrivcn service. the case manager provides continuity of care to clients in a variety of settings both within and outside of the health care system. a case study is used to demonstrate how formal and informal networks of support facilitate efficient and appropriate resource utilization to promote client health. this case study demonstrates the value of consistent coordination with a client who has complex physical, spiritual, substance use and mental health needs. the authors will show how they liaised with the housing authority, police, social services as well as the family physician, clinic staff and a hospital emergtncy room to ensure this client did not fall between the cracks. tarek hussain recognition of the importance of community involvement and sectoral cooperation in health and !ocial services, formalized in alma-ata declaration in , was reinforced at riga meeting held at the mid·point between alma-ata and the year . then at the th anniversary of alma-ata declaration, ir was declared that 'primary health care is everybody's business'. health does not exist in isolation. health cannot be defined only as an outcome of 'medical care' but also as one of 'social action'; the responsibility of disease prevention and health promotion rests not only on governments, but also with don·govemmentorgan izations, the community, and individuals. the major accomplishment to date may be that rhere is growing realization in the health sector that community involvement is more than a political right-it is absolute necessary. lessons have learned during the implementation of disease-specific l'cltical programmes, such as cdd, ari, and epi; first, integrated and holistic approaches to childcare art needed, and second, the need for community involvement has become evident. imc! is a broad inte-gra ed strategy with an overall objective contributing to reducing child morbidity and mortality in developing countries. and one of the imci components, 'community !mci', which is now broadening ~s an entry point for child-focused community development initiatives. community jmcl/c~ ld health is ~n mtcgrated approach to the promotion of key family and community practices that have impact on: child growth and development, disease prevention, home care for sick, malnourished child~en, a.nd care-seekmg behavior and compliance with advice and treatment. the presentation addres~es, m brief, the ~evel opinent of community !mci, operational aspect of community/im cl, key strategies and tools ava la~le for implementation of c/imci. the paper draws some successful programme examples on working logether for imc! with the community in various countries which had substantial benefns on programme outcomes. p - t (c) healthy child screening: an innovative service initiative ann-marie marcolin and joyce allen . introduction: with mounting attention for creative and integrated models of c~re .that are populallon and community focused, the healthy child screening initiative achiev.es t~ese pnncipl~s and more! . • parkdale high park rotary (sponsorship) the heal~h ~h ld scree? ?g is a ~opl~-centred model of care. agency and professional sector-specific silos are ehmmated, ~rov dmg f~~ hes wit~ one-sto~ access to primary prevention services in a local school gym! children at nsk are rece vmg early mtervent n and appropriate referrals to the right care provider, at the right time a~d in t~e right place. further, with a complimentary focus on prevention, the program serves to keep at nsk children healthy. healthy child screening results: the service model is developed around four distinct phases: ) planned outreach; ) coordinated intake and registration; ) interdisciplinary screening; and ) targeted referral. since the fall and through six collaborative healthy child screenings children ranging in age from to have benefited from this unique service model of care. conclusion: the presentation will provide practical information on the development and implementation of the model. there will also be a focus on lessons learned in building community service provider-hospital relationships. according to statistics canada ( ) % of the toronto population was born outside of canada and % were new immigrants. immigrants often arrive in canada in superior health compared to the canadian born population, but they lose this health advantage over time. changes in immigrant health status over time may be attributed to a variety of factors including barriers to accessing and receiving care as well as limitations in the mainstream health service organizations and their approaches to health care delivery (hyman, ) . for example, immigrant women are less likely to receive pap tests, which places them at a greater risk for developing cervical cancer. similarly, immigrant women receive less mammography screening than their canadian counterparts. the immigrant women's health centre mobile health unit (mhu) was created as an alternative care delivery model to address the need for increased accessibility as well as culturally and linguistically appropriate reproductive health care. toronto western hospital and the immigrant women's health centre have formed a collaborative partnership which incorporates a primary care nurse practitioner and lay ethnocultural counselors providing care on the mhu. currently, a qualitative ethnonursing study is underway to understand the unique experiences of women using the mhu for their reproductive health care as well as the perspectives of the mhu health care providers. based on a literature review and preliminary findings from provider and participant interviews, the proposed presentation will address the themes of health status for immigrant and refugee women, accessibility issues as well strategies to improve their reproductive health care. we will discuss benefits as well as limitations to health care provision using this alternative service delivery model. michael carden, brian edlin, andrew talal, elizabeth getter, and marla shu lntrod.ction: to date most active drug users have not had access to treatment for hepatitis c virus (hcv) infection and substantial barriers continue to exist that interfere with treatment availability for this population. methods: active illicit drug users interested in pursuing hcv care and treatment were recruited in partnership w~th co~munity-based organizations (cbo's) in new york city. baseline data were collected on quahty of hfe, substance use patterns, depression, health care utilization, hcv health beliefs and other relev.ant variables. medical evaluations were conducted, including liver biopsy when indicated, an~ treatment ts ~ffered when no contraindications are present. participants also receive psychiatric evaluahons to determme the appropriateness of interferon treatment. renlts: fifteen individuals have been recruited to date and received an initial medical evaluation. the mean age was years and _the average age of initial heroin or cocaine use was . . eight ( %) ha~ been homeless at least once m the last months and s ( %) were homeless for most or all of this penod. fourteen ( %) had a history of injection drug use with the mean age at first injection being s frsewons v ,an. elrven persc.!ns ( %) reported inje~~ng .heroin or cocaine within the last days while the .wing four ( l'o) reported regular non-m ect on use of cocaine and street-obtained benzodiazepines. sijiy seven percent of the sample (n= ) reported ever being referred to hcv treatment while ( t % ) ftponeddiattreann~nt had been offered by~ ~e.dical provider. none had ever received a liver biopsy or araanent. most believed that hcv was a s gmf cant threat to their health ( %) and that there was a pm)dchance they would eventually die if their hepatitis c was not treated ( %). though individuals % believed that there was no cure for hcv, ( %) reported that they would initiate treatment if i was recommended by their doctor. thirteen ( %) had a current psychiatric diagnosis including «pmsion, anxiety disorder, schizophrenia, schizoaffective disorder, and borderline and antisocial persooaliry disorders. among eight individuals who had the beck depression inventory administered, the mean score was . . attendance rates were % ( / ) at scheduled medical and psychiatric ppointments and % ( / ) at liver biopsy. <andtuions: active drug users, despite experiencing multiple psycho-social problems, can be mgaged in hcv care using a multidisciplinary approach, but require intensive follow-up support. hcv aunnent of active drug users should not be dismissed. n- (c) antiretroviral therapy in mv infected infants: when to initiate therapy an african experience kingsley okonkwo, ademola adeyemo, israel sokeye, and nwaife umeike /""°""ction: as technology for early diagnosis of human immunodeficiency virus [hiv] improves, m to commence highly active antiretroviral therapy [haarn is yet to be fully evaluated. this prospective study describes our initial experience with early haart in hiv infected nigerian infants and rqions the outcome. we also analyzed the socioeconomic implications of early haart therapy in infants in the african setting. method: hiv infected infants were started on haart before months and followed up at mkly intervals.we monitored baseline and monthly cd . conclusion: initial results suggest early haart before months resulted. in improv~d out~ome in african children. treatment appears to be as effective as in developed counmes. in. a~nca as. m most developing countries with limited resources it is possible and effective to use haart m ~~ants if p~oper llloniroring facilities are available. however the occurrence of long-term drug related tox c ty and mk of emergence of resistant viral strains create need for further evaluation of haart in infants. background: most risk factors for cardiovascular disease (cvd) can be mitigated through ~th clinical interventions and lifestyle change. we used data from a telephone survey of new york city (nyc) adults to characterize health care access and healthy behavior among those with three or more cvd risk factors. methods: the study population included respondents to the nyc community health survey (n= , ) self-reporting~ of the following: smoking, diabetes, high cholesterol level, high blood pres· sure, body mass index > , and age > (males) or > (females) (n= , ). results: based on self-report, an estimated . , ( %) of nyc adults have~ or more cvd risk factors. this population is % male, % white, % black, and % with s years of education. most report good access to health care, indicated by having health insurance ( %), regular doctor ( %), their blood pressure checked within last months ( %), and their choles· terol checked within the past year ( % ). only % reported getting at least minutes of exercise ~ times per week and only % eating ~ servings of fruits and vegetables the previous day. among current smokers, % attempted to quit in past months, but only % used medication or counseling. implications: these data suggest that most nyc adults known to be at high risk for cvd have access to regular health care, but most do not engage in healthy lifestyle or, if they smoke, attempt effective quit strategies. more clinic-based and population-level interventions are needed to support lifestyle change among those at high risk of cvd. introduction: recently, much interest has been directed at "obesogenic" (obesity-promoting) (swinburn, egger & raza, ) built environments, and at geographic information systems (gis) as a tool for their exploration. a major geographical concept is accessibility, or the ease of moving from an origin to a destination point, which has been recently explored in several health promotion-related stud· ies. there are several methods of calculating accessibility to an urban feature, each with its own strengths, drawbacks and level of precision that can be applied to various health promotion research issues. the purpose of this paper is to describe, compare and contrast four common methods of calculating accessibility to urban amenities in terms of their utility to obesity-related health promotion research. practical and conceptual issues surrounding these methods are introduced and discussed with the intent of providing health promotion researchers with information useful for selecting the most appropria e accessibility method for their research goal~ ~ethod: this paper describes methodological insights from two studies, both of which assessed the neighbourhood-level accessibility of fast-food establishments in edmonton, canada -one which used a relatively simple coverage method and one which used a more complex minimum cos method. res.its: both methods of calculating accessibility revealed similar patterns of high and low access to fast-food outlets. however, a major drawback of both methods is that they assume the characteristics of the a~e~ities and of the populations using them are all the same, and are static. the gravity potential method is introduced as an alternative, since it is ·capable of factoring in measures of quality and choice. a n~mber of conceptual and pr~ctical iss~es, illustrated by the example of situational influences on food choice, make the use of the gravity potential model unwieldy for health promotion research into sociallydetermined conditions such as obesity. co.nclusions: i~ ~ommended that geographical approaches be used in partnership with, or as a foun~ation for, ~admonal exploratory methodologies such as group interviews or other forms of commumty consultation that are more inclusive and representative of the populations of interest. qilhl in los angeles county ,,..ia shaheen, richard casey, fernando cardenas, holman arthurs, and richard baker ~the retinomax autorefractor has been used for vision screening of preschool age childien. ir bas been suggested to be used and test school age children but not been validated in this age poup. ob;taiw: to compare the results of retinomax autorefractor with findings from a comprehensive i!' examination using wet retinoscopy for refractive error. mllhods: children - years old recruited from elementary schools at los angeles county were iaml with snellen's chart and the retinomax autorefractor and bad comprehensive eye examination with dilation. the proportion of children with abnormal eye examination as well as diesensitiviry and specificity of the screening tools using retinomax autorefractor alone and in combinalion wirh snellen's chart. results of the children enrolled in the study (average age= . ± . years; age range, - years), ?% had abnormal eye examination using retinoscopy with dilation. for the lerinomax, the sensitivity was % ( % confidence interval [ci] %- %), and the specificity was % ( % ci, %- o/o). simultaneous testing using snellen's chart and retinomax resulted in gain in sitiviry ( %, % cl= , ), and loss in specificity ( %, % cl= %- %). the study showed that screening school age children with retinomax autorefractor could identify most cases with abnormal vision but would be associated with many false-positive results. simuhaneous resting using snellen's chart and retinomax maximize the case finding but with very low specificiry. mdhotjs: a language-stratified, random sample of members of the college of family physicians of canada received a confidential survey. the questionnaire collected data on socio-demographic characteristics, medical training, practice type, setting and hcv-related care practices. the self-adminisratd questionnaire was also made available to participants for completion on the internet. batdti: response proportion was %. median age was years ( % female) and the proporlionoffrench questionnaires was %. approximately % had completed family medicine residency lllining in canada; median year of training completion was . sixty-seven percent, % and % work in private offices/clinics, community hospitals and emergency departments, respectively. regarding ~practices, % had ever requested a hcv test and % of physicians had screened for hcv iafrction in rhe past months· median number of tests was . while % reported having no hcv-uaed patients in their practic~, % had - hcv-infected patients. regarding the level of hcv care provided, . % provide ongoing advanced hcv care including treatment and dose monitoring for ctmduions: in this sample of canadian family physicians, most had pro~ided hcv screening. to •least one patient in the past year. less than half had - hcv-infected patients and % provide ~:relared care the role of socio-demographic factors, medical training as wel_i as hcv ca~e percep-lldas rhe provision of appropriate hcv screening will be examined and described at the time of the canference. ' - (c) healthcare services: the context of nepal meen poudyal chhetri """ tl.ction healthcare service is related with the human rights and fundamental righ~ of the ci~ ciaaiuntry. however, the growing demand foi health care services, quality heal~care service, accessib b~ id die mass population and paucity of funds are the different but interrelated issues to .be ~ddressed. m nepat. n view of this context, public health sector in nepal is among other sectors, which is struggling -.i for scarce resources. . . . nepal, the problems in the field of healthcare servic~s do not bnut ~o the. paucity of faads and resources only, but there are other problems like: rural -urban imbalance, regional unbalance, poster sessio~ f the ll ·m ·ted resources poor healthcare services, inequity and inaccessibility of the poor management o , . poor people of the rural, remote and hilly areas for the healthcare services and so on.. . . . · . i f ct the best resource allocation is the one that max m zes t e sum o m ivi ua s u · ea t services. n a , · h d' ·b · · · h . ·t effi.ciency and efficient management are correlated. it might be t e re istn utmn of mes. ence, equi y, . . . . . income or redistribution of services. moreover, maximizanon of available resources, qua tty healthcare services and efficient management of them are the very important and necessary tools and techmques to meet the growing demand and quality healthcare services in nepal. p - (a) an jn-depth analysis of medical detox clients to assist in evidence based decision making xin li, huiying sun, ajay puri, david marsh, and aslam anis introduction: problematic substance use represents an ever-increasing public health challenge. in the vancouver coastal health (vch) region, there are more than , individuals having some probability of drug or alcohol dependence. to accommodate this potential demand for addiction related services, vch provides various services and treatment, including four levels of withdrawal management services (wms). clients seeking wms are screened and referred to appropriate services through a central telephone intake service (access i). the present study seeks to rigorously evaluate one of the services, vancouver detox, a medically monitored -bed residential detox facility, and its clients. doing so will allow decision makers to utilize evidence based decision-making in order to improve the accessibility and efficiency of wms, and therefore, the health of these clients. methods: we extract one-year data (october , -september , from an efficient and comprehensive database. the occupancy rate of the detox centre along with the clients' wait time for service and length of stay (los) are calculated. in addition, the effect of seasonality on these variables and the impact of the once per month welfare check issuance on the occupancy rate are also evaluated. results: among the clients (median age , % male) who were referred by access! to vancouver detox over the one-year period, were admitted. the majority ( %) of those who are not admitted are either lost to follow up (i.e., clients not having a fixed address or telephone) or declined service at time of callback. the median wait time was day [q -ql: - ], the median los was days iq -qt: - ], and the average bed occupancy rate was %. however, during the threeday welfare check issue period the occupancy rate was lower compared to the other days of the year % vs. %, p conclusion: our analysis indicates that there was a relatively short wait time at vancouver detox, however % of the potential clients were not served. in addition, the occupancy rate declined during the welfare check issuance period and during the summer. this suggests that accessibility and efficiency at vancouver detox could be improved by specifically addressing these factors. background: intimate partner violence (ipv) is associated with acute and chronic physical and men· tal health outcomes for women resulting in greater use of health services. yet, a vast literature attests to cultural variations in perceptions of health and help-seeking behaviour. fewer studies have examined differences in perceptions of ipv among women from ethnocultural communities. the recognition, definition, and understanding of ipv, as well as the language used to describe these experiences, may be different in these communities. as such, a woman's response, including whether or not to disclose or seek help, may vary according to her understanding of the problem. methods: this pilot study explores the influence of cultural factors on perceptions of and responses to ipv among canadian born and immigrant young women. in-depth focus group interviews were con· ducted with women, aged to years, living in toronto. open-ended and semi-structured interview questions were designed to elicit information regarding how young women socially construct jpv and where they would go to receive help. interviews were transcribed, then read and independently coded by the research team. codes were compared and disagreements resolved. qualitative software qsr n was used to assist with data management. . ruu~ts_: res~nses_abo~t what constitutes ipv were similar across the study groups. when considering specific ab.us ve ~ tuanons and types of relationships, participants held fairly relativistic views about ipv, especially with regard to help-seeking behaviour. cultural differences in beliefs about normaive m;ile/femal~ relations. familial.roles, and customs governing acceptable behaviours influenced partictpants perceptions about what n ght be helpful to abused women. interview data highlight the social l ter srnfons v suucrural _impact these factors ha:e on you?g women and provide details regarding the dynamics of cibnocultur~ m~uences on help-~eekmg behav ur: t~e ro~e of such factors such as gender inequality within rtlaoo?sh ps and t_he ~erce ved degree of ~oc al solat on and support nerworks are highlighted. collc~ the~ findmgs unde~score the _ mporta_nc_e of understanding cultural variations in percrprions of ipv ~ relanon to ~elp-seekmg beha~ ':'ur. th s_mformation is critical for health professionals iodiey may connnue developmg culturally sensmve practices, including screening guidelines and protorol s. ln addition, _this study demonstr~tes that focus group interviews are valuable for engaging young romen in discussions about ipv, helpmg them to 'name' their experiences, and consider sources of help when warranted. p -s (a) health problems and health care use of young drug users in amsterdam .wieke krol, evelien van geffen, angela buchholz, esther welp, erik van ameijden, and maria prins / trod ction: recent advances in health care and drug treatment have improved the health of populations with special social and health care needs, such as drug users. however, still a substantial number dots not have access to the type of services required to improve their health status. in the netherlands, tspccially young adult drug users (yad) whose primary drug is cocaine might have limited access to drugrreatment services. in this study we examined the history and current use of (drug associated) treatmmt services, the determinants for loss of contact, and the current health care needs in the young drug mm amsterdam study (yodam). methods: yodam started in and is embedded in the amsterdam cohort study among drug mm. data were derived from y ad aged < years who had used cocaine, heroin, ampheramines and i or methadone at least days a week during the months prior to enrolment. res lts:of yao, median age was years (range: - years), % was male and % had dutch nationality at enrolment. nearly all participants ( %) reported a history of contact with drug llt.lnnent services (methadone maintenance, rehabilitation clinics and judicial treatment), mental health car? (ambulant mental care and psychiatric hospital) or general treatment services (day-care, night-care, hdp for living arrangements, work and finance). however, only % reported contact in the past six l!xlllths. this figure was similar in the first and second follow-up visit. among y ad who reported no current contact with the health care system, % would like to have contact with general treatment serl' icts. among participants who have never had contact with drug treatment services, % used primarily cocaine compared with % and % among those who reported past or current contact, respectively. saied on the addiction severity index, % reported at least one mental health problem in the past days, but only % had current contact with mental health services. concl sion: results from this study among young adult drug users show that despite a high contact rm with health care providers, the health care system seems to lose contact with yao. since % indicatt the need of general treatment services, especially for arranging house and living conditions, health m services that effectively integrate general health care with drug treatment services and mental health care might be more successful to keep contact with young cocaine users. mtthods: respondents included adults aged and over who met dsm-iv diagn?snc criteria for an anxiety or depressive disorder in the past months. we performed two sets of logisnc regressmns. thtdichotomous dependent variables for each of the regressions indicated whether rhe respondenr_vis-ud a psychiatrist, psychologist, family physician or social worker in the _past_ months. no relationship for income. there was no significant interaction between educatmn an mco~:· r: ::or respondents with at least a high school education to seek help ~rom any of the four servic p were almost twice that for respondents who had not completed high school. th . d ec of analyses found che associacion becween educacion and use of md-provided care e secon s · · be d · · ·f· ly ·n che low income group for non-md care, the assoc anon cween e ucatlon and was s gm icant on -· . . . . use of social workers was significant in both income groups, but significant only for use of psychologists in che high-income group. . . . conclusion: we found differences in healch service use by education level. ind v duals who have nor compleced high school appeared co use less mental he~lt~ servi~es provided ~y psyc~iatrists, psycholo· gists, family physicians and social workers. we found limited e.v dence _suggesting the influence of educa· tion on service use varies according to income and type of service provider. results suggesc there may be a need to develop and evaluate progr~ms.designe~ to deliver targeted services to consumers who have noc completed high school. further quahtanve studies about the expen· ence of individuals with low education are needed to clarify whether education's relationship with ser· vice use is provider or consumer driven, and to disentangle the interrelated influences of income and education. system for homeless, hiv-infected patients in nyc? nancy sahler, chinazo cunningham, and kathryn anastos introduction: racial/ethnic disparities in access to health care have been consistently documented. one potential reason for disparities is that the cultural distance between minority patients and their providers discourage chese patients from seeking and continuing care. many institucions have incorporated cultural compecency craining and culturally sensicive models of health care delivery, hoping co encourage better relacionships becween patients and providers, more posicive views about the health care system, and, ulcimacely, improved health outcomes for minority patients. the current scudy tests whether cultural distance between physicians and patients, measured by racial discordance, predicts poorer patient attitudes about their providers and the health care system in a severely disadvantaged hiv-infected population in new york city that typically reports inconsistent patterns of health care. methods: we collected data from unscably housed black and latino/a people with hiv who reported having a regular health care provider. we asked them to report on their attitudes about their provider and the health care system using validated instruments. subjects were categorized as being racially "concordant" or "discordant" with their providers, and attitudes of these two groups were compared. results: the sample consisted of ( %) black and ( %) latino/a people, who reported having ( %) black physicians, ( %) latino/a physicians, ( %) white physicians, and ( %) physicians of another/unknown race/ethnicity. overall, ( %) subjects had physicians of a different race/ethnicity than their own. racial discordance did not predict negative attitudes about rela· tionship with providers: the mean rating of a i-item trust in provider scale (lo=high and o=low) was . for both concordant and discordant groups, and the mean score in -icem relationship with provider scale ( =high and !=low) was . for both groups. however discordance was significantly associated with distrust in che health care syscem: che mean score on a -icem scale ( =high discrust and l=low distrust) was . for discordant group and . for che concordant group (t= . , p= . ). we further explored these patterns separacely in black and lacino/a subgroups, and using different strategies ro conceptualize racial/ethic discordance. conclusions: in this sample of unscably housed black and latino/a people who receive hiv care in new york city, having a physician from the same racial/ethnic background may be less important for developing a positive doctor-patient relationship than for helping the patients to dispel fear and distrust about the health care system as a whole. we discuss the policy implications of these findings. ilene hyman and samuel noh . .abstract objectiw: this study examines patterns of mental healthcare utilization among ethiopian mm grants living in toronto. methods: a probability sample of ethiopian adults ( years and older) completed structured face-to-face interviews. variables ... define, especially who are non-health care providers. plan of analysis. results: approximately % of respondents received memal health services from mainstream healthcare providers and % consulted non-healthcare professionals. of those who sought mental health services from mainstream healthcare providers, . % saw family physicians, . % visited a psychiatrist. and . % consulted other healthcare providers. compared with males, a significantly higher proportion gsfer sessions v ri ftlnales consulted non-healthcare_ professionals for emotional or mental health problems (p< . ). tlbile ethiopian's overall use of mamstream healthcare services for emotional problems ( %) did not prlydiffer from the rate ( %) of the general population of ontario, only a small proportion ( . %) rjerhiopians with mental health needs used services from mainstream healthcare providers. of these, !oj% received family physicians' services, . % visited a psychiatrist, and . % consulted other healthll/c providers. our data also suggested that ethiopian immigrants were more likely to consult tradioooal healers than health professionals for emotional or mental health problems ( . % vs. . % ). our bivariate analyses found the number of somatic symptoms and stressful life events to be associated with an increased use of medical services and the presence of a mental disorder to be associated with a dfcreased use of medical services for emotional problems. however, using multivariate methods, only die number of somatic symptoms remained significantly associated with use of medical services for emooonal problems. diu#ssion: study findings suggest that there is a need for ethnic-specific and culturally-appropriate mrcrvention programs to help ethiopian immigrants and refugees with mental health needs. since there ~a strong association between somatic symptoms and the use family physicians' services, there appears robe a critical role for community-based family physicians to detect potential mental health problems among their ethiopian patients, and to provide appropriate treatment and/or referral. the authors acknowledge the centre of excellence for research in immigration and settlement (ceris) in toronto and canadian heritage who provided funding for the study. we also acknowledge linn clark whose editorial work has improved significantly the quality of this manuscript. we want to thank all the participants of the study, and the ethiopian community leaders without whose honest contributions the present study would have not been possible. this paper addresses the impact of the rationalization of health-care services on the clinical decision-making of emergency physicians in two urban hospital emergency departments in atlantic canada. using the combined strategies of observational analysis and in-depth interviewing, this study provides a qualitative understanding of how physicians and, by extension, patients are impacred by the increasing ancmpts to make health-care both more efficient and cost-effective. such attempts have resulted in significantly compromised access to primary care within the community. as a consequence, patients are, out of necessity, inappropriately relying upon emergency departments for primary care services as well as access to specialty services. within the hospital, rationalization has resulted in bed closures and severely rmricted access to in-patient services. emergency physicians and their patients are in a tenuous position having many needs but few resources. furthermore, in response to demands for greater accountability, physicians have also adopted rationality in the form of evidence-based medicine. ultimately, ho~ever, rationality whether imposed upon, or adopted by, the profession significantly undermines physu.: ans' ability to make decisions in the best interests of their patients. johnjasek, gretchen van wye, and bonnie kerker introduction: hispanics comprise an increasing proportion of th.e new york city (nyc) populanon !currently about %). like males in the general population, h spamc males (hm) have a lower prrval,nce of healthcare utilization than females. however, they face additional access barriers such as bnguage differences and high rates of uninsurance. they also bear a heavy burden of health problems lllehasobesity and hiv/aids. this paper examines patterns of healthcare access and ut hzat on by hm compared to other nyc adults and identifies key areas for intervention. . . . and older are significantly lower than the nhm popu anon . v. . , p<. ), though hi\' screening and immunizations are comparable between the two groups. conclusion: findings suggest that hm have less access t? healthcare than hf or nhm. hown r, hm ble to obtain certain discrete medical services as easily as other groups, perhapsdueto!rtor are a hm. i i . subsidized programs. for other services, utilization among s ower. mprovmg acc~tocareinthis group will help ensure routine, quality care, which can lead to a greater use of prevennve services iii! thus bener health outcomes. introduction: cancer registry is considered as one of the most important issues in cancer epidemiology and prevention. bias or under-reporting of cancer cases can affect the accuracy of the results of epidemiological studies and control programs. the aim of this study was to assess the reliability of the regional cancer report in a relatively small province (yasuj) with almost all facilities needed for c llcll diagnosis and treatment. methods: finding the total number of cancer cases we reviewed records of all patients diagnoicd with cancer (icd - ) and registered in any hospital or pathology centre from until i n yasuj and all ( ) surrounding provinces. results: of patients who were originally residents of yasui province, . % wereaccoulll!d for yasuj province. the proportion varies according to the type of cancer, for exarnplecancetsofdiglstive system, skin and breast were more frequently reported by yasuj's health facilities whereas cancmoi blood, brain and bone were mostly reported by neighbouring provinces. the remaining cases ( . % were diagnosed, treated and recorded by neighbouring provinces as their incident cases. this is partly because of the fact that patients seek medical services from other provinces as they believed that the facil. ities are offered by more experienced and higher quality stuffs and their relative's or temporary acooiii' modation addresses were reported as their place of residence. conclusion: measuring the spatial incidence of cancer according to the location of report ortht current address affected the spatial statistics of cancer. to correct this problem recording the permanm! address of diagnosed cases is important. p - (c). providing primary healthcare to a disadvantaged population at a university-run commumty healthcare facility tracey rickards the. c:ommuni~y .h~alth ~linic (chc) is a university sponsored nurse-managed primary bealthwt (p~c:l clime. the clm c is an innovative model of healthcare delivery in canada that has integrated tht principles of phc ser · · h' . vices wit ma community development framework. it serves to provide access to phc services for members of th · · illi · dru is ii be . . e community, particularly the poor and those who use or gs, we mg a service-learning facil'ty f d · · · · · · d rionll h . . .,m.:. · t · . meet c ient nee s. chmc nursing and social work staff and srudents r·--· ipa em various phc activities and h .l.hont" less i . f . outreac services in the local shelters and on the streels to'"" popu auon o fredericton as well th chc · model iii fosterin an on oi : . • e promotes and supports a harm reduction . · local d!or an~ h ng ~art:ersh p with aids new brunswick and their needle exchange program, w tha ing condoms and :xu:t h:~~~e e~aint~nance therapy clients, and with the clie~ts themselves ~_r; benefits of receiving health f ucation, a place to shower, and a small clothing and food oai~· care rom a nurse p · · d d · --""~'i"· are evidenced in th r research that involved needsaans mvo ves clients, staff, and students. to date the chc has unacn- · sessment/enviro i . d ; •• '"""" ll eva uanon. the clinic has also e . d nmenta scan, cost-benefit analysis, an on-go...,, "".'i'~ facility and compassionate lea x~mme the model of care delivery' focusing on nursing roles wi~ cj rmng among students. finally, the clinic strives to share the resu•p v . -arch with the community in which it provides service by distributing a bi-monthly newsletter, and plllicipating in in-services and educational sessions in a variety of situations. the plan for the future is coolinued research and the use of evidence-based practice in order to guide the staff in choosing how much n~ primary healthcare services to marginalized populations will be provided. n- (c) tuming up the volume: marginalized women's health concerns tckla hendrickson and betty jane richmond bdrotbu:tion: the marginalization of urban women due to socio-economic status and other determinants negatively affects their health and that of their families. this undermines the overall vitaliry of urban communities. for example, regarding access to primary health care, women of lower economic surus and education levels are less likely to be screened for breast and cervical cancer. what is not as widely reported is how marginalized urban women in ontario understand and articulate their lack of access to health care, how they attribute this, and the solutions that they offer. this paper reports on the rnults of the ontario women's health network (owhn) focus group project highlighting urban women's concerns and suggestions regarding access to health care. it also raises larger issues about urban health, dual-purpose focus group design, community-based research and health planning processes. mdhods: focus group methodology was used to facilitate a total of discussions with urban and rural women across ontario from to . the women were invited to participate by local women's and health agencies and represented a range of ages, incomes, and access issues. discussions focussed on women's current health concerns, access to health care, and information needs. results were analyzed using grounded theory. the focus groups departed from traditional focus group research goals and had two purposes: ) data collection and dissemination (representation of women's voices), and ) fostering closer social ties between women, local agencies, and owhn. the paper provides a discussion and rationale for a dual approach. rax/ts: the results confirm current research on women's health access in women's own voices: urban women report difficulty finding responsive doctors, accessing helpful information such as visual aids in doctors' offices, and prohibitive prescription costs, in contrast with rural women's key concern of finding a family doctor. the research suggests that women's health focus groups can address access issues by helping women to network and initiate collective solutions. the study shows that marginalized urban women are articulate about their health conctrns and those of their families, often understanding them in larger socio-economic frameworks; howtver, women need greater access to primary care and women-friendly information in more languages and in places that they go for other purposes. it is crucial that urban health planning processes consult directly with women as key health care managers, and turn up the volume on marginalized women's voices. women: an evaluation of awareness, attitudes and beliefs introduction: nigeria has one of the highest rates of human immunodeficiency virus ihivi seroprrvalence in the world. as in most developing countries vertical transmission from mother to child account for most hiv infection in nigerian children. the purpose of this study was ro. determine the awareness, attitudes and beliefs of pregnant nigerian women towards voluntary counseling and testing ivct! for hiv. mnbod: a pre-tested questionnaire was used to survey a cross section '.>f. pregnant women ~t (lrlleral antenatal clinics in awka, nigeria. data was reviewed based on willingness to ~c~ept or re ect vct and the reasons for disapproval. knowledge of hiv infection, routes of hiv transm ssmn and ant rnroviral therapy iart) was evaluated. hsults: % of the women had good knowledge of hiv, i % had fair knowledge while . % had poor knowledge of hiv infection. % of the women were not aware of the association of hreast milk feeding and transmission of hiv to their babies. majority of the women % approved v~t while % disapproved vct, % of those who approved said it was because vct could ~educe risk of rransmission of hiv to their babies. all respondents, % who accepted vc.i ~ere willing to be tnted if results are kept confidential only % accepted to be tested if vc.t results w. be s~ared w .th pinner and relatives % attributed their refusal to the effect it may have on their marriage whale '-gave the social 'and cultural stigmatization associated with hiv infection for their r~fusal.s % wall accept vct if they will be tested at the same time with their partners. ~ of ~omen wall pref~r to breast feed even if they tested positive to hiv. women with a higher education diploma were times v more likely to accept vct. knowledge of art for hiv infected pregnant women as a means of pre. vention of maternal to child transmission [pmtct) was generally poor, % of respondents wm aware of art in pregnancy. conclusion: the acceptance of vct by pregnant women seems to depend on their understanding that vct has proven benefits for their unborn child. socio-cultur al factors such as stigmatizationof hiv positive individuals appears to be the maj_or impedi~ent towards widespread acceptanee of ycr in nigeria. involvemen t of male partners may mpro~e attitudes t~wa~ds vct:the developmentofm novative health education strategies is essential to provide women with mformanon as regards the benefits of vct and other means of pmtct. p - (c) ethnic health care advisors in information centers on health care and welfare in four districts of amsterdam arlette hesselink, karien stronks, and arnoud verhoeff introduction : in amsterdam, migrants report a "worse actual health and a lower use of health care services than the native dutch population. this difference might be partly caused by problems migrants have with the dutch language and health care and welfare system. to support migrants finding their way through this system, in four districts in amsterdam information centers on health care and welfare were developed in which ethnic health care advisors were employed. their main task is to provide infor· mation to individuals or groups in order to bridge the gap between migrants and health care providers. methods: the implementat ion of the centers is evaluated using a process evaluation in order to give inside in the factors hampering and promoting the implementat ion. information is gathered using reports, attending meetings of local steering groups, and by semi-structu red interviews with persons (in)directly involved in the implementat ion of the centers. in addition, all individual and groupcontaets of the health care advisors are registered extensively. results: since four information centers, employing ethnic health care advisors, are implemented. the ethnicity of the health care advisors corresponds to the main migrant groups in the different districts (e.g. moroccan, turkeys, surinamese and african). depending on the local steering groups, the focus of the activities of the health care advisors in the centers varies. in total, around individual and group educational sessions have been registered since the start. most participants were positive about the individual and group sessions. the number of clients and type of questions asked depend highly on the location of the centers (e.g. as part of a welfare centre or as part of a housing corporation). in all districts implementa tion was hampered by lack of ongoing commitment of parties involved (e.g. health care providers, migrant organization s) and lack of integration with existing health care and welfare facilities. discussion: the migrant health advisors seem to have an important role in providing information on health and welfare to migrant clients, and therefore contribute in bridging the gap between migrants and professionals in health care and welfare. however, the lack of integration of the centers with the existing health care and welfare facilities in the different districts hampers further implementation . therefore, in most districts the information centres will be closed down as independent facilicities in the near future, and efforts are made to better connect the position of migrant health advisor in existing facilities. the who report ranks the philippines as ninth among countries with a high tb prevalence. about a fourth of the country's population is infected, with majority of cases coming from the lower socioeconomic segments of the community. metro manila is not only the economic and political capital of the philippines but also the site of major universities and educational institutions. initial interviews with the school's clinicians have established the need to come up with treatment guidelines and protocols for students and personnel when tb is diagnosed. these cases are often identified during annual physical examinations as part of the school's requirements. in many instances, students and personnel diagnosed with tb are referred to private physicians where they are often lost to follow-up and may have failure of treatment due to un monitored self-administered therapy. this practice ignores the school clinic's great potential as a tb treatment partner. through its single practice network (spn) initiative, the philippine tuberculosis initiatives for the private sector (philippine tips), has established a model wherein school clinics serve as satellite treatment partners of larger clinics in the delivery of the directly observed treatment, short course (dots) protocol. this "treatment at the source" allows school-based patients to get their free government-suppl ied tb medicines from the clinic each day. it also cancels out the difficulty in accessing medicines through the old model where the patient has to go to the larger clinic outside his/her school to get treatment. the model also enables the clinic to monitor the treatment progress of the student and assumes more responsibility over their health. this experience illustrates how social justice in health could be achieved from means other than fund generation. the harnessing of existing health service providers in urban communities through standardized models of treatment delivery increases the probability of treatment success, not only for tb but for other conditions as well. p - (c) voices for vulnerable populations: communalities across cbpr using qualitative methods martha ann carey, aja lesh, jo-ellen asbury, and mickey smith introduction: providing an opportunity to include, in all stages of health studies, the perspectives and experiences of vulnerable and marginalized populations is increasingly being recognized as a necessary component in uncovering new solutions to issues in health care. qualitative methods, especially focus groups, have been used to understand the perspectives and needs of community members and clinical staff in the development of program theory, process evaluation and refinement of interventions, and for understanding and interpreting results. however, little guidance is available for the optimal use of such information. methods: this presentation will draw on diverse experiences with children and their families in an asthma program in california, a preschool latino population in southern california, a small city afterschool prevention program for children in ohio, hiv/aids military personnel across all branches of the service in the united states, and methadone clinic clients in the south bronx in new york city. focus groups were used to elicit information from community members who would not usually have input into problem definitions and solutions. using a fairly common approach, thematic analysis as adapted from grounded theory, was used to identify concerns in each study. next we looked across these studies, in a meta-synthesis approach, to examine communalities in what was learned and in how information was used in program development and refinement. results: while the purposes and populations were diverse, and the type of concerns and the reporting of results varied, the conceptual framework that guided the planning and implementation of each study was similar, which led to a similar data analysis approach. we will briefly present the results of each study, and in more depth we will describe the communalities and how they were generated. conclusions: while some useful guidance for planning future studies of community based research was gained by looking across these diverse studies, it would be useful to pursue a broader examination of the range of populations and purposes to more fully develop guidance. background: the majority of studies examining the relationship between residential environments and cardiovascular disease have used census derived measures of neighborhood ses. there is a need to identify specific features of neighborhoods relevant to cardiovascular disease risk. we aim to ) develop methods· data on neighborhood conditions were collected from a telephone survey of s, fesi· dents in balth:.ore, md; forsyth county, nc; and new york, ny. a sample of of the i.ni~~l l'elpondents was re-interviewed - weeks after the initial interview t~ measure the tes~-~etest rebab ~ ty of ~e neighborhood scales. information was collected across seven ~e ghborho~ cond ~ons (aesth~~ ~uah~, walking environment, availability of healthy foods, safety, violence, social cohesion, and acnvmes with neighbors). neighborhoods were defined as census tracts or homogen~us census tra~ clusters. ~sycho metric properties.of the neighborhood scales were accessed by ca~cu~~.ng chronba~h s alpha~ (mtemal consistency) and intraclass correlation coefficients (test-r~test reliabilmes) .. pear~n s .corre~anons were calculated to test for associations between indicators of neighborhood ses (tncludmg d mens ons of race/ ethnic composition, family structure, housing, area crowding, residential stability, education, employment, occupation, and income/wealth) and our seven neighborhood scales. . chronbach's alphas ranged from . (walking environment) to . (violence). intraclass correlations ranged from . (waling environment) to . (safety) and wer~ high~~~ . ~ for ~urout of the seven neighborhood dimensions. our neighborhood scales (excluding achv hes with neighbors) were consistently correlated with commonly used census derived indicators of neighborhood ses. the results suggest that neighborhood attributes can be reliably measured. further development of such scales will improve our understanding of neighborhood conditions and their importance to health. childhood to young adulthood in a national u.s. sample jen jen chang lntrodfldion: prior studies indicate higher risk of substance use in children of depressed mothers, but no prior studies have followed up the offspring from childhood into adulthood to obtain more precise estimates of risk. this study aimed to examine the association between early exposure to maternal depl'elsive symptoms (mds) and offspring substance use across time in childhood, adolescence, and young adulthood. methods: data were obtained from the national longitudinal survey of youth. the study sample includes , mother-child/young adult dyads interviewed biennially between and with children aged to years old at baseline. data were gathered using a computer-assisted personal interview method. mds were measured in using the center for epidemiologic studies depression scale. offspring substance use was assessed biennially between and . logistic and passion regression models with generalized estimation equation approach was used for parameter estimates to account for possible correlations among repeated measures in a longitudinal study. rnlllta: most mothers in the study sample were whites ( %), urban residents ( %), had a mean age of years with at least a high school degree ( %). the mean child age at baseline was years old. offspring cigarette and alcohol use increased monotonically across childhood, adolescence, and young adulthood. differential risk of substance use by gender was observed. early exposure to mds was associated with increased risk of cigarette (adjusted odds ratio (aor) = . , % confidence interval ( ): . , . ) and marijuana use (aor = . , % ci: . , . ), but not with alcohol use across childhood, adolescence, and young adulthood, controlling for a child's characteristics, socioeconomic status, ~ligiosity, maternal drug use, and father's involvement. among the covariates, higher levels of father's mvolvement condluion: results from this study confirm previous suggestions that maternal depressive symptoms are associated with adverse child development. findings from the present study on early life experi-e~ce have the potential to inform valuable prevention programs for problem substance use before disturbances become severe and therefore, typically, much more difficult to ameliorate effectively. the ~act (~r-city men~ health study predicting filv/aids, club and other drug transi-b~) study a multi-level study aimed at determining the association between features of the urban enyjronment mental health, drug use, and risky sexual behaviors. the study is randomly sampling foster sessions v neighborhood residents and assessing the relations between characteristics of ethnographically defined urban neighborhoods and the health outcomes of interest. a limitation of existing systematic methods for evaluating the physical and social environments of urban neighborhoods is that they are expensive and time-consuming, therefore limiting the number of times such assessments can be conducted. this is particularly problematic for multi-year studies, where neighborhoods may change as a result of seasonality, gentrification, municipal projects, immigration and the like. therefore, we developed a simpler neighborhood assessment scale that systematically assessed the physical and social environment of urban neighborhoods. the impact neighborhood evaluation scale was developed based on existing and validated instruments, including the new york city housing and vacancy survey which is performed by the u.s. census bureau, and the nyc mayor's office of operations scorecard cleanliness program, and modified through pilot testing and cognitive testing with neighborhood residents. aspects of the physical environment assessed in the scale included physical decay, vacancy and construction, municipal investment and green space. aspects of the social environment measured include social disorder, social trust, affluence and formal and informal street economy. the scale assesses features of the neighborhood environment that are determined by personal (e.g., presence of dog feces), community (e.g., presence of a community garden), and municipal (e.g., street cleanliness) factors. the scale is administered systematically block-by-block in a neighborhood. trained research staff start at the northeast corner of an intersection and walk around the blocks in a clockwise direction. staff complete the scale for each street of the block, only evaluating the right side of the street. thus for each block, three or more assessments are completed. we are in the process of assessing psychometric properties of the instrument, including inter-rater reliability and internal consistency, and determining the minimum number of blocks or street segments that need to be assessed in order to provide an accurate estimate of the neighborhood environment. these data will be presented at the conference. obj«tive: to describe and analyze the perceptions of longterm injection drug users (idus) about their initiation into injecting. toronto. purposive sampling was used to seek out an ethnoculturally diverse sample of idus of both genders and from all areas of the city, through recruitment from harm reduction services and from referral by other study participants. interviews asked about drug use history including first use and first injecting, as well as questions about health issues, service utilization and needs. thematic analysis was used to examine initiation of drug use and of injection. results: two conditions appeared necessary for initiation of injection. one was a developed conception of drugs and their (desirable) effects, as suggested by the work of becker for marijuana. thus virtually all panicipants had used drugs by other routes prior to injecting, and had developed expectations about effects they considered pleasureable or beneficial. the second condition was a group and social context in which such use arose. no participants perceived their initiation to injecting as involving peer pressure. rather they suggested that they sought out peers with a similar social situation and interest in using drugs. observing injection by others often served as a means to initiate injection. injection served symbolic purposes for some participants, enhancing their status in their group and marking a transition to a different social world. concl ion: better understanding of social and contextual factors motivating drug users who initiate injection can assist in prevention efforts. ma!onty of them had higher educational level ( %-highschool or higher).about . yo adffiltted to have history of alcohol & another . % had history of smoking. only . % people were on hrt & . % were receiving steroid. majority of them ( . ) did not have history of osteoporosis. . % have difficulty in ambulating. only . % had family history of osteoporosis. bmd measurements as me~sured by dual xray absorptiometry (dexa) were used for the analysis. bmd results were compare~ w ~ rbc folate & serum vitamin b levels. no statistical significance found between bmd & serum v taffiln b level but high levels of folate level is associated with normal bmd in bivariate and multivariate analysis. conclusion: in the studied elderly population, there was no relationship between bmd and vitamin b ; but there was a significant association between folate levels & bmd. introduction: adolescence is a critical period for identity formation. western studies have investigated the relationship of identity to adolescent well-being. special emphasis has been placed on the influence of ethnic identity on health, especially among forced migrants in different foreign countries. methodology: this study asses by the means of an open ended question identity categorization among youth in three economically disadvantaged urban communities in beirut, the capital of lebanon. these three communities have different histories of displacement and different socio-demographic makeup. however, they share a history of displacement due to war. results and conclusion: the results indicated that nationality was the major category of identification in all three communities followed by origin and religion. however, the percentages that self-identify by particular identity categories were significantly different among youth in the three communities, perhaps reflecting different context in which they have grown up. mechanical heart valve replacement amanda hu, chi-ming chow, diem dao, lee errett, and mary keith introduction: patients with mechanical heart valves must follow lifelong warfarin therapy. war· farin, however, is a difficult drug to take because it has a narrow therapeutic window with potential seri· ous side effects. successful anticoagulation therapy is dependent upon the patient's knowledge of this drug; however, little is known regarding the determinants of such knowledge. the purpose of this study was to determine the influence of socioeconomic status on patients' knowledge of warfarin therapy. methods: a telephone survey was conducted among patients to months following mechan· ical heart valve replacement. a previously validated -item questionnaire was used to measure the patient's knowledge of warfarin, its side effects, and vitamin k food sources. demographic information, socioeconomic status data, and medical education information were also collected. results: sixty-one percent of participants had scores indicative of insufficient knowledge of warfarin therapy (score :s; %). age was negatively related to warfarin knowledge scores (r= . , p = . ). in univariate analysis, patients with family incomes greater than $ , , who had greater. than a grade education and who were employed or self employed had significantly higher warfarm knowledge scores (p= . , p= . and p= . respectively). gender, ethnicity, and warfar~n therapy prior to surgery were not related to warfarin knowledge scores. furthermore, none of t~e. m-hospital tea~hing practices significantly influenced warfarin knowledge scores. however, panic ~ants who _rece v~d post discharge co~unity counseling had significantly higher knowledge scores tn comp~r son with those who did not (p= . ). multivariate regression analysis revealed that und~r~tandmg the ~oncept of ?ternational normalized ratio (inr), knowing the acronym, age and receiving ~ommum !' counseling after discharge were the strongest predictors of warfarin kn~wledge. s~ oeconom c status was not an important predictor of knowledge scores on the multivanate analysis. poster sessions v ~the majority of patients at our institution have insufficient knowledge of warfarin therapy.post-discharge counseling, not socioeconomic status, was found to be an important predictor of warfarin knowledge. since improved knowledge has been associated with improved compliance and control, our findings support the need to develop a comprehensive post-discharge education program or, at least, to ensure that patients have access to a community counselor to compliment the in-hospital educatiop program. brenda stade, tony barozzino, lorna bartholomew, and michael sgro lnttotl#ction: due to the paucity of prospective studies conducted and the inconsistency of results, the effects of prenatal cocaine exposure on functional abilities during childhood remain unclear. unlike the diagnosis of fetal alcohol spectrum disorder, a presentation of prenatal cocaine exposure and developmental and cognitive disabilities does not meet the criteria for specialized services. implications for public policy and services are substantial. objective: to describe the characteristics of children exposed to cocaine during gestation who present to an inner city specialty clinic. mnbods: prospective cohort research design. sample and setting: children ages to years old, referred to an inner city prenatal substance exposure clinic since november, . data collection: data on consecutive children seen in the clinic were collected over an month period. instrument: a thirteen ( ) page intake and diagnostic form, and a detailed physical examination were used to collect data on prenatal substance history, school history, behavioral problems, neuro-psychological profile, growth and physical health of each of the participants. data analysis: content analysis of the data obtained was conducted. results: twenty children aged to years (mean= . years) participated in the study. all participants had a significant history of cocaine exposure and none had maternal history or laboratory (urine, meconium or hair) exposure to alcohol or other substances. none met the criteria of fetal alcohol spectrum disorder. all were greater than the tenth percentile on height, weight, and head circumference, and were physically healthy. twelve of the children had iqs at the th percentile or less. for all of the children, keeping up with age appropriate peers was an ongoing challenge because of problems in attention, motivation, motor control, sensory integration and expressive language. seventy-four percent of participants had significant behavioral and/or psychological problems including aggressiveness, hyperactivity, lying, poor peer relationships, extreme anxiety, phobias, and poor self-esteem. conclusion: pilot study results demonstrated that children prenatally exposed to cocaine have significant learning, behavioural, and social problems. further research focusing on the characteristics of children prenatally exposed to cocaine has the potential for changing policy and improving services for this population. methods: trained interviewers conducted anonymous quantitative surveys with a random sample (n= ) of female detainees upon providing informed consent. the survey focused on: sociodemographic background; health status; housing and neighborhood stability and social resource availability upon release. results: participants were % african-american, % white, % mixed race and % native american. participants' median age was , the reported median income was <s , year, and % reported receiving a high school diploma or equivalent. women reported a number of health conditions rypical of underserved populations, including asthma ( %), sexually transmitted infections ( %), high blood pressure ( %), hcv ( %), diabetes ( %) and hiv ( %). nearly half ( %) did not anticipate having a place to stay for at least days upon release. factors significantly associated housing stability upon release were: high family support score (adjusted odds ratio [aor) . ; % confidence interval ( % cl) . , . ), high neighborhood stability score (aor . ; % cl . , . ), wanting a commercial sex worker (csw) support group (aor . ; % cl . , . ); and identifying as bisexual (aor . ; % cl . , . ). women desired employment ( %), housing ( %), education ( %), drug treattnent ( %), help with custody of children ( %), childcare ( %), and domestic violence suppon ( %) services. conclusions: female detainees represent one of urban centers' most marginalized pcjpwatioos. short periods of detention represent a unique opportunity for _interven?~ns bri~ co~s and public health institutions. service providers should collaborate ~ th local ~ails to .p~de a con uwnof care for female detainees upon release that includes transportation , housing, residential drug treallllcnt, employment, education, family reunification, childcare and domestic viol~nce su~rt. ~pecial attenlion is warranted to lesbian and bisexual women and csws, who may be especially margmalized &om family and service-based support networks. introduction: "health care and ethnic minority immigrants" examines how health care policy dil· ferences between canada and the united states impact the health-related hardships, access and use of preventative care, and health outcomes of urban ethnic minority immigrants in both countries. methods: the findings of this paper build on the results of my qualitative comparative study of hotel workers in vancouver, bc and seattle, wa that revealed greater health related hardships for similarly matched employees in seattle compared to vancouver. in this paper, i examine the generalizability of these findings at the cross-national level for similar ethnic minority immigrant groups. i compare the impact of health care policy differences on specific groups that have emigrated to cities in both canada and the united states. these include immigrants from china, viemam, philippines, west indies, africa, sri lanka, pakistan, and latin america. comparative statistical analysis -utilizing rel· evant data from statistics canada and the u.s. census -reveal the extent to which health policy differ· ences help explain how current health policy in the united states disadvantages urban ethnic minority immigrants. results: many ethnic minority immigrants are a part of the working poor, a group which disproportionately lacks health insurance coverage in the united states. their position in the labour market makes them most vulnerable to exclusion from health care services. the data reveals how current u.s. health policy creates barriers for recently arrived ethnic minority immigrants to access health insurance and care. it remains difficult to ascribe health outcome differences directly to policy differences because of the challenge in disentangling the complex interacting interventing variables, including income inequality, that determine health outcomes. yer suggestive evidence suggests that health policy in the united states is harming the health of urban ethnic minority immigrants. the current health policy regime in the united states harms the health access, care, and outcomes of urban ethnic minority immigrants. comparing the fortunes of similar immigrants in cana· dian and u.s. cities reveals these patterns of disadvantage and some of their consequences. these barriers are an understudied factor in the sociological literature on "segmented assimilation" and social exclu· sion. the paper ends with policy recommendatio ns to improve access to health care among ethnic minor· ity immigrants in both countries, with the goal of reducing health related hardships, and improving health outcomes. mass index deyu pan, richard baker, and keith norris badtgrou~ over the past decades, there has been dramatic increase in prevalence of obesity in the us population. however, the relationship between obesity and the prevalence of cardiovascular dis· ease (cv~) risk factors in different race/ethnic groups over time is not well known. . ik~rgn: _we use cross-sectional , nationally representative surveys: national health and nutri· t nal examination survey (nhanes iii - (n= ) and nhanes nhanes - , including white, black, and hispa~ic races who were no~preg~ant, aged to years. res lt : the preval~nce of high cholesterol level (~ mg/dl), untreated high blood pressure ( : l / mm hg) an~ diabetes were calculated according to bmi group (lean, < ; overweight, - ; and obese, : ) for different race/ethnicity groups. over the approximately years period (from l ~ ~o [ ] [ ] [ ] [ ] , reducrion in cvd risk factors in non-hispanic white has been observed. for mmonty race/~hnicity groups, black and hispanic, there had been increases in prevalence in high blood fa pressure and diabetes. the lean group experienced larger increase in prevalence of those cvd risk ctors. . fo~~ the prevalence in cvd risk factors over time had reduced in most of the bmi ca egoes r t e w ~~e population. however, for black and hispanic, prevalence of of cvd risk factors ave generauy uncreased, especially in overweight and obese groups. methods: strategies identified to achieve these goals include: developing meaningful neighbourhood and district boundaries for comparing health information, providing free access to neighbourhood health profiles (including relevant data at the smallest level for which valid rates could be calculated); mapping relationships of inequality at a variety of nested levels; providing a range of formats (maps, tables) to meet the needs of users; providing technical support; seeking user input to advance and improve the site; and conducting workshops to foster access and use of data for decision-making , advocacy and collaboration. an evaluation strategy is being developed to assess the efforts and impact of these strategies. a preliminary assessment of the results of the first six months of activity will be completed in october . results: significant differences in health are shown at all the geographic levels indicating success in developing the boundaries. results tabulated for the first six months use of the site include: site visits; media use; reference/acknow ledgement of the site in other documents; number of contacts through presentations and workshops; feedback from users identifying strengths and limitations; and, response from health decision makers. members of the partnership are identifying additional tools and services to further support actions that reduce health inequalities. the assessment will be used to develop more specific goals, targets and monitoring mechanisms. conclusions: our experience with paper-based health profiles indicates that they have been used extensively for program planning and advocacy. the greater availability of information in a publiclyavailable web-based format is expected to translate into even greater usefulness and wider application. the web site has had considerable usage to date, extensive media coverage. site users and workshop participants have provided positive feedback and suggestions for next steps. the six month review will be available in october . in india, more than and a half people are hiv-positive and half a million have aids. india currently has the largest number of positive people in the world, oumumbering south africa and accounting for nearly one tenth of the global hiv/aids prevalence. the world bank predicts that by , there will be million hiv/aids cases in india. the central challenge facing hiv prevention efforts in south asia today is learning how to respond to the societal determinants of vulnerability to hiv. hiv/aids is an issue largely engulfed by social stigma. stigma and discrimination are often considered the foremost barriers to effective poster sess ns v prevention and care initiatives. stigma can make a person afraid of disclosing their status~ ~yone el se, and may make them feel depressed or alone. stigma can .also le~d to poor adherence to medicanon, ~ likelihood to access health and social services, and less desire to hve. hiv+ men and women may beafraidtotd! their co-workers that they have hiv for fear of their reactions or for fear of losing their jobs. in a study conducted of people living with hiv/aids in delhi, india ov~r. -~, many respo~ts shared their experiences of discrimination in their families, in their communmes, an~ m health ~e settmgs. these findings will be shared in the workshop, and will be compa~ed to m~ ex~nences workmg as an ~ co~l~ at the center for aids prevention studies in san francisco, cahforma and congreso de lannos unidos m philadelphia, pennsylvania. the workshop will include an overview of hiv/aids in urban contexts in tht united states (los angeles, san francisco, new york, philadelphia) and south asia (delhi, hyderabad, chennai). differences in methods for outreach, prevention and treatment efforts between devdoped world and developing world contexts will be discussed. a large portion of the workshop will be centered on discussion. participants will engage in an exercise to categorize their ideas of stigma. the workshop will also include a powerpoint presentation on the quantitative data gathered from the survey. the number of homeless and runaway youth is increasing in toronto, which is currently home to out of youth in the gt a who live alone, and it is the preferred locale for the street-involved and homeless youth. the city's youth population is expected to grow by nearly % by , the school dropout rate is rising, and there are is a paucity of empirical data on what works with these at-risk youth. over a two-year period, ( ) ( ) ( ) , youthlink-inner city, conducted an evaluation of the impact of a harm reduction program aimed at reducing street youth's risk of contracting/infecting others with the hep c virus, which has both short-term and long-term deleterious effects. demographic data from street-youth, along with resources/services used, employment methods, type and frequency of drug use, health status, police contacts, and their views of program impact were analyzed using a standardized sur· vey. additionally, focus groups with youth, agency staff and community key informants were conducted, as well as in-depth interviews with three youth, over a sixth-month period. this paper details study results, which both inform both practice and future study about what works, why it works, and how best to work with these vulnerable youth. sho~ed .that the wasteland in this area was contaminated by as cd zn pb cu simultaneously. the con-ta~matton of as ~d was quit significant. the contamination problems and environmental issues in this region are very. serious. the awareness on environmental and health issues was investigated by spot survey and analysis. overall awareness among the residents in the region is very poor. the measures must be taken to assu~e t~e .sustainable economy development by local and central gorvernments. keywords nandan guangx ; mmmg area; environmental awareness. concern like, epileptic fits, vision problems, earache, cough of more than weeks and urinary problems. ninety-five subjects did not take bath regularly and were exposed to sex. the health problems identified are only of a particular point of time and it may be difficult to interpret the depth of "iceberg" of the street children's world also draw the health-illness continuum. periodic interaction and follow-up is very difficult as they generally disappear from the research setting due to their frequent mobility for survival measures. as per the prediction of the iceberg theory, only some problems may have been identified, larger problems in respect to their health may not have been identified. in spite of various limitations, this attempt had proven that, it is possible to enter the street children world, explore the iceberg of illnesses, and establish data of health-illness continuum through an effective nursing agency. it is recommended to deworm these children, provide nutritional education, establish "condom corners" and "street children help line" in the city and urban slum areas and undertake action research on their health. malnutrition is a serious problem in developing countries like bangladesh. malnutrition causes a great deal of child suffering. malnutrition is one of the major causes of morbidity and mortality among the child. the aim of present study was to investigate the nutritional status and its relation to socioeconomic conditions of urban disadvantaged child of under five years age. nutritional status was determined by anthropoemetric measurement(heig ht, weight, mid-arm circumference etc.). determination of total protein and serum albumin were done for biochemical examination. haematological examination was done by blood haemoglobin profile estimation by cynmethhaemoglob in method and determination of haematocrit value or packed cell volume (pcv). stool examination for ova of hook worm, round worm, trichuris species and other species were also done. relevant information on socioeconomic characteristics was recorded by interviewing the house hold head using pretested questionnaire. our study demonstrated that nutritional status of the children are positively correlated with family income, parents level of formal education and negatively related to the family size. the effect of family income on the nutritional status, haematological and biochemical indices of urban disadvantaged child under five will be discussed in detail which will help us to determine proper way of utilization of health care facilities exists in developing countries. introduction: with the increase in morbidity and reduction in mortality and with the introduction of highly active antiretroviral therapy (haart), there is increasing focus on the determinants of healthrelated quality of life (hrqol) in hiv-infection. the focus on the present study is to examine the relationship between social support, depression, and hiv disease severity, and the extent to which these variables impact on hrqol in adult men with hiv-infection. methods: as part of a larger ongoing natural history study focusing on the neurobehavioural complications of hiv and aids, we administered questionnaires to assess depression (beck depression inventory), social support, and hrqol (mos-hiv) to adult men with hiv-infection. a structured interview was used to collect health information and data on hiv disease severity. physical and mental health summary scores (phs and mhs) were derived through principal components analysis. participants were grouped according to level of social support: "well supported" (n= ), "moderately supported" (n= ), "little or ineffective support" (n= ). analysis of variance was conducted to assess the effects of three levels of perceived social support, depression status (present vs absent), and hiv disease severity (aids vs non-aids) on mental and physical health dimensions of hrqol. potential interaction effects were also evaluated. results: social support was found to have a significant effect on both mhs and phs. presence of depression was found to have a significant effect on mhs but not phs. hiv disease severity (presence of aids diagnosis) was found to have a significant effect on phs but not mhs. manov a analyses revealed no significant interactions effects. conclusions and implications: level of social support, presence of depression and hiv disease severity were shown to have independent effects on hrqol. feeling "well supported" appears to have significant benefits for mental and physical health. biological indicators of hiv disease appear to have a selective impact on physical health while presence of depression is related to significant reductions in mental health. the development and evaluation of behavioural interventions to improve perceived social support network and depression will likely result in significant improvements in health outcomes of adults with hiv and aids. introduction: ongoing medical advances have greatly enhanced the longevity of penons living with aids (plwa). however, for certain subgroups living with hiv/aids, including, members of minority groups, women and the economically underprivilege d, aids outcomes have not changed so favorably. one obvious factor to consider when explaining disparities in aids outcomes is the environ· ment within which an individual resides. few studies of aids outcomes have focused on how commu· nity setting influences the effectiveness of care delivery. the principle research questions were: ) what is the relationship between the locations of areas with concentrations of pl wa and the distribution of both primary and ancillary service providers? ) how has the widespread availability of haart (after ) impacted aids outcomes at the community level? ) how do aids mortality and fatality rates vary when related community characteristics, such as household income, ethnic mix, and geographic access to primary and ancillary hiv/aids services are considered? we examine this issue across residential communities in the los angeles area. methods: los angeles county's comprehensive aids service providers database (compiled and maintained by aids project los angeles) was geo-referenced and distances between weighted mean population centers and the nearest hiv/aids service providers were calculated to provide a measure of access which was then merged with aids diagnosis and mortality data along with relevant socioeconomic and population indicators and for analysis using bivariate and multivariate statistics at the zip code level. results: there is a growing disparity in hiv/aids outcomes between low-income minority areas and affluent non-minority areas in the post-haart era (p = . ). ancillary aids services such as case management and counseling and testing are located near the places where low income hiv/aids service consumers are likely to live (p =. ). in spite of having more access to ancillary services low income areas continue to be associated with smaller decreases post-haart aids mortality rates (p= . ). conclusions: given the increasing disparities in aids outcomes between lower and upper income communities in the post -haart era, more specific research into the capacities of aids services providers and the efficiency of their interventions is required. although it is clear that ancillary services are operating in the areas of greatest need, their effectiveness remains limited. understanding the reasons for t~is, be they lack of adequate resources for inner city service providers, failure to reach target popula· tmns or other causes, requires additional research. in ? , y.out~ who were able to speak either french or english and had been absent from their parent's/ c~regivers ~es. dence for at least three consecutive nights took part in the survey which consisted of inter· viewer-adm ms tered question~aires. p.arti~i~an~s were recruited from drop in centres in cities across <?-nada.y~uth self-report as either using in ect on or non-injection drugs. statistical analyses were car· r ed out using sas version . the 'home' is a contested site for many women living in urban areas. women living in poverty and using illicit drugs are largely excluded from participation in dominant 'home-base' gender roles of wife and mother because of economic disadvantage. they thus 'make home' in ways that are specific to their everyday experiences. while research has established links between housing, health and drug use, this literature does not tend to consider the meanings that home may have within the lives of women who lack access to adequate tenured living spaces. this presentation reports the findings of my master's thesis work. using grounded theory methodology within a poststructuralist feminist conceptual framework, i conducted in-depth, open-ended interviews with women living in the toronto area. the women were recruited from within the community through posters at different social service agencies (e.g., drop-in centres, community health centres). they were asked to describe their housing experiences and what home meant to them over the course of their lives. through the data analysis process, a substantive theory of 'making home' for women living in poverty and using illicit drugs emerged. the central concept of making home is a continual process of learning about and interacting with the environment. the process of making home entails different subprocesses: finding home (knowing what is available and accessible, and accessing home), adaptation, and leaving home. the different meanings of home that women developed from their experiences and knowledge emerged as critical components for the process of making home. the women i interviewed were very mobile and experienced constant change with regards to home. home was not considered only in relation to physical living space. home could be made within a relationship or with regards to a possession. while dominant meanings of home relation to tenured living spaces are generally positive, my research indicated that home could also be a negative context. the presentation will describe my research process and findings as well as the theoretical and policy implications of my results. in the western democracies, social citizenship bundles the right to social provision (defined as a share of the social good, not necessarily proportionate to the market value of a citizen's contribution) with participation in the paid labour force. for this reason, social citizenship rights, which usually involve some kind of redistributive measures, are a key mechanism by which states ensure economic equality, or at least, economic equality of opportunity, but are also a mechanism of social exclusion. social rights are inscribed around a single kind of relationship, that which exists between a male family breadwinner and the paid labor market; those who make economic contributions that fall outside this relationship -such as unpaid care-work, or, work that occurs in shadow or underground economiesare to a greater or lesser degree barred from accessing citizen-based social provisions. furthermore, social provision that occurs outside of the breadwinner/market-eco nomy dyad is very often meanstested and is accompanied by regulatory state apparatuses (this includes a range of social services, from welfare payments, to child-care subsidies, to disability pensions). social citizenship is thus stratified; the legal relationship that is at the heart of social citizenship acts as a form of social closure against claims for a share of the social good made by those who are 'lesser' citizens than others. of particular interest in this paper is how citizenship inequalities translate into inequalities in the social provisions that emerge from economic participation: the right to safety on the job, protection from employer harassment, protection from the vagaries of the market as well the right to adequate, comprehensive, and appropriate health services. drawing on mixed methods, longitudinal data from adult sex workers (n= ) located in two research sites with different social welfare regimes -one in canada and one in the u.s. -we examine the consequences of working in a "shadow" or "underground" economy on various facets of health and access to health services, taking into consideration the mediating role that citizenship constructs and social welfare regimes play in accessing other key social and economic determinants of health. methods: the study population included methadone patients (re)admitted at the mhs in the period from / / to / / , born in the netherlands, morocco, surinam, dutch antilles or turkye, and officially registered in the population register of amsterdam. the population register was used to ascer· rain the vital status. causes of death were provided by the central bureau of statistics. mortality was categorised as hiv related, directly drug related (overdose) and other.mortality. results: the methadone patients had the following characteristics: years of age at entry; % male; % ethnic minority; % ever injected. in total, personyear (py) of observation time and deaths ( % hiv related, % overdose; % other) were observed. hence, the crude mortality rate was / py ( % ci - / py). the percentage of (ever) injectors was higher among the native dutch than among the ethnic minorities, % and % respectively. higher rates were observed among native dutch drug users compared to those belonging to an ethnic minority (age adjusted hazard ratio (hr) . ( % ci . - . ). the age adjusted hr of (ever) injecting drug users versus non injecting users was . ( % cl . - . ). after additional adjustment for route of administration a non significant difference between the dutch and ethnic minorities remained (hr . , % cl . - . , p-value . . conclusion: the mortality rate among the heroin users in amsterdam is strongly affected by the high prevalence of non-injecting drug use. moreover, this study confirms that differences in mortality between the native dutch and the ethnic minorities is related to differences in route of administration. the ongoing reduction of injecting drug use (due tot selctieve mortality, and switching route ofadministration and popularity of crack cocaine) may lead to a further reduction of mortality rates among heroin users in amsterdam. interventions preventing the initiation of injecting should be encouraged. . introduction: food insecurity is an inequality that is central in the lives of many low-income cana· d ans. people lack food security when regular access to nutritious food is limited or variable due to high prices'. low income, lack of transportation or inadequate food distribution, or they become disadvan· taged m other w~ys through the acquisition of food. a group comprising academics, health profession· als, and commumty workers who have experience in food insecurity, developed a pilot study in ottawa that sought to und~rstand the lived experience of food insecurity. the study also used the united states department of agriculture (usda) community food security module. methods: a series of group meetings determined the best research approaches; questionnaires and consent forms were developed by a working group. twenty-three self-identified food insecure respon· dents were interviewed. the data were analysed using frequency distributions· the food security module was coded according to the usda coding guide, and open-ended responses w~re coded using a grounded approach. renlts: preliminary results from our pilot study have given the research team cause for considerable concern. out of households without children, experienced food insecurity with hunger; ~ere at the severe l~vel. out of households with children, experienced food insecurity with hunger. ~•rst person reflecnons commonly featured feelings of depression low self-esteem and despair. participants' account tha d . an cu ty gettmg to the store, severely limited putting knowledge and skills mto practice. l'oster sessions v conclusion: based on these early findings, our research team is looking to challenge what appear to be assumptions about poverty and food insecurity and for best ways to use this information. some policy approaches and interventions that encourage people to eat better and exercise more, may be missing the mark for low-income individuals, and may serve to maintain food insecurity. future research will build on this pilot. with methods augmentation, and a comprehensive knowledge dissemination plan, we hope co contribute to research and policy frameworks at all levels. ps- (a) mental health and the corrections system: population-based analyses in urban, semi-urban, and rural settings julian somers, robert watts, and michelle patterson introduction: according to recent epidemiological research, rates of mental disorders vary considerably across countries and across regions within countries. nevertheless, rates of mental disorders (including substance use disorders) are consistently higher in populations involved in the corrections sys- em. courts have long recognized the heavy burden of mental illness within their purview, and have developed innovative programs to better manage the needs of such individuals. the majority of these innovations (e.g., specialized courts) exist in urban settings. however, few studies have examined the degree of variability in rates of different mental disorders between courts in urban and other settings (e.g., semi-urban, rural). variability between courts in different settings, if present, holds implications for needs-based resource planning. the present study was conducted as part of a long-term inter-ministerial collaboration in british columbia (bc). analyses were conducted on linked administrative data regarding population health and correctional services. a database was constructed including all individuals sentenced in bc in a single year (n= , ). corrections records were matched to records of health services utilization (hospital and outpatient services) for mental disorders and substance use disorders in the years preceding sentencing. services for mental health and substance-related problems were aggregated into three groups: severe mental illness (smi); less-severe mental illness (lsmi); alcohol/other drug (ad). courts were grouped, based on their annual volumes, inro three categories: "urban"; "semi-urban" and "rural." rates of service use for mental disorders were compared between groups for -year and -years preceding sentencing. results: there were significant differences in the rates of mental disorders in courts of different size (urban, semi-urban, rural) . however, differences between the rates of disorders within each of these groups exceeded the discrepancies between groups. comparatively high and low rates of disorders were observed in courts of each size. moreover, the courts with the highest rates of certain disorders (e.g., ad) did not have the highest rates of other types of mental disorders (e.g., smi). conclusions: rates of mental disorders differed significantly among the annual populations sentenced across courts in bc. urban courts (which process comparatively large numbers of people) have implemented services to address the needs of the mentally ill. the present analyses strongly suggest that program development should be closely linked to the demonstration of need. the results caution that a uniform approach to court programs for the mentally ill is likely to be inefficient, over-supplying services in some settings and underestimating need in others. results: public settings used for injection are characterized by highly unhygienic conditions, the presence of unsafely disposed syringes, limited availability of sterile syringes and a lack of sterile water for injecting. a number of unsafe injection practices observed were common among public injectors. the presence of police officers nearby and the potential of assault by street predators fostered rushed injecting among those consuming drugs in public spaces. the ecological features of these environments encourage unhygienic and unsafe injecting practices, heighten risk for overdose and the transmission of blood borne viruses. introduction: approximately % of women experience depression in the first weeks or months after giving birth. although it has been argued that postpartum depression (ppd) is a culture-bound p~ nomenon, experienced only in western, industrialized countries, recent international research studies have confirmed that the prevalence of ppd is similar around the world. however, little is known about variables that may influence the experience of ppd in women from diverse cultures and immigrant women. research is needed to identify the role culture may play in the presentation of ppd (i.e., types of symptoms most commonly reported), how women from various racial, ethnic and cultural backgrounds perceive and attribute their symptoms of ppd, and finally, how culture can be appropriately addressed in ppd treatment programs. method: to examine the role of culture in ppd, semi-structured interviews and self-report question· naires were administered to clients of the women's health centre of st. joseph's health centre, tor· onto. participants were identified as either first generation canadians (relative newcomen) (n= ) or second generation canadian (parents were immigrants to canada) (n= ). data were collected qd these two groups of women based on: severity of depression, symptom presentation, perceived role of social supports and culturally-specific traditions, and barriers and responses to treatment. the interview data were analyzed using qualitative methods (thematic content analysis), and the following themes were identified: ) stress about passing on their culture to their children, ) lack of social support and feelings of isolation, ) perceived importance or lack of importance of cultural based tra· ditions, ) conflicts with family members. about cultural traditions and beliefs, ) mental health stigma within ethnic communities and beyond, ) race-and sex-based discrimination, and ) language barriers. conclrllion: identifying the role culture plays in the presentation of ppd, and how women from diverse backgrounds perceive and attribute their symptoms of ppd, is critical in order to establishcultur· ally appropriate guidelines for treatment options. furthermore, information gathered from this study can be used to develop policies and resources for delivering culturally competent care for newcomer wo~ who are dealing with ppd as well as the issues around acculturation (i.e., language barriers, racism). llus is of particular importance for urban health centers which provide postpartum care to diverse groups of women, and particularly recent immigrants or newcomers. ps-~ (al. contaminated 'therapeutic landscape': perceptions of the aamjiwnaang fint nation keyln smith and isaac luginaah . in~: this. paper pres;ents the findings of an ongoing study among the aamjiwnaang f!rst nanon. aam wnaang is located m the heart of samia's 'chemical valley', surrounded by cherrucal ~(ants such as esso, imperial oil, shell, suncor energy, and canada's largest hazardous waste disposal sate. safety kleen. this fint nation community is located within the st. clair river •area of concem'. as destgna~ by health canada for the population of samia and the surrounding region. although this comm_umty, by way of. its proximity to the numerous chemical plants is already exposed to high levels pollu~on, recent che?ucal dumping in ~mjiwnaang, as well as a failed proposal for another ethanol plant m the community, only helped to mtensify community concerns about potential health impacts of exposure. research on the cultural beliefs and traditions of first nation communities has established that th~ ~isting rel~tionship between first nations people and 'mother earth' is not only physical, but also_ spmtual. in this study we explore how the complex relationship between the aamjiwnaang first naaon and 'mother earth' be ha · · · i .. may c ngmg a contammated 'therapeutic' landscape. the study a so ~lores h?w aam wnaang residents are coping with these changes and with the probable conramina· boa of their community. ra!jts: aamjiwnaang residents acknowledge that they are living in a contaminated environment and are being impacted by emissions from the surrounding 'chemical valley' especially for future generations, and have expressed concerns that members of the community and mother earth are 'sick' as a result of this exposure. while moving from that 'place' has been discussed, residents have strong personal and generational connections to the land and insist however, that aamjiwnaang is their 'home' and will remain that way despite growing community concerns about the impact from industry. the contribution of this study lies in the direct involvement of community leadership in designing and conducting this research and distributing the results to further local policy development regarding community concerns on the reserve. background: truck driver are at very high risk for drug abuse because the factor contributing to drug abuse among driver are multiple. it is important to gain an understanding of the key factors that contributing to drug abuse among truck drivers. methods: seventy-truck driver aged - years were conveniently selected from the population. all the participants were male. an interview schedule was developed in the light of literature data and data were collected by personal interview with informed consent in selected urban area of eastern part of nepal. results: a considerable percentage of truck driver have less knowledge about drug abuse, its effect on body and their complication. majority of the participants ( %) explained that lack of education, financial crisis were leading factors of drug abuse. the average numbers of respondents were believed that lack of meaning in life, marital disharmony. friendship with drug abuser, stress, tiredness, modernization of life pattern and freedom from the home pressure were the influencing risk factors to drug abuse. conchuion: this study reveals those truck drivers are at risk in urban area for developing drugs abuse, mostly influenced by social and environmental factors. hence, these groups should undergo certain educational programme to prevent not only drug abuse, but also prevent transmission of infectious disease among these groups. introduction: food insecurity is an inequality that is central in the lives of many low-income canadians. our group of university researchers, health professionals, and community developers conducted a study in ottawa with community workers who work with people identified as food insecure. the purpose of the study was to understand the nature of their work, and their perspectives, perceptions and experiences of the causes and consequences of food insecurity. (a parallel study was conducted with food insecure participants). methods: sampling was through local knowledge of organizations involved in the provision of food to community members. written permission for the researchers to contact workers in confidence was obtained from each organization. thirteen in-depth interviews were conducted. the interviews consisted of a number of open-ended questions. the data were collated, and analysed using a grounded approach. results: workers interviewed represented organizations that offered diverse programming and methods of food distribution intended to address the needs of the community. the provision of food was seen as a necessary response to address hunger that arose for the majority from poverty caused by low income, or levels of government income support and safety nets that were insufficient to support food requirements. workers reported that food requirements varied according to different. ethnic backgrounds, ages of recipients and family configurations, and with food preferences, and d'.etary (health) requirements. workers' observations of the effects of insufficient food on adults and children such as depression, low energy and non-participation or social disengagement matched those of food insecure respondents. food insecurity was cited as "another srressor among the mountain of problems." overall, workers presented a picture of a silent, stigmatized, poor population including children, and a lack of advocacy to address the issues. be tha th · ·ty the results suggest that workers and organizations, like the commuruty mem rs t ey msecun • · · · · f ilab'l' f food · t d ·n thei·r ab 'l 'ty to address food insecurity. l m tanons m terms o ava ty o , serve, are restnc e . . funding, and donations appeared to set the para? eters of pr~g:am r.espon~ to commuruty food msecurity. workers were concerned with program des g": and a~m mstranon that m general addr~d hunger on an emergency short-term basis, although food msecunty was long-ter_m for ~any. sustainable solutions that include knowledge translation strategies, and health and social pohcy responses were suggested and will be explored in future research that hopes to build on this pilot. background: socioeconomic deprivation as well as low levels of soc!al s.uppoi:r have .been associated with poor outcomes following cardiac surgery. pre-operative depression m ~anents with coron~ry artery disease awaiting cabg ranges from - % and is an independent predictor of post-operanve mortality. since st. michael's hospital has a large inner city population, this study was designed to determine the both the prevalence of depressive symptomatology (ds) in patients awaiting cabg as well as its relationship with socioeconomic status (ses) and social support. methods: consecutive patients referred for isolated cabg were invited to complete the centre for epidemiological studies depression scale (ces-d) as well as a social support scale and a life stressors inventory. a ces-d score of : represents mild ds and a score of : represents moderate to severe ds. participants also recorded information on functional status, perceived progression of heart failure, demographic and ses variables. all participants with ces-d scores : were considered to have ds. results: of the patients ( %) who returned the survey, ( . %) of participants had a ces-d score : with ( . %) of those having scores suggestive of severe depression. females and those with ongoing medical concerns tended to have more ds (p= . and p= . respectively). age was not related to ds. perceived worsening of symptoms and increased ccs angina class were significantly related to the presence of ds (p= . and p= . respectively) but not the number of diseased heart vessels. satisfaction with personal relationships including having someone to confide in (p= . ), feeling lonely (p= . ) and not having a partner (p= . ) were significantly related to ds. being very upset by a recent breakup in the immediate family was also significantly related to ds (p= . ). having greater than a grade education was the only ses variable related to ds (p= . ). multivariate logistic regression suggested that not being partnered and having low education were the most significant predictors of ds. conclnsion: pre-operative depression is present in at least one quarter of patients referred for cabg. since ds is related to poor outcomes following cabg, single patients with few social supports and low education should be considered at high risk for ds. these findings support the need for the development of supportive interventions in patients at risk in order to decrease post-operative morbidity. this study examines the relationship between childhood sexual abuse, sexual assault during adolescence, and hiv-risk-related behaviours in a sample of homeless youths. over the past decade, there has been increasing research devoted to the impact of childhood sexual abuse. some studies have suggested that the experience of childhood sexual abuse is associated with substance use and abuse, at· risk sexual behaviour and subsequent higher rates of hiv infection (ompad et al., ; cinq-mars et al., ; brown et al., ) . other studies have found that childhood abuse, especially sexual abuse, is c_o~n among stree~ youth (noell et al. ). this study compares sexually abused males and females livtng on the street ~th non-sexually abused street youth, with regards to unsafe sexual behaviours and e~ures to potmnal t:dv sources (e.g., tattooing, body piercing and injection drug use). the hypothe-sis oft~ ~nt study is that the prevalence of hn-risk-related behaviours will be higher among street youth vtctuns of sexual abuse than those who have not been sexually abused. the sample includes youths aged to who met specific criteria's for itinerancy ( male and female, with a mean ~of . y· and a standard deviation of . ). they were recruited through five organisations working ~th~ you~ and were~ of an ongoing cohort study. all youth completed a to minute ques· ~onnaue on their sexual behaviours, use of drugs and alcohol and other hiv risk behaviours. oral spec· unens for hiv testing were. also collected. a total of ( . %) youth reported at least one incident of ~i •~use/assault ( ~ girls ( . % of all the girls) and boys ( . % of all the boys]). preliminary descnpnve analyses pomt to sexually abused/assaulted youth showing the highest prevalence of sexual poster sessions v at-risk behaviours. for example, . % of sexual abuse/assault victims have engaged in prostitution in their lives compared with . % in the non-sexually abused/assaulted group. in addition, . % of sexual abuse/assault victims reported having injected drugs, compared with . % in the non-sexually abused/assaulted group. more statistical analyses will bring other significant factors to light, especially when we analyze separately those victim of childhood sexual abuse as compare to those victim of sexual assault after childhood. elucidating the risk factors for getting involved in hiv-risk-related behaviours is important for the development of comprehensive and appropriate prevention and treatment intervention strategies. introduction: new immigrants and refugees to canada frequently emigrate from regions of the world where intestinal parasitic infections with worms are endemic. of note, some of these parasites area capable of surviving for years to decades within a given host and can have life threatening consequences many years after initial infection. thus, early diagnosis and treatment of intestinal parasitic worms is considered important in high risk immigrant populations, however there remains a lack of consensus regarding the best method of accomplishing this. diagnosing worm infections through stool examinations is costly and has limited sensitivity, while presumptive treatment of all immigrants, although advocated by some, is expensive and results in healthy individuals being unnecessarily treated. herein, we examine the utility of a hematologic marker (i.e. peripheral blood eosinophilia) as a screening instrument to identify parasitic worm infections in new immigrants to toronto. we identified adults, years of age or older, who were screened for intestinal parasitic infections by stool examination as part of a recently developed screening protocol at a downtown toronto community health centre. we examined the prevalence of infections with worms and subsequently evaluated the impact of several demographic factors on the presence of worm infections. we also determined the sensitivity and specificity of peripheral blood eosinophilia (defined as greater than eosinophils per ml) as a marker for intestinal parasitic worm infections. results: overall, % of the immigrants tested had evidence of at least one worm infection on a single stool examination, while % of such individuals bad infections with multiple worms concurrently. age did not appear to be associated with the presence of worms, however % of males had evidence of worm infections compared with % of females (p= . ). immigrants from asia, sub-saharan africa, and central america had the highest burden of overall infection. the sensitivity and specificity of peripheral blood eosinophilia for worm infections was % and % respectively. conclusions: one in five recent immigrants presenting to a community health centre in downtown toronto had evidence of at least one intestinal parasitic worm infection. the highest burden of illness was in men and in those emigrating from less developed regions of the world. peripheral blood eosinophilia is a poor screening test for worm infections however its presence is highly suggestive of the existence of worms in new immigrants. more than a decade ago, the journal of american college health recommended that a national study be conducted to measure the health status of african american college students, 'both health disparities and [their] positive healthful behaviors' (fennell, ) . it was later decided that when exploring the level of health risk behaviors for african american students, gender is an important variable and should be included in the research (fennell, ) . at historically black college and universities (hbcus) college health researchers must tackle gender disparities through highly-effective health promotion and disease prevention programs. the purpose of this review is to examine the literature that addresses the overarching health behaviors (i.e. risky sexual behavior, poor diet, smoking, physical inactivity, etc.) of african american men who attend hbcus. despite the various social, cultural, and academic benefits of african american students who attend hbcus, the number of research studies that adequately address their health and health behaviors is limited. studies indicate that african american men who attend hbcus are actively engaged in poor health behaviors. compared to females at hbcus, african american men are more likely to behave in ways that could result in injuries and the use tobacco, alcohol, and ~ther dru~. the city of toronto has recently proposed to conduct a street count of the homeless. like proposals that have come before, this most recent proposal is controversial among many homeless advocates and service providers because it is perceived as intrusive, likely to undercount the target population, and unnecessary for addressing the problem. advocates of the count view it as necessary to gauge the scope of the problem and advise city leaders about how to most effectively direct resources ro.the various homeless services. this paper first reviews the history of efforts to count homeless populat ns m toronto, describing the motivations and arguments of people on both sides of the issue. second, the paper reviews the methodological complexities of counting homeless populations, describing approaches that use shelter-counts, administrative data and street observations. those interested in counts for toronto and elsewhere can benefit from this review of approaches that have been proposed and carried out in other municipalities. third, the paper proposes a new community-base d strategy that joins the skills of methodologists, local experts, and service providers to ensure a fair and accurate count. the method of systematic social observation avoids some of the problems of early counts by utilizing a repeated identification approach to minimize undercount bias. the method also has the advantage of involving and compensating homeless individuals for assisting with the street count estimates. the estimation approach can be implemented on a rolling basis throughout the year. drug transitions) is a multi-level study aimed at examining the associations between features of the urban environment and mental health, drug use, and risky sexual behaviors. research participants are being recruited in new york city (nyc) neighborhoods. an essential first step in the implementation of this study was to delineate boundaries for each target neighborhood that could then be used to establish sampling frames and as key units of analytic interest. although many neighborhood studies rely on pre-established definitions (e.g. those used for the census or administrative purposes), such definitions do not always reflect contemporary settlement patterns. we felt that street level observations were a neces· sary component of the definition process. methods: the procedures used to delineate neighborhoods were: ( ) development of census block maps of targeted areas; ( ) review of land use maps and census tract data to ensure, prior to going into the field, tha.t particular blocks are residential and likely to have sufficient population for recruitment purposes; and ( ) field vislts and observation in each of the targeted areas. field observations focused on: housing characteristics, including housing type and condition; characteristics of commercial areas, such as likely customer base (e.g. local or no~, socio-economic status and ethnicity of customers); pedestrian volume (including con· gregauons of people m parks and outside stores or residences); obstructions to pedestrian traffic (e.g. ma or thoroughfares, multi-block industry or institutions); and maintenance and use of open spaces. results: in making the final decisions regarding neighborhood boundaries and the inclusion or exclusion of particular. blocks, we considered a broad range of factors including evidence of homogeneity an~ heterogeneity (socmeconomic, ethnic, housing type, environmental) across blocks within and blocks ad acent to a nei.ghborhood, and across the sample neighborhoods; the potential for efficient recruit· ment of appropriate particip.ants (i.e. sufficient local pedestrian traffic); and boundaries used in reporting census data (s? that population data can be used in our analysis). . altho~gh utilization of field observations for neighborhood definitions is relatively time consuming (ap~~ox mately hours for a block area, with more diverse neighborhoods taking even longer), we annc p~t~ that it will substantially improve the quality and consistency of our data gath· ~rmg ~nd analyse~. spec f c e?'amples from neighborhoods defined through this process will be given dur· m~ this presentatmn. we will also discuss the merits and limitations of characterizing neighborhoods usmg street level observations. has been no consideration for how social networks are associated with sse. the objective of this study was to identify personal and social network characteristics associated with being a recipient of sse. in this cross-sectional study, idus who injected in the past months were recruited from syringe exchange programs in montreal, canada, between april and january . information on each participant and on the persons with whom contact had occurred in the past month were elicited using a structured, interviewer-administe red questionnaire. participants provided detailed demographic and drug use information on up to idu members with whom drugs or injecting materials were shared. using logistic regression, personal and network characteristics were examined in relation to receipt of sterile syringes. res.its: of idus, % reported receiving sterile syringes in the past month from another idu. the sample mean age was years (range - ), % male, % caucasian, and % cocaine injectors. in multivariate analyses adjusted for age and gender, recipients of sterile syringes were more likely than non-recipients to share drugs after preparation ( r= . ( . - . )), to require help or to have helped inject another idu (or= . ( . - . )), to have asked someone to get sterile syringes from a syringe exchange program (or= . [ . - . )), to lend syringes (or= . [ . - . ) ) and to use drug preparation water that was previously used by another iou ( r= . ( . - . ) ) during the past months. recipients also had a higher rate of change (p= . ) of idus in their drug injecting network during the past month. with respect to social networks, % ( / ) of idu network members were providers of sterile syringes and were more likely than non-providers to inject everyday (or= . ( . - . )). when stratified by their role as a sexual partner or as someone who provides support (e.g. friend, family member), further risk behaviours were observed in relation to sharing injecting materials with the participant. conclusion: recipients of sterile syringes and their idu network members had several high-risk behaviours for infection with bloodborne diseases. sse may afford an opportunity for the dissemination of other salutary behaviours such as information sharing on safe injecting practices between recipients and distributors. furthermore, drug injecting networks may be an avenue to reach idus who may not otherwise be exposed to preventive measures. there are numerous sources of stigma and labelling of mental and physical illness. first, the sociocultural dimension to stigma and labelling clearly influences patients, families, health care professionals and society's perception and treatment of illness. this creates multiple challenges related to illness identification and recovery, particularly in culturally diverse societies. second, the media is a major source of stigma and stereotyping with regard to a variety of mental and physical illnesses. despite increased public knowledge of many illnesses, studies have shown that stigma has intensified over the years in certain cases. a third element of stigma and labels appears with the use of diagnosis as a solution to human problems with the result that difficult to treat patients are repudiated and social issues are unaddressed. this presentation will serve to outline the development of stigma, various expressions of stigma, and consequences of stigma. it will provide some practical recommendations for the reduction of stigma related to mental and physical illness. purpose: to assess the knowledge, attitude, and practice about immunization for parent of - years old hispanic and african american children in los angeles county (lac). methods: we conducted two cluster surveys in lac. the sample was selected with probability proportionate to estimated size at the first stage and simple random sample of children at the second stage. data were collected through interview. we absuacted vaccine coverage data from immunization record card (irc) at home or from clinic records. the participation was % in hispanics and % in african americans populations. irc was not available at home for % of african american and % of hispanic children. results: all parents perceived their children got all necessary vaccine~. fa~orable attitudes to.w~rd immunization were reported by % of african american and % of h s?amc parents. '.he m~ ority of the parents ( % african american and % hispanic) agreed that vaccines prevent senous d se~ses among children. regarding vaccine safety, significantly more hispanic parents ( %) than african american parents ( %) mentioned that vaccines are safe. introduction: cervical cancer has been shown to be preventable by papanicolau tests in heterosexual women; however, the utility of papanicolau test in lesbians is controversial. cervical cancer is caused by the human papillomavirus (hpv) which is transmitted by sexual _intercourse; howev_er, its' transmission by homosexual intercourse is also controversial. the goal of this study was to review the evidence for papanicolau tests in lesbians. methods: a pub med, ovid ( ovid ( to , and cochrane library search was performed using the mesh headings "homosexuality , female," "vaginal smears," and "papillomavirus, human." in pub med, the clinical queries feature was used with "diagnosis" and "broad, sensitive" filters. a google advanced search of the internet was conducted with the terms "lesbian," "cervical cancer," and "pap rest." the url was limited to ".ca," ".edu," or ".gov." results: the search yielded original articles and reviews, but no cochrane reviews. none of the publications were canadian. website hits were found and selected websites were reviewed. studies showed that lesbians have fewer papanicolau tests than heterosexual women; however, many reported risk factors for cervical cancer, including multiple past or current sexual partners (male and female), early age of first coitus, history of sexually transmitted diseases, and cigarette smoking. hpv has been detected in - % of lesbians and - % of lesbians who have never had sex with men. case studies of abnormal papanicolau tests in lesbians who have never had sex with men have also been reponed. sexual transmission of hpv among lesbians can be explained by several factors: ) - % of lesbians have had sex with men and - % of lesbians continue to have sex with men. ) hpv may be transmitted by sexual behaviours among women, like digital-vaginal sex, digital-anal sex, oral sex, and the use of insertive sex toys. ) hpv transmission requires only skin-to-skin contact. genital hpv has been identified on human fingers. some professional organizations, like the society of obstetricians and gynecologists of canada and the american cancer society, recognize the need for papanicolau tests in lesbians. other organizations, like the canadian cancer society, do not have official policy statements. the current ontario cervical screening program does not specifically address lesbians. conclusion: although the data was limited, most studies recommended that lesbians should receive papanicolau tests. the frequency of these tests was controversial. policy makers and professional organizations should address the needs of this special population and make specific recommendations . monique chaaya, ahia sibai, hiam chemaitelly, and zana el roueiheb . literature concerning the mental and physical effect of work at an old age is contradictory. in addinon, urban environments are physically and socially harsh with reduced potential for income generation and employment and increased potential for depression. the present paper is an attempt to study how do work, or lack of work, link to the experience of depression among older adults in underprivileged lebanese urban communities. the data comes from a cross-sectional survey, where elderly residing in underprivileged communities in beirut, including a palestinian refugee camp, were successfully inter-v ewed through face-to-face interviews. logistic regression was performed to assess the effect of work on depression ad_justing for many other covariates. data showed that . % of people aged years and more were still workmg. there was a highly protective effect of work on depression in elderly males (or= . , % cl= . - . ). the current study is the first of its kind in the arab region and more work shou_ld be _don_e in this area. it is important for the lebanese government to consider elderly rights for social mclus n m terms of employment opportunities. amam nuru-jeter, nancy adler, and burton singer . l~u~on:_ the socioeconomic gradient is perhaps the most persistent and significant finding in social epidem ological research. the insistent nature of the ses effect is evidenced by its significance after acc?untmg for ~umerous confounds. the significance and magnitude of the effect, however, varies by ::•al group. evidence_ o_f the relative effect of race and ses is inconclusive. further, less attention has f ~ ptid to the specific interactions of race and ses than to examinations of which is a better predictor d ~ th. ~sues are further complicated by the explanatory complexity of the various measures of ses anl . owht ey relate to the health of various social groups. understanding the specific nature of these re a ons ips s necessary for guiding he ith d · i · · h a an soc a po mes and programs aimed at improving t e poster sessions v health of our most disadvantaged groups, and therefore population health, overall. this study examines the synergistic effects of ses with both race and gender in predicting group differences in mortality. methods: analyses use data from the national longitudinal mortality survey (n= , ) for the years , , and - ; and were linked to the national death index for deaths occurring through . results were confirmed using data from the national mortality followback survey for people who died in (n= , ) and the national health interview survey (denominator). we used correlation analysis and the standardized mortality ratio to examine ses (education and income), race, and gender as predictors of group differences in changes in mortality. results: for the total population, analyses support the income gradient showing significant declines in mortality ratios from low to high income along the income strata. education shows a significant drop in mortality with completion of high school and completion of college, exhibiting a threshold rather than a gradient effect. compared to whites, blacks receive diminishing health returns for each subsequent level of income and education; with whites closely mirroring the total population in ses thresholds. similarly, compared to men, women do not experience the same health gains at comparable ses levels. for education, black men and women only show significant mortality declines upon completion of high school. the ses gradient operates differently among race and gender subgroups. threshold effects suggest resource gains in life opportunities at particular milestones along the ses gradient. further, ses matters less for blacks and women compared to whites and men suggesting differing implications for health and social policy aimed at reducing disparities. objective: we assessed the impact of diabetes in a large puerto rican community of chicago by measuring the prevalence of diagnosed diabetes and calculating the diabetes mortality rate. methods: we analyzed data from a comprehensive health survey conducted in randomly selected households in community areas. questions on diagnosed diabetes and selected risk factors were asked. in addition, mortality data were analyzed in order to calculate the age-adjusted diabetes mortality rate. when possible, rates were compared to those found in other studies. results: the diabetes prevalence located in this community ( . %: % cl= . %- . %) is one of the highest ever reported for puerto ricans. for instance, it is more than three times higher than the prevalence for the us ( . %) and twice the prevalence for puerto ricans in new york ( . %) and puerto rico ( . %- . %). diagnosed diabetes was found to be significantly associated with obesity (p= . ). the prevalence was particularly high among older people, females, those horn in the us, and those with a family history. the diabetes mortality rate ( . per , population) was more than twice the rate for all of chicago ( . ) and the us ( . ). conclusions: understanding why the diabetes and mortality rates for puerto ricans in this commu· nity are so much higher than those of other communities is imperative. collaboration between researchers, service providers and community members can help address the issues of diabetes education, early screening and diagnosis and effective treatment needed in this community. introduction: sars is a respiratory illness that is spread from person to person through dose contact. this infectious disease outbreak was unusual due to the high rate of infection among health care workers. the aim of the study is to explore the demographic and attitudinal determinants of psychological distress due to sars among health care workers of a toronto hospital. methods: a total of adult participants completed questionnaires co assess psychological distress (impact of event scale -jes) and attitudes to sars. of these, participants completed the questionnaire during the sars i outbreak, and participants completed the questionnaire during the sars ii outbreak. participants also provided information on demographic variables, including occupation and exposure to sars. principal components analysis was used to derive eight attitudinal scales: fear: system, protection, prevention, job stress, stigma, instrumental coping, and psychological copm~. l ear regression analyses were applied to evaluate the associations of the demographic and amtudmal variables, as well as time, with psychological distress. . . regression analyses showed that time and higher scores on fear, ob stress, stigma'. and instrumental coping were associated with a higher total ies score: (r =. ). contrary to expectations, none of the demographic variables was associated with total ies score. conclusion: the presence of psychological distress in health care workers is indicative of intrusive or avoidant responses to thoughts, feelings, and memories associated with the sars outbreak. this study shows that ( ) fear for one's health and the he~lth of.others, ( ) ex~erien~in~ job stress, ( )_tbe per· ception of stigma, ( ) usage of instrumental copmg skills, ~n~ ( ) t m_e s grufi~an~ly c~nmb~te to increased psychological distress in health care workers. potential mterventmns during mfecttous diseaie outbreaks in health care settings should be targeted to minimize the impact of these factors. purpose: the purpose of this study was to expand knowledge regarding feeding practices, know!· edge and nutritional beliefs of mothers currently residing in the dominican republic (dr). the rising incidence of obesity in children is a major national health concern and obesity in first and second-generation immigrant children also continues to rise. we know that parents (particularly mothers) shape children's early diet patterns and that immigrant mothers experience additional challenges related to acculturation and assimilation into a new culture, however there is a paucity of literature concerning the effect of immigrant adaptation to american culture on the nutrition of children. in addition, new immigrant knowledge about the causes of obesity and the resulting health implications for childhood obesity has not been assessed and reported. this qualitative study used focus group methodology to discuss views and practices related to the introduction of food for infants and feeding practices for young children, along with a discussion on knowledge and beliefs related to the causes and health implications of child· hood obesity. ten dominican mothers' of young children (birth to years old) who reside in a small town in the western frontier area of the dr were participants in the focus group. results from this srudy will be compared to results from an identical study that will be conducted in fall with new immi· grant mothers from the dr to the boston area. we will compare feeding practices, beliefs and knowledge about nutrition for young children between these two groups. methods: using participatory principles, a focus group design was used to interview a group of mothers in the dr. the investigator along with a bilingual translator conducted the focus group. the session was tape recorded and is currently in the process of being transcribed and translated. transcribed data will be systematically analyzed themes will be identified. a qualitative data analysis software will be used to organize and code the data according to the specific aims of the study. supporting quotations will be selected to substrate each theme. lmpli~tions for urban health practice: an ultimate goal of this study is to lay a foundation for understanding the process of acculturation on feeding practices of mothers when they immigrate to the us. understanding beliefs, knowledge and feeding practices that mothers use with young children will help m ~he ~evelopment of culturally and linguistically appropriate educational strategies and materials for use m primary prevention of pediatric obesity. in canada more than seventy-five percent of immigrants choose to stay in three major urban centers of toronto, montreal and vancouver. approximately fifty percent of the immigrants eventually set· tie m ~~e greater tor<_>nto area. there is mounting evidence that the increasing immigrant population has a_ sigmfic~nt health disadvantage over canadian-born residents. this health disadvantage manifests particularly m the ma "ority of "mm "gr t h h d be · · h . . . . an s w o a en m canada for longer than ten years. this group as ~n associ~te~ with higher risk of chronic disease such as cardiovascular diseases. this disparity twccb n ma onty of the immigrant population and the canadian-born population is of great importance to ur an health providers d" · i i · b as isproporttonate y arge immigrant population has settled in the ma or ur an centers. generally the health stat f · · · · · · h h been . us most mm grants s dynamic. recent mm grants w o av_e ant •;ffca~ada _for less ~han ~en years are known to have a health advantage known as 'healthy imm • ~ants r::r · ~:s eff~ ~ defined by the observed superior health of both male and female recent immi- immigrant participation in canadian society particularly the labour market. a new explanation of the loss of 'healthy immigrant effect' is given with the help of additional factors. lt appears that the effects of social exclusion from the labour market leading to social inequalities first experienced by recent immigrant has been responsible for the loss of healthy immigrant effect. this loss results in the subsequent health disadvantage observed in the older immigrant population. a study on patients perspectives regarding tuberculosis treatment by s.j.chander, community health cell, bangalore, india. introduction: the national tuberculosis control programme was in place over three decades; still tuberculosis control remains a challenge unmet. every day about people die of tuberculosis in india. tuberculosis affects the poor more and the poor seek help from more than one place due to various reasons. this adversely affects the treatment outcome and the patient's pocket. many tuberculosis patients become non-adherence to treatment due to many reasons. the goal of the study was to understand the patient's perspective regarding tuberculois treatment provided by the bangalore city corporation. (bmc) under the rntcp (revised national tuberculosis control programme) using dots (directly observed treatment, short course) approach. bmc were identified. the information was collected using an in-depth interview technique. they were both male and female aged between - years suffering from pulmonary and extra pulmonary tuberculosis. all patients were from the poor socio economic background. results: most patients who first sought help from private practitioners were not diagnosed and treated correctly. they sought help form them as they were easily accessible and available but they. most patients sought help later than four weeks as they lacked awareness. a few of patients sought help from traditional healers and magicians, as it did not help they turned to allopathic practitioners. the patients interviewed were inadequately informed about various aspect of the disease due to fear of stigma. the patient's family members were generally supportive during the treatment period there was no report of negative attitude of neighbours who were aware of tuberculosis patients instead sympathetic attitude was reported. there exists many myth and misconception associated with marriage and sexual relationship while one suffers from tuberculosis. patients who visited referral hospitals reported that money was demanded for providing services. most patients had to borrow money for treatment. patients want health centres to be clean and be opened on time. they don't like the staff shouting at them to cover their mouth while coughing. conclusion: community education would lead to seek help early and to take preventive measures. adequate patient education would remove all myth and conception and help the patients adhere to treatment. since tb thrives among the poor, poverty eradiation measures need to be given more emphasis. mere treatment approach would not help control tuberculosis. lntrod#ction: the main causative factor in cervical cancer is the presence of oncogenic human papillomavitus (hpv). several factors have been identified in the acquisition of hpv infection and cervical cancer and include early coitarche, large number of lifetime sexual partners, tobacco smoking, poor diet, and concomitant sexually transmitted diseases. it is known that street youth are at much higher risk for these factors and are therefore at higher risk of acquiring hpv infection and cervical cancer. thus, we endeavoured to determine the prevalence of oncogenic hpv infection, and pap test abnormalities, in street youth. ~tbods: this quantitative study uses data collected from a non governmental, not for profit dropin centre for street youth in canada. over one hundred females between the ages of sixteen and twentyfour were enrolled in the study. of these females, all underwent pap testing about those with a previous history of an abnormal pap test, or an abnormal-appearing cervix on clinical examination, underwent hpv-deoxyribonucleic (dna) testing with the digene hybrid capture ii. results: data analysis is underway. the following results will be presented: ) number of positive hpv-dna results, ) pap test results in this group, ) recommended follow-up. . the results of this study will provide information about the prevalence of oncogemc hpv-dna infection and pap test abnormalities in a population of street youth. the practice implic~ tions related to our research include the potential for improved gynecologic care of street youth. in addition, our recommendations on the usefulness of hpv testing in this population will be addressed. methods: a health promotion and disease prevention tool was developed over a period of several years to meet the health needs of recent immigrants and refugees seen at access alliance multicultural community health centre (aamchc), an inner city community health centre in downtown toronto. this instrument was derived from the anecdotal experience of health care providers, a review of medical literature, and con· sultations with experts in migration health. herein we present the individual components of this instrument, aimed at promoting health and preventing disease in new immigrants and refugees to toronto. results: the health promotion and disease prevention tool for immigrants focuses on three primary health related areas: ) globally important infectious diseases including tuberculosis (tb), hiv/aids, syphilis, viral hepatitis, intestinal parasites, and vaccine preventable diseases (vpd), ) cancers caused by infectious diseases or those endemic to developing regions of the world, and ) mental illnesses includiog those developing among survivors of torture. the health needs of new immigrants and refugees are complex, heterogeneous, and ohen reflect conditions found in the immigrant's country of origin. ideally, the management of all new immigrants should be adapted to their experiences prior to migration, however the scale and complexity of this strategy prohibits its general use by healthcare providers in industrialized countries. an immigrant specific disease prevention instrument could help quickly identify and potentially prevent the spread of dangerous infectious diseases, detect cancers at earlier stages of development, and inform health care providers and decision makers about the most effective and efficient strategies to prevent serious illness in new immigrants and refugees. lntrodmction: as poverty continues to grip pakistan, the number of urban street children grows and has now reached alarming proportions, demanding far greater action than presently offered. urbanization, natural catastrophe, drought, disease, war and internal conflict, economic breakdown causing unemployment, and homelessness have forced families and children in search of a "better life," often putting children at risk of abuse and exploitation. objectives: to reduce drug use on the streets in particular injectable drug use and to prevent the transmission of stds/hiv/aids among vulnerable youth. methodology: baseline study and situation assessment of health problems particularly hiv and stds among street children of quetta, pakistan. the program launched a peer education program, including: awareness o_f self and body protection focusing on child sexual abuse, stds/hiv/aids , life skills, gender and sexual rights awareness, preventive health measures, and care at work. it also opened care and counseling center for these working and street children ar.d handed these centers over to local communities. relationships among aids-related knowledge and bt:liefs and sexual behavior of young adults were determined. rea.sons for unsafe sex included: misconception about disease etiology, conflicting cultural values, risk demal, partner pressur~, trust and partner significance, accusation of promiscuity, lack of community endorsement of protecnve measures, and barriers to condom access. in addition socio-economic pressure, physiological issues, poor community participation and anitudes and low ~ducation level limited the effectiveness of existing aids prevention education. according to 'the baseline study the male children are ex~ to ~owledge of safe sex through peers, hakims, and blue films. working children found sexual mfor~anon through older children and their teachers (ustad). recommendation s: it was found that working children are highly vulnerable to stds/hiv/aids, as they lack protective meas":res in sexual abuse and are unaware of safe sexual practices. conclusion: non-fatal overdose was a common occurrence for idu in vancouver, and was associated with several factors considered including crystal methamphetamine use. these findings indicate a need for structural interventions that seek to modify the social and contextual risks for overdose, increased access to treatment programs, and trials of novel interventions such as take-home naloxone programs. background: injection drug users (idus) are at elevated risk for involvement in the criminal justice system due to possession of illicit drugs and participation in drug sales or markets. the criminalization of drug use may produce significant social, economic and health consequences for urban poor drug users. injection-related risks have also been associated with criminal justice involvement or risk of such involvement. previous research has identified racial differences in drug-related arrests and incarceration in the general population. we assess whether criminal justice system involvement differs by race/ethnicity among a community sample of idus. we analyzed data collected from idus (n = , ) who were recruited in san francisco, and interviewed and tested for hiv. criminal justice system involvement was measured by arrest, incarceration, drug felony, and loss/denial of social services associated with the possession of a drug felony. multivariate analyses compared measures of criminal justice involvement and race/ethnicity after adjusting for socio-demographic and drug-use behaviors including drug preference, years of injection drug use, injection frequency, age, housing status, and gender. the six-month prevalence of arrest was highest for whites ( %), compared to african americans ( %) and latinos ( % ), in addition to the mean number of weeks spent in jail in the past months ( . vs. . and . weeks). these differences did not remain statistically significant in multivariate analyses. latinos reported the highest prevalence of a lifetime drug felony conviction ( %) and mean years of lifetime incarceration in prison ( . years), compared to african americans ( %, . years) and whites ( %, . years). being african american was independently associated with having a felony conviction and years of incarceration in prison as compared to whites. the history of involvement in the criminal justice system is widespread in this sample. when looking at racial/ethnic differences over a lifetime including total years of incarceration and drug felony conviction, the involvement of african americans in the criminal justice system is higher as compared to whites. more rigorous examination of these data and others on how criminal justice involvement varies by race, as well as the implications for the health and well-being of idus, is warranted. homelessness is a major social concern that has great im~act on th~se living.in urban commu?ities. metro manila, the capital of the philippines is a highly urbanized ar~ w. t~ the h gh~st concentration of urban poor population-an estimated , families or , , md v duals. this exploratory study v is the first definitive study done in manila that explores the needs and concerns of street dwdlent\omc. less. it aims to establish the demographic profile, lifestyle patterns and needs of the streetdwdlersindit six districts city of manila to establish a database for planning health and other related interventions. based on protocol-guid ed field interviews of street dwellers, the data is useful as a template for ref!!. ence in analyzing urban homelessness in asian developing country contexts. results of the study show that generally, the state of homelessness reflects a feeling of discontent, disenfranchisem ent and pow!!· lessness that contribute to their difficulty in getting out of the streets. the perceived problems andlar dangers in living on the streets are generally associated with their exposure to extreme weather condirioll! and their status of being vagrants making them prone to harassment by the police. the health needs of the street dweller respondents established in this study indicate that the existing health related servias for the homeless poor is ineffective. the street dweller respondents have little or no access to social and health services, if any. some respondents claimed that although they were able to get service from heallh centers or government hospitals, the medicines required for treatment are not usually free and are beyond their means. this group of homeless people needs well-planned interventions to hdp them improve their current situations and support their daily living. the expressed social needs of the sucet dweller respondents were significantly concentrated on the economic aspect, which is, having a perma· nent source of income to afford food, shelter, clothing and education. these reflect the street dweller' s need for personal upliftment and safety. in short, most of their expressed need is a combination of socioeconomic resources that would provide long-term options that are better than the choice of living on the streets. the suggested interventions based on the findings will be discussed. . methods: idu~ aged i and older who injected drugs within the prior month were recruited in usmg rds which relies on referral networks to generate unbiased prevalence estimates. a diverse and mon· vated g~o~p of idu "seeds." were given three uniquely coded coupons and encouraged to refer up to three other ehgibl~ idu~, for which they received $ usd per recruit. all subjects provided informed consent, an anonymous ~t erv ew and a venous blood sample for serologic testing of hiv, hcv and syphilis anti~!· results. a total of idus were recruited in tijuana and in juarez, of whom the maion!)' were .male < .l. % and . %) and median age was . melhotls: using the data from a multi-site survey on health and well being of a random sample of older chinese in seven canadian cities, this paper examined the effects of size of the chinese community and the health status of the aging chinese. the sample (n= , ) consisted of aging chinese aged years and older. physical and mental status of the participants was measured by a chinese version medical outcome study short form sf- . one-way analysis of variance and post-hoc scheffe test were used to test the differences in health status between the participants residing in cities representing three different sizes of the chinese community. regression analysis was also used to examine the contribution of size of the chinese community to physical and mental health status. rmdts: in general, aging chinese who resided in cities with a smaller chinese population were healthier than those who resided in cities with a larger chinese population. the size of the chinese community was significant in predicting both physical and mental health status of the participants. the findings also indicated the potential underlying effects of the variations in country of origin, access barriers, and socio-economic status of the aging chinese in communities with different chinese population size. the study concluded that size of an ethnic community affected the health status of the aging population from the same ethnic community. the intra-group diversity within the aging chinese identified in this study helped to demonstrate the different socio-cultural and structural challenges facing the aging population in different urban settings. urban health and demographic surveillance system, which is implemented by the african population & health research center (aphrc) in two slum settlements of nairobi city. this study focuses on common child illnesses including diarrhea, fever, cough, common cold and malaria, as well as on curative health care service utilization. measures of ses were created using information collected at the household level. other variables of interest included are maternal demographic and cultural factors, and child characteristics. statistical methods appropriate for clustered data were used to identify correlates of child morbidity. preliminary ratdts: morbidity was reported for , ( . %) out of , children accounting for a total of , illness episodes. cough, diarrhoea, runny nose/common cold, abdominal pains, malaria and fever made up the top six forms of morbidity. the only factors that had a significant associ· ation with morbidity were the child's age, ethnicity and type of toilet facility. however, all measures of socioeconomic status (mother's education, socioeconomic status, and mother's work status) had a significant effect on seeking outside care. age of child, severity of illness, type of illness and survival of father and mother were also significantly associated with seeking health care outside home. the results of this study have highlighted the need to address environmental conditions, basic amenities, and livelihood circumstances to improve child health in poor communities. the fact that socioeconomic indicators did not have a significant effect on prevalence of morbidity but were significant for health seeking behavior, indicate that while economic resources may have limited effect in preventing child illnesses when children are living in poor environmental conditions, being enlightened and having greater economic resources would mitigate the impact of the poor environmental conditions and reduce child mortality through better treatment of sick children. inequality in human life chances is about the most visible character of the third world urban space. f.conomic variability and social efficiency have often been fingered to justify such inequalities. within this separation households exist that share similar characteristics and are found to inhabit a given spatial unit of the 'city. the residential geography of cities in the third world is thus characterized by native areas whose core is made up of deteriorated slum property, poor living conditions and a decayed environment; features which personify deprivation in its unimaginable ma~t~de. there are .eviden~es that these conditions are manifested through disturbingly high levels of morbidity and mortality. ban · h h d-and a host of other factors (corrupt n, msens t ve leaders p, poor ur ty on t e one an , . · f · · · th t ) that suggest cracks in the levels and adherence to the prmc p es o socta usnce. ese governance, e c . . . . . ps £factors combine to reinforce the impacts of depnvat n and perpetuate these unpacts. by den· grou o . · "id . . bothh tifying health problems that are caused or driven by either matena _or soc a e~nvanon or , t e paper concludes that deprivation need not be accepted as a way. of hfe a~d a deliberate effon must be made to stem the tide of the on going levels of abject poverty m the third world. to the extent that income related poverty is about the most important of all ramifications of po~erty, efforts n_iu_st include fiscal empowerment of the poor in deprived areas like the inner c~ty. this will ~p~ove ~he willingness of such people to use facilities of care because they are able to effectively demand t, smce m real sense there is no such thing as free medical services. ). there were men with hiv-infection included in the present study (mean age and education of . (sd= . ) and . (sd= . ), respectively). a series of multiple regressions were used to examine the unique contributions of symptom burden (depression, cognitive, pain, fatigue), neuropsychologic al impairment (psychomotor efficiency), demographics (age and education) and hiv disease (cdc- staging) on iirs total score and jirs subscores: ( ) activities of daily living (work, recreation, diet, health, finances); ( ) psychosocial functioning (e.g., self-expression, community involvement); and ( ) intimacy (sex life and relationship with partner). resnlts: total iirs score (r " . ) was associated with aids diagnosis (ii= . , p < . ) and symptoms of pain (ii= - . , p < . ), fatigue (ji = - . , p < . ) and cognitive difficulties (p = . , p < . ). for the three dimensions of the iirs, multiple regression results revealed: ( ) activities of daily living (r = . ) were associated with aids diagnosis (ii = . , p < . ) and symptoms of pain <p =- j , p < . ), fatigue (ji = - . , p < . ) and cognitive difficulties (ji = . , p < . ); ( ) psychosocial functioning (r = . ) was associated with was associated with symptoms of fatigue (ii= - . , p < . ) and cognitive difficulties <ii = . , p < . ); and ( ) intimacy (r = . ) was related to was associated with symptoms of fatigue (ij = - . , p < . ) and cognitive difficulties (ii= . , p < . ). methods: the sif evaluation methodology involves a comprehensive database located at the sif, a randomly selected p~o.spective coh~rt of sif users, and two pre-existing external control cohorts. . . ~ts: in addmon to reporting process data and descriptions of the sif users, we report on data indicating that the establishment of the sif has been independently associated with reductions in public ~':°g ~ (p <?. ), and syringe sharing (aor = . [ %ci: . _ . ); p = . ) and other unsafe m ecnon pract _ces_ (p ~ . ), and increased uptake of detox services (log-rank p = . ). as well, we report on da~ md cat ng that the sif has not prompted adverse changes in community drug use patterns. the vancouver sif has been well accepted by the target population, and while adve~ events s~c~ as overdoses have occurred, these events have been successfully managed. externally compiled data indicate that the sif has been associated with substantial declines in public disorder !'oster sessions v associated with injection drug use, syringe sharing, and increased uptake of detox services. as well, the establishment of the sif has not exacerbated community drug use patterns. ongoing evaluation activities wiu involve assessing the impact of the sif on a variety of outcomes, including infectious disease transmission, fatal overdose, and utilization of health and social services. city, brazil, - maria cristina almeida, waleska caiaffa, renato assum;iio, and fernando proietti dengue cases were described according to time, space, intensity, age, gender, onset of symptoms, residence address and census tract. spatial distribution of two groups (children and women over years old and men aged - ) were compared, under assumption that they have distinct behaviors regarding their displacement around the city. analysis included local moran index, ripley\\'s k function and recurrence of census areas over time. about , cases were identified in seven epidemic waves. concentration of cases in small areas, followed by a spread either in space or time suggested endemic patterns. regarding age-gender groups, distinct patterns suggested that residence might not be a good proxy in determining the local of infection for men aged - . dengue is shifting to endemic pattern in this city and transmission may not be sole related to home environment, suggesting that additional spatial information must be couected aiming efficient control measures. murukan kandamuthan and subodh kandamuthan lnl uduction: illness or disablement of a child may affect the economic functioning of a family as it alters the employment pattern and earnings of parents this paper tries to assess the health status and the quality of life of disabled children, and how generally, severe disablement in a child affected their fami-lies\' finances, and to quantify any such effects the problems faced by children in their home and to provide information relevant to the formation of criteria for new or increased cash support. methods: a case-control study was done in the thiruvananthapuram district, capital city of kerala by selecting a random sample of families with severely disabled children below years and a random sample of normal children matched for age and occupation of the parents. comparative and subjective data were collected. money spent on children\'s medical care, loss of earnings of the parents, and other economic burden to the family due to the disability of the child in the family. a discriminant analysis along with univariate analysis was done to assess the factors that mostly differentiate the disabled and normal children. the mean expenditure of the families with a disabled child was rs. /-per month, which is significantly higher than the corresponding expenditure of rs. /-per month of families with normal child, (t= . , p <. ). of the disabled children, % were not getting any social security payments and % had no special concessions for medical and other educational purposes. the analysis of income and expenditure pattern indicated that financial impact of disablement in a child on the family is significant. the discriminant model results revealed that medical expenditure was a significant variable that differentiated the disabled and normal child. the study found that the health status and quality of life of the disabled children were far from satisfactory. this in fact affected the economic status of the disabled children. in addition to reduced earnings, there are extra costs for disabled children for travel, domestic help, medical care, and health care expenditures (hospital care, physician services, dentistry, drugs and others) for disabled individuals. a strong case can be made for their long-term care by improving the financial support to such families possibly through the introduction of an allowance specially to compensate for the earnings lost by parents due to the disability of their children. widows in india are considered disadvantage group of population. because they are characterized by pangs of separation from spouse, and consequently they go through mental agony, social ~s?lation, and economic dislocation. in addition to these, poverty, landlessness, homelessness, malnutr non etc. endure serious deterioration of their health. according to census , there are million women are widowed and one fourth live in urban areas. there is a noticeable increase of urban widows from the previous census (almost half). the paper examines the type of disability and chronic ailment borne among elderly widows ( years and above). fifty second round of national sample survey aske~ the individuals three sets of questions regarding their health: their status of health, whether they are physically poster sessions v immobile, and whether or not they have had any specific chronic illnesses. although health infrastruc- · ble ·n urban setting in india as compared to rural counterpart, prevalence of tures are arge y ava a . . . . . h · · · h h"gher "n urban areas analysis shows omt problems m old age qmte common c romc ness is muc • . . and nearly percent elderly widows are suffering from this ail'. ent in urban areas. one-fifth of widows are suffering from high/low bp. heart disease, diabetes and urinary problems are much ~ore pre~alent in urban areas though disabilities is comparatively lower in urban areas. however, the d~fference is not statistically significant. disability with respect to vision is more pronounced and one third_ of the total respondents have problems regarding eyesight. one fifths ofdderly widows are _ha.rd of hearing. though disability increases with age, similar trend is not observed with respect to chr~mc illness. the percepnon of self-health among elderly becomes poorer as their age increases. the perceived health status need not be always corrected to objective indicators of health. it is noted that around per~en~ of those perceived their health as "excellenr" or "very good" are found to be suffering from chrome disease of omts and percent have visual disability. to conclude an elderly widow living in urban areas have similar health problems as she jives in rural areas. this can be easily explained, as they were not made aware to seek treatment from health facility. in addition, the study shows that the economic conditions are deterrent factors for their illness. it is essential that intervention should be taken up improving their economic conditions so that wellbeing of this most vulnerable group of the society can be taken care of. heart failure is a disease that affects nearly million people world wide. the united states alone accounts for one third of this population. blacks are stricken with heart failure twice as often as whites. men are more likely to develop chf than women, however since the majority of the chf population are seniors, there are actually more women than men. congestive heart failure (chf) has become a pandemic. as the baby boomer generation ages, the number of chf cases will rise dramatically. (young, j. & mills, r., ). after the age of , each proceeding decade doubles the incidence level of chf. the average person has a in chance of developing heart failure within their lifespan according to the framingham study (nih.gov). individuals aging or older compose over half of the entire documented heart failure population. in this age group, chf is the leading cause of hospitalization. many patients are continuously readmitted. it is estimated that the chf population will increase by one million within the next years. mortality was at % for a two year period and % for five years (young, j. & mills, r., ). data from: aha as technology evolves, the understanding of the nature of heart failure has become clearer. in the beginning of the th century heart failure was diagnosed as a condition that presented with edema (swelling) in the extremities caused by water retention. treatment in the beginning of the past cenrury was limited to abdominal drainage and diuretics. the discovery of the heart's insufficient pumping ability in heart failure patients lead to new surgeries and devices such as heart transplants and ventricular assist devices (bridge until transplant is available). ventricular hypertrophy often occurs before the development of heart failure. hypertrophy is the term given for cardiac remodeling. cardiac remodeling also includes chamber dilation (young, j. & mills, r., ) . chf financial burden the us healthcare financing administration has ranked chf as the highest cost illness in the diagnose-related area. direct costs related to chf in the us for were nearly $ billion. these costs included hospital admissions, physician fees, home health aids and medications. indirect costs were over $ billion in . loss of jobs or death due to chf was the criteria for this category (young, j. & mills, r., ). . introduction: the injection drug user quality of life scale (iduqol) is a relatively new scale ~es gned to capture the unique and individual circumstances that determine quality of life among injection drug users (idus). the life areas comprising the instrument were based on the research literature an~ ~ocus group discussions with idus. the purpose of the present study was to evaluate the content validity of t.h~ iduqol using judgmental methods based on subject matter experts' (smes) ratings. content vah~ ty refers to the de~ee to which elements of an assessment tool are representative of the construct of interest and appropnate for a given population. methods: data were obtained from six smes, from the field of idu research and practice, who ~ere. asked t.o evaluate various aspects of the iduqol, including the title of the instrument, administraon instruchons, clarity of the names and descriptions of each life area, response format, scoring instruc-no~s and examples, record form and whether each life area should be included in the instrument. sme ratings were made using either or point scales. sm es were also given the opportunity to comment on poster sessions v each section and to suggest whether important life areas had been overlooked, were redundant, not relevant, or in need of revision. (cvi) and the ~v.erage ~eviation index (ad) were used to evaluate smes' agreement on ratings of the content vahd ty vanables. both measures provided support for the content validity of various aspects of the iduqol, although results from the stricter ad index noted some areas of disagreement, including the description of particular life areas (e.g., being useful, drugs, sex), the inclusion of some life areas (e.g., drug treatment, education, independence and free choice), and the ease of the scoring instructions. the findings from this study provide (a) content validity evidence to support the use of the iduqol as well as (b) recommendations to suengthen both the instrument (e.g., improved descriptions for some items) and the accompanying administration and scoring manual (e.g., an easier scoring template). changes made to the instrument and its manual make the iduqol even easier for researchers, practitioners, and program evaluators to use as a way of assessing, and tracking changes over time or as a result of interventions in, quality of life in injection drug users. introduction: strict adherence to prescribed regimens is required to derive maximal benefit from highly active antireuoviral therapy (haart) in persons living with hiv/aids (phas). adherence is a key determinant of the degree and durability of viral suppression. adherence is also essential in reducing the spread of hiv and ensuring that today's treatments remain effective for as long as possible. the objective of this study is to conduct a systematic review of the research literature on the effectiveness of education and patient support strategies for improving adherence to haart. methods: a systematic search of the core databases was performed from january until may . randomized controlled trials examining the effectiveness of education and patient support interventions to improve the adherence to haart were considered for inclusion. only those studies that measured adherence at a minimum of six weeks were included. study selection, quality assessments, and data abstraction were performed independently by two reviewers. results: study heterogeneity with respect to differing populations, interventions, outcomes, and length of follow-up did not allow for meta-analysis. we included studies involving , ph as. sample sizes ranged from to . study duration ranged from a single session to a variable number of sessions delivered over one year. many of the interventions involved the provision of an educational component to improve adherence and often addressed strategies to overcome barriers to adherence and the development of problem-solving skills. they ranged from simple interventions (e.g., the provision of reminder devices) to complex interventions (e.g., cognitive-behavioural therapy delivered by licensed psychologists). eleven of the studies demonstrated a statistically significant advantage associated with the described adherence intervention. the advantage associated with adherence outcomes does not seem to translate into the more clinically relevant outcome of viral suppression. only out of studies that reported virological or immunological results found a significant effect associated with the intervention. the studies had several methodological shortcomings. conclusions: there is a need for standardization and methodological rigour in the conduct of adherence trials. some interventions may have a significant impact on improving adherence. further research is required before any specific adherence improving strategy can confidently be incorporated into standard clinical practice. focus groups were used to collect data from a purposive sample of treatmentexperienced participants. focus group data were analyzed using a grou~ded t~eory appr~ach. i:ne themes identified from the interviews were used to identify the effects of ant rerrov rals on quality of hfe. the content of the mos-hiv was appraised against the themes identified from our analysis. participants also completed the mos-hiv survey and were asked whether the survey covered all important aspects of quality of life on antiretroviral medications. results: five key informant interviews and five focus groups with participants were used to identify effects on quality of life that are not directly ~aptu~ed by_ the mos-hiv health survey. our~~ showed that our participants described quality of hfe as mvol~mg_ a set of ~rsonal trad~ffs ~stay alive. in most cases, worsened quality of life was traded-off for gams ~ longevlty from ~~canon use. these eff~'ts or tradeoffs included: ( ) downstream consequences of side effects and toxlanes; ( ) loss of lrufe. pende~t decision-making privileges, ( ) having to choose drugs over ~areer; (~)burden of medication-taking responsibilities; and ( ) living life under a pretense and havmg to hide-the net effect of the tradeoffs, or "prices" to pay led to what was described as "longevity with hn without hope and future~. conclusion: our study highlights five major themes summarizing the impact of haart on quality on life, and suggests that currently used scales for measuring quality of life do not a~atd~ cap~e these findings and the associated consequences. the conceptual framework for measuring quality of bfe in hiv should be reconsidered in order to better capture the important effects of the medications on quality of life. this may involve widening the boundaries of the definition of health-related quality oflife to include aspects such as finances, employment, and housing. we should further consider the development of a haart adverse effect specific instrument, using a broad definition of adverse effect in order to capture all types of adverse impacts of hiv treatments on quality of life. introduction: measles (rubeola) is the most contagious vaccine preventable disease of humans. while cases of measles are uncommon in canada today, the disease continues to be a leading cause of morbidity and death in the developing world. as a result of human migration, measles cases still occur in canada, primari~ among immigrants, returning travelers, and other susceptible groups. canada's national advisory council on immunizations (naci) recommends that immigrants without records of measles immunization be considered for vac:cination since these individuals may not have been appropriately vaccinated in their native country. on rhe other hand, natural immunity to measles in immigrants is likely to be high given the high incidence of disease in developing parts of rhe world. thus it remains unclear if the most efficient strategy to achieve high levels of measles immunity in immigrants should entail initial serologic screening followed by vaccination of susceptible individuals or preemptive vaccination of all persons lacking immunization records. understanding the epidemiology of measles immunity in immigrant populations could help guide such decisions. . methods: we identified adults, years of age or older, who were screened for serologtc immunity to measles as part of a recently developed screening protocol at a downtown toronto community health centre. we subsequently determined if these individuals had any immunization records from their native country or from within canada. we then examined the relationship between several demographic factors and immunity to measles. results: % of immigrants had no prior immunization records. overall, % of the immigrants rested for immunity to measles were found to be immune; % of those under the age of , % of those between and years of age, % of those between and years of age, and % of those years of age or older. gender, education status, household income, and immigration status were nor ~ssoc ated wirh immunity to measles. immunity to measles was lowest among immigrants from eastern europe ( ~%), whil~ immigrants from other regions of the globe had greater than % immunity. c~lusrons: immigrants and refugees appear to have reasonably high levels of immunity to mea· sics, possibly related to natural infection wirh the measles virus. immigrants from eastern europe appear to have slightly. lower l~vel~ of immunity to the measles virus. universal screening for immunity to meales or preemptive vac:cmauon may both be inefficient public health strategies, however further research is needed to corroborate these findings. nancy r~ss, stephane tremblay, saeeda khan, daniel crouse, mark tremblay, and jean-marie berrhelor o~ve: the speed of the rise in obesity in places like canada suggests that rather than a shift in the gcncnc_ com~sirion of the population, the root of the obesity pandemic is an environment that suprrs ~besity. this paper examines the influence of neighbourhood and metropolitan characteristics. bour~lts:. while accounting. for individual socio-demographics and behaviours, residents of neighs with a large proportmn of poorly educated individuals had higher bmis than those living in poster sessions v neighbourhoods with more highly educated individuals (p <. ). residing in a neighbourhood with a high proportion of recent immigrants was associated with lower bmi for men (p<. ), but not women. neighbourhood dwelling density, a proxy for walkability, was not associated with bm! for either sex. metropolitan sprawl was associated with higher male bmi (p=. ) but the effect was negligible for women (p=. ). bmi was significantly lower for women (p<. ) living in a city in the province of quebec, even after accounting for the influence of individual and neighbourhood covariates. conclusions: bm! was strongly patterned by individual-level social position in urban canada. the incremental influence on bmi of neighbourhood related to the neighbourhood's social conditions and not to their physical form. metropolitan sprawl was associated with higher bm! for men, a group with longer car-dependent commutes than women. the findings suggest that both individuals and their environments (both social and physical) influence the distribution of bmi in urban populations. introduction: urban environments have been linked to a range of human health issues. in singapore, prevalence of end stage renal disease (esrd) is predicted to rise ( in to in , kidney international, vol. , . the clinical and economic burden of esrd has promoted development of strategies aimed at preventing the development and progression of chronic kidney disease. these include population based screening programs such as the national kidney foundation, sin-gapore\'s (nkfs) "partnership for prevention."the program, aims to reduce incidence of esrd through comprehensive intervention and screening for early detection of urinary abnormalities, blood pressure (bp), and random blood glucose (rbg). objective of this study is to examine gender, race and age wise prevalence of elevated bp, rbg and proteinuria. methodology: this current analysis includes , subjects, age to years, who underwent screening during september and december . participants were asked to give demographic information and the history of diseases. tests were given to get clinical information such as proteinuria, blood glucose, sbp, and dbp. blood pressure abnormalities were defined according to ]nc vi criteria. proteinuria was defined as the presence of plus or greater protein (equivalent to> mg/di) on dipstick analysis. results: there were , ( . %) males. racial distribution was chinese ( . % ), malay ( . % ), indians ( . %) and others ( . % ).among participants, who were apparently "healthy" (asymptomatic and without history of dm, ht, or kd), gender and race wise % prevalence of elevated (bp> / ), rbg (> mg/di) and positive urine dipstick for protein was as follows male: ( . ; . ; . ) female:( . ; . ; . ) chinese:( . ; . ; ) malay: ( . ; . ; . ) indian:( . ; . ; . ) others: ( . ; . ; . ) total:(l . , . , . ). percentage of participants with more than one abnormality were as follows. those with bp> / mmhg, % also had rbg> mg/dl and . % had proteinuria> i. those with rbg> mgldl, % also had proteinuria> and % had bp> / mmhg. those with proteinuria> , % also had rbg> mg/dl, and % had bp> / mmhg. conclusion: we conclude that sub clinical abnormalities in urinalysis, bp and rbg readings are prevalent across all genders and racial groups in the adult population. the overlap of abnormalities, point towards the high risk for esrd as well as cardiovascular disease. this indicates the urgent need for population based programs aimed at creating awareness, and initiatives to control and retard progression of disease. introduction: various theories have been proposed that link differential psychological vulnerability to health outcomes, including developmental theories about attachment, separation, and the formation of psychopathology. research in the area of psychosomatic medicine suggests an association between attachment style and physical illness, with stress as a mediator. there are two main hypotheses explored in the present study: ( t) that individuals living with hiv who were upsychologically vulne~able" at study entry would be more likely to experience symptoms of depression, anxiety and phys ca! illness over. the course of the -month study period; and ( ) life stressors and social support would mediate the relat nship between psychological vulnerability and the psychological ~nd physical outcomes. . (rsles), state-trait anxiety inventory (stai), beck depr~ssi~n lnvento~ (bdi), and~ _ -item pbys~i symptoms inventory. we characterized participants as havmg psychological vulnerability and low resilience" as scoring above on the raas (insecure attachment) or above on the das (negative expectations about oneself). . . . . . " . . ,, . results: at baseline, % of parnc pants were classified as havmg low resilience. focusmg on anxiety, the average cumulative stai score of the low-resilience group was significandy hi~e~ than that of the high-resilience group ( . sd= . versus . sd= . ; f(l, )= . , p <. ). similar results were obtained for bdi and physical symptoms (f( , )= . , p<. and f( , )= . , p<. , respec· tively). after controlling for resilience, the effects of variance in life stres".°rs averaged over time wa~ a_sig· nificant predictor of depressive and physical symptoms, but not of anxiety. ho~e_ver, these assooan~s became non-significant when four participants with high values were removed. s id larly, after controlling for resilience, the effects of variance in social support averaged over time became insignificant. conclusion: not only did "low resilience" predict poor psychological and physical outcomes, it was also predictive of life events and social support; that is, individuals who were low in resilience were more likely to experience more life events and poorer social support than individuals who were resilient. for individuals with vulnerability to physical, psychological, and social outcomes, there is need to develop and test interventions to improve health outcomes in this group. rajat kapoor, ruby gupta, and jugal kishore introduction: young people in india represent almost one-fourth of the total population. they face significant risks related to sexual and reproductive health. many lack the information and skills neces· sary to make informed sexual and reproductive health choices. objective: to study the level of awareness about contraceptives among youth residing in urban and rural areas of delhi. method: a sample of youths was selected from barwala (rural; n= ) and balmiki basti (urban slums; n= ) the field practice areas of the department of community medicine, maulana azad medical college, in delhi. a pre-tested questionnaire was used to collect the information. when/(calen· dar time), by , fisher exact and t were appliedxwhom (authors?). statistical tests such as as appropriate. result: nearly out of ( . %) youth had heard of at least one type of contraceptive and majority ( . %) had heard about condoms. however, awareness regarding usage of contraceptives was as low as . % for terminal methods to . % for condom. condom was the best technique before and after marriage and also after childbirth. the difference in rural and urban groups was statistically signif· icant (p=. , give confidence interval too, if you provide the exact p value). youth knew that contra· ceptives were easily available ( %), mainly at dispensary ( . %) and chemist shops ( . %). only . % knew about emergency contraception. only advantage of contraceptives cited was population con· trol ( . %); however, . % believed that they could also control hiv transmission. awareness of side effects was poor among both the groups but the differences were statistically significant for pills (p= . ). media was the main source of information ( %). majority of youth was willing to discuss a~ut contraceptive with their spouse ( . %), but not with others. . % youth believed that people in their age group use contraceptives. % of youth accepted that they had used contraceptives at least once. % felt children in family is appropriate, but only . % believed in year spacing. . conclusion: awareness about contraceptives is vital for youth to protect their sexual and reproduc· tive health .. knowledge about terminal methods, emergency contraception, and side effects of various contraceptives need to be strengthened in mass media and contraceptive awareness campaigns. mdbot:ls: elderly aged + were interviewed in poor communities in beirut the capital of f:ebanon, ~e of which is a palestinia~. refugee camp. depression was assessed using the i -item geriat· nc depressi~n score (~l?s- ). specific q~estions relating to the aspects of religiosity were asked as well as questions perta rung to demographic, psychosocial and health-related variables. results: depression was prevalent in % of the interviewed elderly with the highest proportion being in the palestinian refugee camp ( %). mosque attendance significantly reduced the odds of being depressed only for the palestinian respondents. depression was further associated, in particular communities, with low satisfaction with income, functional disability, and illness during last year. condiuion: religious practice, which was only related to depression among the refugee population, is discussed as more of an indicator of social cohesion, solidarity than an aspect of religiosity. furthermore, it has been suggested that minority groups rely on religious stratagems to cope with their pain more than other groups. implications of findings are discussed with particular relevance to the populations studied. nearly thirty percent of india's population lives in urban areas. the outcome of urbanization has resulted in rapid growth of urban slums. in a mega-city chennai, the slum populations ( . percent) face greater health hazards due to overcrowding, poor sanitation, lack of access to safe drinking water and environmental pollution. amongst the slum population the health of women and children are most neglected, resulting in burden of both communicable and non-communicable diseases. the focus of the paper is to present the epidemiology profile of children (below years) in slums of chennai, their health status, hygiene and nutritional factors, the social response to health, the trends in child health and urbanization over a decade, the health accessibility factors, the role of gender in health care and assessment impact of health education to children. the available data prove that child health in slums is worse than rural areas. though the slum population is decreasing there is a need to explore the program intervention and carry out surveys for collecting data on some specific health implications of the slum children. objective: during the summer of there was a heat wave in central europe, producing an excess number of deaths in many countries including spain. the city of barcelona was one of the places in spain where temperatures often surpassed the excess heat threshold related with an increase in mortality. the objective of the study was to determine whether the excess of mortality which occurred in barcelona was dependent on age, gender or educational level, important but often neglected dimensions of heat wave-related studies. methods: barcelona, the second largest city in spain ( , , inhabitants in ) , is located on the north eastern coast. we included all deaths of residents of barcelona older than years that occurred in the city during the months of june, july and august of and also during the same months during the preceding years. all the analyses were performed for each sex separately. the daily number of deaths in the year was compared with the mean daily number of deaths for the period - for each educational level. poisson regression models were fitted to obtain the rr of death in with respect to the period - for each educational level and age group. results: the excess of mortality during that summer was more important for women than for men and among older ages. although the increase was observed in all educational groups, in some age-groups the increase was larger for people with less than primary education. for example, for women in the group aged - , the rr of dying for compared to - for women with no education was . ( %ci: . - - ) and for women with primary education or higher was . ( %ci: . - . ). when we consider the number of excess deaths, for total mortality (>= years) the excess numbers were higher for those with no education ( . for women and . for men) and those with less than primary education ( . for women and - for men) than those with more than primary edm:ation ( . for women and - . for men). conclusion: age, gender and educational level were important in the barcelona heat wave. it is necessary to implement response plans to reduce heat morbidity and mortality. policies should he addressed to all population but also focusing particularly to the oldest population of low educational level. introduction: recently there has been much public discourse on homelessness and its imp~ct on health. measures have intensified to get people off the street into permanent housing. for maximum v poster sessions success it is important to first determine the needs of those to be housed. their views on housing and support requirements have to be considered, as th~y ar~ the ones affected. as few res.earch studies mclude the perspectives of homeless people themselves, httle is known on ho~ they e~penence the mpacrs on their health and what kinds of supports they believe they need to obtain housing and stay housed. the purpose of this study was to add the perspectives of homeless people to the discourse, based in the assumption that they are the experts on their own situations and needs. housing is seen as a major deter· minant of health. the research questions were: what are the effects of homelessness on health? what kind of supports are needed for homeless people to get off the street? both questions sought the views of homeless individuals on these issues. methods: this study is qualitative, descriptive, exploratory. semi-structured interviews were conducted with homeless persons on street corners, in parks and drop-ins. subsequently a thematic analysis was carried out on the data. results: the findings show that individuals' experiences of homelessness deeply affect their health. apart from physical impacts all talked about how their emotional health and self-esteem are affected. the system itself, rather than being useful, was often perceived as disabling and dehumanizing, resulting in hopelessness and resignation to life on the street. neither welfare nor minimum wage jobs are sufficient to live and pay rent. educational upgrading and job training, rather than enforced idleness, are desired by most initially. in general, the longer persons were homeless, the more they fell into patterned cycles of shelter /street life, temporary employment /unemployment, sometimes addictions and often unsuccessful housing episodes. conclusions: participants believe that resources should be put into training and education for acquisition of job skills and confidence to avoid homelessness or minimize its duration. to afford housing low-income people and welfare recipients need subsidies. early interventions, 'housing first', more humane and efficient processes for negotiating the welfare system, respectful treatment by service providers and some extra financial support in crisis initially, were suggested as helpful for avoiding homelessness altogether or helping most homeless people to leave the street. this study is a national homelessness initiative funded analysis examining the experiences and perceptions of street youth vis-a-vis their health/wellness status. through in-depth interviews with street youth in halifax, montreal, toronto, calgary, ottawa and vancouver, this paper explores healthy and not-so healthy practices of young people living on the street. qualitative interviews with health/ social service providers complement the analysis. more specifically, the investigation uncovers how street youth understand health and wellness; how they define good and bad health; and their experiences in accessing diverse health services. findings suggest that living on the street impacts physical, emotional and spiritual well·being, leading to cycles of despair, anger and helplessness. the majority of street youth services act as "brokers" for young people who desire health care services yet refuse to approach formal heal~h care organizational structures. as such, this study also provides case examples of promising youth services across canada who are emerging as critical spaces for street youth to heal from the ravages of ~treet cultur~. as young people increasingly make up a substantial proportion of the homeless population in canada, it becomes urgent to explore the multiple ways in which we can support them to regain a sense of wellbeing and "citizenship." p - (c) health and livelihood implications of marginalization of slum dwellers in provision of water and sanitation services in nairobi city elizabeth kimani, eliya zulu, and chi-chi undie . ~ntrodfldion: un-habitat estimates that % of urban residents in kenya live in slums; yet due to their illegal status, they are not provided with basic services such as water sanitation and health care. ~nseque~tly, the services are provided by vendors who typically provide' poor services at exorbitant prices .. this paper investigates how the inequality in provision of basic services affects health and livelihood circumstances of the poor residents of nairobi slums . . methods: this study uses qualitative and quantitative data collected through the ongoing longitudmal .health and demographic study conducted by the african population and health research center m slum communities in n ·rob" w d · · · · ai . e use escnpnve analytical and qualitative techmques to assess h~w concerns relating to water supply and environmental sanitation services rank among the c~mmumty's general and health needs/concerns, and how this context affect their health and livelihood circumstances. results: water ( %) and sanitation ( %) were the most commonly reported health needs and also key among general needs (after unemployment) among slum dwellers. water and sanitation services are mainly provided by exploitative vendors who operate without any regulatory mechanism and charge exorbitantly for their poor services. for instance slum residents pay about times more for water than non-slum households. water supply is irregular and residents often go for a week without water; prices are hiked and hygiene is compromised during such shortages. most houses do not have toilets and residents have to use commercial toilets or adopt unorthodox means such as disposing of their excreta in the nearby bushes or plastic bags that they throw in the open. as a direct result of the poor environmental conditions and inaccessible health services, slum residents are not only sicker, they are also less likely to utilise health services and consequently, more likely to die than non-slum residents. for instance, the prevalence of diarrhoea among children in the slums was % compared to % in nairobi as a whole and % in rural areas, while under-five mortality rates were / , / and / respectively. the results demonstrate the need for change in governments' policies that deprive the rapidly expanding urban poor population of basic services and regulatory mechanisms that would protect them from exploitation. the poor environmental sanitation and lack of basic services compound slum residents' poverty since they pay much more for the relatively poor services than their non-slum counterparts, and also increase their vulnerability to infectious diseases and mortality. since iepas've been working in harm reduction becoming the pioneer in latin america that brought this methodology for brazil. nowadays the main goal is to expand this strategy in the region and strive to change the drug policy in brazil. in this way harm reduction: health and citizenship program work in two areas to promote the citizenship of !du and for people living with hiv/aids offering law assistance for this population and outreach work for needle exchange to reduce damages and dissemination of hiv/aids/hepatit is. the methodology used in outreach work is peer education, needle exchange, condoms and folders distribution to reduce damages and the dissemination of diseases like hiv/aids/hepatitis besides counseling to search for basic health and rights are activities in this program. law attendance for the target population at iepas headquarters every week in order to provide law assistance that includes only supply people with correct law information or file a lawsuit. presentations in harm reduction and drug policy to expand these subjects for police chiefs and governmental in the last year attended !du and nidu reached and . needles and syringes exchanged. in law assistance ( people living with aids, drug users, inject drug users, were not in profile) people attended. lawsuits filed lawsuits in current activity. broadcasting of the harm reduction strategies by the press helps to move the public opinion, gather supporters and diminish controversies regarding such actions. a majority number of police officer doesn't know the existence of this policy. it's still polemic discuss this subject in this part of population. women remain one of the most under seviced segments of the nigerian populationand a focus on their health and other needs is of special importance.the singular focus of the nigerian family welfare program is mostly on demographic targets by seeking to increase contraceptive prevalence.this has meant the neglect of many areas of of women's reproductive health. reproductive health is affected by a variety of socio-cultural and biological factors on on e hand and the quality of the service delivery system and its responsiveness on the other.a woman's based approach is one which responds to the needs of the adult woman and adolescent girls in a culturally sensitive manner.women's unequal access to resources including health care is well known in nigeria in which stark gender disparities are a reality .maternal health activities are unbalanced,focusi ng on immunisation and provision of iron and folic acid,rather than on sustained care of women or on the detection and referral of high risk cases. a cross-sectional study of a municipal government -owned hospitalfrom each of the geo-political regions in igeria was carried out (atotal of ce~ters) .. as _part ~f t~e re.search, the h~spital records were uesd as a background in addition to a -week mtens ve mvesuganon m the obstemc and gynecology departments. . . . : little is known for example of the extent of gynecological morbtdtty among women; the little known suggest that teh majority suffer from one or more reproductive tr~ct infect~ons. although abortion is widespread, it continues to be performed under ilegal and unsafe condmons. with the growing v poster sessions hiv pandemic, while high riskgroups such ascomn;iercial sex workers and their clients have been studied, little has been accomplished in the large populat ns, and particularly among women, regardmgstd an hiv education. . . conclusions: programs of various governmentalor non-governmental agen,c es to mvolve strategies to broaden the narrow focus of services, and more importan~, to put wo~en s reproducnve health services and information needs in the forefront are urgently required. there is a n~d to reonent commuication and education activities to incorprate a wider interpretation of reproducnve health, to focus on the varying information needs of women, men, and youth and to the media most suitable to convey information to these diverse groups on reproductive health. introduction: it is estimated that there are - youths living on the streets, on their own with the assistance of social services or in poverty with a parent in ottawa. this population is under-serviced in many areas including health care. many of these adolescents are uncomfortable or unable to access the health care system through conventional methods and have been treated in walk-in clinics and emergency rooms without ongoing follow up. in march , the ontario government provided the ct lamont institute with a grant to open an interdisciplinary and teaching medical/dental clinic for street youth in a drop-in center in downtown ottawa. bringing community organizations together to provide primary medical care and dental hygiene to the streetyouths of ottawa ages - , it is staffed by a family physician, family medicine residents, a nurse practitioner, public health nurses, a dental hygienist, dental hygiene students and a chiropodist who link to social services already provided at the centre including housing, life skills programs and counselling. project objectives: . to improve the health of high risk youth by providing accessible, coordinated, comprehensive health and dental care to vulnerable adolescents. . to model and teach interdisciplinary adolescent care to undergraduate medical students, family medicine residents and dental hygiene students. methods: non-randomized, mixed method design involving a process and impact evaluation. data collection-qualitative:a) semi-structured interviews b) focus groups with youth quantitative:a) electronic medical records for months b) records (budget, photos, project information). results: in progress-results from first months available in august . early results suggest that locating the clinic in a safe and familiar environment is a key factor in attracting the over youths the clinic has seen to date. other findings include the prevalence of preventative interventions including vaccinations, std testing and prenatal care. the poster presentation will present these and other impacts that the clinic has had on the health of the youth in the first year of the study. conclusions: ) the clinic has improved the health of ottawa streetyouth and will continue beyond the initial pilot project phase. ) this project demonstrates that with strong community partnerships, it is possible meet make healthcare more accessible for urban youth. right to health care campaign by s.j.chander, community health cell, bangalore, india. introduction: the people's health movement in india launched a campaign known as 'right to health care' during the silver jubilee year of the alma ata declaration of 'health for all' by ad in collahoration with the national human rights commission (nhrc). the aim of the campaign was to establish the 'right to health care' as a basic human right and to address structural deficiencies in the pubic health care system and unregulated private sector . . methods: as part of the campaign a public hearing was organized in a slum in bangalore. former chairman of the nhrc chaired the hearing panel, consisting of a senior health official and other eminent people in the city. detailed documentation of individual case studies on 'denial of access to health care' in different parts of the city was carried out using a specific format. the focus was on cases where denial of health services has led to loss of life, physical damage or severe financial losses to the patient. results: _fourte_en people, except one who had accessed a private clinic, presented their testimonies of their experiences m accessing the public health care services in government health centres. all the people, e_xcept_ one person who spontaneously shared her testimony, were identified by the organizations worki_ng with the slum dwellers. corruption and ill treatment were the main issues of concern to the people. five of the fourteen testimonies presented resulted in death due to negligence. the public health cen· n:s not only demand money for the supposedly free services but also ill-treats them with verbal abuse. five of these fourteen case studies were presented before the national human right commission. the poster sessions v nhrc has asked the government health officials to look into the cases that were presented and to rectify the anomalies in the system. as a result of the public hearing held in the slum, the nhrc identified urban health as one of key areas for focus during the national public hearing. cond#sion: a campaign is necessary to check the corrupted public health care system and a covetous private health care system. it helps people to understand the structure and functioning of public health care system and to assert their right to assess heath care. the public hearings or people's tribunals held during the campaign are an instrument in making the public health system accountable. ps- (a) violence among women who inject drugs nadia fairbairn, jo-anne stoltz, evan wood, kathy li, julio montaner, and thomas kerr background/object ives: violence is a major cause of morbidity and mortality among women living in urban settings. though it is widely recognized that violence is endemic to inner-city illicit drug markets, little is known about violence experienced by women injection drug users (!du). therefore, the present analyses were conducted to evaluate the prevalence of, and characteristics associated with, experiencing violence among a cohort of female idu in vancouver. methods: we evaluated factors associated with violence among female participants enrolled in the vancouver injection drug user study (vidus) using univariate analyses. we also examined self-reported relationships with the perpetrator of the attack and the nature of the violent attack. results: of the active iou followed between december , and may , , ( . %) had experienced violence during the last six months. variables positively associated with experiencing violence included: homelessness (or= . , % ci: . - . , p < . ), public injecting (or= . , % ci: . - . , p < . ), frequent crack use (or= . , % ci: . - . , p < . ), recent incarceration (or = . , % cl: . - . , p < . ), receiving help injecting (or = . , % cl: . - . , p < . ), shooting gallery attendance (or = . , % ci: . - . , p < . ), sex trade work (or = . , % cl: . - . , p < . ), frequent heroin injection (or= . , % cl: . - . , p < . ), and residence in the downtown eastside (odds ratio [or] = . , % ci: . - . , p < . ). variables negatively associated with experiencing violence included: being married or common-law (or = . . % ci: . - . , p < . ) and being in methadone treatment (or = . , % ci: . - . , p < . ). the most common perpetrators of the attack were acquaintances ( . %), strangers ( . %), police ( . %), or dealers ( . %). attacks were most frequently in the form of beatings ( . %), robberies ( . %), and assault with a weapon ( . %). conclusion: violence was a common experience among women !du in this cohort. being the victim of violence was associated with various factors, including homelessness and public injecting. these findings indicate the need for targeted prevention and support services, such as supportive housing programs and safer injection facilities, for women iou. introduction: although research on determinants of tobacco use among arab youth has been carried out at several ecologic levels, such research has included conceptual models and has compared the two different types of tobacco that are most commonly used among the lebanese youth, namely cigarette and argileh. this study uses the ecological model to investigate differences between the genders as related to the determinants of both cigarette and argileh use among youth. methodology: quantitative data was collected from youth in economically disadvantaged urban communities in beirut, the capital of lebanon. results: the results indicated that there are differences by gender at a variety of ecological levels of influence on smoking behavior. for cigarettes, gender differences were found in knowledge, peer, family, and community influences. for argileh, gender differences were found at the peer, family, and community l.evels. the differential prevalence of cigarette and argileh smoking between boys and girls s therefore understandable and partially explained by the variation in the interpersonal and community envi.ronment which surrounds them. interventions therefore need to be tailored to the specific needs of boys and girls. introduction: the objective of this study was to assess the relationship between parents' employment status and children' health among professional immigrant families in vancouver. our target communmes v poster sessions included immigrants from five ethnicity groups: south korean, indian, chine~e, ~ussian, and irani~ with professional degrees (i.e., mds, lawyers, engineers, ma?~ger~, and uru~ers ty professors) w h no relevant job to their professions and those who had been hvmg m the studied area at least for months. methodology: the participants were recruited by collaboration from three local community agencies and were interviewed individually during the fall of . ra#lts: totally, complete interviews were analyzed: from south-east asia, from south asia, from russia and other eastern europe. overall, . % were employed, . % were underemployed, % indicated they were unemployed. overall, . % were not satisfied with their current job. russians and other eastern europeans were most likely satisfied with their current job, while south-east asians were most satisfied from their life in canada. about % indicated that their spouses were not satisfied with their life in canada, while % believed that their children are very satisfied from their life in canada. in addition, around % said they were not satisfied from their family relationship in canada. while most of the responders ranked their own and their spouses' health status as either poor or very poor, jut % indicated that their first child's health was very poor. in most cases they ranked their children's health as excellent or very good. the results of this pilot study show that there is a need to create culturally specific child health and behavioral scales when conducting research in immigrant communities. for instance, in many asian cultures, it is customary for a parent either to praise their children profusely, or to condemn them. this cultural practice, called "saving face," can affect research results, as it might have affected the present study. necessary steps, therefore, are needed to revise the current standard health and behavioral scales for further studies by developing a new scale that is more relevant and culturally sensitive to the targeted immigrant families. metboda: database: national health survey (ministry of health www.msc.es). two thousand interviews were performed among madrid population ( . % of the whole); corresponded to older adults ( . % of the . million aged years and over). study sample constitutes . % ( out of ) of those older adults, who live in urban areas. demographic structure (by age and gender) of this population in relation to health services use (medical consultations, dentist visits, emergence services, hospitalisation) was studied using general linear model univariate procedure. a p . ), while age was associated with emergence services use ( % of the population: %, % and % of each age group) and hos~italisation ( % .oft~~ population: %, % and %, of each age ~oup) (p . ) was fou~d with respect to dennst v s ts ( % vs %), medical consultations ( % vs %), and emergence services use ( % vs %), while an association (p= . ) was found according to hospitalisation ( % vs %). age. an~ g~der interaction effect on health services use was not found (p> . ), but a trend towards bosp tal sanon (p= . ) could be considered. concl.uions: demographic structure of urban older adults is associated with two of the four health se~ices use studi~. a relation.ship ber_ween age. and hospital services use (emergence units and hospitalisanon), but not with ~ut-hosp tal sei:vices (medical and dentist consultations), was found. in addition ro age, gender also contnbutes to explam hospitalisation. . sexua experiences. we exammed the prevalence expenences relation to ethnic origin and other sociodemographic variables as wc i as y j die relation between unwanted sexual experiences, depression and agreuion. we did so for boys and prts separately. mdhods: data on unwanted sexual expcric:nces, depressive symptoms (ce.s-d), aggrc:uion (bohi-di and sociodemographic facron were collected by self-report quescionnairc:s administettd to students in the: nd grade (aged - ) of secondary schools in amsterdam, the netherlands. data on the nature ol unwanted sexual experiences were collected during penonal interviews by trained schoolnursn. ltaijtj: overall prevalences of unwanted sexual experiences for boys and girls were . % and . % respectively. unwanted sexual experiences were more often ttported by turkish ( . %), moroc· an ( . %) and surinamese/anrillian boys ( . %) than by dutch boys ( . %). moroccan and turkish girls, however, reported fewer unwanted sexual experiences (respectively . and . %) than durch girls did ( . %). depressive symptoms(or= . , cl= . - . ) covert agression ( r• . , cl• . - . ) and cmrt aggression (or= . , cl• . - . ) were more common in girls with an unwanted sexual experi· met. boys with an unwanted sexual experience reported more depressive symptoms (or= . ; cl• i . .l· . ) and oven agression (or= . , cl= . - . ) . of the reported unwanted sexual experiences rnpec· timy . % and . % were confirmed by male and female adolescents during a personal interview. cond sion: we ..:an conclude that the prevalence of unwanted sexual experiences among turkish and moroccan boys is disturbing. it is possible that unwanted sexual experiences are more reported hy boys who belong to a religion or culture where the virginity of girls is a maner of family honour and talking about sexuality is taboo. more boys than girls did not confirm their initial disdosurc of an lllwalltc:d sexual experience. the low rates of disclosure among boys suggcsu a necd to educ.:atc hcahh care providen and others who work with migrant boys in the recognition and repomng of exu.il ... iction. viramin a aupplc:tmntation i at .h'yo, till far from tafl'eted %. feedinit pracn~:n panku· lerty for new born earn demand lot of educatton ernpha a• cxdu ve hrealt fecdtnit for dnared rcnoj of months was observtd in only .s% of childrrn thoulh colckturm w. givm n rn% of mwly horn ct.ildrm. the proportion of children hclow- waz (malnounshrdl .con" a• h!jh •• . % anj "rt'i· acimy tc.. compared to data. mother's ~alth: from all is womm in ttprod~uvr •ill' poup, % were married and among marned w~ .\ % only w\"rt' u mic wmr cnntr.-:cruve mt h· odl % were married bdorc thc •ar of yean and % had thnr ftnc prcicnancy hcftitt dlt' •icr nf yean. the lt'f'vicn are not uutfactory or they arc adequate but nae unh ed opumally. of thote' l'h mothen who had deliverrd in last one year, % had nailed ntmaral eum nat on ira" oncc, .~o-... bad matt rhan four ttmn and ma ortty had heir tetanus toxotd tnin,"t or"'" nlht "'"'"· ljn r ned rn· win ronductrd . % dchvcnn and % had home deh\'t'oc'i. ~md~: the tervtcn unbud or u led are !tu than dnarame. the wr· l'kft provided are inadequate and on dechm reprcwnttng a looun t ~p of h hnto good coytti\#' ol wr· ncn. l!.ckground chanpng pnoriry cannoc be ruled out u °"" of thc coatnbutory bc f. ps-ii ia) dcpn:wioa aad anuccy ia mip'mu ia awccr._ many de wn, witco tui~bmjer. jack dekker, aart·jan lttkman, wim gonmc:n. and amoud verhoeff ~ a dutch commumry-bucd icudy thawed -moarh•·prc:yalm«i al . ' . kw anx · ay daorden and . % foi' dqrasion m anmttdam. nm .. p tficantly hlllhn than dwwhrft .. dw ~thew diffamca m pttyalcnca att probably rdarcd to tlk' largr populanoa of napaan ..\mturdam. <turkish %, moroccan %, and surinam % . lndttd. ic'wt'll ltudla hatt ~ ~ high prevalena rata among migrant poupi in rbe ncdwrlands. howc'ytt au ttlluchn iuffenod from wry low raporne rara, or med screnung talel thac lack a ~y yabdarcd ~ in order to study the prevalence of depression and anxiety, and the (barriers to) use of mental health care among the different ethnic groups the following study was recently conducted: . the study consisted of a two-step approach. the first step was mcl~ded m the ~ h ith survey of (ahs), and consisted of three screening scales for depression and aruaety (klo, g::q- and mhl- ). in this survey all respondents were asked_ permission for~ second app~ :' t consisted of a structured interview containing the cidi for aruaety and depression, and questtollllalres on health care seeking, amongst others. all respondents who gave permission for a second approachwere invited by jetter for a suuctured interview with multilingual interviewers at home at a preset date and time in the following week. . in total, dutch, turkish, moroccan and surinam respondents took part in the ahs and gave permission for a second approach. in the second step, fo~ ~ tur~h, m~roc can surinamese and dutch respondents, information from the extensive interview was available (res~nse rates between and % ). since the data collection was completed only recently (june ), prevalence estimates can be presented at the conference for the first time. we have shown that with this approach it is feasible to achieve an acceptable response rate in a study on mental health among migrants. therefore we expect that this study will provide reli· able estimates of depression and anxiety in the turkish, moroccan and surinam migrants in amstw! ~· for the first time. in addition, insight into mechanisms underlying the differences between and within ethnic groups and into barriers to mental health care will provide pretexts for the improvement of pre· vention and mental health care for migrant groups. this study aimed to determine spatial patterns of mortality and morbidity of five major health problems in an urban environment: homicides, pregnancy among adolescents ((< years old), asthma hospitalization among young children(< years old) and two mosquito-borne diseasesdengue and visceral leishmaniasis, during - . all events were obtained through the city health database and, subsequently, geoproccsscd using the address of residence and the geographical and administrative division of the municipality, composed by unit of planning (up), which in tum were formed, each one, by census tract units. two research questions were investigated: are there spatial patterns to the events dis· tribution, and moreover, are these patterns overlapping across space? we use thematic maps, index of comparative mortality/morbidity by up and the overlapped rank of the th worse up rates for each event. a spatial pattern of high rates of homicides, proportion of young mothers and hospitalization of asthma were overlapping in areas social and economically disadvantaged. for mosquito-borne diseases, high rates with great dispersion were found in unprivileged areas in contrast with very low rares among privileged ones. these results pointed toward a coexistence of heavier burden of diseases for those living in areas of the city where misery, poverty, lack of political public health may be modulating social health problems. a possible environmental intervention in one mosquito•bome disease might be playing a role in the occurrence of other. although with limitations, this study may provide useful information for a joint urban planning under the public perspective, articulated for use in health impact assessment. jalil safaei bdrod#aion: the association of socioeconomic status (ses), usually measured by income, and health status is an established result in bcalth studies. the poor and low income individuals have lower health sta· tus then_ those with higher incomes. in general. such finding has been usually obtained from sample surveys on speafic populations. a problem with many sample survey$ is that their results are not comparable aaoss ~ndaries as they may use different sampling methods, ask different questions, categorize the answers differently, or define groups differently. moreover, the sample data need to be standardized using the demographic: katurea of a ~ population. this study, however, uses the national population health survey (nphs) cycle public use mictodata files which is based on a common survey template ·~~three~ area in canada, namely montreal, toronto, and vancouver. it also utili .es the built-m stanclatdizaaon of the nphs data which accounts for its complex survey design. . ~:the stu~ usc:s two well-known measures of health inequalitythe relative index of meqaality and die concentranon indexto capture the extent of income related health inequality among poster sessions v urban female and male populations in each of the three metropolitan areas. personal income is classified into ten groups by the nphs with "no income" as the first group and "more than $ , " as the last. health status is measured by three variables -having a chronic condition (chc), self assessed health (sah), and health utility index (hui) -using appropriate indices. alternative formulations are used to calculate the standard deviations of the estimated or calculated measures. the findings of the study suggest that the measured health inequality depends on the health measure used. for chc and hui the measured inequality indices do indicate poorer health for lower income individulas, however, they are not statistically insignificant. health inequalities are more pronounced when health is measured by sah. the results do not support any systematic ranking of the three metropolitan areas in terms of health inequalities. they do not reveal any systematic pattern of inequality between men and women, either. conclusions: despite the use of highly aggregated nphs data, income related health disparities are observed in the three metropolitan areas in canada. this is more the case with self perceived (sah) health. such disparities are preventable and call for broader health policies that address poverty and low income among other social determinants of health. introduction: the analysis of health indicators under the spatial perspective is configured as an important instrument in the detection of intra-urban differentials. this study aimed to examine the spatial distribution of the births occurred in belo horizonte, in , analyzing the presence of spatial clusters of health indicators for newborns (rn) and their mothers, using data from the information system on live birth database (sinasc). method: for each covered area of the basic units of health (ubs), we calculated the proportion of: adolescent mothers, mothers with less than years of schooling, first pregnancy, mothers with four or more pregnancies, dead babies born on previous pregnancies, stillbirths, cesarean section, less than four prenatal care attendance, moderate and severe hypoxemia in the st and th minutes of life, low or very low birth weight. we used empiric bayesian methods for smoothing the estimates. for spatial analysis, the indicators obtained from the global moran (i) index and local indicators of spatial association (lisa) were used. maps were built to allow the visualization of the spatial clusters. in all analysis, significance statistics was considered p~ . . results: a total of , births of residents in belo horizonte were registered in i. the estimated bayesian proportions for the entire municipality was close to the one observed for all variables. analysis using lisa showed the presence of relevant spatial clusters for adolescent and low educated mothers, dead babies form previous pregnancies, cesarean section, low attendance to the prenatal care especially in area with low socio-demographic characteristics. three areas presented consistent clusters, with important spatial auto-correlation for almost all studied indicators. conclusion: the used methodology was configured as a great instrument of detection risk areas where clustering occurs. it can easily be incorporated in any surveillance system as a mechanism for controlling events related to births in the municipality. moreover, it can be applied to discriminate target areas for prompt public health interventions, such as improving health services access and the consolidation of better obstetric practices. introduction: gentrification, the displacement of low income and non-majority people out of longtime neighborhoods and residences is a global phenomenon. it has been identified as occurring in both developed and less developed countries and as inequality persists or increases, many communities are vulnerable to disruption and loss. while there may be some benefits to gentrification, these benefits are less likely to impact those who have been forced to move out of a gentrifying community or those who remain but economically stressed. . . . . this paper lays out a theoretical framework for dent fymg and ~ddressm~. the_ health consequences of gentrification on residents living in a community prior .to o.r durmg gent~ ~ cat. n. by drawing on the literature of housing, sociology, health and urban plannmg, t places genmf catt~n and neighborhood change into the context of other forces affecting th~ .hea.lth of vulnerable populations. it then proposes solutions to prevent or mitigate the impacts of genmf cat on. results: four main categories of consequences potentiallr re~ult from ~entr~fica~~n: !'°°r housing· related issues, spatial effects, mental health impacts and contr bunons to racial ~spanttes m heal~. the housing issues include increased susceptibility to asthma, lead exposure, allergiesl~topy an~. acetdents/ injuries. spatial effects include reduced access to health ~are, reduce~ access to obslttadinonal food sources, decreased physical activity, and increased obesity. the __ pnmary mental health effects_ :ire increased stress increased risk of depression and disruption of trad t onal support networks. in addinon to the above he~lth issues, gentrification has the potential to increase racial disparities in health by reduc· ing access to long term and multi-culturally experienced health care provide~s. conclusions: public health practice provides a framework for addressmg the health consequences of gentrification. in this context primary prevention would involve preventing gentrification in the first place along with a renewed commitment to helping distressed communities a~~ im_proving the quality ~f life for long term residents. the next layer of meeting the challenges of gentrification would be to assjst long rime residents to stay in a community and thus potentially allowing them to participate in the bene~ts of gentrification (such as better public services). only if all these efforts fail -and these other prevennon strategies must be a priority, public policy should then work to help people and instirutions move to other communities through grants and the provision of alternative safe affordable housing and neighborhoods. sarah romans, marsha cohen, and tonia forte lnh'odlletion: there has been sustained interest in urban rural (ur) differences in mental health over the last years of epidemiological research, with most studies reporting higher urban rates of mor· bidity, particularly when psychotic disorders have been studied. most recently, in britain, urban rates of non-psychotic disorder were greater than rural and semi-rural rates, both before and after the more adverse circumstances of urban dwellers were considered (paykel et al ) . surprisingly, there were no ur differences in help seeking. in canada, wang ( ) found greater urban rates for major depression only after he controlled for the confounding effects of race, immigration, employment and marital status, a result reminiscent of work from the us (blazer et ) . rural participants were less likely to have sought help for their mental health problems. in this study, we sought to examine urban/rural differences in rates of depression and help seeking in canada. method; data came from the canadian community health survey . , a community survey conducted by statistics canada of people aged and older, with the total sample size of , respon· dents, % response. analyses used weighted data; differences were assessed by chi-squared. ra.its: bivariate cross-tabulations showed a modest increase in month depression rates for urban ( . %) over rural ( . %, p= . ) dwellers; there were no ur differences when the sample was examined separately by gender and age group ( - , - , - ) . in general, more urban ( . %) than rural people ( . %, p= . ) had sought mental health treatment in the past year. there was no ur difference in helping seeking amongst those with depression (u . %, r . % ns). amongst the whole population, helping seeking was gendered with more urban men accessing help ( . %) than rural men ( . %, p= . ); this did not apply for women ( . % vs . % p= . ). ~ons: the urban-rural demographic continues to generate intriguing findings, even recently when internal migration is common and people can seek out the environment most conducive to their health, ~th physical and mental. people with depression are a disadvantaged, frequently stigmatized group, with ~r quality of life a_nd often impaired function. unlike many other factors associated wi~h urban or rural hfe per se, depression can be treated. the low help seeking rates is a cause for concern, m both the ur~n and_ rural populations. it behooves researchers, policy makers and service planners to ensutt effective services are available for both humane and economic reasons. methods: using united states census income data, we assigned the manhattan community districts to two major socioeconomic groups, manhattan i and ii. manhattan i is composed of community districts with average household incomes above the median for new york city; manhattan ii is those below. with public new york city department of health death records and us census data, we calculated a "standard" new york city population and estimated mortality rate distributions for manhattan i and ii. we then compared these age-adjusted actual mortality distributions with a standard t-test. results: we explored premature deaths using several cut-off points (before the ages of , , and ), and with subcomparisons for males and females. every comparison showed the wealthier area, manhattan i, to have significantly lower premature mortality rates than the lower income manhattan ii. further, we compared age-adjusted mortality rates among the city's five boroughs, and found no significant differences based on local geography alone. conclusions: these findings suggest that in manhattan, characterized by its extremes of wealth and poverty, health status, as measured by premature mortality, does vary significantly with the local income level. in manhattan, the relative average income by community district varies as much as : . this ratio is greater than that found in the other cities we have studied: for example, the range among tokyo's kus is half that in manhattan, or about : . paris has shown the longest life expectancy and changing premature mortality rates. from our preliminary work, we expect to find less variation in premature mortality rates in comparable cities. this study will continue to explore the relationship of premature mortality rates and life expectancy to income levels and different health systems among wcp cities with a view to measuring health policy options. introduction: according to the world health organization (who), smoking-related illness is currently the world's second major cause of death, currently responsible for one out of ten adult deaths worldwide. the who's framework convention on tobacco control (fctc) aims to reduce tobaccorelated disease and deaths by changing national public policies. mexico, which, according to the who, had smoking prevalences of % among adults in and % among health care providers (hcps) in , ratified the fctc in . objective: to examine knowledge of and attitudes towards cigarette smoking and smoking cessation among hcps, and clinical practices regarding smoking cessation. methods: in june , a convenience sample of hcps from one public clinic in urban oaxaca, mexico, part of mexico's national network of public health care clinics, were interviewed in spanish using a verbally administered questionnaire that was standard among all participants. during primary care outpatient visits, hcps were observed treating patients to assess the relative importance of smoking cessation as a health care priority. results: of the hcps interviewed, including ten physicians, three nurses, and five medical students, % reported smoking regularly. all hcps reported assessing patients' history of smoking, knowledge of the health risks associated with smoking, and feeling qualified to discuss these risks with patients. all hcps reported counseling patients who currently smoked to quit. all hcps reported recommending nicotine replacement therapy (eg., patch and/or gum) and/or behavioral therapy (eg., psychologist, support groups) to patients who smoked. all hcps reported that there was no government funding for smoking cessation, and that all costs associated with smoking cessation were patients' out-of-pocket expenses. observation of hcp interaction with patients revealed that hcps always inquired about smoking history with new patients and rarely inquired about smoking history with returning patients. hcps were not observed counseling patients who reported current smoking on smoking cessation methods and its benefits. observation of the clinical environment suggested a focus on preventative child health (eg., immunization, water-borne illnesses), family planning, and chronic diseases (eg., diabetes, hypertension). conclusions: while the mexican government has made smoking cessation a public health priority and hcps report addressing smoking cessation, observation of hcps suggests: ) smoking status is assessed only in new patients; and ) smoking cessation methods are not addresse~. observ_atio~ of hcps and the clinical environment in a public clinic in oaxaca suggests that smoking cessation s of lower priority than other heath care issues. p - (a) urban agriculture and food and nutrition security in kampala, uganda fiona yeudall, renee sebastian, abdelrahman lubowa, selahadin ibrahim, and donald cole introduction: urban agriculture is an important livelihood strategy contributing to household food security by increasing access and availability to food in urban settings (koc et al., ) . the purpose of poster sessions v rhis study was to examine relationships between child nutritional securiry outcomes, household food security, and urban agriculture activiries in kampala, uga~da. . . questionnaires assessing socio-demographic, farmmg and household food secunry (hfsi characreristics were administered to households. food diversiry was ~lculate~ from ~e number of foods consumed over hours for one child ( - years) per household. heigh~ weight,. nud-upper·ann· circumference (muac) and tricep skinfolds (tsf) were measured for the mdex child. z-sc.ores for height-for·age (haz), weighr-for-age (waz) and body mass index (zbmi) were ~~ulated usmg cen· rres for disease control and prevenrion reference data. z-scores for body composition measures were calculated using nhanes i and ii data for african americans. the lms method was used to c~.t for skewed z·score indices. all dara was checked for normaliry and univariable and backward mulnvanablc linear regression analysis conducted. ruwlts: household food securiry was significantly associated with wealth (b= . , p< 'a acre were more dependenr on assets for hfs. although sex of head of household was ~ot related to j-:ifs, it modi· fied relationships in rhar female headed households had greater food securtry when fai:mmg less than , acre compared ro male headed households, and vice versa. hfs was significantly associated with food diversiry (s= . , p). urbanization, especially in developing countries, has substantially increased the vulnerability of rhe mass of low-income urban dwellers. the livelihoods and quality of life for many of the poor espe· cially in larin america, asia, and africa, have deteriorated significantly over the years. urban areas are increasingly unable to provide for their populations, resulting in poverry, massive unemploymenr, job cuts, poor housing, lack of or poor public services, and a compromised health status. botswana, a country rhat lies in the sourhern parr of africa, has had its share of urban problems such as rhe mush· rooming of squarters and low-income urban sertlements. despite efforts to address the substandard living conditions in low-income urban areas, these problems have continued to grow. these living con· diuons are porenrially stressful to rhe residenrs and likely affects their health. the primary aim of the udy wa to examine the complex relationship between communiry-level stressors and interveners and health-related quality of life among residents of low-income neighborhoods in francistown, botswana. u i"" a croa -icctional quantitative design (both descriptive and explanatory) and using primarily cloae-mded interview• with a random sample of residents, this study examined the role of chrome life trnson and environmental quality on overall health status qualiry of life) and the physical, psy· chological and level of independence domains of health. the major hypothesis of the study was that community-levrl stre sor would influence health-related quality of life and that social capital would moderate these relationships. findings indicate that neighborhood quality is a powerful predictor of healrh tatu rhan socioeconomic status and individual life stressors. social capital was also found to he a ificant positive predictor of healrh and also moderator of structural factors. social capital moderated the effects of low environmental quality on level of indrpendence and on physical health outcomn, but nor on psychological and global health outcomes. these findings suggest that as the environment get betttr. stresson are reduced, hence promoting berter health outcomes. the study ends with implication• for social justice, public health and social work practice, and research, focusing mostly on the ~ole of social capital and the environmental quality in predicting health outcomes. spt· cafically • anenhon should be focused on political and civic society's commitment for social justice and poveny alleviation, ~uction of the threat of insecuriry and violence; cultivating social capital and good governance; and improving the health and social environments, especially housing and environ· mental aiutanon to name a few. urban and other uprisings by non-elites that lead to transitions, can disrupt sexual and injection "risk" networks that transmit infectious diseases by changing mixing patterns. they can also weaken urban social networks, their associated protective norms and their informal social control mechanisms which can lead to increased sexual and drug risk behaviors and violence (fullilove ; wallace & wallace , aral , friedman & reid hankins et al ) . for example, the revolution and transition to theocratic rule, and subsequent urban and national conflicts, have been followed by many urban youth in iran engaging in clandestine high-risk sexual and drug behaviors. in palestine, conflicts and restrictions on movement have led to increased fatalities from chronic diseases due to limited access to hospitals and modern medical facilities (union of palestinian medical relief committees); and heroin use and violence-related blood exposure have also increased. social movements "from below" that are rooted both in urban social network dynamics and in underlying patterns of injustice can have both protective and risky effects. for example, the social movements that led to the collapse of the ussr and its dependent governments in other countries-with subsequent increases in sex trade, alcoholism, drug use, tuberculosis, hiv, stis, and mortality in many localities-were based originally on such city-based movements in eastern europe. their impacts on health were mediated by urban social dynamics and structures. some urban social movements have improved health by prevent· ing the spread of hiv, hepatitis and other diseases. examples include movements of (a) gays and lesbians and (b) drug users. these have been rooted in social networks that overlap with risk networks. theories of urban health should include social conflict as a core concept. mechanisms that generate conflicts and the pathways by which conflicts affect health should be a major part of urban health research agendas. p - (c) demographic characteristics of people seen with tuberculosis in lagos state university teaching hospital (lasuth) chest clinic john bako, adewale akeredolu, and wale alabi tuberculosis has become a resurgent public health problem in recent times in the world. because resources are limited, control programmes frequently must target population at greatest risk. the purpose of this study was to study the demographic characteristics of people seen with tuberculosis in lagos state university teaching hospital. a total of patients who have been both radiologically and bacteriologically confirmed tuberculosis patients were used for this study between january and march. ( %) were males, while ( %) were females. notable risk factors among patients with tuberculosis were overcrowding ( . % ), homelessness ( . %) cigarette smoking ( . % ), alcoholism ( . %), non vaccination ( %), secondary contact ( . %) and poor knowledge ( . l 'x,). man· agement history patterns among the patients were herbs ( . 'yo), orthodox medicine ( .h . .l'x.). intervention targeting early-identified groups may be an effective way to reduce the incidence of tuber· culosis. such intervention should focus on health education, modification of life style and improvement of standard of living. p - (c) profiles in urban health in cities of the americas in the countries of the americas, there is an increasing migration of national and international populations to urban centers. this presentation will focus on some of the issues created by this influx of populations, the ways that cities in countries are dealing with them, and the efforts to promote local participation and solutions in management and decision-making. the methodology used to collect this information has been to draw upon and analyze information produced by the mayor's and ministry of health and development offices in each of the cities under consideration. an analysis of the impact of urbanization on health and health determinants will be presented. the information covers issues such as health status by geographic areas within the cities, highlighting issues such as marginality, barriers and physical, economic and cultural constructs and inequities in the delivery of and access to essential services (such as health, education, water, and basic sanitation). issues of governance and citizen participation will be highlighted to provide insight in~o the balance of power and mechanisms for decision-making at the local level. part of the analysis will show the relationship between democratic processes and social participation. public ~olicies will be reviewed to indicate those that are most beneficial in promoting health and overcoming barriers to it, as well as ways of capitalizing on local assets and resources. final~y, evidence of effectiveness of various strategies will be indicated. the presentation will conclude wuh suggesuons for future strategic directions to improve the quality of life and the promotion of health in large urban centers of the americas. introduction: much of the illicit drug in mexico is concentrated in northern border areas. the mile border between the u.s. and mexico is also characterized by migration; the border crossing between tijuana, baja california, mexico and san diego, california, u.s.a. is rep~rt~dl~ the busiest land border crossing in the world. we attempt to describe the migration scene among m ect on drug users (idus) m tijuana and investigate service needs. methods: migration trends were investigated in a cross-sectional study conducted from february to june among idus in tijuana. enrollment criteria included informed consent, being years or older, and having injected drugs within the prior month. subjects were recruited by respondent-dnven sampling and were administered a quantitative survey and serology for hiv, hcv, and syphilis. logistic regression was used to compare idus who had migrated to the u.s. versus those who had not. results: of idus enrolled, % were male and median age and age at first injection were and , respectively. drug combinations injected most frequently in the past months were heroin ( % and crystal methamphetamine mixed with heroin ( %). of those enrolled, responded to quesnons on migration and drug treatment and were included in this analysis. although % had resided in tijuana for at least years, % of users were born outside of baja california. working outside of mexico was common, with % working abroad in the last years ( % in u.s.), and % in the past year. in the last months, % of idus had crossed the border to the u.s., with % crossing at least once per month. those working outside of mexico in the past year were less likely to have ever received substance abuse treatment, [ % vs. %, or . , ] and were marginally less likely to have received drug treatment in the past months [ % vs. %, or . , % ci ( . - . )]. drug use patterns, age and gender did not differ between migrants and non-migrants, although migrants were more likely to report being in need of substance abuse treatment ( % vs. %, respectively). conclusions: migration is common among idus in tijuana. maintaining drug treatment regimens and determining how to best target education and services to a highly mobile population pose challenges to officials on both sides of the border. these data underscore the need to develop coordinated binational prevention and treatment efforts. introduction: despite the expanding literature on the important role public policy plays in influencing the broader determinants of the public\'s health, profound differences exist among jurisdictions in rhe attention placed upon such activities. we take an international perspective on health by examining rhe d?minant public _health paradigms of canada, usa, uk, and sweden and exploring how these paradigms shape public health practice. _method: we carefully analyze governmental and public health agencies documents to discern ~he dommant para~igms driving public health approaches and practices. we also consider the unique paht · cal and economic contexts within each nation and consider how these contexts drive public health pahcy and approaches. . . ~u~: the canadian and usa public health communities -with some exceptions --focus upon m~ividuahzed approaches to risk management. in contrast, the uk and swedish public health scenes are oriented toward broader approaches to health determinants. we find that the extent to which govern· ments, public health agencies and public health workers concern themselves with public policy approaches £<_> ~ddress ~ro.ad~r .determinants of health depends upon the particular health parad'.~ adhered. ~o withm each urisd ctton. and whether a paradigm is adopted depends upon the ideologi~a and pol~ncal context of each nation. nations such as sweden that have a long tradition of public policies promonng social jus~ce an~ equity are naturally receptive to evolving population health concepts. '[he usa represen~ a ~bey en~ro~~t where such is~ues are clear!~ subordinate. ., our findings mdicate that there s a strong political component that influences pubh ~ealth a~proaches and practi~ within the jurisdictions examined. the implications are that those seek· m~ to raise the broader detennmants of the public's health should work in coalition to raise these issues with non-health organizations and age · ca d d th · - badrgrollnd: in developed countries, social inequalities in health have endured or even worsened comparatively throughout different social groups since the s. in france, a country where access to medical and surgical care is theoretically affordable for everyone, health inequalities are among the high· est in western europe. in developing countries, health and access to care have remained critical issues. in madagascar, poverty has even increased in recent years, since the country wenr through political crisis and structural adjustment policies. objectives. we aimed to estimate and compare the impact of socio· economic status but also psychosocial characteristics (social integration, health beliefs, expectations and representation, and psychological characteristics) on the risk of having forgone healthcare in these dif· fercnt contexts. methods: population surveys conducted among random samples of households in some under· served paris neighbourhoods (n= ) and in the whole antananarivo city (n= ) in , using a common individual questionnaire in french and malagasy. reslllts: as expected, the impact of socioeconomic status is stronger in antananarivo than in paris. but, after making adjustments for numerous individual socio-economic and health characteristics, we observed in both cities a higher (and statically significant) occurrence of reponed forgone healthcare among people who have experienced childhood and/or adulthood difficulties (with relative risks up to and .s respectively in paris and antananarivo) and who complained about unhealthy living conditions. in paris, it is also correlated with a lack of trust in health services. coneluions: aside from purely financial hurdles, other individual factors play a role in the non-use of healthcare services. health insurance or free healthcare seems to be necessary hut not sufficienr to achieve an equitable access to care. therefore, health policies must not only focus on the reduction of the financial barriers to healthcare, but also must be supplemented by programmes (e.g. outreach care ser· vices, health education, health promotion programmes) and discretionary local policies tailored to the needs of those with poor health concern .. acknowledgments. this project was supported by the mal>io project and the national institute of statistics (instat) in madagascar, and hy the development research institute (ird) and the avenir programme of the national institute of health and medical research (inserm) in france. for the cities of developing countries, poverty is often described in terms of the living standard~ of slum populations, and there is good reason to believe that the health risks facing these populations are even greater, in some instances, than those facing rural villagers. yet much remains to be learned ahour the connections between urban poverty and health. it is not known what percentage of all urban poor live in slums, that is, in communities of concentrated poverty; neither is it known what proportion of slum residents are, in fact, poor. funhermore, no quantitative accounting is yet available that would sep· arare the health risks of slum life into those due to a househoid•s own poverty and those stemminic from poveny in the surrounding neighborhood. if urban health interventions are to be effectively targeted in developing countries, substantial progress must be made in addressing these cenrral issues. this paper examines poverty and children's health and survival using two large surveys, one a demographic and health survey fielded in urban egypt (with an oversampling of slums) and the other a survey of the slums of allahabad, india. using multivariate statistical methods. we find, in both settings: ( substan· rial evidence of living standards heterogeneity within the slums; ( strong evidence indicating that household-level poverty is an imponant influence on health; and ( ) staristically significant (though less strong) evidence that with household living standards held constant, neighborhood levels of poverty adversely affect health. the paper doses with a discussion of the implications of these findings for the targeting of health and poverty program interventions. p - (a) urban environment and the changing epidemiological surfacr. the cardiovascular ~ &om dorin, nigeria the emergence of cardiovascular diseases had been explained through the concomitants o_f the demographic transition wherein the prevalent causes of morbidity and monality ~hangr pr~mmant infectious diseases to diseases of lifestyle or chronic disease (see deck, ) . a ma or frustration m the v poster sessions case of cvd is its multifactural nature. it is acknowledged that the environment, however defined is the d · f · t' b tween agents and hosts such that chronic disease pathogenesis also reqmre a me an o mterac ion e . spatio-temporal coincidence of these two parties. what is not clear is which among ~ever~( potennal fac· · h b pace exacerbate cvd risk more· and to what extent does the ep dem olog cal trans · tors m t e ur an s ' . . . . tion h othesis relevant in the explanation of urban disease outlook even the developmg cities like nigeri~: thesis paper explorer these within a traditional city in nigeria. . . . the data for the study were obtained from two tertiary level hospitals m the metropolis for years ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) . the data contain reported cases of cvd in the two facilities for the period. adopting a series of parametric and non-parametric statistics, we draw inferences between the observed cases of cvds and various demographic and locational variables of the patients. findings: about % of rhe cases occurred in years ( ) ( ) ( ) coinciding with the last year of military rule with great instability. . % occurred among male. . % also occurred among people aged - years. these are groups who are also likely to engage in most stressful life patterns. ~e study also shows that % of all cases occurred in the frontier wards with minor city areas also havmg their •fair' share. our result conformed with many empirical observation on the elusive nature of causation of cvd. this multifactoral nature had precluded the production of a map of hypertension that would be consistent with ideas of spatial prediction. cvd -cardiovascular diseases. mumbai is the commercial capital of india. as the hub of a rapidly transiting economy, mumbai provides an interesting case study into the health of urban populations in a developing country. with high-rise multimillion-dollar construction projects and crowded slums next to each other, mumbai presents a con· trast in development. there are a host of hi-tech hospitals which provide high quality care to the many who can afford it (including many westerners eager to jump the queue in their healthcare systems-'medical tour· ism'), at the same time there is a overcrowded and strained public healthcare system for those who cannot afford to pay. voluntary organizations are engaged in service provision as well as advocacy. the paper will outline role of the voluntary sector in the context of the development of the healthcare system in mumbai. mumbai has distinct upper, middle and lower economic classes, and the health needs and problems of all three have similarities and differences. these will be showcased, and the response of the healthcare system to these will be documented. a rising hiv prevalence rate, among the highest in india, is a challenge to the mumbai public healthcare system. the role of the voluntary sector in service provision, advocacy, and empowerment of local populations with regards to urban health has been paramount. the emergence of the voluntary sector as a major player in the puzzle of urban mumbai health, and it being visualized as voices of civil society or communiry representatives has advantages as well as pitfalls. this paper will be a unique attempt at examining urban health in india as a complex web of players. the influence of everyday socio·polirical-cultural and economic reality of the urban mumbai population will be a cross cutting theme in the analysis. the paper will thus help in filling a critical void in this context. the paper will thus map out issues of social justice, gender, equiry, effect of environment, through the lens of the role of the voluntary sector to construct a quilt of the realiry of healthcare in mumbai. the successes and failures of a long tradi· tion of the active advocacy and participation of the voluntary sector in trying to achieve social justice in the urban mumbai community will be analyzed. this will help in a better understanding of global urban health, and m how the voluntary sector/ngos fir into the larger picture. ba~und: o~er. half _of n~irobi's . million inhabitants live in illegal informal settlements that compose yo of the city s res dent al land area. the majority of slum residents lack access to proper san· iranon and a clean and adequate water supply. this research was designed to gain a clearer understand· mg of what kappr · · · h f . . opnate samtanon means or the urban poor, to determine the linkages between gender, hvehhoods, and access to water and sanitation, and to assess the ability of community sanitation blocks to meet water and sanitation needs in urban areas. m~tbojs_: _a household survey, gender specific focus groups and key informant interviews were conducted m maih saba, a peri-urban informal settlement. qualitative and quantitative research tools were u~ to asses~ the impact and effectiveness of community sanitation blocks in two informal settlements. results ropna e samtarmn me u es not only safe and clean latrines, but also provision ° adequate drainage and access to water supply for cleaning of clothes and homes. safety and cleanliness poster sessions v were priorities for women in latrines. levels of poverty within the informal settlements were identified and access to water and sanitation services improved with increased income. environmental health problems related to inadequate water and sanitation remain a problem for all residents. community sanitation blocks have improved the overall local environment and usage is far greater than envisioned in the design phase. women and children use the blocks less than men. this is a result of financial, social, and safety constraints. the results highlight the importance a need to expand participatory approaches for the design of water and sanitation interventions for the urban poor. plans need to recognize "appropriate sanitation" goes beyond provision of latrines and gender and socioeconomic differences must be taken into account. lessons and resources from pilot projects must be learned from, shared and leveraged so that solutions can be scaled up. underlying all the challenges facing improving water and sanitation for the urban poor are issues of land tenure. p - (c) integrating tqm (total quality management), good governance and social mobilization principles in health promotion leadership training programmes for new urban settings in countries/ areas: the prolead experience susan mercado, faren abdelaziz, and dorjursen bayarsaikhan introduction: globalization and urbanization have resulted in "new urban settings" characterized by a radical process of change with positive and negative effects, increased inequities, greater environmental impacts, expanding metropolitan areas and fast-growing slums and vulnerable populations. the key role of municipal health governance in mitigating and modulating these processes cannot be overemphasized. new and more effective ways of working with a wide variety of stakeholders is an underpinning theme for good governance in new urban settings. in relation to this, organizing and sustaining infrastructure and financing to promote health in cities through better governance is of paramount importance. there is a wealth of information on how health promotion can be enhanced in cities. despite this, appropriate capacity building programmes to enable municipal players to effectively respond to the challenges and impacts on health of globalization, urbanization and increasing inequity in new urban settings are deficient. the who kobe centre, (funded by the kobe group( and in collaboration with regional offices (emro, searo, wpro) with initial support from the japan voluntary contribution, developed a health promotion leadership training programme called "prolead" that focuses on new and autonomous structures and sustainable financing for health promotion in the context of new urban settings. methodology: country and/or city-level teams from areas, (china, fiji, india, japan, lebanon, malaysia, mongolia, oman, philippines, republic of korea, tonga and viet nam) worked on projects to advance health promotion infrastructure and financing in their areas over a month period. tools were provided to integrate principles of total quality management, good governance and social mobili .ation. results: six countries/areas have commenced projects on earmarking of tobacco and alcohol taxes for health, moblization of sports and arts organizations, integration of health promotion and social health insurance, organizational reforms, training in advocacy and lobbying, private sector and corporate mobilization and community mobilization. results from the other six areas will be reported in ..;obcr. conclusions: total quality management, good governance and social mobilization principles and skills are useful and relevant for helping municipal teams focus on strategic interventions to address complex and overwhelming determinants of health at the municipal level. the prolead training programmes hopes to inform other processes for building health promotion leadership capacity for new urban settings. the impact of city living and urbanization on the health of citizens in developing countries has received increasing attention in recent years. urban areas contribute largely to national economies. however, rapid and unplanned urban growth is often associated with poverty, environmental degradation and population demands that outstrip service capacity which conditions place human health at risk. local and national governments as well as multi national organizations are all grappling with the challenges of urbanization. with limited data and information available, urban health characteristics, including the types, quantities, locations and sources in kampala, are largely unknown. moreover, there is n? basis for assessing the impact of the resultant initiatives to improve health ~onditions amo~g ~o": ": um ties settled in unplanned areas. since urban areas are more than the aggregation ?f ~?pie w~th md_ v dual risk factors and health care needs, this paper argues that factors beyond the md v dual, mcludmg the poster sessions v · i d h · i · ment and systems of health and social services are determinants of the health soc a an p ys ca environ . of urban populations. however, as part of an ongoing study? ~s pape~ .addresses the basic concerns of urban health in kampala city. while applying the "urban hvmg conditions and the urban heal~ pen· alty" frameworks, this paper use aggregated urban health d~ta t~ explore the role of place an~ st tu· tions in shaping health and well-being of the population m kampala by understanding how characteristics of the urban environment and specific features of the city are causally related to health of invisible and forgotten urban poor population: results i~dica~e that a .range o~ urb~n he~l~h hazards m the city of kampala include substandard housing, crowdmg, mdoor air poll.ut on, msuff c ent a~d con· taminated water, inadequate sanitation and solid waste management services, vector borne .diseases, industrial waste increased motor vehicle traffic among others. the impact of these on the envtronment and community.health are mutually reinforcing. arising out of the withdra"'.al of city pl~nning systems and service delivery systems or just planning failure, thousands of people part cularl~ low-mc~me groups have been pushed to the most undesirable sections of the city where they are faced with ~ va_r ety ~f envj· ronmental insults. the number of initiatives to improve urban health is, however, growing mvolvjng the interaction of many sectors (health, environment, housing, energy, transportation and urban planning) and stakeholders (local government, non governmental organizations, aid donors and local community groups). key words: urban health governance, health risks, kampala. introduction: the viability of urban communities is dependent upon reliable and affordable mass transit. in particular, subway systems play an especially important role in the mass transit network, since they provide service to vast numbers of ridersseven of the subway systems worldwide report over one billion passenger rides each year. surprisingly, given the large number of people potentially affected, very little is known about the health and safety hazards that could affect both passengers and transit workers; these include physical (e.g., noise, vibration, accidents, electrified sources, temperature extremes), biological (e.g., transmission of infectious diseases, either through person-to-person spread or vector-borne, for example, through rodents), chemical (e.g., exposure to toxic and irritant chemicals and metals, gas emissions, fumes), electro-magnetic radiation, and psychosocial (e.g., violence, workstress). more recently, we need to consider the threat of terrorism, which could take the form of a mass casualty event (e.g., resulting from conventional incendiary devices), radiological attack (e.g., "dirty bomb"), chemical terrorist attack (e.g., sarin gas), or bioterrorist attack (e.g., weapons grade anthrax). given the large number of riders and workers potentially at risk, the public health implications are considerable. methods: to assess the hazards associated with subways, a structured review of the (english) litera· ture was conducted. ruults: based on our review, non-violent crime, followed by accidents, and violent crimes are most prevalent. compared to all other forms of mass transit, subways present greater health and safety risks. however, the rate of subway associated fatalities is much lower than the fatality rate associated with automobile travel ( . vs. . per million passenger miles), and cities with high subway ridership rates have a % lower per capita rate of transportation related fatalities than low ridership cities ( . versus . annual deaths per , residents). available data also suggest that subway noise levels and levels of air pollutants may exceed recommended levels. . ~: there is a paucity of published research examining the health and safety hazards associated with subways. most of the available data came from government agencies, who rely on passively reported data. research is warranted on this topic for a number of reasons, not only to address important knowled~ gaps, but also because the population at potential risk is large. importantly, from an urban perspecnve, the benefits of mass transit are optimized by high ridership ratesand these could be adversely affu:ted by unsafe conditions and health and safety concerns. veena joshi, jeremy lim. and benjamin chua ~ ~rban health issues have moved beyond infectious diseases and now centre largely on chrome diseases. diabetes is one of the most prevalent non-communicable diseases globally. % of adult ¥ benefit in providing splash pads in more parks. given the high temperature and humidity of london summers, this is an important aspect and asset of parks. interviewed parents claimed to visit city parks anywhere between to days per week. corrduion: given that the vast majority of canadian children are insufficiently active to gain health benefits, identifying effective qualities of local parks, that may support and foster physical activity is essential. strategies to promote activity within children's environments are an important health initiative. the results from this study have implications for city planners and policy makers; parents' opinions of, and use of city parks provides feedback as to the state current local parks, and modifications that should be made for new ones being developed. this study may also provide important feedback for health promoters trying to advocate for physical activity among children. introdt clion: a rapidly increasing proportion of urban dwellers in africa live below the poverty line in overcrowded slums characterized by uncollected garbage, unsafe water, and deficient sanitation and overflowing sewers. this growth of urban poverty challenges the commonly held assumption that urban populations enjoy better health than their rural counterparts. the objectives of this study are (i) to compare the vaccination status, and morbidity and mortality outcomes among children in the slums of nairobi with rural kenya, and (ii) to examine the factors associated with poor child health in the slums. we use data from demographic and health survey representative of all slum settlements in nairobi city carried out in by the african population & health research center. a total of , women aged - from , households were interviewed. our sample consists of , children aged - months. the comparison data are from the kenya demographic and health survey. the outcomes of interest include child vaccination status, morbidity (diarrhea, fever and cough) and mortality, all dichotomized. socioeconomic, environmental, demographic, and behavioral factors, as well as child and mother characteristics, are included in the multivariate analyses. multilevel logistic regression models are used. l'nlimin ry rest lts: about % of children in the slums had diarrhea in the two weeks prior to the survey, compared to % of rural children. these disparities between the urban poor anj the rural residents are also observed for fever ( % against %), cough ( % versus %), infant mortality ( / against / ), and complete vaccination ( % against %). preliminary multivariate results indicate that health service utilization and maternal education have the strongest predictive power on child morbidity and mortality in the slums, and that household wealth has only minor, statistically insignificant effects. conclruion: the superiority of health of urban children, compared with their rural counterparts, masks significant disparities within urban areas. compared to rural residents, children of slum dwellers in nairobi are sicker, are less likely to utilize health services when sick, and stand greater risk to die. our results suggest policies and programs contributing to the attainment of the millennium development goal on child health should pay particular attention to the urban poor. the insignificance of socioeconomic status suggests that poor health outcomes in these communities are compounded by poor environmental sanitation and behavioral factors that could partly be improved through female education and behavior change communication. introduction: historic trade city surat with its industrial and political peace has remained a center of attraction for people from all the comers of india resulting in to pop.ulatio~ explosio~ a~d stressed social and service infrastructure. the topography,dimate and demographic profile of the city s threat to the healthy environment. aim of this analysis is to review the impact of managemt'nt reform on health indicators. method: this paper is an analysis of the changing profile of population, sanitary infr~s~rucrure, local self government management and public health service reform, secondary health stat st cs data, health indicator and process monitoring of years. . . health of entire city and challenge to the management system. plague outbr~ak ( ) was the turning point in the history of civic service management including p~blic ~e~lth service management. ~ocal self government management system was revitalized by reg~lar_ field v s ts o~ al~ cadre~, _decentraltzanon of power and responsibility, equity, regular vigilant momtormg, commumcanon facility, ream_approach and people participation. reform in public health service management was throu_gh stan~~rd zed intervention protocol, innovative intervention, public private partnership, community part c panon, academic and service institute collaboration and research. sanitation service coverage have reached nearer to universal. area covered by safe water supply reached to %( ) from % ( ) and underground drainage to % ( ) from % ( ) the overhauling of the system have reflected on health indicators of vector and water born disease. malaria spr declined to . ( ) from . 'yo(! ) and diarrhea case report declined to ( ) from ( ). except dengue fever in no major disease outbreaks are reported after . city is recipient of international/national awards/ranking for these achievements. the health department have developed an evidence and experience based intervention and monitoring system and protocol for routine as well as disaster situation. the health service and management structure of surat city have emerged as an urban health model for the country. introduction: the center for healthy communities (chc) in the department of family and com· munity medicine at the medical college of wisconsin developed a pilot project to: ) assess the know· ledge, attitudes, and behaviors of female milwaukee public housing residents related to breast cancer; develop culturally and literacy appropriate education and screening modules; ) implement the developed modules; ) evaluate the modules; and ) provide follow-up services. using a community-based participatory research model the chc worked collaboratively with on-site nurse case management to meet these objectives. methods: a "breast health kick off event" was held at four separate milwaukee public housing sites for elderly and disabled adults. female residents were invited to complete a -item breast health survey, designed to accommodate various literacy levels. responses were anonymous and voluntary. the survey asked women about their previous physical exams for breast health, and then presented a series of state· ments about breast cancer to determine any existing myths. the final part gathered information about personal risk for breast cancer, the highest level of education completed, and whether the respondents h;td ever used hormone replacement therapy and/or consumed alcohol. responses were collected for descriptive analysis. results: a total of surveys (representing % of the total female population in the four sites) were completed and analyzed. % reported that they had a physical exam in the previous rwo years. % of respondents indicated they never had been diagnosed with breast cancer. % reported having had a mammogram and % having had a clinical breast exam. those that never had a mammogram reported a fear of what the provider would discover or there were not any current breast problems ro warrant an exam. % agreed that finding breast cancer early could lower the chance of dying of cancer. over % reported that mammograms were helpful in finding cancer. however, % believed that hav· ing a mammogram actually prevents breast cancer. % indicated that mammograms actually cause cancer and % reported that a woman should get a mammogram only if there is breast cancer in her family. conclusion: this survey indicates that current information about the importance of mammograms and clinical breast exams is reaching traditionally underserved women. yet there are still critical oppor· tunities to provide valuable education on breast health. this pilot study can serve as a tool for shaping future studies of health education messages for underserved populations. located in a yourh serv· ~ng agency m downtow~ ottawa, the clinic brings together community partners to provide primary medical care. and dent~i hygiene t? the street youths of ottawa aged - . the primary goal of the project is to provide accessible, coordinated, comprehensive health and dental care to vulnerable adolescents. these efforts respond to the pre-existing body of evidence suggesting that the principle barrier in accessing such care for these youths are feelings of intimidation and vulnerability in the face of a complex healthcare system. the bruyere fhn satellite clinic is located in the basement of a downtown drop-in and brings together a family medicine physician and her residents, a dental hygienist and her nd year students, a nurse practitioner, a chiropodist and public health nurses to provide primary care. the clinic has been extremely busy and well received by the youth. this workshop will demonstrate how five community organizations have come together to meet the needs of high risk youths in ottawa. this presentation will showcase the development of the clinic from its inception through its first year including reaction of the youths, partnerships and lessons learned. it will also focus on its sustainability without continued funding. we hope to have developed a model of service delivery that could be reproduced and sustained in other large cities with faculties of medicine. methods: non-randomized, mixed method design involving a process and impact evaluation. data collection-qualitative-a) semi structured interviews with providers & partners b)focus groups with youth quantitative a)electronic medical records for months records (budget, photos, project information). results: ) successfully built and opened a medicaudental clinic which will celebrate its year anniversary in august. ) over youths have been seen, and we have had over visits. conclusion: ) the clinic will continue to operate beyond the month project funding. ) the health of high risk youth in ottawa will continue to improve due to increased access to medical services. p - (a) health services -for the citizens of bangalore -past, present and future savita sathyagala, girish rao, thandavamurthy shetty, and subhash chandra bangalore city, the capital of karnataka with . million is the th most populous city in india; supporting % of the urban population of karnataka, it is considered as one of the fastest growing cities in india. known as the 'silicon valley of india', bangalore is nearly years old. bangalore city corporation (bmp), is a local self government and has the statutory commitment to provide to the citizens of bangalore: good roads, sanitation, street lighting, safe drinking water apart from other social obligations, cultural development and poverty alleviation activities. providing preventive and promotive heahh services is also a specific component. the objective of this study was to review the planning process with respect to health care services in the period since india independence; the specific research questions being what has been the strategies adopted by the city planners to address to the growing needs of the population amidst the background of the different strategies adopted by the country as a whole. three broad rime ranges have been considered for analysis: the s, s and the s. the salient results are: major area of focus has been on the maternal and child care with activities ranging from day-care to in-patient-care; though the number of institutions have grown from to the current day , their distribution has been far from satisfactory; obtaining support from the india population projects and major upgradarions have been undertaken in terms of infrastructure; over the years, in addition to the dispensaries of modern system of medicine, local traditional systems have also been initiated; the city has partnered with the healthy cities campaign with mixed success; disease surveillance, addressing the problems related to the emerging non-communicable diseases including mental health and road traffic injuries are still in its infancy. isolated attempts have been made to address the risks groups of elderly care and adolescent care. what stands out remarkably amongst the cities achievements is its ability to elicit participation from ngos, cbos and neighbourhood groups. however, the harnessing of this ability into the health sector cannot be said totally successful. the moot question in all the above observed development are: has the city rationally addressed it planning needs? the progress made so far can be considered as stuttered. the analysis and its presentation would identify the key posirive elements in the growth of banglore city and spell a framework for the new public health. introduction: anaemia associated with pregnancy is a major public health problem all over the world. different studies in different parts of india shown prevalence of anaemia between - %. anaemia remains a serious health problem in pregnancy despite of strong action taken by the government of india through national programmes. in the present study we identified th~ social beha~iors, responsible for low compliance of if a tablets consumption in pregnancy at community level and intervention was given with new modified behaviors on trial bases. . in vadodara urban. anganwadies out of were selected from the list by random sampling for tips (trials of improved practices) study. . . participants: pregnant women ( , intervention group+ , control. group) registered m the above anganwadies. study was conducted in to three phases: phase: . formative research and baseline survey (frbs). data was collected from all pregnant women to identify behaviors that are responsible for low compliance of ifa tablets. both qualitative and quantitative data were collected. haemoglobin was estimated of all pregnant women by haemo-cue. phase: . phase of tips. behaviors were identified both social & clinical for low compliance of ifa tablets consumption in pregnancy from frbs and against those, modified behaviors were proposed to pregnant women in the intervention group on trial bases by health education. trial period of weeks was given for trial of new behaviors to pregnant women in the interven· tion group. phase: . in this phase, feedbacks on behaviors tried or not tried were taken from pregnant women in intervention group. haemoglobin estimation was carried out again in all pregnant women. at the end of the study, messages were formulated on the bases of feedbacks from the pregnant women. results: all pregnant women in the intervention group had given positive feedback on new modified behaviors after intervention. mean haemoglobin concentration was higher in intervention group ( . ± . gm%) than control group ( . ± . gm%). ifa tablets compliance was improved in intervention group ( . %) than control group ( . %). conclusion: all pregnant women got benefits after trial of new modified behaviors in the intervention group. messages were formulated from the new modified behaviors, which can be used for longterm strategies for anaemia control in the community. introduction: in order to develop a comprehensive mch handbook for pregnant women and to assess its effect among them, a pilot study was carried out at the maternal and child health training institute (mchti), in dhaka, bangladesh. methods: from mchti a sample of pregnant women was selected and all subjects were women who were attending the first visit of their current pregnancy by using a random sampling method. of the subjects, women were given the mch handbook as case and women were not given the handbook as control. data on pre and post intervention of the handbook from the cases and controls were taken from data recording forms between the st of november and st of october, and data was analysed by using a multilevel analysis approach. this was a hospital-based action (case-control) research, and was applied in order to measure the outcome of pre and post intervention following the introduction of the handbook. data was used to assess the effects of utilisation of the handbook on women's knowledge, practice and utilisation of mch services. results: this study showed that the change of knowledge about antenatal care visits was . % among case mothers. knowledge of danger signs improved . %, breast feeding results . %, vaccination . % and family planning results improved . % among case. results showed some positive changes in women's attitudes among case mothers and study showed the change of practice in antenatal care visits was .u. % in the case. other notable changes were: change of practice in case mother's tetanus toxoid (ti), . %; and family planning . %. in addition, handbook assessment study indicated that most women brought the handbook on subsequent visits ( . %), the handbook was highly utilised (i.e. it was read by . %, filled-in by . %, and was used as a health education tool by . %). most women kept the handbook ( . %) and found it highly useful ( . %) with a high client satisfaction rate of . %. conclusion: pregnant women in the case group had higher knowledge, better practices, and higher utilisation of mch services than mothers in the control groups who used alternative health cards. if the handbook is developed with a focus on utilising a problem-oriented approach and involving the recomendations .of end~users, it is anticipated that the mch handbook will contribute significantly to ensuring the quahry of hfe of women and their children in bangladesh. after several meetmgs to identify the needs of the community, a faso clinic was opened at ncfs. health care professionals from smh joined with developmental and social service workers from ncfs to implement the faso diagnostic process and to provide culturally appropriate after-care. the clinic is unique in that its focus is the high risk urban aboriginal population of toronto. it accepts referrals of not only children and youth, but also of adults. lessons learned: response to the faso clinic at native child and family services has been overwhelming. aboriginal children with f asd are receiving timely diagnosis and interventions. aboriginal youth and adults who have been struggling with poveny, substance abuse, and homelessness are more willing to enter the ncfs centre for diagnosis and treatment. aboriginal infants prenatally exposed to alcohol born at st. michael's hospital or referred by other centres have access to the developmental programs located in both of the partnering agencies. the presentation will describe the clinic's development, and will detail the outcomes described, including interventions unique to the aboriginal culture. p - (c) seeds, soil, and stories: an exploration of community gardening in southeast toronto carolin taran, sarah wakefield, jennifer reynolds, and fiona yeudall introduction: community gardens are increasingly seen as a mechanism for improving nutrition and increasing food security in urban neighbourhoods, but the evidence available to support these claims is limited. in order to begin to address this gap in a way that is respectful of community knowledge and needs, the urban gardening research opportunities workgroup (ugrow) project explored the benefits and potential risks of community gardening in southeast toronto. the project used a community-based research (cbr) model to assess community gardens as a means of improving local health. the research process included interviews, focus groups, and participant observation (documented in field notes). we also directly engaged the community in the research process, through co-learning activities and community events which allowed participants to express their views and comment on emerging results. most of the research was conducted by a community-based research associate, herself a community gardener. key results were derived from these various sources through line-by-line coding of interview transcripts and field note review, an interactive and iterative process which involved both academic and community partners. results: these various data sources all suggest that enhanced health and access to fresh produce are important components of the gardening experience. they also highlight the central importance of empowering and community-building aspects of gardening to gardeners. community gardens were thought to play a role in developing friendships and social support, sharing food and other resources, appreciating cultural diversity, learning together, enhancing local place attachment and stewardship, and mobilizing to solve local problems (both inside and outside the garden). potential challenges to community gardens as a mechanism for communiry development include bureaucratic resistance to gardens, insecure land tenure and access, concerns about soil contamination, and a lack of awareness and under· standing by community members and decision-makers of all kinds. conclusion: the results highlight many health and broader social benefits experienced by commu· nity gardeners. they also point to the need for greater support for community gardening programs, par· ticularly ongoing the ongoing provision of resources and education programs to support gardens in their many roles. this research project is supported by the wellesley central health corporation and the centre for urban health initiatives, a cihr funded centre for research development hased at the univer· sity of toronto. p - (c) developing resiliency in children living in disadvantaged neighbourhoods sarah farrell, lorna weigand, and wayne hammond the traditional idea of targeting risk reduction by focusing on the development of eff~ctive coping strategies and educational programs has merit in light of the research reportmg_ that_ ~ lupl.e forms of problem behaviour consistently appear to be predicted by increasing exposure to den_uf able risk factors. as a result, many of the disadvantaged child and youth studies have focused on trymg to better _unde.r· stand the multiple risk factors that increase the likelihood of the development of at nsk behaviour m ch ldren/youth and the potential implications for prevention. this in turn has led t_o. the conclus on that community and health programs need to focus on risk reduction by helpm~ md v duals develop more effective coping strategies and a better understanding of the limitations of cenam pathologies, problematic v poster sessions coping behaviours and risk factors potentially inheren~ in high needs co~unities. ~owever, another ai:ea of research has proposed that preventative interventions should cons de~ .~rotecnve fa~ors alo~~ with reducing risk factors. as opposed to just emphasizing problems, vulnerab ht es, and deficits, a res liencybased perspective holds the belief that children, youth and their families. have strengths, reso~ce.s and the ability to cope with significant adversity in ways that are not only effective, but tend to result m mcreased ability to constructively respond to future adversity. with this in mind, a participatory research project sponsored by the united way of greater toronto was initiated to evaluate and determine the resiliency profiles of children - years (n = ) of recent immigrant families living in significantly disadvantaged communities in the toronto area. the presentation will provide an overview of the identified protective factors (both intrinsic and extrinsic) and resiliency profiles in an aggregated format as well as a summary of how the children and their parents interpreted and explained these strength-based results. as part of the focus groups, current community programs and services were examined by the participants as to what might be best practices for supporting the development and maintaining of resiliency in children, families and communities. it was proposed that the community model of assessing resiliency and protective factors as well as proposed best strength-based practice could serve as a guide for all in the community sector who provide services and programs to those in disadvantaged neighbourhoods. p - (c) naloxone by prescription in san francisco, ca and new york, ny emalie huriaux the harm reduction coalition's overdose project works to reduce the number of fatal overdoses to zero. located in new york, ny and san francisco, ca, the overdose project provides overdose education for social service providers, single-room occupancy hotel (sro) residents, and syringe exchange participants. the project also conducts an innovative naloxone prescription program, providing naloxone, an opiate antagonist traditionally administered by paramedics to temporarily reverse the effects of opiate overdose, to injection drug users (idus). we will describe how naloxone distribution became a reality in new york and san francisco, how the project works, and our results. the naloxone prescription program utilizes multiple models to reach idus, including sro-and street-based trainings, and office-based trainings at syringe exchange sites. trainings include information on overdose prevention, recognition, and response. a clinician conducts a medical intake with participants and provides them with pre-filled units of naloxone. in new york, funding was initially provided by tides foundation. new york city council provides current funding. new york department of mental health and hygiene provides program oversight. while the new york project was initiated in june , over half the trainings have been since march . in san francisco, california endowment, tides foundation, and san francisco department of public health (sfdph) provide funding. in addition, sfdph purchases naloxone and provides clinicians who conduct medical intakes with participants. trainings have been conducted since november . to date, nearly individuals have been trained and provided with naloxone. approximately of them have returned for refills and reported that they used naloxone to reverse an opiate-related overdose. limited episodes of adverse effects have been reported, including vomiting, seizure, and "loss of friendship." in new york, individuals have been trained and provided with naloxone. over overdose reversals have been reported. over half of the participants in new york have been trained in the south bronx, the area of new york with the highest rate of overdose fatalities. in san francisco, individuals have been trained and provided with naloxone. over overdose reversals have been reported. the majority of the participants in san francisco have been trained in the tenderloin, th street corridor, and mission, areas with the highest rates of overdose fatalities. the experience of the overdose project in both cities indicates that providing idus low-threshold access to naloxone and overdose information is a cost-effective, efficient, and safe intervention to prevent accidental death in this population. p - (c) successful strategies to regulate nuisance liquor stores using community mobilization, law enforcement, city council, merchants and researchers tahra goraya presenta~ion _will discuss ~uccessful environmental and public policy strategies employed in one southen: cahf?rmna commumty to remedy problems associated with nuisance liquor stores. participants ~ be given tools to understand the importance of utilizing various substance abuse prevention str~tegi~ to change local policies and the importance of involving various sectors in the community to a~_ st with and advocate for community-wide policy changes. recent policy successes from the commultles of pa~ad~na and altad~na will highlight the collaborative process by which the community mobilized resulnng m several ordmances, how local law enforcement was given more authority to monitor poster sessions v nonconforming liquor stores, how collaborative efforts with liquor store owners helped to remove high alcohol content alcohol products from their establishments and how a community-based organiz,uion worked with local legislators to introduce statewide legislation regarding the regulation of nuisance liquor outlets. p - (c) "dialogue on sex and life": a reliable health promotion tool among street-involved youth beth hayhoe and tracey methven introduction: street involved youth are a marginalized population that participate in extremely risky behaviours and have multiple health issues. unfortunately, because of previous abuses and negative experiences, they also have an extreme distrust of the adults who could help them. in , toronto public health granted funding to a non governmental, nor for profit drop-in centre for street youth aged - , to educate them about how to decrease rhe risk of acquiring hiv. since then the funding has been renewed yearly and the program has evolved as needed in order to target the maximum number of youth and provide them with vital information in a candid and enjoyable atmosphere. methods: using a retrospective analysis of the six years of data gathered from the "dialogue on sex and life" program, the researchers examined the number of youth involved, the kinds of things discussed, and the number of youth trained as peer leaders. also reviewed, was written feedback from the weekly logs, and anecdotal outcomes noted by the facilitators and other staff in the organization. results: over the five year period of this program, many of youth have participated in one hour sessions of candid discussion regarding a wide range of topics including sexual health, drug use, harm reduction, relationship issues, parenting, street culture, safety and life skills. many were new youth who had not participated in the program before and were often new to the street. some of the youth were given specific training regarding facilitation skills, sexual anatomy and physiology, birth control, sexually transmitted infections, hiv, substance use/abuse, harm reduction, relationships and discussion of their next steps/future plans following completion of the training. feedback has been overwhelmingly positive and stories of life changing decisions have been reported. conclusion: clearly, this program is a successful tool to reach street involved youth who may otherwise be wary of adults and their beliefs. based on data from the evaluation, recommendations have been made to public health to expand the funding and the training for peer leaders in order ro target between - new youth per year, increase the total numbers of youth reached and to increase the level of knowledge among the peer leaders. p - (c) access to identification and services jane kali replacing identification has become increasingly more complex as rhe government identification issuing offices introduce new requirements rhar create significant barriers for homeless people to replace their id. new forms of identification have also been introduced that art' not accessible to homekss peoplt-(e.g. the permanent resident card). ar rhe same time, many service providers continue to require identifi· cation ro access supports such as income, housing, food, health care, employment and employmt·nt training programs. street health, as well as a number of other agencies and community health centres, h, , been assisting with identification replacement for homeless peoplt· for a number of years. the rnrrt·nr challenges inherent within new replacement requirements, as well as the introduction of new forn ' of identification, have resulted in further barriers homeless people encounter when rrring to access t:ssential services. street health has been highlighting these issues to government identification issuing offices, as well as policy makers, in an effort to ensure rhar people who are homeless and marginalized have ac'ess to needed essential services. bandar is a somali word for •·a safe place." the bandar research project is the product of the regent park community health centre. the research looks ar the increasing number of somali and afri· can men in the homeless and precariously house population in the inner city core of down~own toronto. in the first phase of the pilot project, a needs assessment was conducted to dennfy barners and issues faced by rhe somali and other african men who are homeless and have add cr ns issues. th_e second phase of rhe research project was to identify long rerm resources and service delivery mechamsms that v poster sessions would enhance the abiity of this population to better access detox, treatment, and post treatment ser· vices. the final phase of the project was to facilitate the development of a conceptual model of seamless continual services and supports from the streets to detox to treatment to long term rehabilitation to housing. "between the pestle and mortar" -safe place. p - (c) successful methods for studying transient populations while improving public health beth hayhoe, ruth ewert, eileen mcmahon, and dan jang introduction: street youth are a group that do not regularly access healthcare because of their mis· trust of adults. when they do access health care, it is usually for issues severe enough for hospitalization or for episodic care in community clinics. health promotion and illness prevention is rarely a part of their thinking. thus, standard public health measures implemented in a more stable population do not work in this group. for example, pap tests, which have dearly been shown to decrease prevalence of cer· vical cancer, are rarely done and when they are, rarely followed up. methods to meet the health care needs and increase the health of this population are frequently being sought. methods: a drop-in centre for street youth in canada has participated in several studies investigating sexual health in both men and women. we required the sponsoring agencies to pay the youth for their rime, even though the testing they were undergoing was necessary according to public health stan· dards. we surmised that this would increase both initial participation and return. results: many results requiring intervention have been detected. given the transient nature of this population, return rates have been encouraging so far. conclusion: it seems evident that even a small incentive for this population increases participation in needed health examinations and studies. it is possible that matching the initial and follow-up incentives would increase the return rate even further. the fact that the youth were recruited on site, and not from any external advertising, indicates that studies done where youth trust the staff, are more likely to be successful. the presentation will share the results of the "empowering stroke prevention project" which incor· porated self-help mutual aids strategies as a health promotion methodology. the presentation will include project's theoretical basis, methodology, outcomes and evaluation results. self-help methodology has proven successful in consumer involvement and behaviour modification in "at risk," "marginalized" settings. self-help is a process of learning with and from each other which provides participants oppor· tunities for support in dealing with a problem, issue, condition or need. self-help groups are mechanisms for the participants to investigate existing solutions and discover alternatives, empowering themselves in this process. learning dynamic in self-help groups is similar to that of cooperative learning and peertraining, has proven successful, effective and efficient (haller et al, ) . the mutual support provided by participation in these groups is documented as contributory factor in the improved health of those involved. cognizant of the above theoretical basis, in the self-help resource centre initiated the "empowering stroke prevention project." the project was implemented after the input from health organizations, a scan of more than resources and an in-depth analysis of risk-factor-specific stroke prevention materials indicated the need for such a program. the project objectives were:• to develop a holistic and empowering health promotion model for stroke prevention that incorporates selfhelp and peer support strategies. • to develop educational materials that place modifiable risk factors and lifestyle information in a relevant context that validates project participants' life experiences and perspectives.• to educate members of at-risk communities about the modifiable risk factors associated with stroke, and promote healthy living. to achieve the above, a diverse group of community members were engaged as "co-editors" in the development of stroke prevention education materials which reflected and validated their life experiences. these community members received training to become lay health promoters (trained volunteer peer facilitators). in collaboration with local health organizations, these trained lay health promoters were then supported in organizing their own community-based stroke prevention activities. in addition, an educational booklet written in plain language, entitled healthy ways to prevent stroke: a guide for you, and a companion guide called healthy ways to pre· vent stroke: a facilitator's guide were produced. the presentation will include the results of a tw<>tiered evaluation of the program methodology, educational materials and the use of the materials beyond the life of the project. this poster presentation will focus on the development and structure of an innovative street outreach service that assists individuals who struggle mental illness/addictions and are experiencing homelessness. the mental health/outreach team at public health and community services (phcs) of hamilton, ontario assists individuals in reconnecting with health and social services. each worker brings to the ream his or her own skills-set, rendering it extremely effective at addressing the multidimensional and complex needs of clients. using a capacity building framework, each ream member is employed under a service contract between public health and community services and a local grassroots agency. there are public health nurses (phn), two of whom run a street health centre and one of canada's oldest and most successful needle exchange programs, mental health workers, housing specialists, a harm reduction worker, youth workers, and a united church minister, to name a few. a community advisory board, composed of consumers and professionals, advises the program quarterly. the program is featured on raising the roors 'shared learnings on homelessness' website at www.sharedlearnings.ca. through our poster presentation participants will learn how to create effective partnerships between government and grassroots agencies using a capacity building model that builds on existing programs. this study aims to assess the effects of broadcasting a series of documentary and drama videos, intended to provide information about the bc healthguide program in farsi, on the awareness about and the patterns of the service usage among farsi-speaking communities in the greater vancouver area. the major goals of the present study were twofold; ( ) to compare two methods of communications (direct vs. indirect messages) on the attitudes and perceptions of the viewers regarding the credibility of messengers and the relevance of the information provided in the videos, and ( ) to compare and contrast the impact of providing health information (i.e., the produced videos) via local tvs with the same materials when presented in group sessions (using vcr) on participants' attitudes and perceptions cowards the bc healrhguide services. results: through a telephone survey, farsi-speaking adults were interviewed in november and december . the preliminary findings show that % of the participants had seen the aired videos, from which, % watched at least one of the 'drama' clips, % watched only 'documentary' clip, and % watched both types of video. in addition, % of the respondents claimed that they were aware about the program before watching the aired videos, while % said they leaned about the services only after watching the videos. from this group, % said they called the bchg for their own or their "hildren's health problems in the past month. % also indicated that they would use the services in the future whenever it would be needed. % considered the videos as "very good" and thought they rnuld deliver relevant messages and % expressed their wish to increase the variety of subjects (produ\:e more videos) and increase the frequency of video dips. conclusion: the results of this study will assist public health specialists in bc who want to choose the best medium for disseminating information and apply communication interventions in multi\:ultural communities. introduction: many theorists and practitioners in community-based research (cbr) and knowledge transfer (kt) strongly advocate for involvement of potential users of research in the development of research projects, yet few examples of such involvement exist for urban workplace health interventions. we describe the process of developing a collaborative research program. methods: four different sets of stakeholders were identified as potential contributors to and users of the research: workplace health policy makers, employers, trade unions, and health and safety associations. representatives of these stakeholders formed an advisory committee which met quarterly. over the month research development period, an additional meetings were held between resc:ar~h~rs and stakeholders. in keeping with participant observation approaches, field notes of group and md v ~ ual meetings were kept by the two co-authors. emails and telephone calls were also documented. qu~h tative approaches to textual analysis were used, with particular attention paid to collaborattve v poster sessions relationships established (as per cbr), indicators of stakeholders' knowledge utilization (as per kt), and transformations of the proposed research (as per cbr). results: despite initial strong differences of opinion both among stakeho~ders .an~ between stakeholders and researchers, goodwill was noted among all involved. acts of rec~proc ty included mu.rual sharing of assessment tools, guidance on data utilization to stakeho~der orga~ zat ns, and suggestions on workplace recruitment to researchers. stakeholders demonstrated mcreases m concep~ual. un~erstand ing of workplace health e.g. they more commonly discussed more complex,. psychosocial md cators of organizational health. stakeholders made instrumental use of shared materials based on research e.g. adapting their consulting model to more sophisticated dat~ analysis. sta~ehol?~rs recogni_zed the strategic use of their alliance with researchers e.g., transformational leadership trainmg as a~ inducement to improve health and safety among small service franchises. stakeholders helped re-define the research questions, dramatically changed the method of recruitment from researcher cold call to stakeholderbased recruitment, and strongly influenced pilot research designs. owing a great deal to the elaborate joint development process, the four collaboratively developed pilot project submissions which were all successfully funded. conclusion: the intensive process of collaborative development of a research program among stakeholders and researchers was not a smooth process and was time consuming. nevertheless, the result of the collaborative process was a set of projects that were more responsive to stakeholder needs, more feasible for implementation, and more broadly applicable to relevant workplace health problems. introduction: environmental groups, municipal public health authorities and, increasingly, the general public are advocating for reductions in pesticide use in urban areas, primarily because of concern around potential adverse health impacts in vulnerable populations. however, limited evidence of the relative merits of different intervention strategies in different contexts exists. in a pilot research project, we sought to explore the options for evaluating pesticide reduction interventions across ontario municipalities. methods: the project team and a multi-stakeholder project advisory committee (pac), generated a list of potential key informants (kl) and an open ended interview guide. thirteen ki from municipal government, industry, health care, and environmental organizations completed face to face or telephone interviews lasting - minutes. in a parallel process, a workshop involving similar representatives and health researchers was held to discuss the role of pesticide exposure monitoring. minutes from pac meetings, field notes taken during ki interviews, and workshop proceedings were synthesized to generate potential evaluation methods and indicators. results: current evaluation activities were limited but all kls supported greater evaluation effons beginning with fuller indicator monitoring. indicators of education and outreach services were imponant for industry representatives changing applicator practices as well as most public health units and environmental organizations. lndictors based on bylaw enforcement were only applicable in the two cities with bylaws, though changing attitudes toward legal approaches were being assessed in many communities. the public health rapid risk factor surveillance system could use historical baseline data to assess changes in community behaviour through reported pesticide uses and practices, though it had limited penetration in immigrant communities not comfortable in english. pesticide sales (economic) data were only available in regional aggregates not useful for city specific change documentation. testing for watercourse or environmental contamination might be helpful, but it is sporadic and expensive. human exposure monitoring was fraught with ethical issues, floor effects from low levels of exposure, and prohibitive costs. clinical episodes of pesticide exposure reported to the regional poison centre (all ages) or the mother risk program (pregnant or breastfeeding women) are likely substantial underestimates that would be need to be supplemented with sentinel practice surveillance. focus on special clinical populations e.g., multiple chemical sensitivity would require additional data collection efforts . . conc~ons: broad support for evaluation and multiple indicators were proposed, though con-s~raints associate~ with access, coverage, sensitivity and feasibility were all raised, demonstrating the difficulty of evaluating such urban primary prevention initiatives. interventionists. an important aim of the youth monitor is to learn more about the health development of children and adolescents and the factors that can influence this development. special attention is paid to emo· tional and behavioural problems. the youth monitor identifies high-risk groups and factors that are associated with health problems. at various stages, the youth monitor chancrs the course of life of a child. the sources of informa· tion and methods of research are different for each age group. the results arc used to generate various kinds of repons: for children and young persons, parents, schools, neighbourhoods, boroughs and the municipality of rotterdam and its environs. any problems can be spotted early, at borough and neigh· bourhood level, based on the type of school or among the young persons and children themselves. together with schools, parents, youngsters and various organisations in the area, the municipal health service aims to really address these problems. on request, an overview is offered of potentially suitable interventions. the authors will present the philosophy, working method, preliminary effects and future developments of this instrument, which serves as the backbone for the rotterdam local youth policy. social workers to be leaders in response to aging urban populations: the practicum partnership program sarah sisco, alissa yarkony, and patricia volland "'" tliu:tion: across the us, . % of those over live in urban areas. these aging urban popu· lations, including the baby boomers, have already begun encounter a range of heahh and mental hcahh conditions. to compound these effects, health and social service delivery fluciuates in cities, whit:h arc increasingly diverse both in their recipients and their systems. common to other disciplines (medicine, nursing, psychology, etc.) the social work profession faces a shortage of workers who are well-equipped to navigate the many systems, services, and requisite care that this vast population requires. in the next two decades, it is projected that nearly , social workers will be required to provide suppon to our older urban populations. social workers must be prepared to be aging-savvy leaders in their field, whether they specialize in gerontology or work across the life span. mllhotu: in , a study conducted at the new york academy of medicine d<> :umcntcd the need for improved synchroniciry in two aspects of social work education, classroom instruction and the field experience. with suppon from the john a. hanford foundation, our team created a pilot proj~"t entitled the practicum pannership program (ppp) in master's level schools of social work, to improvt" aginr exposure in field and classroom content through use of the following: i) community-university partnrr· ships, ) increased, diverse student field rotations, ll infusion of competcn ."}'·drivm coursework, enhancement of field instructors' roles, and ) concentrated student recruitment. we conductt"d a prr· and post-test survey into students' knowledge, skills. and satisfaction. icarlja: surveys of over graduates and field inltnk."tors rcflected increased numlk-n of . rrm:y· univmity panncrships, as well as in students placed in aging agencin for field placements. there wa marked increase in student commitments to an aging specialization. onr year por.t·gradu:nion rcvealrd that % of those surveyed were gainfully employed, with % employed in the field of aginic. by com· bining curricular enhancement with real-world experiences the ppp instilled a broad exposurr for llu· dents who worked with aging populations in multiple urban settings. coltdtuion: increased exposure to a range of levels of practicr, including clinical, policy/ajvocaq, and community-based can potentially improve service delivery for older adulh who live in elfin, and potentially improve national policy. the hanford foundation has now elected to uppon cxpantion of the ppp to schools nationwide (urban and rural) to complement other domntic initiatives to cnhalk"c" holistic services for older adults across the aging spectrum. bodrgnn.ntl: we arc a team of rcscarcbcn and community panncn working tcj c(her to develop an in"itepth understanding of the mental health needs of homeless youth ~ages to ) (using qualiutivc and quantitative methods ' panicipatory rncarch methods). it is readily apparmt that '-neless youth cxpcricnce a range of mental health problems. for youth living on the street, menul illnew may be either a major risk factor for homelessnal or may frequently emcsge in response to coping with rhe multitudinous stressors associated with homclcslllcsi including exposure to violence, prasutt to pamaplte in v poster sessions survival sex and/or drug use. the most frequent psychiatric diagnoses amongst the homeless gencrally include: depression, anxiety and psychosis. . . . the ultimate ob ective of the pr~am of rei:e~ is to ~evelop a plan for intervention to meet the mental health needs of street youth. prior t_o pl~nnmg mtervenbons, .it is necessary to undertake a comprehensive assessment ~f mental health needs m this ~lnerable populanon. thus, the immediate objective of this research study is to undertake a comprehensive assessment of men· tal health needs. . . melbotlology: a mixed methodology triangulating qualitative, participatory acnon and quantitative methods will capture the data related to mental health needs of homeless youth. a purposive sample of approximately - subjecrs. ages to , is currently being ~ted ~participate from the commu.nity agencies covenant house, evergreen centre fo~ srrc;et youth, turning p? ?t and street ~ serv~. youth living on the street or in short -term residennal programs for a mmimum of month pnor to their participation; ages to and able to give infonned consent will be invited to participate in the study. o..tcomes: the expected outcome of this initial survey will be an increased understanding of mental health needs of street youth that will be used to develop effective interventions. it is anticipated that results from this study will contribute to the development of mental health policy, as well as future programs that are relevant to the mental health needs of street youth. note: it is anticipated that preliminary quantitative data ( subjects) and qualitative data will be available for the conference. the authors intend to present the identification of the research focus, the formation of our community-based team, relevance for policy, as well as preliminary results. p - (a) the need for developing a firm health policy for urban informal worken: the case of despite their critical role in producing food for urban in kenya, urban farmers have largely been ignored by government planners and policymakers. their activity is at best dismissed as peripheral eveo, inappropriate retention of peasant culture in cities and at worst illegal and often some-times criminal· ized. urban agriculture is also condemned for its presumed negative health impact. a myth that contin· ues despite proof to the contrary is that malarial mosquitoes breed in maize grown in east african towns. however, potential health risks are insignificant compared with the benefits of urban food production. recent studies too rightly do point to the commercial value of food produced in the urban area while underscoring the importance of urban farming as a survival strategy among the urban poor, especially women-headed households. since the millennium declaration, health has emerged as one of the most serious casualties consequent on the poverty, social exclusion, marginalisation and lack of sustain· able development in africa. hiv/aids epidemic poses an unprecedented challenge, while malaria, tuber· culosis, communicable diseases of childhood all add to the untenable burden. malnutrition underpins much ill-health and is linked to more than per cent of all childhood deaths. kenya's urban poor people ~ace ~ h~ge burde~ of preventable and treatable health problems, measured by any social and bi~ medical md cator, which not only cause unnecessary death and suffering, but also undermine econonuc development and damage the country's social fabric. the burden is in spite of the availability of suitable tools and re:c=hnology for prevention and treatment and is largely rooted in poverty and in weak healah •rstems. this pa~ therefore challenges development planners who perceive a dichotomy instead of con· tmuum between informal and formal urban wage earners in so far as access to health services is con· cemed. it i~ this gap that calls for a need to developing and building sustainable health systems among the urban mformal ~wellers. we recommend a focus on an urban health policy that can build and strengthen the capacity of urban dwellers to access health services that is cost-effective and sustainable. such ~ health poli<=>: must strive for equity for the urban poor, displaced or marginalized; mobilise and effect ~ely use sufficient sustainable resources in order to build secure health systems and services. special anenti_on. should ~ afforded hiv/aids in view of the unprecedented challenge that this epidemic poses to africa s economic and social development and to health services on the continent. methods: a review of the literature led us to construct three simple models and a composite model of exposure to traffic. the data were collected with the help of a daily diary of travel activities using a sample of cyclists who went to or come back from work or study. to calculate the distance, the length of journey, and the number of intersections crossed by a cyclist different geographic information systems (gis) were operated. statistical analysis was used to determine the significance between a measure of exposure on the one hand, and the sociodemographic characteristics of the panicipants or their geographic location on the other hand. restlltj: our results indicate that cyclists were significantly exposed to road accidents, no matter of where they live or what are their sociodemographic characteristics. we also stress the point that the fact of having been involved in a road accident was significantly related to the helmet use, but did not reduce the propensity of the cyclists to expose themselves to the road hazards. condlllion: the efforts of the various authorities as regards road safety should not be directed towards the reduction of the exposure of the vulnerable users, but rather towards the reduction of the dangers to which they could face. keywords: cyclist, daily diary of activities, measures of exposure to traffic, island of montreal. p - (a) intra urban disparities and environmental health: some salient features of nigerian residential neighbourhoods olumuyiwa akinbamijo intra urban disparities and environmental health: some salient features of nigerian residential neighbourhoods abstract urbanization panicularly in nigerian cities, ponends unprecedented crises of grave dimensions. from physical and demographic viewpoints, city growth rates are staggering coupled with gross inabilities to cope with the consequences. environmental and social ills associated with unguarded rapid urbanization characterize nigerian cities and threaten urban existence. this paper repons the findings of a recent study of the relationship between environmental health across inrraurban residential communities of akure, south west nigeria. it discuses the typical urbanization process of nigerian cities and its dynamic spatial-temporal characteristics. physical and socio-demographic attributes as well as the levels and effectiveness of urban infrastructural services are examined across the core residential districts and the elite residential layouts in the town. the incidence rate of cenain environmentally induced tropical diseases across residential neighborhoods and communes is examined. salient environmental variables that are germane to health procurement in the residential districts, incidence of diseases and diseases parasitology, diseases prevention and control were studied. field data were subjected to analysis ranging from the univariate and bivariate analysis. inferential statistics using the chi-square test were done to establish the truthfulness of the guiding hypothesis. given the above, the study affirms that there is strong independence in the studied communities, between the environment and incidence of diseases hence health of residents of the town. this assertion, tested statistically at the district levels revealed that residents of the core districts have very strong independence between the environment and incidences of diseases. the strength of this relationship however thins out towards the city peripheral districts. the study therefore concludes that since most of the city dwellers live in urban deprivation, urban health sensitive policies must be evolved. this is to cater for the urban dwellers who occupy fringe peripheral sites where the extension of facilities often times are illegally done. urban infrastructural facilities and services need be provided as a matter of public good for which there is no exclusive consumption or access even for the poorest of the urban poor. many suffer from low-self esteem, shame and guilt about their drug use. in addition, they often lack suppon or encounter opposition from their panners, family and friends in seeking treatment. these personal barriers are compounded by fragmented addiction, prenatal and social care services, inflexible intake systems and poor communication among sectors. the experience of accessing adequate care between services can be overwhelming and too demanding. the toronto centre for substance use in pregnancy (t-cup) is a unique program developed to minimize barriers by providing kone-stop" comprehensive healthcare. t-cup is a primary care based program located in the department of family medicine at st. joseph\'s health centre, a community teaching hospital in toronto. the interdisciplinary staff provides prenatal and addiction services, case management, as well as care of newborns affected by substance use. regular care plan meetings are held between t-cup, labour and delivery nurses and social workers in the y poster sessions maternity and child care program. t-cup also connects "'.omen with. inpatient treatment programs and community agencies such as breaking the cycle, an on-site counselmg group for pregnant substance users. · f · d d h ith method: retrospective chart review, qualitative patient ~ans action stu ~· an ea care provider surveys are used to determine outcomes. primary outcomes mclude changes m maternal su~tance use, psychosocial status and obstetrical complications (e.g. pre-rupture of membrane, pre-eclampsia, placen· ral abruption and hemorrhage). neonatal measures ~~nsisted of .bir~h pa_rame~ers, length of h~spital st.ay and complications (e.g. feral distress, meconium stammg, resuscitation, aund ce, hypoglycemia, seventy of withdrawal and treatment length). chart review consisted of all t-cup patients who met clinical cri· reria for alcohol or drug dependence and received prenatal and intra-partum care at st. joseph's from october to june . participants in the qualitative study included former and current t-cup patients. provider surveys were distributed on-site and to a local community hospital. raulb: preliminary evaluation has demonstrated positive results. treatment retention and satisfaction rates were high, maternal substance use was markedly reduced and neonatal outcomes have shown to be above those reported in literature. conclusion: this comprehensive, primary care model has shown to be optimal in the management of substance use in pregnancy and for improving neonatal outcomes. future research will focus on how this inexpensive program can be replicated in other health care settings. t-cup may prove to be the optimal model for providing care to pregnant substance users in canada. lntrod ction: cigarette smoking is one of the most serious health problems in taiwan. the prevalence of smoking in is . % in males . % in females aged years and older. although the government of taiwan passed a tobacco hazards control act in , it has not been strongly enforced in many places. therefore, community residents have often reported exposure of second hand smoke. the purpose of the study was to establish a device to build up more smoke-free environments in the city of tainan. methods: unique from traditional intervention studies, the study used a healthy city approach to help build up smoke-free environments. the major concept of the approach is to build up a healthy city platform, including organizing a steering committee, setting up policies and indicators, creating intersectoral collaboration, and increasing community participation. first, more than enthusiastic researchers, experts, governmental officers, city counselors and community leaders in tainan were invited in the healthy city committee. second, smoke-free policies, indicators for smoke-free environments, and mechanisms for inter-departmen· tal inspections were set up. third, community volunteers were recruited and trained for persuading related stakeholders. lastly, both penalties and rewards were used for help build up the environments. raults: aher two-year ( aher two-year ( - execution of the project, the results qualitatively showed that smoke-free environments in tainan were widely accepted and established, including smoke-free schools, smoke-free workpla~es, smoke-free households, smoke-free internet shops, and smoke-free restaurants. smoke~s were. effectively educated not to smoke in public places. community residents including adults and children m the smoke-free communities clearly understand the adverse effects of environmental tobacco smoke and actively participated anti-smoking activities. conclruions: healthy city platform is effective to conquer the barrier of limited anti-smoking rc:sources. nor. only can it enlar:ge community actions for anti-smoking campaigns, but also it can provide par_merships for collaboratjon. by establishing related policies and indicators the effects of smoke· free environments can be susta ·ned a d th · · · ' · n e progression can be monitored m a commuruty. these issues are used ~· oi::c it~ goals, weuha identifies issues that put people's health at risk. presently, team com~u:c: ran ee~tion !earns. (iats) that design integrative solutions ~tesj'°~ g om six to fifteen members. methods in order to establish wo-poster sessions v projects for weuha, the following approach was undertaken: i. a project-polling template was created and sent to all members of the alliance for their input. each member was asked to identify thdr top two population groups, and to suggest a project on which to focus over a - month period for each identified population. . there was a % response to the poll and the top three population groups were identified. data from the toronto community health profile database were utilized to contextualize the information supplied for these populations. a presentation was made to the steering committee and three population-based projects were selected, leaders identified and iats formed. three population-based projects: the population-based projects and health care issues identified are: newcomer prenatal uninsured women; this project will address the challenges faced by providers to a growing number of non-insured prenatal women seeking care. a service model where the barrier of "catchments" is removed to allow enhanced access and improved and co-ordinated service delivery will be pilot-tested. children/obesity/diab etes: using a health promotion model this team will focus on screening, intervention, and promoting healthy lifestyles (physical activity and nutrition) for families as well as for overweight and obese children. seniors health promotion and circle of discharge: this team will develop an early intervention model to assist seniors/family unit/caregivers in accessing information and receiving treatment/care in the community. the circle of discharge initiative will address ways of utilizing community supports to keep seniors in the community and minimize readmissions to acute care facilities. results/expected outcomes: coordinated and enhanced service delivery to identified populations, leading to improved access, improved quality of life, and health care for these targeted populations. introduction: basic human rights are often denied to high-risk populations and people living with hiv/aids. their rights to work and social security, health, privacy, non discrimination, liberty and freedom of movement, marriage and having a family have been compromised due to their sero-positive status and risk of being positive. the spread of hiv/aids has been accelerating due to the lack of general human rights among vulnerable groups. to formulate and implement effective responses needs dialogue and to prevent the epidemic to go underground barriers like stigma need to be overcome. objective: how to reduce the situation of stigma, discrimination and human rights violations experienced by people living with hiv/aids and those who are vulnerable to hiv/aids. methodology and findings: consultation meetings were strm.-rured around presentations, field visits, community meetings and group work to formulate recommendations on how govt and ngos/cbos should move forward based on objective. pakistan being a low prevalence country, the whole sense of compl;u:enc.:y that individuals are not subject to situations of vulnerable to hiv is the major threat to an explosion in th•· epidemic, therefore urgent measures are needed to integrate human rights issues from the very start of the response. the protection and promotion of human rights in an integral component of ;tll responses to the hiv/aids epidemic. it has been recognized that the response to hiv/aios must he multi sectoral and multi faceted, with each group contributing its particular expertise. for this to occur along with other knowlcdg<" more information is required in human rights abuses related to hiv/ aids in a particular scenario. the ~·on sultarion meetings on hiv/aids and human rights were an exemplary effort to achieve the same ohj<..:tivc. recommendations: the need for a comprehensive, integrated and a multi-sectoral appro;u.:h in addressing the issue of hiv/aids was highlighted. the need social, cultural and religious asp•·ct' to he: prominently addressed were identified. it was thought imperative measures even in low prevalence countries. education has a key role to play, there is a need for a code of ethics for media people and h<"alth care providers and violations should be closely monitored and follow up action taken. p - (c) how can community-based funding programs contribute to building community capacity and how can we measure this elusive goal? mary frances maclellan-wright, brenda cantin, mary jane buchanan, and tammy simpson community capacity building is recognized by the public health agency of canada (phac) as an important strategy for improving the overall health of communities by enabling communities to addre~s priority issues such as social and economic determinants of health. in / phac.:, alberta/nwf region's population health fund (phf) supported community-based projects to build community capacity on or across the determinants of health. specifically, this included creating accessible and sup· portive social and physical environments as well as creating tools and processes necessary for healthy policy development and implementation. the objective of this presentation is to highlight how the community capacity building tool, developed by phac ab/nwf region, can demonstrate gains in v poster sessions · · the course of a pror· ect and be used as a reflective tool for project planning and community capacity over . . . . i · a art of their reporting requirements, pro ect sites completed the community caparny eva uanon. s p . . th t i ii i'd d . building tool at the beginning and end of their ~ne-year prorect. e oo ~o ects va an reliable data in the context of community-based health prorects. developed through a vigorous ~nd collabora ve research process, the tool uses plain languag~ to expl~re nine key f~atures o~ commuruty cap~city with 't ch with a section for contextual information, of which also mdude a four-pomt raong ems, ea f fu d · scale. results show an increase in community capacity over the course o the nde prorects. pre and post aggregate data from the one-year projects measure~ statistic.ally si~n~ficant changes for of the scaled items. projects identified key areas of commumty capacity bmldmg that needed strengthemng, such as increasing participation, particularly among people with low incomes; engaging community members in identifying root causes; and linking with community groups. in completing the tool, projects examined root causes of the social and economic determinants of health, thereby exploring social justice issues related to the health of their community. results of the tool also served as a reflec· cion on the process of community capacity building; that is, how the project outcomes were achieved. projects also reported that the tool helped identify gaps and future directions, and was useful as a project planning, needs assessment and evaluation tool. community capacity building is a strategy that can be measured. the community capacity building tool provides a practical means to demonstrate gains in community capacity building. strengthening the elements of community capacity building through community-based funding can serve as building blocks for addressing other community issues. needs of marginalized crack users lorraine barnaby, victoria okazawa, barb panter, alan simpson, and bo yee thom background: the safer crack use coalition of toronto (scuc) was formed in in response to the growing concern for the health and well-being of marginalized crack users. a central concern was the alarm· ing hepatitis c rate ( %) amongst crack smokers and the lack of connection to prevention and health ser· vices. scuc is an innovative grassroots coalition comprised of front-line workers, crack users, researcher! and advocates. despite opposition and without funding, scuc has grown into the largest crack specific harm reduction coalition in canada and developed a nationally recognized sarer crack kit distribution program (involving community-based agencies that provide outreach to users). the success of our coalition derives from our dedication to the issue and from the involvement of those directly affected by crack use. setting: scuc's primary service region is greater toronto, a diverse, large urban centre. much ofour work is done in areas where homeless people, sex trade workers and drug users tend to congregate. recently, scuc has reached out to regional and national stakeholders to provide leadership and education. mandate: our mandate is to advocate for marginalized crack users and support the devdopmentof a com.p.rehensive harm reduction model that addresses the health and social needs facing crack users; and to fac htare the exchange of information between crack users, service providers, researchers, and policy developers across canada. owrview: the proposed workshop will provide participants with an overview of the devdopment of scuc, our current projects (including research, education, direct intervention and consultation), our challenge~ and s~ccesses and the role of community development and advocacy within the coalition. pre-senter~ will consist of community members who have personal crack use experience and front-line work· ers-, sc.uc conducted a community-based research project (toronto crack users perspectives, ) , in w~ich s focus groups with marginalized crack users across toronto were conducted. participants iden· t f ed health and social issues affecti h b · · · d " red . . ng t em, arrsers to needed services, personal strategies, an oue recommendations for improved services. presenters will share the methodology, results and recommen· datmns resulting from the research project. conc/usio": research, field observations and consultations with stakeholders have shown that cradck shmoke~s are at an. increased risk for sexually transmitted infections hiv/aids hepatitis c, tb an ot er serious health issues health · ff, · ' ' · · . · issues a ectmg crack users are due to high risk behavmurs, socio· economic factors, such as homeless d. · · · · d · . . ness, scrsmmat on, unemployment, violence incarceraoons, an soc a so at on, and a lack of comprehe · h i h · ' ns ve ea t and social services targeting crack users. · · sinct · s, owever arge remains a gross underesurnaoon. poster sessions v these are hospital-based reports and many known cases go unreported. however teh case, young age at first intercourse, inconsistent condom use and multiple partnersplace adolescents at high risks for a diverse array of stls, including hiv. about % of female nigerian secondary school students report initiating sexual intercourse before age years. % of nigerian female secondary school students report not using a condom the last time they had sexual intercourse. more than % of urban nigerian teens report inconsistent condom use. methods: adolescents were studied, ages to , from benin city in edo state. the models used were mother-daughter( ), mother -son( ), father -son ( ), and father-daughter( ). the effect of parent-child sexual communicationat baseline on child\'s report of sexual behavior, to months later were studied. greater amounts of sexual risk communication were asociated with markedly fewer episodes of unprotected sexual intercourse, reduced number of sexual partners and fewer episodes of unprotected sexual intercourse. results: this study proved that parents can exert more influence on the sexual knowledge attitudes and practise of their adolescent children through desired practises or rolemodeling, reiterating their values and appropriate monitoring of the adolescents\' behavior. they also stand to provide information about sexuality and various sexual topics. parental-child sexual communication has been found to be particularly influential and has been associated with later onset of sexual initiation among adolescents, less sexual activity, more responsible sexual attitudes including greater condom use, self efficacy and lower self -reported incidence of stis. conclusions: parents need to be trained to relate more effectively with their children/wards about issues related to sex and sexuality. family -based programs to reduce sexual risk-taking need to be developed. there is also the need to carry out cross-ethnicaland cross-cultural studies to identify how parent-child influences on adolescent sexual risk behavior may vary in different regions or countries, especially inthis era of the hiv pandemic. introduction: public health interventions to identify and eliminate health disparities require evidence-based policy and adequate model specification, which includes individuals within a socioecological context, and requires the integration of biosociomedical information. multiple public and private data sources need to be linked to apportion variation in health disparities ro individual risk factors, the health delivery system, and the geosocial environment. multilevel mapping of health disparities furthers the development of evidence-based interventions through the growth of the public health information network (phin-cdc) by linking clinical and population health data. clinical encounter data, administrative hospital data, population socioenvironmental data, and local health policy were examined in a three-level geocoded multilevel model to establish a tracking system for health disparities. nj has a long established political tradition of "home rule" based in elected municipal governments, which are responsible for the well-being of their populations. municipalities are contained within counties as defined by the us census, and health data are linked mostly at the municipality level. marika schwandt community organizers from the ontario coaliti~n again~t pove~, .along ":ith ~edical practitioners who have endorsed the campaign and have been mvolved m prescnbmg special diet needs for ow and odsp recipients, will discuss the raise the rates campaign. the organizati~n has used a special diet needs supplement as a political tool, meeting the urgent needs o.f .poor ~ople m toront~ while raising the issues of poverty as a primary determinant of health and nutrtnous diet as a preventative health mea· sure. health professionals carry the responsibility to ensure that they use all means available to them to improve the health of the individuals that they serve, and to prevent future disease and health conditions. most health practitioners know that those on social assistance are not able to afford nutritious foods or even sufficient amounts of food, but many are not aware of the extra dietary funds that are available aher consideration by a health practitioner. responsible nurse practitioners and physicians cannot, in good conscience, ignore the special needs diet supplement that is available to all recipients of welfare and disabiliry (ow and odsp). a number of toronto physicians have taken the position that all clients can justifiably benefit from vitamins, organic foods and high fiber diets as a preventative health measure. we know that income is one of the greatest predictors of poor health. the special needs diet is a health promotion intervention which will prevent numerous future health conditions, including chronic conditions such as cardiovascular disease, cancer, diabetes and osteoporosis. many communiry health centres and other providers have chosen to hold clinics to allow many patients to get signed up for the supplement at one time. initiated by the ontario coalition against poverty, these clinics have brought together commu· niry organizers, community health centers, health practitioners, and individuals, who believe that poverty is the primary determinant of poor health. we believe that rates must be increased to address the health problems of all people on social assistance, kids, elders, people with hiv/aids -everyone. even in the context of understaffing, it could be considered a priority activity that has potentially important health promotion benefits. many clients can be processed in a two hour clinic. most providers find it a very interesting, rewarding undertaking. in the ontario coalition for social justice found that a toronto family with two adults and two kids receives $ , . this is $ , below the poverty line. p - (c) the health of street youth compared to similar aged youth beth hayhoe and ruth ewert . lntrod~on: street youth are at an age normally associated with good health, but due to their risky ~hav ours and th~ conditions in which they live, they experience health conditions unlike their peer~ an more stable env r~nments. in addition, the majority of street youth have experienced significant physical, sexual ~nd em.ot onal abuse as younger children, directly impacting many of the choices they make around their physical and emotional health. we examined how different their health really is. . , methodl: using a retrospective analysis of the years of data gathered from yonge street mis· ~ • evergreen health centre, the top conditions of youth were examined and compared with national tren~s for similar aged youth. based on knowledge of the risk factors present in the group, rea· sons for the difference were examined. d' ~its: street youth experience more illness than other youth their age and their illnesses can bt . irect t ·~kc~ to the. conditions in which they live. long-term impacts of abus~ contribute to such signif· ~~nt t e t d~slpl air that youth may voluntarily engage in behaviours or lack of self care in the hope at t cir ve~ w perhaps come to a quicker end. concl non: although it has ion b k h th' dy clearly shows d'fi . h g ee~ no~n t at poverty negatively affects health, ~siu be used to make ; erence m t .e health of this particular marginalized population. the infonnanon can relates to th . ecommendatio.ns around public policy that affects children and youth, especially as it e r access to appropriate health care and follow up. p - (cl why do urban children · b gt . tarek hussain an adesh die: how to save our children? the traditional belief that urban child alid. a recent study (dhs d fr r~n are better off than rural children might be no longer v urban migrants are highata th om h c~untn~s i demonstrates that the child survival prospects of rural· er an t ose m their r j · · ·grants. in bangladesh, currently million ~r~ ~ gm and lower than those of urban non-idi million. health of the urban ~ p~e are hvmg m urban area and by the year , it would be so the popu at on s a key a eals that urban poor have the worse h h . concern. recent study on the urban poor rev ea t situation than the nation as a whole. this study shows that infant poster sessions v mortality among the urban poor as per thousand, which are above the rural and national level estimates. the mortality levels of the dhaka poor are well above those of the rest of the city's population but much of the difference in death rates is explained by the experience of children, especially infants. analyzing demographic surveillance data from a large zone of the city containing all sectors of the population, research showed that the one-fifth of the households with the least possessions exhibited u child mortality almost three times as high as that recorded by the rest of the population. why children die in bangladesh? because their parents are too poor to provide them with enough food, clean water and other basic needs to help them avoid infection and recover from illness. researchers believed that girls are more at risk than boys, as mothers regularly feed boys first. this reflects the different value placed on girls and boys, as well as resources which may not stretch far enough to provide for everyone. many studies show that housing conditions such as household construction materials and access to safe drinking water and hygienic toilet facilities are the most critical determinants of child survival in urban areas of developing countries. the present situation stressed on the need for renewed emphasis on maternal and child healthcare and child nutrition programs. mapping path for progress to save our children would need be done strategically. we have the policies on hand, we have the means, to change the world so that every child will survive and has the opportunity to develop himself fully as a healthy human being. we need the political will--courage and determination to make that a reality. p - (c) sherbourne health centre: innovation in healthcare for the transgendered community james read introduction: sherbourne health centre (shc), a primary health care centre located in downtown toronto, was established to address health service gaps in the local community. its mission is to reduce barriers to health by working with the people of its diverse urban communities to promote wellness and provide innovative primary health services. in addition to the local communities there are three populations of focus: the lesbian, gay, bisexual, transgendered and transexual communities (lgbtt); people who are homeless or underhoused; and newcomers to canada. shc is dedicated to providing health services in an interdisciplinary manner and its health providers include nurses, a nurse practitioner, mental health counsellors, health promoters, client-resource workers, and physicians. in january shc began offering medical care. among the challenges faced was how to provide responsive, respectful services to the trans community. providers had considerable expertise in the area of counselling and community work, but little in the area of hormone therapy -a key health service for those who want to transition from one gender to another. method: in preparing to offer community-based health care to the trans community it was clear that shc was being welcomed but also being watched with a critical eye. trans people have traditionally experienced significant barriers in accessing medical care. to respond to this challenge a working group of members of the trans community and health providers was created to develop an overall approach to care and specific protocols for hormone therapy. the group met over a one year period and their work culminated in the development of medical protocols for the provision of hormone therapy to trans individuals. results: shc is currently providing health care to registered clients who identify as trans individuals (march ) through primary care and mental health programs. in an audit of shc medical charts (january to september ) female-to-male (ftm) and male-to-female (mtf) clients were identified. less than half of the ftm group and just over two-thirds of the mtf group presented specifically for the provision of hormones. based on this chart audit and ongoing experience shc continues to update and refine these protocols to ensure delivery of quality care. conclusion: this program is an example of innovative community-based health delivery to a population who have traditionally faced barriers. shc services also include counselling, health promotion, outreach and education. p - (c) healthy cities for canadian women: a national consultation sandra kerr, kimberly walker, and gail lush on march , the national network on environment and women's health held a pan-canadian consultation to identify opportunities for health research, policy change, and action. this consultation also worked to facilitate information sharing and networking between canadian women working as urban planners, policy makers, researchers, and service workers on issues pertaining to the health of women living in canadian cities. methods: for this research project, participants included front-line service workers, policy workers, researchers, and advocates from coast to coast, including francophone women, women with disabilities, racialized women, and other marginalized groups. the following key areas were selected as topics for du.bnes i alto kading .:auk of end·sugr ieaal clileue ia singapore, accounting for more than so% of new can singapore (nkfs) to embark on a prevention program (pp) empo~r d ahc j u f dieir condition bttter, emphasizing education and disease sdf·managemen lkilla a. essennal camponenn of good glycaemic control. we sought explore the effects of a pecialijed edu.:a on pro· pun od glycacmic conuol, as indicated by, serum hba ic values budine serum hba ic values were determined before un<k-rgmng the education progr ;am, which couisted of comprehensive dietary advice, ideal weight goals, and improving lipid profiln. serum hbaic values were obtained ar , , months later to determine impact of the program. analy • wu done uling paired !·tests significant reduction in hba le levels from ro month• was observed in females, chinese race, older age group(> so yean). ohew-ibmi ~ .nwm , wai hip ratio> l),up to primary and above secondary level education and those having om urine iclt showed that increasing hbalc levels ( ) had increasing urmary protein ( .± ; . ±i ih so± ) and crearinine (s .s ± s ± ; ioi± s) levels fbg rnults showed that the management nf d abetn m the nkfs preven· tion programme is effec;rive. results also indicated har hba le leve have a linnr trend wnh unnary protein and creatinine which are imponant determinants of renal diseate tal family-focused cinical palbway promoce politivc outcollln for ua inner city canu allicy ipmai jerrnjm care llctivirits in preparation for an infanr'' dilchargr honlr, and art m endnl lo improve effi.:k'fl.:tn of c.are. lere i paucity of tttran:h, and inconsi trncy of rnulta on ht-•m!*- of f m ly·fc"-'uw d nm a: to determinr whrthrr implrmentation of family.focuted c:pt n ntnn.tt.tl unit w"n mg an inner city ;ommunity drcl't'aki leftarh of lf•y (i.osi and rromclll'i family uo•fkllon and rt. j nest for dikhargr. md odt: family-focuk"d cpi data wm coll«ted for all infant• horn btrwttn and wft"k• t"lal mi atr who wrtt . dm ed to the ntonatal unit lmgdl of -.y . n. . day'o p c o.osi ind pma . d•mr., ho.nr . t . n. . ± i. i wb, p < o.os) wett n« fiamly f.lfrt n the pre.(]' poup. ~ .fxtmon icofn for famihn wrre high. and families noctd thc:y wnr mott prepued to ah thrar t..lby "'-· thett was .a cosi uving of s , (cdn) per patient d teharpd home n the pmi-cp poap c.-pated the p"''lfoup· cortclaion· lmplrmrnr.rion of family·foanrd c:p. in a nrona . i umt tc"fyidi an nnn an com· muniry decre.ned length of'"'" mft with a high dcgrft of family uujamon, and wrre coll~nt at least % percent of the kathmandu population lives in slum like conditions with poor access to basic health services. in these disadvantaged areas, a large proportion of children do not receive treatment due to inaccessibility to medical services. in these areas, diarrhea, pneumonia, and measles, are the key determinants of infant mortality. protein energy malnutrition and vitamin a deficiency persists and communicable diseases are compounded by the emergence of diseases like hiv/aids. while the health challenges for disadvantaged populations in kathmandu are substantial, the city has also experienced various forms of innovative and effective community development health programs. for example, there are community primary health centers established by the kathmandu municipality to deliver essential health services to targeted communities. these centers not only provide equal access to health services to the people through an effective management system but also educate them hy organizing health related awareness programs. this program is considered one of the most effective urban health programs. the paper/presentation this paper will review large, innovative, and effective urhan health programs that are operating in kathmandu. most of these programs are currently run by international and national ngos a) early detection of emerging diseases in urban settings through syndromic surveillance: data pilot study kate bassil of community resources, and without adequate follow-up. in november shelter pr.oviders ~et with hospital social workers and ccac to strike a working group to address some of th~ issues by mcre.asing knowledge among hospital staff of issues surrounding homelessness, and to build a stro?g workmg relationship between both systems in hamilton. to date the hswg has conducted four w~lkmg to~ of downtown shelters for hospital staff and local politicians. recently the hswg launched its ·~ool.k t for staff working with patients who are homeless', which contains community resources and gu dehnes to help with effective discharge plans. a scpi proposal has been submitted to incre~se the capacity of the hswg to address education gaps and opportunities with both shelters and hospitals around homelessness and healthcare. the purpose of this poster presentation is to share hamilton's experience and learnings with communities who are experiencing similar issues. it will provide for intera~tion around shared experiences and a chance to network with practitioners across canada re: best practices. introduction and objectives: canadians view health as the biggest priority for the federal government, where health policies are often based on models that rely on abstract definitions of health that provide little assistance in the policy and analytical arena. the main objectives of this paper are to provide a functional definition of health, to create a didactic model for devising policies and determining forms of intervention, to aid health professionals and analysts to strategize and prioritize policy objectives via cost benefit analysis, and to prompt readers to view health in terms of capacity measures as opposed to status measures. this paper provides a different perspective on health, which can be applied to various applications of health such as strategies of aid and poverty reduction, and measuring the health of an individual/ community/country. this paper aims to discuss theoretical, conceptual, methodological, and applied implications associated with different health policies and strategies, which can be extended to urban communities. essentially, our paper touches on the following two main themes of this conference: •health status of disadvantaged populations; and •interventions to improve the health of urban communities.methodology: we initially surveyed other models on this topic, and extrapolated key aspects into our conceptual framework. we then devised a theoretical framework that parallels simple theories of physkal energy, where health is viewed in terms of personal/societal health capacities and effort components.after establishing a theoretical model, we constructed a graphical representation of our model using selfrated health status and life expectancy measures. ultimately, we formulated a new definition of health, and a rudimentary method of conducting cost benefit analysis on policy initiatives. we end the paper with an application example discussing the issues surrounding the introduction of a seniors program.results: this paper provides both a conceptual and theoretical model that outlines how one can go about conducting a cost-benefit analysis when implementing a program. it also devises a new definition and model for health barred on our concept of individual and societal capacities. by devising a definition for health that links with a conceptual and theoretical framework, strategies can be more logically constructed where the repercussions on the general population are minimized. equally important, our model also sets itself up nicely for future microsimulation modeling and analysis.implications: this research enhances one's ability to conduct community-based cost-benefit analysis, and acts as a pedagogical tool when identifying which strategies provide the best outcome. p - (a) good playgrounds are hard to find: parents' perceptions of neighbourhood parks patricia tucker, martin holmes, jennifer irwin, and jason gilliland introduction: neighbourhood opportunities, including public parks and physical activity or sports fields hav~ been. iden.tified as correlates to physical activity among youth. increasingly, physical activity among children s bemg acknowledged as a vital component of children's lives as it is a modifiable determinant of childh~d obesity. children's use of parks is mainly under the influence of parents; therefore, the purpose of this study was to assess parents' perspectives of city parks, using london ontario as a case study.m~~: this qualitative study targeted a heterogeneous sample of parents of children using local parks w thm london. parents with children using the parks were asked for minutes of their time and if willing, a s.hort interview was conducted. the interview guide asked parents for their opinion 'of city parks, particularly the one they were currently using. a sample size of parents is expected by the end of the summer.results: preliminary findings are identifying parents concern with the current jack of shade in local parks. most parents have identified this as a limitation of existing parks, and when asked what would make the parks better, parents agree that shade is vital. additionally, some parents are recognizing the v poster sessions focused discussions during the consultation: . women in _poverty . women with disability . immi· grant and racialized women . the built and _physica_l environment. . . . . r its· participants voiced the need for integration of the following issues withm the research and policy :::na; t) the intersectional nature of urban women's health i~sues wh~ch reflects the reality of women's complex lives ) the multisectional aspect of urban wo_m~n s health, ss~es, which reflects the diversity within women's lives ) the interse~roral _dynamics within _womens hves and urban health issues. these concepts span multiple sectors -mdudmg health, educat n, and economics -when leveraging community, research, and policy support, and engaging all levels of government.policy jmplicatiom: jn order to work towards health equity for women, plans for gender equity must be incorporated nationally and internationally within urban development initiatives: • reintroduce "women" and "gender" as distinct sectors for research, analysis, advocacy, and action. •integrate the multisectional, intersectional, and intersecroral aspects of women's lives within the framework of research and policy development, as well as in the development of action strategies. • develop a strategic framework to house the consultation priorities for future health research and policy development (for example, advocacy, relationship building, evidence-based policy-relevant research, priority initiatives}.note: research conducted by nnewh has been made possible through a financial contribution from health canada. the views expressed herein do not necessarily represent the views of health canada.p - (c) drugs, culture and disadvantaged populations leticia folgar and cecilia rado lntroducci n: a partir de un proyecto de reducci n de daiios en una comunidad urbana en situ· aci n de extrema vulnerahilidad surge la reflexion sobre el lugar prioritario de los elementos sociocuhurales en el acceso a los servicios de salud de diferentes colectivos urbanos. las "formas de hacer, pensar y sentir" orientan las acciones y delimitan las posibilidades que tienen los individuos de definir que algo es o no problema, asf como tambien los mecanismos de pedido de ayuda. el analisis permanenre del campo de "las culturas cotidianas" de los llamados "usuarios de drogas" aporta a la comprension de la complejidad del tema en sus escenarios reales, y colabora en los diseiios contextualizados de politicas y propuestas socio-sanitarias de intervenci n, tornandolas mas efectivas.mitodos: esta experiencia de investigaci n-acci n que utiliza el merodo emografico identifica elementos socio estructurales, patrones de consumo y profundiza en los elementos socio-simb icos que estructuran los discursos de los usuarios, caracterizandolos y diferenciandolos en tanto constitutivos de identidades socia les que condicionan la implementaci n del programas de reduccion de daiios.resultados: los resultados que presentaremos dan cuenta de las caracteristicas diferenciadas v relaciones particulares ~ntre los consumidores de drogas en este contexto espedfico. a partir de este e~tudio de caso se mtentara co ? enzar a responder preguntas que entendemos significativas a la hora de pensar intcrvcnciones a la med da de poblaciones que comparten ciertas caracteristicas socio-culturales. (cuales serian las .motivaciones para el cambio en estas comunidades?, cque elementos comunitarios nos ayudan a i:nnstnur dema~~a? • cque tenemos para aprender de las "soluciones" que ellos mismos encuenrran a los usos problemat cos? methods: our study was conducted by a team of two researchers at three different sites. the mapping consisted of filling in a chart of observable neighbourhood features such as graffiti, litter, and boarded housing, and the presence or absence of each feature was noted for each city block. qualitative observations were also recorded throughout the process. researchers analyzed the compiled quantitative and qualitative neighbourhood data and then analyzed the process of data collection itself.results: this study reveals the need for further research into the effects of physical environments on individual health and sense of well-being, and perception of investment in neighbourhoods. the process reveals that perceptions of health and safety are not easily quantified. we make specific recommendations about the mapping methodology including the importance of considering how factors such as researcher social location may impact the experience of neighbourhoods and how similar neighbourhood characteristics are experienced differently in various spaces. further, we discuss some of the practical considerations around the mapping exercise such as recording of findings, time of day, temperature, and researcher safety.conclusion: this study revealed the importance of exploring conceptions of health and well-being beyond basic physical wellness. it suggests the importance of considering one's environment and one's own perception of health, safety, and well-being in determining health. this conclusion suggests that attention needs to be paid to the connection between the workplace and the external environment it is situated in. the individual's workday experience does not start and stop at the front door of their workplace, but rather extends into the neighbourhood and environment around them. our procedural observations and recommendations will allow other researchers interested in the effect of urban environments on health to consider using this innovative methodology. introduction: responding ro protests against poor medical attention for sexually assaulted women and deplorable conviction rates for sex offenders, in the late s, the ontario government established what would become over hospital-based sexual assault care and treatment centres (sactcs) across the province. these centres, staffed around the clock with specially trained heath care providers, have become the centralized locations for the simultaneous health care treatment of and forensic evidence collection from sexually assaulted women for the purpose of facilitating positive social and legal outcomes. since the introduction of these centres, very little evaluative research has been conducted to determine the impact of this intervention. the purpose of our study was to investigate it from the perspectives of sexually assaulted women who have undergone forensic medical examinations at these centres.method: women were referred to our study by sactc coordinators across ontario. we developed an interview schedule composed of both closed and open-ended questions. twenty-two women were interviewed, face-to-face. these interviews were approximately one-to-two hours in length, and were transcribed verbatim. to date, have been analyzed for key themes.results: preliminary findings indicate that most women interviewed were canadian born ( 'yo), and ranged in age from to years. a substantial proportion self-identified as a visible minority ( 'x.). approximately half were single or never married ( %) and living with a spouse or family of origin ( %). most were either students or not employed ( %). two-thirds ( %) had completed high school and onethird ( %) was from a lower socio-economic stratum. almost two-fifths ( %) of women perceived the medical forensic examination as revictimizing citing, for example, the internal examination and having blood drawn. the other two-thirds ( %) indicated that it was an empowering experience, as it gave them a sense of control at a time when they described feeling otherwise powerless. most ( %) women stated that they had presented to a centre due to health care concerns and were very satisfied ( % ) with their experiences and interactions with staff. almost all ( %) women felt supported and understood.conclusions: this research has important implications for clinical practice and for appropriately addressing the needs of sexually assaulted women. what is apparent is that continued high-quality medical attention administered in the milieu of specialized hospital-based services is essential. at the same time, we would suggest that some forensic evidence collection procedures warrant reevaluation. the study will take an experiential, approach by chroruclmg the impa~ of the transition f m the streets to stabilization in a managed alcohol program through the techruque of narrative i~:uiry. in keeping with the shift in thinking in the mental health fie!~ ~his stu~y is based on a paradigm of recovery rather than one of pathology. the "inner views of part c pants hves as they portray their worlds, experiences and observations" will be presented (charm~z, , ~· ~)-"i?e p~ of the study is to: identify barriers to recovery. it will explore the exj?cnence of ~n~t zanon pnor to entry into the program; and following entry will: explore the meanmg ~nd defirutto~s of r~overy ~~d the impact of the new environment and highlight what supports were instrumental m movmg pan apants along the recovery paradigm.p -st (a) treating the "untreatable": the politics of public health in vancouver's inner city introdudion: this paper explores the everyday practices of therapeutic programs in the treadnent of hiv in vancouver's inner city. as anthropologists have shown elsewhere, therapeutic programs do not siinply treat physical ailments but they shape, regulate and manage social lives. in vancouver's inner city, there are few therapeutic options available for the treatment of -ilv. public health initiatives in the inner city have instead largely focused on prevention and harm reduction strategies such as needle exchange programs, safe injection sites, and safer-sex education. epidemiological reports suggest that less than a quarter of those living with hiv in the downtown eastside (dtes) are taking antiretroviral therapies raising critical questions regarding the therapeutic economy of antiretrovirals and rights to health care for the urban poor.methods: this paper is drawn from ethnographic fieldwork in vancouver's otes neighborhood focusing on therapeutic programs for hiv treatment among "hard-to-reach" populations. the research includes participant-observation at inner city health clinics specializing in the treatment of hiv; semi· structured interviews with hiv positive participants, health care professionals providing hiv treatment, and administraton working in the field of inner city public health; and, lastly, observation at public meetings and conferences surrounding hiv treatment.r.awlts: hiv prevention and treatment is a central concern in the lives of many residents living in the inner city -although it is just one of many health priorities afflicting the community. concerns about drug resistance, cost of antiretrovirals, and illicit drug use means that hiv therapy for most is characterized by the daily observation of their medicine ingestion at health clinics or pharmacies. daily observed treatment (dot) is increasingly being adopted as a strategy in the therapeutic management of "untreatable" populations. dot programs demand a particular type of subject -one who is "compliant" to the rules and regimes of public health. over emphasis on "risky practices," "chaotic lives," and "~dh~rence" preve~ts the public health system from meaningful engagement with the health of the marginalized who continue to suffer from multiple and serious health conditions and who continue to experience considerable disparities in health.~ the ~ffec~s of hiv in the inner city are compounded by poverty, laclc of safe and affordable houamg, vanous llegal underground economies increased rates of violence and outbreaks of ~~~·~ly tr~nsmitted infections, hepatitis, and tuberculosi: but this research suggests 'that public health uunauves aimed at reducing health disparities may be failing the most vulnerable and marginal of citiztl s. margaret malone ~ vi~lence that occurs in families and in intimate relationships is a significant urban, ~unity, and pu~hc health problem. it has major consequences and far-reaching effects for women, ~~--renho, you~ sen on, and families. violence also has significant effects for those who provide and ukllc w receive health care violence · · i · · . all lasses, · is a soc a act mvolvmg a senous abuse of power. it crosses : ' : ' ~ s;nden, ag~ ~ti~, cultures, sexualities, abilities, and religions. societal responseshali ra y oc:used on identificatton, crisis intervention and services for families and individuajs.promoten are only "-"--:-g to add h · ' · i in intimate relationshi with"-~"'.". ress t e issues of violence against women and vjoence lenga to consider i~ m families. in thi_s p~per, i analyze issues, propose strategies, and note c~· cannot be full -...l'-~ whork towards erad canng violence, while arguing that social justice and equity y -. ucvcu w en thett are people wh mnhod: critical social theory, an analysis that addresses culturally and ethnically diverse communities, together with a population health promotion perspective frame this analysis. social determinants of health are used to highlight the extent of the problem of violence and the social and health care costs.the ottawa charter is integrated to focus on strategies for developing personal skills, strengthening community action, creating supportive environments, devdoping healthy public policies, and re-orientating health and social services. attention is directed to approaches for working with individuals, families, groups, communities, populations, and society.ratdts: this analysis demonstrates that a comprehensive interdisciplinary, multisectoral, and multifaceted approach within an overall health promoting perspective helps to focus on the relevant issues, aitical analysis, and strategies required for action. it also illuminates a number of interacting, intersecting, and interconnecting factors related to violence. attention, which is often focused on individuals who are blamed for the problem of violence, is redirected to the expertise of non-health professionals and to community-based solutions. the challenge for health promoters working in the area of violence in families and in intimate relationships is to work to empower ourselves and the communities with whom we work to create health-promoting urban environments. social justice, equiry, and emancipatory possibilities are positioned in relation to recommendations for future community-based participatory research, pedagogical practices for health care practitioners, and policy development in relation to violence and urban health. the mid-main community health center, located in vancouver british columbia (bc), has a diverse patient base reflecting various cultures, languages, abilities, and socio-economic statuses. due to these differences, some mid-main patients experience greater digital divide barriers in accessing computers and reputable, government produced consumer health information (chi) websites, such as the bc healthguide and canadian health network. inequitable access is problematic because patient empowerment is the basis of many government produced chi websites. an internet terminal was introduced at mid-main in the summer of , as part of an action research project to attempt to bridge the digital divide and make government produced chi resources useful to a broad array of patients. multi-level interventions in co-operation with patients, with the clinic and eventually government ministries were envisioned to meet this goal. the idea of implementing multi-level interventions was adopted to counter the tendency in interactive design to implement a universal solution for the 'ideal' end-user [ ), which discounts diversity. to design and execute the interventions, various action-oriented and ethnographic methods were employed before and during the implementation of the internet terminal. upon the introduction of the internet terminal, participant observation and interviews were conducted using a motion capture software program to record a digital video and audio track of patients' internet sessions. this research provided insight into the spectrum of patients' capacities to use technology to fulfil their health information needs and become empowered. at the mid-main clinic it is noteworthy that the most significant intervention to enhance the usefulness of chi websites for patients appeared to be a human rather than a technological presence. as demonstrated in other ethnographic research of community internet access, technical support and capacity building is a significant component of empowerment ( ). the mid-main wired waiting room project indicates that medical practitioners, medical administrators, and human intermediaries remain integral to making chi websites useful to patients and their potential empowerment. ( ) over the past years the environmental yo~th alliance has been of~ering a.youth as~t. mappin~ program which trains young people in community research and evaluation. wh ~st the positive expenenc~ and relationships that have developed over this time attest to the success of this program, no evaluations has yet been undertaken to find out what works for t.he youth, what ~ould be changed, and what long term outcomes this approach offers for the youth, their local community, and urban governance. these topics will be shared and discussed to help other community disorganizing and uncials governments build better, youth-driven structures in the places they live.p - (a) the world trade center health registry: a unique resource for urban health researchers deborah walker, lorna thorpe, mark farfel, erin gregg, and robert brackbill introduction: the world trade center health registry (wfchr) was developed as a public health response to document and evaluate the long-term physical and mental health effects of the / disaster on a large, diverse population. over , people completed a wfchr enrollment baseline survey, creating the largest u.s. health registry. while studies have begun to characterize / bealth impacts, questions on long-term impacts remain that require additional studies involving carefully selected populations, long-term follow-up and appropriate physical exams and laboratory tests. wtchr provides an exposed population directory valuable for such studies with features that make ita unique resource: (a) a large diverse population of residents, school children/staff, people in lower man· hattan on / including occupants of damaged/destroyed buildings, and rescue/recovery/cleanup work· ers; (b) consent by % of enrollees to receive information about / -related health studies; (c) represenration of many groups not well-studied by other researchers; (c) email addresses of % of enrollees; (d) % of enrollees recruited from lists with denominator estimates; and (e) available com· parison data for nyc residents. wfchr strives to maintain up-to-date contact information for all enrollees, an interested pool of potential study participants. follow-up surveys are planned.methods: to promote the wtchr as a public health resource, guidelines for external researcher.; were developed and posted on (www.wtcregistry.org) which include a short application form, a twopage proposal and documentation of irb approval. proposals are limited to medical, public health, or other scientific research. researchers can request de-identified baseline data or have dohmh send information about their studies to selected wfchr enrollees via mail or email. applications are scored by the wtchr review committee, comprised of representatives from dohmh, the agency for toxic subst~nces and disease registry, and wtchr's scientific, community and labor advisory committees. a data file users manual will be available in early fall .~suits: three external applications have been approved in , including one &om a non-u.s. ~esearcher, all requesting information to be sent to selected wtchr enrollees. the one completed mail· mg~~ wtchr enrollee~ (o , wfc tower evacuees) generated a positive survey response rate. three additional researchers mtend to submit applications in . wfchr encourages collaborations between researchers and labor and community leaders.conclusion: studies involving wtchr enrollees will provide vital information about the long· term health consequences of / . wtchr-related research can inform communities, researcher.;, policy makers, health care providers and public health officials examining and reacting to and other disasters. t .,. dp'"f'osed: thi is presentation will discuss the findings of attitudes toward the repeat male client iden· ie as su e a and substance us'n p · · · · i · 'd . . - g. articipants will learn about some identified effective strategies or service prov ers to assist this group of i · f men are oft · d bl men. n emergency care settings, studies show that this group en viewe as pro emaric patient d i r for mental health p bl h h an are more ikely to be discharged without an assessmen !) ea rofr ems t. an or er, more cooperative patients (forster and wu · hickey er al., · r y resu ts om this study suggest th · · ' ' l · d tel' mining how best to h . d at negative amtudes towards patients, difficu nes e · as well pathways l_e_ p patientsblan ~ck of conrinuity of care influence pathways to mental health care. • uc\:ome pro emat c when p ti k · che system. m a ems present repeatedly and become "get stuc id methods: semi-structured intervie d . · (n= ), ed nurses (n= ) other ed ;s were con ucted with male ed patients (n= ), ed phys oans ' sta (n= ) and family physicians (n= ). patients also completed a poster sessions v diagnostic interview. interviews were tape-recorded, transcribed verbatim and managed using n . transcripts were coded using an iterative process and memos prepared capture emergent themes. ethics approval was obtained and all participants signed a detailed informed consent form.introduction: urban settings are particularly susceptible to the emergence and rapid spread of nt•w or rare diseases. the emergence of infectious diseases such as sars and increasing concerns over the next influenza pandemic has heightened interest in developing and using a surveillance systt·m which detects emerging public health problems early. syndromic surveillance systems, which use data b, scd on symptoms rather than disease, offer substantial potential for this by providing near-real-rime data which are linked to an automated warning system. in toronto, we are piloting syndromic data from the · emergency medical services (ems) database to examine how this information can be used on an ongoing basis for the early detection of syndromes including heat-related illness (hri), and influenza-like-illness (ill). this presentation will provide an outline of the planned desi_gn of this system and proposed evaluation. for one year, call codes which reflect heat-related illness or influenza-like-illness will be selected and searched for daily using software with a multifactorial algorithm. calls will he stratified by call code, extracted from the -ems database and transferred electronically to toronto public health. the data will be analyzed for clusters and aberrations from the expected with the realtime outbreak and disease surveillance (rods) system, a computer-based public health tool for the early detection of disease outbreaks. this -ems surveillance system will be assessed in terms of its specificity and sensitivity through comparisons with the well-established tracking systems already in place for hr! and ill. others sources of data including paramedic ambulance call reports of signs and . this study will introduce complementary data sources t~ the ed ch e~ complamt an~ o~~rthe-counter pharmacy sales syndromic surveillance data currently bemg evaluated m ~ther ontar~o cltles. . syndromic surveillance is a unique approach to proactive(~ dete~tmg early c.hangesm the health status of urban communities. the proposed study aims to provide evidence of differential effectiveness through investigating the use of -ems call data as a source of syndromic surveillance information for hr! and ili in toronto. introduction: there is strong evidence that primary care interventions, including screening, brief advi<:e, treatment referral and pharmacotherapy are effective in reducing morbidity and mortality caused by substance abuse. yet physicians are poor at intervening with substance users, in part because of lack of time, training and support. this study examines the hypothesis that shared care in addictions will result in decreased substance use and improved health status of patients, as well as increased use of primary care interventions by primary care practitioners (pcps). methods: the addiction medicine service (ams) at st. joseph's health centre's family medicine department is in the process of being transformed from its current structure as a traditional consult service into a shared care model called addiction shared care (asc). the program will have three components: education, office systems and clinical shared care. as opposed to a traditional consult service, the patient will be booked with both a primary care liaison worker (pcl) and addictions physician. patients referred from community physicians, the emergency department and inpatient medical and psychiatric wards will be recruited for the study as well as pcps from the surrounding community. the target sample size is - physicians and a similar number of patients. after initial consult, patient will be recruited into the study with their consent. the shared-case model underlines the interaction and collaboration with the patient's main pcp. asc will provide them with telephone consults, advice, support and re-assessment for their patients, as well as educational sessions and materials such as newsletters and informational kits.results: the impact of this transition on our patient care and on pcp's satisfaction with the asc model is currently being evaluated through a grant provided by the ministry of health & long term care. a retrospective chart review will be conducted using information on the patient's substance use, er/clinic visits, and their health/mood status. pcp satisfaction with the program will be measured through surveys and focus groups. our cost-effectiveness analysis will calculate the overall cost of the program per patient..conclusion: this low-cost service holds promise to serve as an optimal model and strategy to improve outcomes and reduce health care utilization in addict patients. the inner city public health project introduction the inner city public health project (icphp) was desi.gned to explore new an~ innovative ways to reach marginalized inner city populations that par-t c pate m high health-nsk beha~ ors. much of this population struggles with poverty, addictions, mental illness and homelessness, creatmg barriers to accessing health services and receiving follow-up. this pro ect was de~igned to evaluat~ .~e success of offering clinics in the community for testing and followup of communicable diseases uuhzmg an aboriginal outreach worker to build relationships with individuals and agencies. v n(demographics~ history ~f testi~g ~nd immunization and participation in various health-risk behaviors), records of tesnng and mmumzat ons, and mterviews with partner agency and project staff after one year.. results: t~e chr ~as i~strumental in building relationships with individuals and partner agencies ' .° the c~mmun_ ~ re_sultmg m req~ests for on-site outreach clinics from many of the agencies. the increase m parnc pat n, the chr mvolvement in the community, and the positive feedback from the agen? staff de~onstrated that.the project was successfully creating partnerships and becoming increasingly integrated m the community. data collected from clients at the initial visit indicated that the project was reaching its target populations and highlighted the unique health needs of clients, the large unmet need for health services and the barriers that exist to accessing those services. ~usion: the outreach clinics were successful at providing services to target populations of high health-nsk groups and had great support from the community agencies. the role of the chr was critical to the success of the project and proved the value of this category of health care worker in an urban aboriginal population. the unmet health needs of this disadvantaged population support the need for more dedicated resources with an emphasis on reducing access barriers. building a caring community old strathcona's whyte avenue, a district in edmonton, brought concern about increases in the population of panhandlers, street people and homeless persons to the attention of all levels of government. the issue was not only the problems of homelessness and related issues, but feelings of insecurity and disempowerment by the neighbourhood residents and businesses. their concerns were acknowledged, and civic support was offered, but it was up to the community itself to solve the problem. within a year of those meetings, an adult outreach worker program was created. the outreach worker, meets people in their own environments, including river valley camps. she provides wrap-around services rooted in harm reduction and health promotion principles. her relationship-based practice establishes the trust for helping clients with appropriate housing, physical and/or mental health issues, who have little or no income and family support to transition from homelessness. the program is an excellent example of collaboration that has been established with the businesses, community residents, community associations, churches, municiple services, and inner-city agencies such as boyle street community services. statistics are tracked using the canadian outcomes research institute homes database, and feedback from participants, including people who are street involved. this includes an annual general meeting for community and people who are homeless. the program's holistic approach to serving the homeless population has been integral, both in creating community awareness and equipping residents and businesses to effectively interact with people who are homeless. through this community development work, the outreach worker engages old strathcona in meeting the financial and material needs of the marginalized community. the success of this program has been surprising -the fact is that homeless people's lives are being changed; one person at a time and the community has been changed in how they view and treat those without homes. over two years, the program has successfully connected with approximately seventy-five individuals who call old strathcona home, but are homeless. thirty-six individuals are now in homes, while numerous others have been assisted in obtaining a healthier and safer lifestyles by becoming connected with other social/health agencies. the program highlights the roots of homelessness, barriers to change and requirements for success. it has been a thriving program and a model that works by showing how a caring community has rallied together to achieve prosperous outcomes. the spn has created models of tb service delivery to be used m part~ers~ p with phannaceunca compa-. · · -. t' ns cooperatives and health maintenance orgamzanons (hmos). for example, the mes, c v c orgamza , . · b tb d' · spn has established a system with pharmaceutical companies that help patients to uy me cmes at a special discounted rate. this scheme also allows patients to get a free one-_month's worth of~ dru_g supply if they purchase the first months of their regimen. the sy_s~e~s were ~es gned to be cm~pattble with existing policies for recording and documentation of the ph hppme national tuberculosis program (ntp). aside from that, stakeholders were also encouraged to be dots-enabled through the use of m~nual~ and on-line training courses. the spn initiative offers an alternative in easing the burden of tb sc:rv ce delivery from rhe public sector through the harnessing of existing private-sector (dsos). the learnmgs from the spn experience would benefit groups from other locales that _work no~ only on ~ but other health concerns as well. the spn experience showcases how well-coordinated private sector involvements help promote social justice in health delivery in urban communities.p - (c) young people in control; doing it safe. the safe sex comedy juan walter and pepijn v. empelen introduction: high prevalence of chlamydia and gonorrhoea have been reported among migrants youth in amsterdam, originating from the dutch antilles, suriname and sub-sahara africa. in addition, these groups also have high rates of teenage-pregnancy (stuart, ) and abortions (rademakers ), indicating unsafe sexual behaviour of these young people. young people (aged - ) from the so· called urban scene (young trendsetters in r&b/hip hop music and lifestyle) in amsterdam have been approached by the municipal health service (mhs) to collaborate on a safe sex project. their input was to use comedy as vehicle to get the message a cross. for the mhs this collaboration was a valuable opportunity to reach a hard-to-reach group.mdhods: first we conducted a need assessment by means of a online survey to assess basic knowledge and to similtaneously examine issues of interest concerning sex, sexuality, safer sex and the opposite sex. second, a small literature study was conducted about elements and essential conditions for succesful entertainment & education (e&e) (bouman ), with as most important condition to ensure that the message is realistic (buckingham & bragg, ) . third a program plan was developed aiming at enhancing the stl/hiv and sexuality knowledge of the young people and addressing communication and educational skills, by means of drama. subsequently a safe sex comedy show was developed, with as main topics: being in love, sexuality, empowerment, stigma, sti, hivand safer sex. the messages where carried by a mix of video presentation, stand up comedy, spoken word, rap and dance.results: there have been two safe sex comedy shows. the attendance was good; the group was divers' with an age range between and year, with the majority being younger than year. more women than men attended the show. the story lines were considered realistic and most of the audients recognised the situations displayed. eighty percent of the audients found the show entertaining and % found it edm:arional. from this %, one third considers the information as new. almost all respondents pointed our that they would promote this show to their friends.con.clusion: the s.h<_>w reached the hard-to-reach group of young people out of the urban scene and was cons d_ered entert~mmg, educational and realistic. in addition, the program was able in addressing important issues, and impacted on the percieved personal risk of acquiring an sti when not using condoms, as well as on basic knowledge about stl's. introduction: modernity has contributed mightily to the marginality of adults who live with mental illnesses and the subsequent denial of opportunities to them. limited access to social, vocational, educational, and residential opportunities exacerbates their disenfranchisement, strengthening the stigma that has been associated with mental illness in western society, and resulting in the denial of their basic human rights and their exclusion from active participation in civil society. the clubhouse approach tn recovery has led to the reduction of both marginality and stigma in every locale in which it has been implemented judiciously. its elucidation via the prism of social justice principles will lead to a deeper appreciation of its efficacy and relevance to an array of settings. methods: a review of the literature on social justice and mental health was conducted to determine core principles and relationships between the concepts. in particular, fondacaro and weinberg's ( ) conceptualization of social justice in community psychology suggests the desirability of the clubhouse approach in community mental health practice. a review of clubhouse philosophy and practice has led to the inescapable conclusion that there is a strong connection between clubhouse philosophy-which represents a unique approach co recovery--and social justice principles. placing this highly effective model of community mental health practice within the context of these principles is long overdue. via textual analysis, we will glean the principles of social justice inherent in the rich trove of clubhouse literature, particularly the international standards of clubhouse development.results: fondacarao and weinberg highlight three primary social justice themes within their community psychology framework: prevention and health promotion; empowerment, and a critical pnsp<"<·tive. utilizing the prescriptive principles that inform every detail of clubhouse development and th<" movement toward recovery for individuals at a fully-realized clubhouse, this presentation asserts that both clubhouse philosophy and practice embody these social justice themes, promote human rights, and empower clubhouse members, individuals who live with mental illnesses, to achieve a level of wdl-heing and productivity previously unimagined.conclusion: a social justice framework is critical to and enhances an understanding of the clubhouse model. this model creates inclusive communities that lead to opportunities for full partic pil!ion civil society of a previously marginalized group. the implication is that clubhouses that an· based on the international standards for clubhouse programs offer an effective intervention strategy to guarantee the human rights of a sizable, worthy, and earnest group of citizens. to a drastic increase in school enrollment from . million in to . million in .s. however, while gross enrollment rates increased to °/., in the whole country after the introduction of fpe, it remained conspicuously low at % in the capital city, nairobi. nairobi city's enrollment rate is lower .than thatof all regions in the country except the nomadic north-eastern province. !h.e.d sadvantage of children bas_ed in the capital city was also noted in uganda after the introduction of fpe m the late s_-many_ education experts in kenya attribute the city's poor performance to the high propornon of children hvmg m slums, which are grossly underserved as far as social services are concerned. this paper ~xammes the impact of fpe and explores reasons for poor enrollment in informal settlements m na rob city. methods: the study utilizes quantitative and qualitative schooling data from the longitudinal health and demographic study being implemented by the african population and health research center in two informal settlements in nairobi. descriptive statistics are used to depict trends in enrollment rates for children aged - years in slum settlements for the period - . results: the results show that school enrollment has surprisingly steadily declined for children aged - while it increased marginally for those aged - . the number of new enrollments (among those aged years) did not change much between and while it declined consistently among those aged - since . these results show that the underlying reasons for poor school attendance in poverty-stricken populations go far beyond the lack of school fees. indeed, the results show that lack of finances (for uniform, transportation, and scholastic materials) has continued to be a key barrier to schooling for many children in slums. furthermore, slum children have not benefited from fpe because they mostly attend informal schools since they do not have access to government schools where the policy is being implemented.conclusion: the results show the need for equity considerations in the design and implementation of the fpe program in kenya. without paying particular attention to the schooling needs of the urban poor children, the millennium development goal aimed at achieving universal primary education will remain but a pipe dream for the rapidly increasing number of children living in poor urban neighborhoods.ps- (c) programing for hiv/aids in the urban workplace: issues and insights joseph kamoga hiv/aids has had a major effect on the workforce. according to !lo million persons who are engaged in some form of production are affectefd by hiv/aids. the working class mises out on programs that take place in communities, yet in a number of jobs, there are high risks to hiv infection. working persons sopend much of their active life time in workplaces and that is where they start getting involved in risky behaviour putting entire families at risk. and when they are infected with hiv, working people face high levels of seclusion, stigmatisation and some miss out on benefits especially in countries where there are no strong workplace programs. adressing hiv/aids in the workplace is key for sucessfull responses. this paper presents a case for workplace programing; the needs, issues and recommendations especially for urban places in developing countries where the private sector workers face major challenges. key: cord- -wr j j authors: vasudevan, gayathri; singh, shanu; gupta, gaurav; jalajakshi, c. k. title: mgnrega in the times of covid- and beyond: can india do more with less? date: - - journal: indian j labour econ doi: . /s - - - sha: doc_id: cord_uid: wr j j covid- has ushered in a renewed focus on health, sanitisation and, in unexpected ways, on the need for productive employment opportunities in rural india. mgnrega, the rural employment guarantee programme, has had a mixed track record in terms of providing adequate employment to those who need it the most, the quality of asset creation and adequacy of wages offered. this paper makes a case for reorienting a small portion of mgnrega spending to create micro-entrepreneurs out of the ‘reverse migrating’ masons, electricians, plumbers and others in rural areas who can directly contribute to augmenting health and sanitization infrastructure in the likely new normal. this will provide relief to those whose livelihoods have been severely impacted and eventually lower dependence on public finances. we propose approval of a new work type for sanitization works without any hard asset creation under mgnrega and roping in the private sector for its project management skills to quickly skill up the returning migrants as well as to match work with workers on an ongoing basis. in rural areas, major livelihood activities are irregular mainly due to seasonal fluctuations in agriculture and allied activities. this leads to periodic withdrawal from labour force, especially by the marginal labourers, who shift back and forth between what is reported as domestic and gainful work. many workers migrate to other parts of the country in search of work. lack of alternate livelihoods and skill development are the primary causes of migration from rural areas. due to covid- pandemic, india is facing a severe challenge of unemployment and reverse migration (fig. ) . migrant workers are heading back to their native places in the hope of sustaining themselves better than they would be able to manage in hostile living conditions in host locations with limited work opportunities. most migrant workers are daily-wage earners, and absence of work for extended periods makes it difficult to afford high cost of living in urban areas. added to this is the uncertainty around the timelines for normalization of the current situation. mahatma gandhi national rural employment guarantee act (referred to as mgnrega hereafter) was introduced by government of india in to target causes of chronic poverty through the 'works' (projects) that are undertaken, and thus ensuring sustainable development for all. mgnrega is the largest work guarantee programme in the world with the primary objective of guaranteeing days of wage employment per year to rural households. the programme emphasizes on strengthening the process of decentralization by giving a significant role to panchayati raj institutions (pris) in planning and implementing these works. this paper critically evaluates the suitability of mgnrega in its current form as a panacea for alleviating stress in rural india. the key question we discuss here is whether mgnrega can provide meaningful work in the post-covid- world, how more employment could be generated with the same effective spending and reliance on projects under mgnrega be reduced going forward. the focus of the scheme is on rural employment and asset creation. a total of days of work is guaranteed per household with the budget shared in : ratio by centre and states. the daily wage has recently been increased to rs. by the centre although there is significant interstate variation in the wages paid (increased wage rates effective from april, and notified on march, ). in many cases, the scheme wage rates are lower than the minimum wages in respective states. spending under mgnrega projects is mandated to be at least % on wages to unskilled labour with the remaining % for semi-skilled/skilled labour and material. however, there are exceptions to this. one of the prominent examples is construction of toilets. the scheme is implemented via gram panchayats. the centre's focus is on 'convergence' with spending on other major schemes. convergence in this context implies that where possible, the objective of jobs and asset creation under mgnrega is be achieved in alignment with the schemes rolled out by other departments. mgnrega funds cannot be used for other schemes, but the reverse is what convergence aims to promote. more than projects are permissible under mgnrega and classified into four main categories, namely: public works relating to natural resources management, individual assets for vulnerable sections, common infrastructure for deendayal antyodaya yojana-national rural livelihoods mission (day-nrlm) compliant self-help groups, and rural infrastructure. total fy - spending by the centre was rs. , crores, while the original budget for fy was rs. , crores. in the wake of covid- -related reverse migration, the centre has recently enhanced this amount by rs. , crores. in the financial year - , approximately crore workers availed of work under the scheme. mgnrega is also one of the focus areas in the centre's recently announced rs. lakh crore stimulus package. however, as we discuss in the following sections, this would not be enough to provide meaningful employment to the large number of returnee migrants, and a meaningful reorientation of spending can help create a pool of micro-entrepreneurs in short time. with a possibility of reasonable income-generating opportunities outside mgnrega-related works, this pool is expected to have lower dependence on government spending in future. a study by institute of social and economic change (isec ) of projects between fy and fy under mgnrega reveals the following top categories: rural connectivity ( %), water conservation ( %), land development ( %), renovation of water bodies ( %), flood control ( %), micro-irrigation works ( %), provision of irrigation facility ( %), drought proofing ( %) and other activities, as approved by ministry of rural development, ( %). however, as with schemes of this scale and nature, work completion rates under mgnrega have been low at least for the period under consideration (table ) . besides other factors such as time taken for completing documentation and abandonment of non-feasible projects, this also demonstrates the need for better project management and execution skills. the following is an extract (section . ) from the nd report of the standing committee on rural development ( development ( - presented to the th lok sabha. "the working group on mgnrega have also mentioned that findings related to quality, durability and rate of work completion suggest that the problem is not in the design of the act but the usefulness of the scheme is dependent on the strength of its implementation at the field level. for instance, lack of planning in areas like potential demand and need for mgnrega works, participation of villagers and prioritization of works in the gram sabha (gs), and focus on creation of productive assets based on principles of watershed, etc., can greatly reduce the development potential of mgnrega. taking up of planned works, relevant to the need of the region and demand of the beneficiaries is also vital for ensuring ownership of assets and their development utility in the long run." the most distressed section of migrants is what has been termed in the literature as vulnerable circular migrants (srivastava ) . these include both short-term seasonal and long-term (semi-permanent) occupationally vulnerable workers. srivastava ( ) has estimated that there were approximately . crore short-duration circular migrant workers in - . of these . crore, about . crore were engaged in non-agriculture work, . crore were in urban areas, and . crore were working in other states ( . crore of out of . crore in urban locations). in the same study, the number of vulnerable long-term circular migrant workers has been estimated at . crores in . putting together the numbers of short-term seasonal/ circular and long-term occupationally vulnerable workers gives us about . crore workers whose livelihoods may have been adversely impacted with the onset of covid . about . crore ( . crores short-term above and . crores longterm) of these . crore migrants were estimated to be a part of the workforce in urban india-the epicentre of covid in india. a little less than half of these . crore workers- . crores-were interstate migrant workers in . based on - nss data used in srivastava ( ) , states that primarily contribute to short-duration out-migration for employment are bihar ( . %), uttar pradesh ( %) and west bengal ( %), madhya pradesh ( . %), jharkhand ( . %) and rajasthan ( . %). these states also had the highest shares in interstate outmigrants reflecting their low levels of income. uttar pradesh and bihar also have more than % share in long-term out-migration. the task force on eliminating poverty constituted by niti aayog in (occasional paper ) has noted that, on average, most beneficiaries under mgnregs have been able to avail of only days of work and recommends better targeting of the scheme to ensure the poorest of the poor get the promised days of work opportunity. if - % of . crores migrant workers in urban india (including the . crores interstate workers in above) return to their home destinations, the scheme has to accommodate between . and . crores new workers. this will add roughly - % to the pool of existing workers, and the current employment situation in the country will also force inactive users to demand employment under mgnrega. the incremental allocation (over last year's actuals) is about rs. , crores. considering these numbers, the average availability of work per person will reduce further below days and is inadequate in addressing the challenges facing rural india. this reverse migration has altered the labour market's demand and supply dynamics significantly. areas that previously had negative net migration rates are now expected to be labour surplus. locations that were attractive for labour to migrate to, will find it difficult to attract and retain labour. what this essentially means is that locations that were hitherto the biggest sources of migrant workers will have an excess supply of unskilled/semi-skilled labour available to work at low reservation wages. given the continued requirements around social distancing, we expect movement of people to be somewhat restricted and a more-or-less closed labour market in the foreseeable future. this will mean that some portion (~ - % ) of migrants will stay back in their villages and not return to the places of work soon. on the other hand, covid- has demonstrated the gaps in india's health and sanitisation infrastructure. in addition, sanitisation has assumed unprecedented importance in our lives, in both rural and urban india. rural india can benefit from effectively utilising this surplus labour in augmenting its health and sanitization infrastructure. table shows that top districts account for % of all male migrants. the next % is spread over the districts shown against numbers to . these are the areas that need intervention on an urgent basis. early/incomplete data collected by the office of relief commissioner, government of uttar pradesh, in table suggest % of returning migrants are unskilled. governments, both at the centre and in states, are facing several challenges today. at the top of the list is rehabilitation of returning migrants including provision of quarantine facilities, covid screening, essential supplies, etc. equally critical is to immediately provide these workers income-earning opportunities, especially to seasonal migrants who are unlikely to migrate for work soon. at the very least, they are not expected to return with families leaving behind - adults in the village. on health and sanitisation fronts, adequate health facilities including those for mental health are required given the large number of people back in villages now and most having returned after long period of hardships and joblessness. sanitisation needs to be ensured as per new requirements, and necessary steps need to be taken at local levels to ensure there is no spread of infection in rural areas. in addition, restoration of public and private property post-cyclone amphanrelated destruction is also an important focus area for governments in west bengal and odisha. a. sanitisation of public and private assets. it must be noted that sanitisation is to be seen as something distinct from regular cleaning work. overall, public places such as schools, anganwadis, health centres, common areas, shops, community assets such as panchayat office, post office, police chowki, cooperative society offices and bank branches where a lot of people come in contact with each other need effective sanitisation. the new physical distancing norms also necessitate construction of individual toilets versus community toilets in order to abate spread of communicable diseases. while unavoidable where common services are provided (e.g. bus stands, train station), common toilets in residential areas are not very effective in disease prevention. the jal jeevan mission which aims to provide piped water to every household needs to be fast tracked by reaching more and more households at the earliest. with respect to health-related aspects, additional construction is required particularly to attend to critical services like maternal labour rooms which are being currently doubled up as isolation wards. similarly, non-covid-related medical services which have been side-lined for lack of space and resources need augmenting including construction of adequate physical space and healthcare workers. it is well documented that the returning indian soldiers from world war i carried h n influenza to the rest of the country ultimately resulting in the death of . crore indians. the current reverse migration from cities (the epicentres of covid- ) to rural areas has potential for the wider spread of disease in rural areas which have far inferior medical facilities and preparedness than urban india. temporary structures to host screening, testing and quarantine facilities for these migrant workers need immediate work. c. frequency of cleaning (and sanitisation) work needs to be far more than that in the pre-covid world. d. storage for agriculture produce: creation of small warehouses at the village level for storage of produce. there is a well-documented shortage of storage space in india (oecd ). it is estimated that lack of storage facilities depresses the realised price as well as results in direct wastage of - % of physical output ( - % in overall supply chain). e. restoration of public and private property post-cyclone amphan-related destruction. the we propose the following changes to the existing mgnrega guidelines. . a new category of works without any physical asset creation as such needs to be approved. . funding from mgnrega for paying wages to sanitization and hygiene workers. works. these will be labour and material contractors. there are not any as of now for sanitisation and hygiene-related works. these fpc will be different from the existing mates or mistris as they would need to quickly acquire skills in short time that were, in the pre-covid times, acquired over a period of time with experience. mates or mistris are experts for overseeing work assigned to their group of workers ~ in each group. . sanitisation as a concept is new, so trained manpower is necessary. sanitisation and hygiene workers (different from those currently involved in cleaning jobs) will drive sanitization efforts across the gp. both the fpc and sanitisation workers will be collectively called sanitisation and hygiene entrepreneurs (she). ing in the project management expertise with respect to quickly mobilising, skilling and maintaining a pool of sanitisation and hygiene workers for gp level works as well as in matching workers to work outside mgnrega projects. we represent these project management consultants as pmcs hereafter in the note. under mgnrega, % of total expenditure can be on administrative expenses. of this, % needs to be utilised at the gp level. these funds can be utilised on the skilling of she. as we show later in this note, just this portion of funds will not be enough and governments need to make more funding available through other components of mgnrega and other schemes. states need to propose changes to be made in the scheme to centre given there will be no asset creation and the work is of regular nature. the proposal needs to include the following: justification for the work, areas where the work will be undertaken, number of wage seekers to be employed (employment potential), nature of durable asset to be created, expectations from the work to strengthen the livelihood base of the rural poor, other benefits that may accrue such as continued employment opportunities, strengthening of the local economy and improving the quality of lives of people. the model project should contain the following: unit cost of the work, the split between labour and material component and between skilled and semi-skilled component, transparency and accountability mechanisms, expected final outcome (asset that will be created), benefit to the livelihood base of the rural poor and any other benefit likely to accrue. what we propose is to build a pool of micro-entrepreneurs involved in: . sanitisation and hygiene activities . infrastructure development/rehabilitation projects gram panchayats (gp) could use these mainly sanitisation and health entrepreneurs (she) to take care of sanitisation and hygiene needs with respect to public and private assets under the new normal. work guarantee under mgnrega could act as a floor for basic sustenance, and a one-time government subsidy for training and buying equipment could get a large number of these workers take the first steps towards sustainable self-employment. these she need not restrict themselves to work allocated by gp and could also take on private work related to health and sanitisation. however, on their own, workers lack information on how to go about providing these services. on the other side, gp will find it difficult to get hold of such service providers who are trained. gp will want this at the lowest possible costs which can be provided by someone who is locally based and whose services can also be used on an ad hoc basis. it is in this context that private sector organizations with experience in project management of large-scale interventions can be roped in. experience of private sector organisations that have engaged considerably with the panchayati raj department and understand the skills and rural space quite well will be useful. given their project management experience, these institutions can monitor quality of the work, train workers to improve their skills and ensure quality assurance to the villages. support needs to be provided on an urgent basis to masons, plumbers, electricians and painters-a large category of returnees to rural india in the current situation. this support comes not only in the form of capacity building via professionalisation of skills but also as forward and backward market linkages, business skills, compliance and support in obtaining loans from the formal financial system to ensure an increased income to these micro-contractors. details of specific mgnrega works/ tasks that these workers can be involved in are provided in "appendix". these project management consultants can act as a platform assisting and working with the gram panchayats on the one hand and service providers/contractors/workers on the other. they must have the necessary skills to train and create a talent pool of fair practice contractors (fpc) who can work on creating new as well as disinfecting existing common infrastructure at the village level and also private assets. they should also maintain a database through their skilling initiatives of a pool of trained workers to draw on. these she (workers as well as the fpcs) come with a stamp of quality from the pmc on the basis of its training, mentoring and monitoring interventions. this is not the case currently even though gram panchayats have been allocating work to contractors. pmc will assist the gps to assess their works requirement (for infrastructure build-up as well as for embedding sanitisationrelated measures) and create the project requirement documents. from the talent pool of contractors and workers, pmc will screen and choose micro-entrepreneurs, facilitate the contract process and monitor the work done by them to ensure quality output. pmc will monitor the quality of work, using photographic evidence. given the new requirements around sanitization needs, gps may not be equipped to handle this on their own. at the moment, contractors and workers mainly learn on the job. in our experience, they are not aware of the most efficient ways of working and organizing their services business. pmc can use technology to bring the service providers and the customers (gps) together in an efficient manner. pmc must be equipped to conduct online training for contractors/workers and also create a portal for gps which will have a template for them to assess the requirement and create a 'project document' and process contract. for the she, only a part of their overall business needs to come from gps as discussed above. through extensive training on different aspects related to running a small business, pmc's intervention can empower them with the necessary skills and infrastructure to expand private income-enhancing opportunities. once self-sufficient and connected with a pool of available workers facilitated by the pmc's technology platform, she can look at opportunities outside their own villages for expansion and over a short period of time lessen their dependence on work opportunities funded under mgnrega. from the point of view of supporting economic activity, another concept that merits attention is that of common service centres (csc). these csc aimed at shortening the end-to-end value chains are already being piloted by organisations such as selco foundation in bengaluru. csc involve establishment of infrastructure (physical and digital, in sizes and prices that are affordable) and systems (standard operating procedures, efficient use of technology) in a manner that can respond to local needs and be a catalyst for economic activities in a local area. some of the common services these csc can provide include: tailoring centres, mechanic shops, local provision stores with refrigeration for perishable consumables, agriculture-related storage infrastructure and equipment. these csc can also be used as telemedicine centres for first level testing and care in the fight against covid- at the village level. depending on the predominant livelihood in the region, agriculture processing or value-add facilities can be developed. the facilities could be government or cooperative owned, but run on revenue-based model-providing cold storage facilities for horticulture produce, milk chilling, agriculture processing, or food processing units. in summary, what the above examples demonstrate is that it is possible to reduce reliance on public funding beyond the initial grant and create an avenue for further job creation in rural areas without putting undue strain on public finances. given the huge requirement for sanitisation, we expect sanitisation workers to earn at least rs. , - , a month on a sustainable basis without necessarily relying on public funds after the first days of work under mgnrega. as shown in the table below, based on our assumptions, spending of rs. , crores (including rs. crores one-time) will be required to train, endow with initial start-up material and employ a new breed of sanitization and hygiene entrepreneurs as well as plumbers, electricians, masons and telemedicine workers in , villages across the country for a period of days. after this time, these workers should be in a strong position to take on private work in rural as well as in urban areas and earn far more than the subsistence wages under mgnrega. the training would be done by appointed pmcs who would develop an ecosystem for sanitization services and connect these workers with work in rural and urban areas on an ongoing basis. this paper has attempted to quantify the scale of reverse migration india is witnessing in the current times and the action needed to make mgnrega spending more effective. we also analysed the profile of these migrants and which areas people are migrating back to. the scale of reverse migration and the lack of opportunities in rural india despite enhancements in fund allocation to mgnrega point to a grim situation. projects under mgnrega have had limited completion rate in the past, and the scheme overall has been inadequate in providing the assured minimum days of work to those who need it the most. in the new normal, healthcare, sanitisation and hygiene will have a priority focus. a project management discipline, connecting labour to work opportunities and vice versa and the need for micro-self-employment is the need of the hour. more can be achieved with the same level of public finances if people are connected to and shown the way to private income enhancement opportunities. impact of mgnrega on wage rate, food security and rural urban migration: a consolidated report. project leader-prof ministry of rural development, government of india eliminating poverty: creating jobs and strengthening social programs. niti aayog, government of india committee for agriculture implementation of mahatma gandhi national rural employment guarantee act understanding circular migration in india: its nature and dimensions, the crisis under lockdown and the response of the state. institute for human development job role-wise categorization of permitted works for mason, plumber, electrician and painter. key: cord- -ekaqbruo authors: novosad, p.; jain, r.; campion, a.; asher, s. title: the covid- mortality effects of underlying health conditions in india: a modelling study date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: ekaqbruo objective: to model how known covid- comorbidities will affect mortality rates and the age distribution of mortality in a large lower middle income country (india), as compared with a high income country (england), and to identify which health conditions drive any differences. design: modelling study. setting: england and india. participants: , , respondents aged to to the district level household survey- and annual health survey in india. additional information on health condition prevalence on individuals aged to was obtained from the health survey for england and the global burden of diseases, risk factors, and injuries studies (gbd). main outcome measures: the primary outcome was the proportional increase in age-specific mortality in each country due to the prevalence of each covid- mortality risk factor (diabetes, hypertension, obesity, chronic heart disease, respiratory illness, kidney disease, liver disease, and cancer, among others). the combined change in overall mortality and the share of deaths under from the combination of risk factors was estimated in each country. results: relative to england, indians have higher rates of diabetes ( . % vs. . %), chronic respiratory disease ( . % vs. . %), and kidney disease ( . % vs. . %), and lower rates of obesity ( . % vs. . %), chronic heart disease ( . % vs. . %), and cancer ( . % vs. . %). population covid- mortality in india relative to england is most increased by diabetes (+ . %) and chronic respiratory disease (+ . %), and most reduced by obesity (- . %), cancer (- . %), and chronic heart disease (- . %). overall, comorbidities lower mortality in india relative to england by . %. accounting for demographics and population health explains a third of the difference in share of deaths under age between the two countries. conclusions: known covid- health risk factors are not expected to have a large effect on aggregate mortality or its age distribution in india relative to england. the high share of covid- deaths from people under in low- and middle-income countries (lmics) remains unexplained. understanding mortality risk associated with health conditions prevalent in lmics, such as malnutrition and hiv/aids, is essential for understanding differential mortality. keywords: covid- , india, low- and middle-income countries, comorbidity covid- infections in low-and middle-income countries (lmics) are rising rapidly, with the burden of mortality concentrated at much younger ages than in rich countries. a range of pre-existing health conditions can increase the severity of covid- infections. it is feared that poor population health may worsen the severity of the pandemic in lmics. the covid- comorbidities that have been studied to date may have only a very small effect on aggregate mortality in india relative to england and do not shift the mortality burden toward lower ages at all. india's younger demographics can explain only a third of the substantial difference in the share of deaths under age between india and england. however, mortality risk associated with health conditions prevalent in lmics, such as malnutrition and hiv/aids, is unknown and research on this topic is urgently needed. as governments around the world ease social distancing measures imposed to limit the transmission of covid- , the number of global cases is rising. a growing share of cases is now coming from low-and middle-income countries (lmics) in asia, africa, and the americas that were largely spared in the initial stages of the pandemic. because the severity of infection is substantially increasing with age, forecasts have projected much lower aggregate mortality rates in lmics than in wealthier countries. [ ] [ ] [ ] however, reported fatality numbers from lmics to date have suggested a much greater share of covid- deaths among the young. . % of deaths in brazil and % of deaths in india have occurred in those under age ; % of deaths in mexico have occurred in those under . [ ] [ ] [ ] in contrast, individuals under have accounted for only - % of deaths in european countries and canada and - % in us states. it is not presently known whether the different age pattern of deaths in lmics is driven by erroneous reporting, differences in infection patterns, younger populations, or worse underlying population health. many modelling studies have presumed that worse population health in poor countries will lead to excess mortality, or else ignored differential population health as a factor entirely. , , to date there has been limited analysis of the prevalence in lmics of the specific conditions associated with increased covid- severity, such as diabetes, obesity, cardiovascular disease, hypertension, and chronic kidney disease, nor of how they change the expected level and age distribution of mortality. , [ ] [ ] [ ] [ ] some studies have adjusted mortality estimates for population comorbidities by treating all comorbidities as equivalent or by multiplying the mortality rate by a fixed amount to adjust for population health. [ ] [ ] [ ] one study combined condition-specific prevalence and hazard ratios from a sample of hospitalizations, but excluded obesity and uncontrolled diabetes, and did not examine mortality or the age distribution of mortality as outcomes. using england as a benchmark, this study examines how comorbidities understood to increase covid- mortality are likely to affect covid- mortality rates in aggregate and across the age distribution in india, identifying the specific risk factors with the largest mortality effects. we further study the extent to which accounting for differences in demographics and underlying health conditions can explain the increased share of deaths among the young in india relative to england. our analysis focuses on india and on the covid- risk factors that are currently documented. india presently has the third highest number of cumulative covid- infections in the world and the highest growth rate in infections of any major country, making it an essential population to study. the methodology is readily adjusted to account for new risk factors or data from other countries and may be useful for modelling the epidemic in a range of lmics. our approach requires three types of data: (i) the relative risk of covid- mortality associated with gender, age, and each health condition; (ii) the age-specific prevalence of each health condition in england and india; and (iii) the age and gender distributions for the two countries. we obtained estimates of covid- mortality risk for a wide range of comorbidities from the opensafely study, a closed cohort study of , , adults from england. this was the largest analysis of comorbidities associated with covid- mortality to date and one of the few studies that estimates risk factors in a multivariate model adjusting for age, sex, and other health conditions. this adjustment is important because many covid- comorbidities are increasing in age and their hazard ratios are thus biased upward in analyses not adjusting for age. the opensafely study enrolled all individuals registered with a general practice within the phoenix partnership system on st february , were years or older upon enrolment, had at least one year of prior medical history within the system, and had recorded age and sex. the underlying dataset represents % of the population of england and the prevalence of health conditions in the study cohort is similar to estimates of population prevalence in england (appendix p ). patients were followed through th april. the outcome was in-hospital death among people with confirmed covid- infections. hazard ratios (hrs) for mortality from a cox proportional hazards model were estimated for a comprehensive list of risk factors described in other studies, adjusted for sex, age, and all other risk factors. as patient-level data from opensafely are not publicly available, we extracted hrs from the paper reporting results of the analysis. ideally, hrs would measure mortality risk conditional upon infection, rather than on clinic attendance (this paper) or hospitalization (as in prior work). , the hrs in this study reflect combined mortality and infection risk; the analysis assumes that pre-existing health conditions are not significant predictors of infection. however, condition hrs measuring mortality risk conditional upon hospitalization are similar to those used here. age distributions and age-specific sex ratios for india and england were obtained from official censuses. we obtained data on age-specific prevalence of health risk factors for india and england from multiple sources, prioritizing biomarker data where available, and matching definitions as closely as possible to the conditions for which hrs are available. we restrict samples to ages - for consistency with the hrs. for india, we used biomarker data from two public population health surveys for obesity, diabetes, and hypertension. the fourth round of the indian district level household survey (dlhs- ) and the second round of the annual health survey (ahs) were conducted between and , jointly cover % of the indian population, and provide the most recent nationwide direct measures of height, weight, fasting plasma glucose (fpg) and blood pressure (bp) for adults of all ages in india. details of dataset construction are provided in the appendix (p ). for england, age-specific prevalences of obesity, hypertension, and diabetes were obtained from the nationally representative health survey for england, which collected symptoms and medical diagnoses for a range of illnesses, as well as direct measures of height, weight, blood pressure, and glycated haemoglobin (hba c). bmi was classified into no evidence of obesity (< kg/m ), obese class one or two ( - . kg/m ), and obese class three ( +kg/m ). hypertension was defined as systolic bp ≥ mm hg or diastolic bp ≥ mm hg (uncontrolled) or a medical diagnosis of hypertension with bp below the thresholds (controlled). controlled and uncontrolled hypertension prevalence were reported separately but combined in the risk estimation for consistency with opensafely. opensafely classified controlled diabetes as hba c > mmols/mol and hba c < mmols/mol, and uncontrolled diabetes as hba c ≥ mmols/mol. corresponding thresholds for the one-time fpg measures in the indian dataset are not well defined. in england, prevalence was reported based on a threshold of hba c ≥ mmol/mol ( . %). therefore, we followed the standard screening and diagnosis thresholds recommended by the who and international diabetes federation and defined uncontrolled diabetes in india as a plasma glucose reading ≥ mg/dl [ . mmol/l] if fasting or ≥ mg/dl [ . mmol/l] if not fasting. we used the corresponding recommended threshold of hba c ≥ mmol/mol ( . %) for uncontrolled diabetes in england. in both countries, we classified individuals with biomarkers below the thresholds but with a diagnosis of diabetes as having controlled diabetes. age-specific prevalence for asthma, chronic heart disease, kidney disease, stroke, dementia, haematological malignancies, and all other cancers were drawn from the global burden of diseases, risk factors, and injuries studies (gbd) for india and england. opensafely reports separate hrs for cancers diagnosed < year ago, - . years ago, and ≥ years ago; because the year of diagnosis is unavailable in gbd, we used a single classification for each class of cancers and the hr for diagnosis < year ago. for chronic respiratory disease, we used copd prevalence from the gbd for india and modelled copd prevalence from the clinical practice research datalink cohort database for england. gbd prevalence of parkinson's disease, epilepsy, multiple sclerosis, and motor neuron disease were combined and classified as neurological disorders. the following risk factors were not available for india and were excluded from the analysis for both england and india for comparability: fibrosing lung disease, bronchiectasis or cystic fibrosis, lupus, asthma with no recent ocs use, cancers diagnosed more than a year ago, organ transplant, and spleen disease. given that the relationship between smoking and covid- mortality remains under debate, we excluded it from the analysis. we also excluded ethnicity and socioeconomic status, which cannot be measured comparably across england and india and are unlikely to have similar relative risk in the two countries. the opensafely study reports hrs for each age group, sex, and health condition with females - years with no conditions as the reference group. we transform the hr for each health condition c into a relative risk ( ! ) assuming a population mortality rate r of %: to obtain continuous relative risk for age, we used a polynomial interpolation for the log hr at each age, renormalizing with age as the reference group (appendix p ). the increase in population mortality risk from a given health condition is increasing in the condition's relative risk for covid- mortality and its prevalence at each age. we defined the age-and conditionspecific population relative risk +,! of condition c at age a as: +,! is the prevalence of condition c at age a. +,! describes the proportional increase in mortality at age a driven by health condition c. we combined prrs to obtain an age-specific population relative risk of mortality arising from the combined prevalence of all of the health conditions : + isolates the expected mortality difference at each age between india and england that is driven by the combined prevalence of all of the health conditions studied. this approach implicitly assumes that the health conditions are uncorrelated with each other. without microdata on the full set of health conditions, this assumption is unavoidable, but will bias the england vs. india comparison only if the correlation of health conditions is substantially different in the two countries. we explore the possible extent of this bias in the appendix. by using age-specific prevalence, our analysis fully accounts for the substantial correlations between age and health conditions. we next calculated the increase in population mortality from each health condition across all ages, taking into account the age-specific prevalence of each health condition, its relative risk, and the population share at each age. the condition-specific population relative risk of each health condition across the full population ( ! ) is given by: ] ! is greater when the relative risk of condition c is higher, and when its prevalence is higher at ages with higher population and greater mortality risk. the combined effect on population mortality of all of the health conditions is given by the product of each condition-specific ! . finally, we aggregated the population relative risks across health conditions in order to model the age distribution of deaths in each country. the number of deaths at each age + is the product of the mortality rate of the reference group ( -year-old women with no other risk factors), the population at age a, the age-specific population relative risk of the full set of health conditions, the prr of gender, and the direct relative risk of covid- mortality for an individual at age a ( + ): we plotted the age distribution of deaths as shares of all deaths rather than in levels, eliminating the need to assume a reference group mortality rate. we summarized the shape of the distribution by reporting the share of expected deaths in each country that are under the age of . we present results from three models: (i) england's demographics and health distribution; (ii) india's demographics and health distribution; and (iii) india's demographics but england's age-specific prevalence of health risk factors. the third model allowed us to examine the mortality shift that comes from differences in population health alone. the funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing. the corresponding author had full access to the data in the study and had final responsibility for the decision to submit for publication. because this study uses existing epidemiological data, it was not appropriate to involve patients or the public in the research. demographic characteristics and overall prevalence of risk factors are substantially different in india relative to england (table ) . . % of indian adults are below the age of , compared to . % of english adults. indians have substantially lower rates of obesity and cancer ( . % and . % in india compared with . % and . % in england), but higher rates of uncontrolled diabetes, kidney disease, and chronic liver disease ( . %, . %, and . % in india and . %, . %, and . % in england). was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which this version posted july , . . we show age-specific prevalence differences between india and england for the conditions for which we have biomarkers in india and are more precisely estimated (figure ), as well as age-specific prevalence of all conditions for both countries (appendix p ). overall rates of diabetes are higher in india at all ages, but diabetes in india is overwhelmingly uncontrolled, while three quarters of diabetes is controlled in england. hypertension (the sum of controlled and uncontrolled) is higher in india at young ages ( . % for ages - in india and . % in england) but lower at higher ages ( . % at ages - in india and . % in england) and is overwhelmingly uncontrolled. conversely, obesity rates are higher at all ages in england. age india england all rights reserved. no reuse allowed without permission. was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which this version posted july , . . the age-specific population relative risk across all health conditions combined ( + ) is higher in india than in england at nearly all ages, but the difference in + between the two countries is below % at every age (figure ). modelled age-specific mortality rates in india are highest relative to england between ages and . age-specific population relative risk from combined health conditions (prra) the + reflects the age-specific prevalence and associated risk of each health condition. taking risk, prevalence, and population at every age into account provides the full population relative risk of each health condition ( ! ) -the proportional increase in population mortality across all ages driven by each health condition (table ). was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which this version posted july , . . uncontrolled diabetes, which is associated with substantial mortality risk ( ! . ), increases total mortality by % in india ( ! . ), but only % in england ( ! . ), reflecting its significantly higher prevalence in india at all ages. in contrast, controlled diabetes, more common in england than india, raises mortality by % in england and only % in india ( ! . vs . ). in addition to uncontrolled diabetes, the health conditions causing the largest increases in mortality in india are kidney disease ( ! = . ), and chronic respiratory disease ( ! = . ). in england, the most consequential health conditions are obesity (combined ! across all obesity classes = . ), and kidney disease ( ! = . ). comparing the percentage difference between the ! of each health condition between india and england (figure ), the condition with the largest differential impact on mortality between the two countries is uncontrolled diabetes, which increases population mortality by . % in india relative to england. mortality in india relative to england is also increased by chronic respiratory disease (+ . %) and chronic liver disease (+ . %), but decreased by the differential prevalence of obesity (combined - . %), cancer (- . %), and controlled diabetes (- . %). no other risk factor has an effect of greater than ± . % on india's relative mortality. the combined effect of health conditions leads to . % higher mortality in england than in india, reflecting england's higher age-specific prevalence of certain conditions like obesity and cancer, as well as its older age structure that increases population share at ages with worse health. this differential mortality risk does not include the direct effect of older age, which is associated with substantial risk ( ! . for age - , . above ) and magnifies england's mortality disadvantage substantially. was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which this version posted july , . . combining the population relative risk from health conditions with the direct effect of demographics on mortality, we modelled the density of deaths across the age distribution (figure ). in england, . % of expected deaths are below age , closely matching the . % observed in england through may and the . % reported in the opensafely dataset. in india, . % of modelled deaths are below age , which is substantially lower than the % observed in case reports. applying england's age-specific prevalence of health conditions to india's demographic distribution, in order to isolate the effect of health conditions from demographics, results in a distribution nearly identical to the india model. in other words, differences in health conditions between india and england have almost no effect on mortality, indicating that the modelled shift toward younger populations comes from the demographic distribution alone. in the appendix, we test sensitivity to uncertainty in prevalences and hrs (appendix pp [ ] [ ] [ ] . the latter estimates cover alternate hazard ratios estimated from other studies. , we also test sensitivity to alternate assumptions about covariance of health conditions (appendix p ). in all cases, we find that the population relative risk from health conditions in england is greater than in india, and that accounting for health conditions cannot explain any of the higher incidence of mortality among the young in india relative to england. we used the best publicly available data on population health to examine the extent to which demographics and pre-existing health conditions known to increase covid- mortality can account for the disproportionately high share of covid- deaths in younger populations observed in india relative to england. we show that differences in population health do not significantly shift the relative age distribution of disease severity and slightly lower aggregate mortality in india relative to england. higher was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint (which this version posted july , . . prevalence of diabetes and respiratory illness raise mortality risk relative to england, but these effects are offset by lower rates of obesity, heart disease, and cancer. while the indian age distribution substantially shifts expected mortality toward the young, it explains less than a third of the difference in the share of deaths under compared with england. epidemiologic models have typically assumed that comorbidities will exacerbate the mortality of covid- in india and other poorer countries relative to rich countries. we found that comorbidities identified as key risk factors in rich countries do not increase expected mortality in india relative to england, in aggregate or among the young. this suggests that understanding the other factors that may explain the differential mortality among the young observed in lower income contexts, such as different patterns of infection, under-resourced health systems, or comorbidities unique to lmics, should be a priority for further research. this study improves upon prior work by examining the extent to which comorbidities can explain the younger incidence of covid- mortality in lmics, by estimating mortality effects of specific comorbidities, and by calibrating a model with a comprehensive set of comorbidity hazard ratios drawn from a large-sample multivariate analysis of covid- mortality. models calibrated with bivariate hazard ratios or raw prevalences of comorbidities among severe cases are likely to overstate the effect of pre-existing health conditions because of the significant increase in all comorbidities with age alongside the direct effect of age on covid- mortality. the key limitation of this study is that there are virtually no data on the covid- mortality risks associated with health conditions that are more common in lmics than in high income countries, such as protein calorie malnutrition, micronutrient deficiency, and hiv/aids. if these conditions make individuals more susceptible to severe infections, then population health may indeed exacerbate the severity of covid- in lmics. understanding the extent to which health conditions endemic to poor countries affect covid- severity is an urgent priority, particularly as policy responses increasingly focus on identifying and isolating high risk individuals. our analysis is also constrained by the limited and changing evidence on risk factors for covid- severity. based on the availability of existing measures, our model assumed that health condition relative risks are age-invariant. however, data from new york's epidemiological surveillance system suggest that hypertension and diabetes may contribute more to mortality at younger ages, which would exacerbate the burden of illness among the young in lmics. further, if illness severity and the quality of prior medical management of pre-existing health conditions change mortality risk for the same diagnosis across contexts, applying hrs from england may understate mortality risk in india. finally, hazard ratios which are not conditioned on infection may reflect infection risk in addition to disease severity risk and thus may not translate directly to the indian context. recognizing these limitations, we have posted our analysis on an open web platform, allowing estimates to be calibrated with different risk factors, hazard ratios, and data from other countries, as more research on the virus emerges. coronavirus disease (covid- ) situation report - . world health organization case-fatality rate and characteristics of patients dying in relation to covid- in italy demographic science aids in understanding the spread and fatality rates of covid- the impact of covid- and strategies for mitigation and suppression in low-and middle-income countries analysis of clinical and demographic heterogeneity of patients dying 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organization global burden of disease collaborative network. global burden of disease study (gbd ) results. seattle, united states: institute for health metrics and evaluation (ihme) projecting the copd population and costs in england and scotland smoking, ace- , and covid- : ongoing controversies epidemiology, clinical course, and outcomes of critically ill adults with covid- in new york city: a prospective cohort study smart containment: how low-income countries can tailor their covid- response all authors have completed the icmje uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: asher and novosad had financial support from emerging ventures for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. key: cord- -d t m xc authors: gressel, christie m.; rashed, tarek; maciuika, laura aswati; sheshadri, srividya; coley, christopher; kongeseri, sreeram; bhavani, rao r title: vulnerability mapping: a conceptual framework towards a context-based approach to women’s empowerment date: - - journal: world dev perspect doi: . /j.wdp. . sha: doc_id: cord_uid: d t m xc • women’s empowerment interventions are not as effective as hoped or intended. • could be an issue with intervention design and implementation. • research reveals that there are several limitations to existing women’s empowerment approaches. • these include disregard of context, a non-holistic approach, difficulty measuring variables, etc. • vulnerability mapping may be able to address these limitations; we present an adapted framework. the fact that women's empowerment (we) is vital to a better world is well-documented and founded upon immense achievements made by international women's movements over the last seven decades (international women's health coalition, n.d.; inter-parliamentary union ; un women ; unesco, ; united nations, n.d.; women deliver, n.d.; world bank group, n.d.; world economic forum ; world health organization. n.d.) . the global demand for effective interventions in support of we is evident in the united nations (un) sustainable development agenda, which lists "achieving gender equality and empowering all women and girls" as the fifth of its sustainable development goals (sdgs) -as well as treating gender equality as a cross-cutting issue within all of the sdgs (united nations, n.d.) . this demand is also reflected by the number of organizations and projects dedicated to we. a simple google search by the authors of this paper revealed over international bodies and countless domestic organizations that deliver programs working on we issues since the s. despite all the efforts devoted to we, statistics show that globally, women still experience disrespect, disempowerment, and discrimination across all lines of race, religion, ethnicity, socioeconomic status, and ability (em , n.d.; international institute for sustainable development n.d.). one cannot help but to pose the troubling question of why these countless efforts and projects on we do not appear to have lasting impacts on the various challenges that women face, nor in eradicating gender inequalities. while acknowledging the controversial nature of this question and the likely absence of a single, agreed-upon answer, we start this paper with a proposition that the fundamental issues underlying persistent barriers to we lay in existing intervention recommendations that, while well-intentioned, are too often unidimensional. that is, they fail to completely consider the complexities of their target populations' situation, resulting in only short-term success, failed efforts, and unintended consequences. india is an important example of this phenomenon, in that there has been a monumental investment in gender equality programs over the past two decades (ministry of finance, ) but, in general, unacceptably low returns on investment. in , the indian government instituted a requirement that a substantial portion of the national budget is earmarked as "gender budgeting" to promote gender equality and improve services for women, especially the very poor. in its first year, this amounted to approximately inr billion (us$ billion). by , the gender budget accounted for nearly % of the national budget, or over inr . trillion (us$ . billion). (ibid). however, india's gender equality score from the wef gender gap index has only marginally improved, with india receiving a . % gender equality score and ranking th out of countries in , while in only receiving a . % score and ranking a dismal th (out of countries) (wef, ). india's limited progress in we has also been noted by international organizations, including the un university world institute for development economics research (unu-wider) and un women (grown, addison, and tarp ; un women, un desa ) . this is not meant to discount all of the effort made towards we in india, but rather to suggest that there is certainly room for improvement. we propose in this paper that barriers to we persist either because the theoretical frameworks and means of tackling such barriers are sometimes unsuited to the context in which they are applied, or because critical factors are missing in the conception, design, measurement, or best practices of we interventions. we explore this proposition through a review of we history, theory, and methodology of implementation. our goal in reexamining we in practice is to identify key areas within the field that can be improved upon through the introduction of several conceptual and theoretical constructs from the literature of vulnerability mapping (vm) and assessment as articulated through the climate change and disaster reduction and response fields. we do not expect the reader to accept our proposal as final. instead, we invite them to explore its plausibility with us, as well as investigate the possible implications for extending dialogues and debates in the we literature. we have organized this paper to mirror the logic we used in debating and pursuing our inquiry. we first present evidenceboth from the literature and humanitarian realmsthat signify the importance of we and how it has become a trending item on respective agendas worldwide. we then revisit the history of we and present the findings of a systematic review of the we literature. building on this background, we identify those elements that have either been widely called upon throughout we literature as necessary for improving we, or those elements that are absent from the existing approaches to present the primary gaps in current efforts. from there, we briefly review vm and assessment literature to outline how these methods can fill those gaps. we then present a conceptual framework, including definitions and a theoretical model, that blends these two fields to provide an improved approach to future we endeavors. many of the indicators that comprise gender equality as the fifth sdg are to ensure equal treatment, opportunity to thrive, and the safety and security of women. the un states: "providing women and girls with equal access to education, health care, decent work, and representation in political and economic decision-making processes will fuel sustainable economies and benefit societies and humanity at large" . the role and specific needs of women are also featured in sdgs - , and . furthermore, the un highlights ending all forms of discrimination against women as a basic human right, as well as a powerful enabler of development as a part of their sdgs, highlighting the need for gender equality to be reached on a global scale. despite the immense amount of effort and research that has already gone into projects that contain we components, evidence shows there remain unacceptable social, political, economic, and physical conditions that affect women excessively. for instance, women and girls, especially in rural areas, are often disproportionately affected by various circumstances that limit or restrict their access to education, decent work, and essential services and resources, as well as inhibit their participation in community involvement and decision making (malhotra and mather, ; . the factors contributing to such circumstances are diverse, often location-specific, and hinging upon local cultural norms, socioeconomic aspects, political and legal structures, and geographical constraintsamong other influences. in india alone, there is a dire need to address the inequalities and disadvantages that women face daily. according to the most recent indian census, women comprise % of india's population, and yet partake in only a fraction of the overall resources and opportunities (government of india, ). despite fulfilling traditional roles as primary caregivers to their families-to men, children, elderly, and disabled-women continue to remain the most vulnerable and marginalized population in society. furthermore, women are not simply a subgroup of disempowered people-women are a "cross-cutting category of individuals" who are members of all disempowered sections of society (malhotra and schuler, ) . the vulnerability of women stems from various issues-many of which affect women on a global scale-including malnutrition, low education levels, early mortality, female feticide, income disparity, and family violence . the indian census also reported that only % of women in rural india were engaged in gainful employment, and only % of indian women were literate (government of india, ). data collected from india's national family health surveys ( - ) have shown a relationship between a woman's level of education and higher rates of poverty, domestic violence and infant mortality (international institute for sciences, ). additionally, approximately % of pregnant, rural women in india suffer from ironrelated anemia, to which - % of maternal deaths are attributed. (ibid). further, women continue to have no assured rights regarding inheritance of property, and it is estimated that one in three has no rights over household decisions on spending. (ibid). the above is just a brief overview of the issues that women face daily in india, and which prevents many of them from emerging out of generations of poverty. the global picture is much larger and more complex. across the globe, women of all walks of life face discrimination and challenges. despite the legal, educational, and economic rights that women in developed nations tend to enjoy more compared to developing nations, they too still experience discrimination, lack of adequate political representation, and high rates of domestic violence, rape, and sexual assault. the gender pay gap remains unacceptable in most developed nations, with south korea in the lead with a pay gap of % (world economic forum, ) . the united states ranks th in terms of adequate female representation in politics (inter-parliamentary union ). australia and the united states report more than % of women have experienced physical or sexual violence from a non-intimate partner (un, ) , and australia, great britain and the united states report more than % of women have experienced physical or sexual violence from an intimate partner. (ibid). women in the us have high rates of chronic disease, emotional distress, and breast cancer (commonwealth fund, ) . the world happiness report shows a significant decrease in overall happiness in the us over the last several decades, which is theorized to be linked to feelings of social isolation due to social media usage (helliwell et al., ) . a long-term study of middle-aged women from the us found correlations between higher rates of women's suicide and feelings of social isolation (tsai et al., ) . the issue of social isolation has many more facets that have been investigated in terms of physical health and well-being, but the topic merits more attention in a we context as well. achieving a global society in which women are empowered delivers both an improved sense of well-being within women themselves and better global development. women comprise approximately fifty percent of the world's population and ensuring that half of the human race has access to basic human rights, decent work, and improved physical and mental well-being not only works towards the un's sdg realization, but also potentially decreases the likelihood of international conflict, civil unrest, and political displacement or refuge seeking (un women, ) . it is from this perspective that we discuss below the history and literature of the we movement to set the stage for introducing a revised theoretical framework. modern we as a concept and movement began in the s, with a grassroots approach that focused on we as a shift in unjust and unequal power relations between men and women. this original movement focused on raising women's consciousness and awareness of their rights and humanity (cornwall, ) . since the s, however, we has become a buzzword concept that governments, non-profit organizations, researchers, development agencies, donor organizations, banks and philanthropists have adopted as a mechanism for development and as an indicator of progress (batliwala, ) . at its inception, we focused on three main themes: ( ) acknowledging that empowerment requires a shift in power relations built on critical consciousness, ( ) empowerment as relationalin that women are part of a larger social context, and that any experience of empowerment or disempowerment is relational to her social context, and ( ) empowerment as a dynamic process as opposed to a static end state (batliwala, ; cornwall, ; rowlands, ) . another important point brought to the forefront of the early empowerment programs is acknowledging that empowerment is not universal to all women in all circumstances, and that empowerment in one area of a woman's life does not equate to empowerment in all areas (ibid). in later iterations, the we movement shifted towards a development objective, resting upon the premise that we signifies improved development. this shift in the fundamental understanding of the issue is reflected by a change in approach, away from grassroots transfers in power relations towards a method that emphasizes empowerment in one or two key areas disseminating to empowerment in all areas of a woman's life (batliwala, ) . an apt example of this is the emphasis placed on an economic empowerment objective, with a focus on interventions such as microcredit loans, women's self-help groups, the reintroduction of cottage industries, agricultural subsidies, innovations and management schemes, and employment opportunities (addae, ; malhotra and schuler, ; raj, ) . while these interventions have demonstrated increased access to decent work and increased economic rights and proven that these are undeniably important for women; economic empowerment does not necessarily equate to empowerment in other areas of life. this focus on economic empowerment as a "magic-bullet" concept indicates a lack of consideration for a woman's wider context and can have unintended negative consequences (batliwala and dhanraj, ) . while economic empowerment has received a great deal of attention, it is not the only area that has been targeted by this "magic-bullet" idea. legal empowerment, specialized educational interventions, and sex workers and contraceptives are a few of the other specialized areas that have also been addressed (jana et al., ) . recent trends in we initiatives are still developmentally oriented, but this is shifting incrementally. experts in the field, such as naila kabeer, deepa narayan and srilatha batliwala, are pushing empowerment workers towards a more holistic and contextualized understanding of how to engage women in empowering themselves. deepa narayan's most recent work, chup (narayan-parker, ) reflects upon india's cultural systems that are barriers to true empowerment, even within india's middle and upper classes. chup reveals that even when women are educated, economically secure, and aware of their legal rights, they are still subject to powerful cultural oppression. likewise, while narayan's work focuses on india's women, she notes that the similarities to developed western countries are difficult to dismiss. there is a need for empowerment initiatives that engage women in personal transformation in addition to economic, educational, legal and other developmental empowerment approaches. joy deshmukh-ranadive has termed this type of empowerment an expansion in "mental space," and argues that it is the most crucial component of empowerment, as it allows women to move away from constraints (both internal and external) and towards affirmative action (deshmukh-ranadive ). how we has been approached since its inception in the s is reflected in how it is defined, as well as in some of the most prevalent theories that have been presented in the literature. various definitions have been proposed, emphasizing different aspects of the empowerment process. these definitions lay the foundation for respective approaches to propose how empowerment is measured and what indicators are used. in terms of the theoretical approach, empowerment studies often focus on concepts such as agency-which can be understood as the capacity to act in areas of their personal lives and health, their family life, as well as access to resources and achievements or results (batliwala, (batliwala, , batliwala and dhanraj, ; cornwall, ; cornwall and edwards, ; beteta et al., ; kabeer , kabeer , mason, ; sen, ) . the relationship between agency, resources, and achievements forms the foundation of most definitions of empowerment, although there are many variations on the understanding of each of these three concepts. naila kabeer focuses on a woman's choice-making ability, stating that empowerment is: "the expansion in people's ability to make strategic life choices in a context where this ability was previously denied to them" (kabeer, ) . deepa narayan notes that empowerment, in its broadest context, is "…the expansion of freedom of choice and action to shape one's life. it implies control over resources and decisions" (narayan, ) . she comments on the fact that empowerment is limited in impoverished populations due to their inherent powerlessness when relating to formal and informal institutions, and that this powerlessness is a culturally systemic inequality. narayan's exact definition of empowerment is "…the expansion of assets and capabilities of poor people to participate in, negotiate with, influence, control, and hold accountable institutions that affect their lives. this definition can be applied to understand and track changes in the unequal relationships between poor people and the state, markets, or civil society, as well as gender inequalities, even within the household" (narayan, ) . shireen jejeebhoy uses the terms autonomy and empowerment interchangeably, focusing on control and access to resources. she defines autonomy as "…the control women have over their own livesthe extent to which they have an equal voice with their husbands in matters affecting themselves and their families, control over material and other resources, access to knowledge and information, the authority to make independent decisions, freedom from constraints on physical mobility, and the ability to forge equitable power relationships within families" (jejeebhoy and sathar, ) . however, other authors make the argument that autonomy is not equivalent to empowerment, stressing that autonomy implies independence whereas empowerment may well be achieved through interdependence (govindasamy, ; malhotra and mather, ) . still more authors include concepts such as amount of influence over external actions that matter to their welfare (batliwala and dhanraj, ) , altering relations of power that constrain women's options, autonomy, and which adversely affect health and wellbeing (sen, ) , and "…a process whereby women become able to organize themselves to increase their own self-reliance, to assert their independent right to make choices and to control resources which will assist in challenging and eliminating their own subordination" (keller and mbewe, ) . empowerment can be considered a universal process with several universal components; it must also be recognized that gender inequality or disempowerment, like poverty, is not one dimensional, and can be expressed or experienced in many different forms. naila kabeer reflects in her analysis of the un's gender equality goals, "gender relations, like all social relations, are multi-stranded: they embody ideas, values, and identities…they determine the distribution of resources; and they assign authority, agency, and decisionmaking power. this means that gender inequalities are multi-dimensional and cannot be reduced to some single and universally agreed set of priorities," (kabeer, ) . kabeer goes on to argue that effective empowerment measures require contextual, participatory approaches. women must be engaged in identifying what they experience as inequality, and interventions must be contextualized to those specific women's circumstances (ibid.). cornwall also identified the need to address context as important to successful we interventions when evaluating current approaches to we (cornwall, ) . by identifying the context-relevant vulnerabilities that women face throughout their lives, contextualized, optimized interventions can be proposed and implemented to empower rural women in india. each of these definitions reflect the various interpretations that authors and authorities in the field have proposed in terms of agency, access and resources. depending upon the method of implementation, methodology, or approach, the variations in these concepts have an impact on an empowerment intervention. for example, if empowerment is seen as primarily a lack of resources or access to education, an intervention may be designed that provides micro-credit loans and scholarships for girls to attend school. will these interventions also be able to tackle the cultural, political, or personal factors that inhibit empowerment in a given context? will it be able to provide the same level of success in other contexts or times? as will be seen in the next section, there are further challenges involved in empowerment methodologies because it is such a vast and, essentially, ephemeral concept that is tied as much to local culture, contexts and conditions as it is to global or national development measures. while the theory of empowerment has a strong and well-explored foundation that includes several suggestions for measurement methods (narayan, ) , the application of practical interventions or programs is inconsistent in approach, quite difficult to replicate, and harder still to measure. as the examples we provide below show, empowerment approaches to implementation and methods for measurement often lack the adaptability required for broad application among varied groups. this makes it challenging to produce, replicate, or scale effective programs beyond their initial implementation. empowerment is not a static outcome. rather, it is a dynamic means of achieving a state of balance and harmony between the genders, and as such, it is often difficult to measure the what and the how of we due to the inherent complexity of the empowerment process (malhotra and schuler ) . to mitigate over-complexity, measurement indicators tend to focus on one aspect of empowerment at a time. for example, some frameworks evaluate achievements on a national scale, such as political participation, literacy rates, or decreasing maternal death rates (care usa, ). other frameworks will look at women's community participation, and yet others will look at the amount of influence she wields within the household and family units (alkire et al., ; roy et al., ) . while this might make practical sense, the results are unable to reflect some of the relational aspects of empowerment across different areas of life or dimensions. malhotra and schuler's analysis of we programs reveals six dimensions of empowerment that are commonly assessed at the different levels: economic, socio-cultural, familial/interpersonal, legal, political, and psychological ( ). this conception is similar to deshmukh-ranadive's theory of empowerment spaces, where she argues that empowerment can occur in mental, social-cultural, physical, political, and economic spaces of an individual's life ( ) . the intersection of these six dimensions (or five spaces) with the three contexts or scales (i.e., national, community, or household) typically assessed through empowerment frameworks produces a great deal of latitude in approach and variation in measurement indicators. in terms of indicators or assessments of empowerment, most conceptual frameworks rely on the three main components mentioned previously: resources, agency, and achievements. this basic model is adapted from description of the empowerment process. resources refer to the pre-conditions present, or natural, social and institutional resources available to women . agency refers to an expansion in mental space, and the ability to identify goals and act towards realizing them (deshmukh-ranadive, ; mosedale, ) . achievements are the outcomes of resources and agency-the realization of goals set, and actions taken malhotra and schuler, ) . identifying indicators to measure each of these components that can also reflect the various dimensions and their contexts is a challenging task, as there are no single or collection of indicators that definitively state if a woman is empowered at a given point in time. furthermore, given that variables are context-sensitive, what can measure empowerment indicators in geographic setting "a," may be quite different than the set of variables used to measure empowerment in geographic setting "b." likewise, within the same geographic setting, the variables used to measure empowerment may vary by additional distinctions, such as caste, religion, class, socio-economic status, etc. as previously mentioned, empowerment is a dynamic, relational process rather than a fixed or static outcome. due to its dynamic nature, it becomes more practical for scholars to evaluate the various components rather than empowerment as a whole. mason ( ) outlines four options for measurement as well as critiques on their limitations: ) measuring factors that are hypothesized to empower women; for example: paid employment, control of birth control and family planning, higher education, etc. this method is not entirely viable, as factors that may empower some women can also disempower others or the same women under different circumstances. ) measuring outcomes, such as fewer child marriages, increased girl education rates, increased access to decent healthcare, etc. while positive outcomes are ideal, it is challenging to demonstrate causation and isolate the specific factors yielding the expected empowerment outcome(s). ) observational studies to showcase changes in a woman's interactions and role within the household. it is argued that this type of measurement may bear the most accurate results, but it is also timeconsuming, difficult to capture adequately, and in circumstances where women are most oppressed (i.e., restricted in speech, movement, etc.), may not reveal much of anything due to the nature of their role within the household. ) measurement through self-reporting and sample surveys allows for larger quantities of data to be collected but poses problems in reporting distortion due to issues in question framing, privacy concerns, and validation difficulties, to name a few. (ibid.). when empowerment initiatives do not take into consideration the complexities of context or disregard the importance of women's participation in identifying both issues and solutions, we programs may yield unintended negative consequences for the participants. in a comparison of economic empowerment initiatives across asia, correlations have been drawn between women's increased earning power and increased domestic violence in pakistan, india and bangladesh, although these findings have not been consistent with other asian countries (mason, ) . victims of domestic violence can also redirect this type of behavior at other women and children within the household, thus perpetuating the cycle of violence throughout generations (deshmukh-ranadive, ) . furthermore, the implementation of microfinance loans and self-help groups has, in some contexts, shown a trend of increasing emotional stress in the women who report an increase in contributions to household income ( van kempen, ). this type of negative effect is by no means universal but indicates that further thought needs to be given to how empowerment is approached to include assessments of local cultural contexts that can inform how an intervention could be received. another method of assessment are the multiple indices that have been developed to measure gendered empowerment. some of them, such as the social institutions and gender index, the gender inequality index, the gender gap index, and the gender development index, aggregate data across several domains, but do not directly measure individual empowerment or disempowerment, and (as are many such scales) are often unable to adequately represent the complex and nuanced situation of a population (alkire et al., ) . the women's empowerment in agriculture index (weai) (gupta et al., ) attempts to address this by measuring at the individual level across five domains relevant to the agricultural sector. the hunger project further developed this into a non-sectoral index, the women's empowerment index (wei) (nkwake et al., ) . these both identify indicators at an individual or household level for empowerment and attempt to capture a wider range of indicators of we. although widely celebrated as a more successful means of assessing we, there are limitations to this approach that should be highlighted. gupta et al ( ) conducted a study wherein the weai scale was adapted to the indian context. while the researchers found the tool to be useful and adequate for broader domains, they also were forced to heavily adapt and supplement the survey in order to make it relevant to their particular context. similarly, the wei scale has been touted as an effective tool for measuring certain aspects of we but failing to capture more nuanced experiences of disempowerment that point to root-causes. some researchers have found that only by heavily supplementing this and similar scales with qualitative assessments have they been able to utilize the tool effectively (nkwake et al., ) . this aptly leades to the next point: in another review of empowerment indices, it is noted that a significant problem with this approach to measurement is that, being primarily survey-driven, a respondent may be "boxed in" to a certain selection of responses that may not necessarily reflect their actual experience. this can lead to a sort of deconstruction of complex information, which can result in loss of nuance and deeper understanding (nkwake et al., ) . such studies have recommended qualitative measures to fill in these gaps, but there is a general lack of systematized tools that can account for both the global empowerment indicators and contextualized experiences of empowerment. although the global trajectory of improving women's lives is on an upward swing, this review of literature has revealed several limitations to the theory and methodology involved in both the evaluation of we and the design and implementation of interventions. the following elements we have identified contain four (the first three) limitations that are inextricably interrelated. however, we list them individually because we believe that each one needs to be examined in isolation in order to understand their impacts upon future we works. a. this is not a new critique and has been an oft-repeated call for both theory and fieldwork to appreciate local contexts, from the early reforms of sociology and anthropology. despite the long history of demanding greater sensitivity to context, there is still evidence that many programs or frameworks do not adequately address context. this includes defining we from within local culture, values, goals, environment, and time. it also includes a broadening of perspective so that all contexts can be appreciated. b. in order to address the context-based limitations mentioned in point a, a systematic and holistic framework is needed to approach the many contexts of a woman's life. c. furthermore, a time-based aspect is needed in terms of the initial evaluation, implementation, and measurement of empowerment interventions, so that empowerment can be addressed as a developmental process for women as well as their families and communities. . inadequate measurement tools to effectively address the complexities reflected in points a, b, and c (above). a. address the inherent measurement issues that are presented by complex relationships between the distinct contexts, dimensions, scales, and indicators that can be evaluated in the context of empowerment over time. . overly siloed approaches to implementation. a. many interventions are unidimensional in approach, targeting specific development markers to "activate" empowerment throughout other aspects of a woman's life. b. interventions are not designed to engage with factors outside of their immediate sphere of influence to identify and mitigate potential unintended consequences that can occur within a particular location's society, culture, economy, environment, traditions, etc., as well as monitor the effects of an intervention over time. . missing sustainability as an integral part of we. a. many interventions do not adequately ensure their sustainability over time, in terms of long-term success, adaptability, and replicability. b. likewise, interventions do not always adequately ensure sustainability in terms of effects on the environment and future generations. by addressing these primary limitations, we initiatives can work towards encompassing both the critical consciousness-raising elements identified by batliwala ( ) as integral to sustainable personal empowerment, as well as the development objectives that have focused on driving the economic advancement of women that, as mentioned, can have mixed results in terms of empowerment. ultimately, the goal of we is to bring about positive change in the lives of women, their families and their communities on a global scale while respecting the cultural norms, the values and the integrity of diverse populations. the complication with this lies in that exact point-women are a part of geographically, socially, culturally, politically and economically distinct communities. what may work in one location with one collection of factors may not work in another. this is compounded by vague frameworks, imprecise indicators, and difficulty taking measurements. to address the aforementioned fundamental challenges, we propose that it will be beneficial to examine the problems and the solutions from another angle. instead of only identifying an empowerment objective (financial, legal, etc.) to apply to a specific community, one could identify the unique elements that hinder women's engagement in active participation in that element, as well. this is changing the narrative: what is affecting women negatively-and how can these women move towards an improved state within the context of their own unique circumstances? this approach would allow for context-specific evaluation of factors that contribute to a woman's vulnerability-or vulnerability mapping. if done properly, such a map would be able to capture both the indicators as well as the inherent challenges in the process of empowerment. it is important to note here that although the term 'vulnerability' may seem to imply an inherent deficit on the part of women, the term 'vulnerability' in this context refers to the myriad cultural, social, economic, health-related, education-related, environmental, physical and subtle factors that contribute to the we process or, conversely, a state of disempowerment. the contributions of these factors can refer to either positive support or negative hindrances. it is not the intention of this proposal to imply that we are seeking solutions to 'fix' women or their problems. rather, since each woman lives within a unique context, the goal is to better understand the complex factors of a woman's vulnerability and then leverage that understanding to augment her strengths and provide additional skills and solutions in those areas where she faces the greatest challenges. another important point to emphasize is that, although this paper refers to empowerment as an instrument of development, it is more about developmental change in the context of social transformation in order to improve women's lives, and less about reaching development markers for the sake of reaching them. as authors, like chant ( ) have emphasized, instrumentalizing women to alleviate poverty in many ways goes against the very principles of we. furthermore, it is a crucial value of the authors of this paper that women's opinions, happiness, and contextualized perspectives are incorporated into the empowerment process, and their voices heard and respected. in order to evaluate the complexity of we, it is necessary to comprehensively evaluate the many variables which systematically affect it-particularly in order to capture the relationships that each variable has with one another at different contexts. this paper argues that the use of vm and assessment can leverage this type of multivariable, multirelational evaluation to gain a holistic understanding of the contextualized factors that either hinder or support the empowerment process, and ultimately optimize empowerment interventions based on that information. in order to comprehend how vm can be used in the context of we, it is important to understand the origins of vulnerability assessment and vulnerability studies. the field is vast and has had varied applications in almost every discipline. however, for our purposes we draw the concept of vulnerability from disaster risk reduction and climate change adaptation frameworks (bankoff, ; birkmann et al., ; birkmann and wisner, ; cardona, ; cutter et al., ; hufschmidt, ; unisdr, unisdr, , wisner ; wisner et al., ) . the disaster management and climate change fields have been developing vulnerability assessment methods for more than eighty years. their works have provided the base from which many ngos, government agencies, and philanthropic organizations take inspiration in the wake of natural disasters, industrial catastrophes, and in dealing with the ever-increasing effects of climate change on both developed and developing nations. establishing a common definition for the term vulnerability is a challenging task, as vulnerability, like we, is in an ever-evolving state. over the past decade, various fields have developed their own working definitions relevant to the context and scope of their work. the natural sciences approach to vulnerability has dealt primarily with the concept that events such as volcanic eruptions, earthquakes, etc., are natural phenomena that humans have no control over. it is also concerned with the geographical components that influence the impact of natural hazards. thus, to the natural sciences, vulnerability is closely connected with the calculation of probability of such an event happening in a given time period or geographic area and the factors (e.g., soil stability, rate of erosion, climate change, etc.) that will either mitigate or augment disastrous impacts (cardona, ) . the applied sciences understand vulnerability in terms of physical structures and infrastructures (e.g., waterproofing of building foundations, strength of utility lines, construction materials, etc.). this classically scientific discipline considers the fragility of such elements when exposed to a natural disaster, and the approach relies upon quantifiable data, probabilistic modeling, and data estimates to determine vulnerability. as such, it is frequently relied upon by engineering measures, insurance companies and governments in policy evaluation decisionmaking processes (cardona, ) . as a related but distinct approach, the social sciences recognize vulnerability as a state that exceeds physical damage in the event of a hazard. the concept of vulnerability must also encompass the population's ability to cope, respond and recover effectively to a hazard (cardona, ) . this understanding of vulnerability recognizes that social, political, and economic conditions of a population (or subsets of populations) determine the extent of their vulnerability in the event of a hazard, and that hazards may affect various locations differently due to discrepancies in these conditions. furthermore, the social sciences have posited that due to these conditions, many people are pushed into more vulnerable positions because of their marginalized standing-whether social, political, economic, or other. this would indicate that a natural hazard would much more negatively affect those populations (wisner et al., ) . vulnerability studies focus on day-to-day elements in a community that put it at greatest risk in a disaster event-either primary or secondary impacts, or slow-moving events such as soil erosion or water stress. vulnerability studies take place in both developing and developed nations, rural and urban communities, and have a wide range of applications. vulnerability assessment and mapping focus on identifying the location and geographic distribution of such elements and their impacts. the overall goal of a vulnerability map is to evaluate a community's major resources and infrastructures and how these resources are distributed. it also deals with understanding what underlying factors are at play. these factors include (but are not limited to): structural factors (race, religion, caste, etc.); life-cycle factors (age, disability, transitions in life such as marriage, motherhood, or adolescence, etc.); conflict and violence factors (personal security, war, criminal activities, etc.); infrastructural factors (government, transportation, corruption, etc.); economic factors (unemployment, non-traditional economies, single-income homes, etc.); and environmental factors (climate change, proximity to water, proximity to disaster proneareas, etc.) (mileti, ; rashed, ) . traditional methods for assessing vulnerability are typically participatory in nature and require collaborative efforts between subject matter experts and local stakeholders to ensure both local priorities and universal standards are taken into account. in rural areas in developing nations, a technique called vulnerability capacity assessment (vca) is used by governments, ngos and development agencies. some of the most well-known examples of vca include red cross/red crescent, giz, oxfam, and among others (giz, ; moret, ; palestine red crescent societies, ; turnbull and turvill, ; ulrichs et al., ) . vca activities draw upon local indigenous knowledge holders, expert analysis, and incorporating local stakeholders' priorities in the disaster mitigation and response process. in developed urban areas vulnerability assessment uses expert analysis, augmented by the use of technology resources such as geographic information systems and input from local first response agencies, and disaster management agencies (porter et al., ; rashed and weeks, ) . the subsequent development of mitigation and response plans are thus based on an informed and contextualized basis of knowledge. these can take different forms depending on the requirements of the location and priorities of the community, but often have elements of both applied and social science approaches. the united nations office for disaster risk reduction addresses all three of these components in their definition of vulnerability: "the conditions determined by physical, social, economic and environmental factors or processes, which increase the susceptibility of a community to the impact of hazards." (unisdr, ) . for the purposes of this paper, this is the base definition of vulnerability from which we build our theoretical framework, as it acknowledges all of the disparate components that contribute to vulnerability, including the root causes of vulnerability as identified by several scholars (porter et al., ; rashed & weeks, ; j. ribot, ; j.c. ribot & peluso, ) these root causes of vulnerability (social and cultural disparities, lack of access to institutional support or opportunities, and human-constructed inequalities, etc.), also contribute to the time-based component of vulnerability that was described in earlier sections on existing limitations on empowerment theories. to address these diverse and dynamic issues, we will incorporate in our framework a more holistic list of dimensions, a more nuanced operational definition of "hazard" from different contexts (especially cultural components), as well as a temporal consideration. we feel that the cultural and time-based components of vulnerability have been under-appreciated in existing approaches to we. time does not just imply preparation for future events or adaptation over time, but an acknowledgment of the importance of time in a more mundane sense, i.e. the effect of seasonal weather, migration patterns, regular cultural events, etc. as we have shown how vm has demonstrated its utility for several fields, we propose in this paper that vm can also directly be utilized to address the limitations identified in we approaches previously described in this paper. table below summarizes both the limitations and how vm can be used to address them. the table underpins the conceptual framework that we will detail later. in order to translate a system or approach from one field to another, some adaptations must be made. while disaster relief and climate change focus on the effects of a hazard or stressor impact, in the context of we there is often no single stressor, but rather a multitude of stressors and circumstances that coalesce into hindrances to we. to start adapting the vm approach to apply it to the assessment of we it is necessary to establish a system of definitions which clarifies the connection between women's vulnerability and the empowerment process and elements of empowerment that vm must address. presented below are a set of definitions identified and reworked for the purposes of the proposed approach to incorporate the concept of vulnerability into we. we have drawn on accepted terms and concepts in both the existing vulnerability literature and we theory to drive these definitions. fig. is a visual representation of the following concepts and definitions. (rashed et al., ) . this paper defines women's empowerment as "the process of increasing women's choices and capacity to make discerning decisions towards sustainability and resilience." this definition of empowerment rests upon the definitions provided by such authors as naila kabeer, deepa narayan, shireen jeejeebhoy, anju malhotra, srilatha batliwala, cornwall; cueva beteta, and amartya sen, drawing upon concepts from each of them, and incorporating a few new complementary components from vm and assessment. an in-depth explanation of the key components (underlined in the above definition) is presented below. as mentioned elsewhere in this article, empowerment is not a static outcome, but a process which emphasizes the holistic nature of empowerment rather than focusing on a final destination. the static outcome perspective can neither account for the temporal component, nor the nuances that can be found in the intricacies inherent in the study of empowerment. these intricacies encompass the understanding that women must find and build the inner resources in order to engage with b) development of a systematic and holistic approach that can account for the many contexts of society along with the various aspects or dimensions of empowerment that impact a woman. c) incorporating a time-based aspect into the initial evaluation, implementation, and measurement of empowerment interventions a) vm is fundamentally contextual and geographically based, with a focus on understanding impact factorsboth positive and negative. in this regard, vm provides a foundation for evaluating factors that inhibit or support we in a given location, and for suggesting context-sensitive interventions accordingly instead of a "one-size fits all" solution based on theory. b) vm is a direct application of systems thinking. while vm does focus on a community as a whole, it gives equal attention to its constituent parts and views the community as a hierarchy of nested systems that influence each other (i.e., households made of individuals, communities made of households, etc.). as such, a vm approach can be adapted to the need for a holistic approach to evaluating we, and further highlights the contextualized approach needed to effectively evaluate and improve we circumstances. c) vulnerability assessments address the time-based component of an impact or stressor, which can be adapted to understand the changes that take place in the empowerment process over time. in fact, as the paper shows below, changes in we status are defined by the direction of change in the vulnerability status over time (whether they are positive changes or negative changes). inadequate measurement tools a) existing tools are not sensitive to the complex relationships between the distinct contexts, dimensions, scales and indicators of empowerment; a) vm provides geospatial containment of we factors in a given location. this builds upon both physical and non-physical contexts, capturing a wide range of variables across each of the areas impacted by or impacting we. moreover, the mapping process itself generates spatially explicit measures (e.g., distance proximity, spatial connectivity, geographic association, etc.) that are important to the understanding of we and otherwise difficult to generate by other approaches. overly siloed approaches to implementation a) many interventions are unidimensional in approach. b) interventions are susceptible to causing potential unintended consequences. as an extension of the systems thinking approach, vm provides a thorough assessment of the relationships (i.e., feedback) between variables, which makes it possible to understand the interdependencies of variables. b) by recognizing the complex relationships and interactions between variables, researchers can more easily identify and avoid unintended consequences in intervention practice; for example, the resistance of men to we due to disruptions in household power dynamics without adequate support. missing sustainability as an integral part of we a) many interventions do not adequately ensure their sustainability over time. b) nor sustainability in terms of effects on the environment and future generations. a+b) many vm methods originated from the sustainable hazard mitigation paradigm, which rests upon the following six pillars of sustainability: • environmental qualityimplies that human activities in a particular locale should not reduce the carrying capacity of the ecosystem for any of its inhabitants. quality of lifeentails many issues such as income, education, health care, employment, legal rights, and other standards that local communities should define. • plan for disaster resiliencya locale is able to withstand any extreme event without suffering devastating losses. • economic vitalityrecognizing that vital local economies are essential to tolerating damage and disaster losses. • inter-and intra-generational qualitynot precluding a future generation's opportunity for satisfying lives by exhausting resources in the present generation, destroying necessary natural systems, or passing along unnecessary hazards. • participatory processadopting a consensus-building approach among all the people who have a stake in the outcome of the decision being pondered (rashed, ) . the empowerment process. choice becomes a medium through which women have the ability to actualize these inner resources externally. furthermore, the inclusion of increasing a woman's choices speaks to the fact that many women, due to a variety of reasons, do not have options to choose from. this is sometimes because of social, cultural, or legal restrictions, but also reflects the reality that women who live at or below the poverty line have limited options to make decisions outside of those which support meeting basic needs such as food, shelter and clothing. in reality, this increase in choice not only represents a wider range of options, but also the discernment or capacity to choose what might be best for their own situation and aspirations. in this definition, capacity reflects the ability to translate the inner engagement with empowerment into action. this can be reflected through making choices, voicing opinions in the household, and community engagement, among many other avenues. in other words, capacity is the leveraging of skills and confidence into actions that are seen as beneficial to themselves and their communities. decision making is often considered the crux of we (narayan, ) . it is often referred to as meaningful decisions, or decisions that affect the state of their lives . this definition includes both of these components and expands upon them to include the need to equip women with sufficient education and information to make decisions based on knowledge rather than relying solely upon traditions or the influence of others-thus the ability to discern throughout the decision-making process becomes crucial. the un's sdgs have become a de facto guide for approaching development work, especially in contexts like india. sustainability, as such, is a theme that recurs throughout the history of we, but not consistently and often leading to disagreements between researchers of different fields (chant, ) . the introduction of the sdgs and the inclusion of we as a cross-cutting theme did much to cement the role of we in all levels of sustainable development. we would like to reiterate this, this and argue that it is impossible to separate sustainability from we. fundamentally, it is impossible to attain we without attaining sustainability alongside it, and vice versa, as the two are inextricably interlinked. likewise, women are also the most vulnerable to the consequences of poor sustainability, with studies clearly demonstrating how gender is a primary mediator for how demographic, socioeconomic and agro-ecological contexts are experienced-with women bearing the brunt of devastation due to climate change (arora-jonsson, ; rao et al., ) . there are two considerations for the central role of we in sustainable development: ) it has been documented that we leads to the realization of the un's sustainable development goals (quisumbing, ; taukobong et al., ) . ) a large percentage of the world's female population are caretakers of society: especially the natural environment, in addition to playing the role of mother, role-model, primary caregiver to the elderly and infirm, and teacher to future generations (rao et al., ) . in these two roles, empowered women are able to steward sustainable practices as well as ensure the values of sustainability are passed onto future generations. at a more philosophical level, we is the pathway to gender equality, or a state of sustainable balance and harmony between the genders, which is a human rights goal in and of itself. the last concept in the definition is resilience, which reflects a woman's ability to recover efficiently from negative impacts or stressors that occur in her life, thus improving both her life and the lives of her family and community, as well as working towards the sustainability and resilience of future generations. resilience is a term that carries with it all of the complexities of society in general (folke, ; timmerman, ) . within the concept of resilience is the individual and collective ability to withstand and recover from destructive events or processes. in some ways, resilience implies self-reliance in that a 'resilient individual' has a greater ability to navigate through negative occurrences. this approach to resilience comes from heavily critiqued positions on sustainable development that shift the responsibility for social justice and protection from state governments to the individuals themselves (comfort et al., ) . in another sense, resilience also requires strong networks and structures that can distribute the cost of destructive events or systems so that the collective can more easily recover (folke, ) . this more communal approach accounts for the wider social systems in the measurement of resilience, as they all play a role. it is this latter sense of resilience that most accurately reflects our proposed framework. beyond an explanation of each key concept, it is possible to map the concepts to the adaptation process that is detailed further below. the process of empowerment takes place in various contexts and dimensions. choice, decision making, and capacity are products of empowerment domains. sustainability and resilience both inform and are produced by the interaction between empowerment contexts, domains and dimensions. vm allows the dynamic process of we to be evaluated holistically by capturing the state of we at the point of time at which it is mapped, and from there evaluate changes at different points in time. the definition of we provides the reference point from which the progression of we over time can be measured through the changing states in the concepts of choice, capacity and decisions that women are able to engage in. it is important to note here that the change may reflect either an increase or a decrease in empowerment. while it may appear to be disheartening to recognize a decrease in empowerment, it is actually vitally important information, as it illuminates the true nature of the factors that inhibit empowerment. the value that comes out of this mapping is in understanding the relationships between the various factors, constraints, indicators, intervention impacts, domains, contexts and dimensions. fig. below conceptualizes the relationship between these terms. the definition of each term is outlined below. these concepts are explored further in the modified definition of vulnerability proposed by this paper in the context of we, which defines women's vulnerability as "a state of women's empowerment at a given point of time, determined as the net product of interactions between multiple factors, constraints, and intervention impacts shaping women's choices and capacity to make discerning decisions across all the domains and contexts of women's empowerment." these multiple factors, constraints, and impacts are explained in much more detail in the following sections. dimensions: a we dimension represents an area or aspect of life in which a woman is more empowered or more vulnerable, or any combination of both. this paper suggests six dimensions: ( ) environmental quality; ( ) economic vitality; ( ) education & skill development; ( ) health; ( ) social, political, cultural environments; and ( ) safety & security. the six dimensions have been identified from both the vm field and we theory and are intended to encompass all circumstances of a woman's life. these six dimensions are deeply interconnected and affect one another in complex ways. there are also layers of sub-dimensions contained within each, that further affect other dimensions and sub-dimensions. domains: beyond these six dimensions, four domains of empowerment have been recognized as integral to the empowerment process. each of the four domains is a collection of elements that influence, support or infringe upon empowerment. these four domains are also complexly interrelated, and changes in one domain may changes in other domains. furthermore, each of these domains is context specific. they may have different meanings at different levels of society, leading to different decisions being taken and different understandings of a situation. these domains are: • access domain: the range of elements (including the right or privilege) impacting one's, group's or community's ability to obtain or make use of opportunities related to women empowerment. • opportunities domain: the range of resources or assets (material, financial, human, social, political, etc.) that are available to empower individuals, groups, or communities. • awareness domain: the range of elements that reflect one's, group's or community's consciousness, knowledge and understanding of factors, constraints, and processes surrounding we. • mental space domain: the range of beliefs, norms, or values held by individuals (e.g., cognitive model) or groups or entire society (e.g., culture or tradition), which affect attitude and behavior (typically at the subconscious level) towards elements or processes influencing women empowerment. this domain concept is drawn from joy deshmukh-ranadive's empowerment framework (deshmukh-ranadive, ) . mental space can be considered the most important domain, as it is only when there is an increase in the mental space domain that the other three domains can be leveraged effectively. deshmukh-ranadive explains it: "mental space consists of the feeling of freedom that allows a person to think and act. an expansion of this space implies a change in perceptions, leading to a feeling of strength. mentally there is a movement away from restriction and constraints, which facilitates action in a positive direction. mental space facilitates "power within." the most important condition for empowerment to take place is an expansion of the person's mental space." (deshmukh-ranadive, ) contexts: as mentioned throughout this paper, a woman's context is one of the most vital components to understanding her level of empowerment. the inherent difficulties associated with measurement and context require that both individual levels of context as well as the relationship between measurement and context be considered in tandem in order to gain a holistic perspective of a woman's life. specifically, context, or levels of context, can be defined as: the scale or level at which we can be observed or measured. these specific contexts include: individual, household, community, state, nation, and the global context. as with the other concepts being introduced throughout this adaptive process, context levels are complexly interlinked. however, each context is also characterized by unique dynamics that occur specifically at that context. it is important to note that the 'smaller' the context is the more frequently it is a component of a 'larger' context, and therefore is influenced by the impacts of an event or decision or norm that takes place at a 'larger' context. for example, an individual woman's opinions on educating her daughter would be considered "individual context", but when taken in tandem with her household context, is only one part of the equation, and the larger household context will most likely be more influential in the decision-making process. similarly, community norms, an even larger context, will help to form household opinions and norms. this is one of the reasons that measurement of we is so difficult, and why we is so often measured only at one level of context. factors: these are elements or processes that leverage we at a given context to achieve potentials (or higher levels of empowerment). there are two primary types of factors: resistance and resilience factors. resistance factors increase a woman's ability to maintain psychological, financial, social, health and welfare balance and to make informed decisions when faced with external shock or stressors. resilience factors increase women's speed of recovery from stressors and difficult circumstances. both of these factors operate and exist within and between the four empowerment domains detailed above. constraints: these are elements or processes that restrict women from achieving their potential (or higher level of empowerment) at a given context. similar to factors, constraints are both resistance and resilience related, playing the same roles in her ability to make decisions and recover in the face of hardships. again, they also exist and operate within the four empowerment domains. interventions: they refer to elements, events, processes, and/or actions resulting in a change within the empowerment domains and their interrelations. interventions in this sense refer to external forces, not necessarily intentionally designed activities facilitated by an ngo or government agency, but any type of decisions, actions, or life changes that affect a woman's empowerment domains within a certain context. the response to the intervention is the resulting impact or feedback. impact or feedback: it refers to the changes that occur within and between empowerment domains due to an intervention. impacts and feedback can have negative or positive results, which can be immediate or delayed. this type of impact or feedback can lead to either an increase or decrease of the overall status of we within a given context. indicators: these are the criteria used to measure factors, constraints, and impacts within or between empowerment domains at a given context. given the immense complexity of women's empowerment as a general field, any program of implementation will require a rigorous and thorough approach. this paper identifies the following core values as guiding principles and enduring beliefs for the successful implementation of any action or effort aiming at improving the status of we. • societal good: the ultimate goal of we is to bring about a fundamental shift in society for the good of allmen, women, society and the environment. this is the number one consideration that must be taken into account when approaching we through research and implementation. no woman lives in isolationshe is always in connection to others. • sustainable: in a similar manner, it is important to consider sustainability when considering decision making, designing interventions, producing goods, or even researching we. as mentioned in the definition of we, we can be a powerful path toward attaining global sustainability and development, but at a personal level sustainability leads towards self-reliance in women. sustainability also leads towards increased development, gender equality, social change, and environmental considerations. • systems-oriented: systems-orientation, in this context, refers to using a systems-thinking approach to evaluate the complex dynamics of we holistically. as mentioned previously, one of the primary issues that we evaluation faces is the use of proxy indicators or a prescriptive method simply because we is such a difficult, complex and nebulous concept to measure. systems thinking by design deals with complexity and can be employed to capture the vast components and their relationships to generate the holistic understanding needed of existing vulnerabilities and strengths, as well as the impacts of any interventions or solutions. • participatory and inclusive: it is important to remember that the empowerment process is about women engaging and participating in their life situations in a more dynamic manner. this requires that any approach incorporate women's opinions and ideas into the process. and while we ostensibly focuses on women, it is impossible to exclude the men in their lives, their children, and the communities they live in. all must be taken into account in order to succeed. this is inherently linked to the previous point of being systems oriented. • transparent and authentic: given that we is a universal issue it is of no benefit to anyone if successful measures towards empowerment are not made public and available in a transparent manner. furthermore, it is vital to the success of any endeavor to establish a level of trustboth with the women being worked with and the world at large. this level of trust should take into account respect for all opinions: those of individual women, their communities, as well as in reporting results to the public and academic communities. • accountable: those undertaking a we endeavor need to maintain a level of accountability. similar to the previous values of transparency and authenticity, this includes being accountable to the women, their families, and their communities, as well as to the information being shared through publications and studies. accountability becomes crucial when considering the sensitive nature of the empowerment process within social and cultural norms across all geographic contexts. • innovative: innovation in we refers to using science and technology to better capture, understand and model the problems and issues (factors, constraints, intervention and their impacts). innovation also means identifying effective ways to equip women and communities with relevant, contextual knowledge on we issues, and designing and delivering programs that keep all members of the community engaged, productive and creative in the way they approach we challenges. the authors started this paper with a question: given the tremendous efforts towards women's empowerment and gender equality, why do there appear to be few lasting impacts on the various challenges that women face? the paper offers a discussion on the possible answers through an exploration of the history, definitions, theory and methodologies that we literature and evidence may provide. the discussion highlights a number of important structural issues that are currently not addressed by we in mainstream development efforts. these include disregard for context; inadequate measurement tools; overly siloed approaches to implementation; and a disregard of sustainability as an integral part of we. we believe that answer to the question posed above can be found in fundamentally shifting the approach to we through some key considerations: approaching the topic from a holistic, contextual perspective; identifying those factors which inhibit a woman's empowerment as well as areas of strength, and optimizing the design and implementation of future we interventions. this is not a new proposition, and is one that has been argued now for decades; however, when one examines we interventions in practice, it becomes clear that far more contextual sensitivity is required. the disaster management and climate change fields have been working with multivariable problems for decades and have developed methods and solutions that are able to encompass the social and cultural human factors which exacerbate natural disasters through vm. the use of vm for we can provide a path forward by aiding in capturing more details of the various contexts, domains, and dimensions that a woman experiences daily, as well as the relationships between them, ultimately revealing the complex system that a woman exists within and areas that require attention, and through this address the four main limitations listed above. this paper is a first attempt to discover how improvements may be made by proposing a conceptual method for adapting vulnerability mapping and assessment to the unique nature of we, including proposed definitions that integrate the two fields and some general considerations for implementation. this foundation is built on the field experience of the authors, a study of existing approaches, and the expertise of leaders in disaster management. the definitions presented express we in terms of change in the status in women's vulnerability over time in addition to spatial context. the change can be both positive (implying decreased vulnerability or empowerment) or negative (implying increased vulnerability or disempowerment) at a given point of time. to capture the change and its trajectory, one needs to simultaneously address multiple dimensions of empowerment: health; economic vitality; environmental quality; culture, society and politics; safety and security; and education and skill development. these dimensions represent the mediums through which vulnerability is manifested and can be mapped and measured in a given context and a given point of time. the process of empowerment itself (that is, a change in women's vulnerability status over time) takes place in the four domains of empowerment: access, awareness, opportunities, and mental space. it is the place in which those who seek improvement in we should focus their solutions. finally, the paper introduced the concept of we contexts (individual, household, community, etc.) . contexts represent the level or "scale" at which we is observed. we domains and dimensions are context-dependent, which means the factors that influence change in we and the way they are manifested will change by the changing level of observations. in an initial attempt to articulate the interplay of the contexts, dimensions and domains and to explain how the adapted system works together, the paper presented an explanation of the mechanisms of we. these include the concepts of impacts and feedback, factors, constraints, and interventions. a systematic approach to evaluating empowerment will require a thorough understanding of these mechanisms over time. likewise, any attempt to map women's vulnerability in a given point of time will need to look at these elements as a means of measuring vulnerability. all of these components together comprise the advancing women's empowerment through systems oriented model expansion (awesome) framework. given that the awesome framework offers a proposed methodology to the study and measurement of we, the next logical action calls for empirical testing to validate the approach in various contexts. the framework's definitions and conceptualizations of the relationships between we and vm require further testing and translation into replicable and reliable methodology to demonstrate usability across contexts. the research lab that the authors are associated with is currently in the process of further empirical testing, although due to covid- restrictions, progress has been greatly slowed. nevertheless, the conceptual framework indicates the potential to successfully engage women in ways that will honor their voices and contexts, prioritize their well-being, and ensure the sustainability of both their physical environments and within their own empowerment processes. gaining an understanding of the factors that inhibit or support a woman's state of empowerment may enable interventions to be optimized, so as to better avoid the types of short-or long-term, negative repercussions. as this is currently a conceptual framework, the empirical limitations of this proposed approach are unknown. it is clear, even from this point, that it is a process-intensive approach, requiring longitudinal monitoring and detailed data collection. this may be prohibitive to some organizations. however, the authors see great promise in the potential it offers and hope to advance knowledge in this area to improve intervention design and policy development. the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. effect of microfinance on women' s empowerment : a review of the literature association between social integration and suicide among women in the united states the women's empowerment in agriculture index virtue and vulnerability: discourses on women, gender and climate change mapping vulnerability: disasters, development and people when rights go wrong development in practice 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region resources, agency, achievements: re¯ections on the measurement of women's empowerment discussing women's empowerment. sida studies gender equality and women's empowerment: a critical analysis of the third millennium development goal the conditions and consequences of choice: reflections on the measurement of women s empowerment f or social development. context, policy and planning for the empowerment of zambia's women farmers do schooling and work empower women in developing countries? the case of sri lanka women's empowerment as a variable in international development measuring women's empowerment: learning from cross-national research disasters by design vulnerability assessment methodologies: a review of the literature assessing women's empowerment: towards a conceptual framework measuring empowerment chup: breaking the silence about india's women understanding women's empowerment using an exploratory mixed-methods index vulnerability and capacity assessment: a partecipatory action research of the palestinian society in disaster preparedness natural hazard mitigation saves women ' s empowerment and nutrition an evidence review gender empowerment index: a choice of progress or perfection. the lancet global health a qualitative comparative analysis of women's agency and adaptive capacity in climate change hotspots in asia and africa sustainable hazards mitigation presented at the amrita vishwa vidyapeetham, amritapuri: international colloquium: women's empowerment, vulnerability mapping, and community-led sanitation assessing vulnerability to earthquake hazards through spatial multicriteria analysis of urban areas vulnerability before adaptation: toward transformative climate action a theory of access empowerment examined women empowerment index: construction of a tool to measure rural women empowerment level in india inequality reexamined markets and freedoms: achievements and limitations of the market mechanism in promoting individual freedoms does addressing gender inequalities and empowering women and girls improve health and development programme outcomes? vulnerability resilience and collapse of society. a review of models and possible climatic applications participatory capacity and vulnerability analysis: a practitioner's guide climate change & food security vulnerability assessment: toolkit for assessing community-level potential for adaptation to climate change united nations: gender equality and women's empowerment violence against women prevalence data: surveys by country no. country survey coverage year intimate partner violence (%) intimate partner and/ or non-partner violence (%) forced first sex (%) abuse during pregnancy. un women progress on the sustainable development goals: the gender snapshot unesco priority gender equality action plan for - united nations educational scientific and cultural organization unisdr terminology on disaster risk reduction proposed updated terminology on disaster risk reduction: a technical review sustainable development knowledge platform: goal the 'downside' of women empowerment in india: an experimental inquiry into the role of expectations global gender gap report vulnerability as concept, model, metric, and tool. women deliver. n.d gender this chart shows the reality behind the gender pay gap | world economic forum global gender gap report gender, equity, human rights the authors would like to express our gratitude to the center for women's empowerment and gender equality team for their tireless collaborative process in the conceptual phases of this work. we would also like to express our sincere gratitude to sri mata amritanandamayi devi, chancellor of amrita vishwa vidyapeetham and world-renowned humanitarian for guiding us and inspiring us every step of the way. key: cord- - im l y authors: ratta, barkha; yadav, brijesh singh; pokhriyal, mayank; saxena, meeta; sharma, bhaskar title: microarray chip based identification of a mixed infection of bovine herpesvirus and bovine viral diarrhea from indian cattle date: - - journal: curr microbiol doi: . /s - - - sha: doc_id: cord_uid: im l y bovine herpesvirus (bhv ) and bovine viral diarrhea virus (bvd ) are endemic in india although no mixed infection with these viruses has been reported from india. we report first mixed infection of these viruses in cattle during routine screening with a microarray chip. of the probes of bhv and of the bvd probes in the chip gave positive signals for the virus. the virus infections were subsequently confirmed by rt-pcr. we also discuss the implications of these findings. indian cattle and buffalo populations ( million and million, respectively) are the largest in the world, and india is emerging as one of the largest milk-producing countries of the world. the health and productivity of indian cattle and buffalo populations are dependent on the absence or the low scale presence of many endemic diseases which are prevalent elsewhere, particularly bovine viral diarrhea (bvd) and bovine herpesvirus (bhv ). bvd is a disease which is endemic in developed countries. it is only in this century [ , , ] that the virus has been isolated from indian livestock, though serological evidence of the existence of this virus was reported in s [ ] . both bvd virus genotypes and have been reported [ , [ ] [ ] [ ] [ ] ] . bvdv, a member of the pestivirus genus of the family flaviviridae, has been linked to a number of clinical conditions of cattle, viz., diarrhea, abortions, congenital abnormalities, and birth of persistently infected animals [ ] . acute bvdv infections in postnatal life are mostly inapparent [ ] . bvdv generally induces severe immunosuppression in affected animals. the immunosuppression is associated with transient leukopenia, neutrophil dysfunction, and other immunological disturbances [ , ] . the immunosuppressive effect impairs the ability of the animal to clear virus or bacteria from its blood and tissues [ , ] . infectious bovine rhinotracheitis/infectious pustular vulvovaginitis caused by bhv was first reported in the us in s and in india in . bhv is a member of genus varicellovirus, subfamily alphaherpesviriniae of the family herpesviridae. bhv causes several diseases in cattle including rhinotracheitis [ ] , vaginitis, balanoposthitis, abortion, conjunctivitis, and enteritis [ ] . the world organization for animal health [oie] lists bhv as a list b-notifiable disease. oies list b diseases are transmissible diseases that are of socioeconomic and/or public health importance and that are significant in international trade. acute bhv infection, regardless of whether there are clinical signs of disease, leads to latent infection. latently infected cattle show no disease unless the latent infection is reactivated [ ] . in india, the virus has been isolated from states of orissa [ ] , karnataka [ ] , and gujarat [ ] . the serological evidence for the existence of bhv in indian domestic and wild livestock [ ] indicates that this disease is widespread in india. bhv and bvd are the two diseases that are difficult to manage and eradicate because of latent infections. mixed infections with these two viruses have been reported from different countries [ , ] . the economic cost of mixed infection has not been determined but is apparently high. in india, the seroprevalence of both bvd and bhv in indian livestock is known. so far, no report of mixed infections of these viruses from indian livestock has been reported. we report the first mixed infection of bhv and bvd in indian cattle using a microarray chip that we have developed, and discuss the implications of the findings and also the use and utility of microarray chips for identifying mixed and emerging infections. the clinical sample collected from the institute's veterinary polyclinic was obtained from a cow which had aborted fetus ( months) and was having fever. we have been designing and testing microarray chips for identification of animal viruses. different versions of chips have been tested and an earlier version of the chip identified newcastle disease virus from sheep [ ] . the chip used here for testing the clinical samples contained unique probes representing different viruses and random probes. the probes were designed using e-array (https://earray.chem.agilent.com) or array designer (www. premierbiosoft.com) and were analyzed using blast program individually before including the same in the chip. the probe design criteria were ( ) length of oligonucleotide probes - . ( ) the tm (melting point) of the probes °c ± . ( ) the gc content of the probes - %. ( ) the maximum poly nucleotide tract allowed was six. ( ) % homology with target sequence with at least nucleotide contiguous matches at end and less than % homology with nontarget sequence. the random probes included in the chip were taken from mda (microbial detection array) chip [ ] . the chip was fabricated commercially (agilent technologies, usa) as per our design. total rna was extracted using trizol Ò reagent (invitrogen) according to manufacturer's protocol. the quality of total rna was checked by nanodrop spectrophotometer and bioanalyzer. the total rna was labeled with cyanine -ctp labeling dye using quick-amp labeling kit one-color (agilent) according to manufacturer's protocol. the purified cy -labeled samples were hybridized on agilent's microarray hybridization chamber using agilent microarray hybridization chamber kit (g a) according to manufacturer's instruction. the total rna was amplified by quantitect Ò whole transcriptome amplification kit (qiagen, cat no. ) according to the manufacturer's protocol. after hybridization, the arrays were scanned with an agilent scanner. the microarray data from scanned images were extracted with agilent feature extraction software version . . . the signal intensities, retrieved from raw data text file generated from hybridized image file using feature extraction software, were sorted by genus and species of the virus. many methodologies have been employed for identifying a virus from microarray data. these include hybridization intensity based on expected and observed intensity [ ] or on log odd ratio [ ] , number of probes giving positive signal, or even percentage of probes giving positive signal [ ] . we had adopted percentage of probes giving positive signals for making virus call. this method of making a virus call is easy and has % as cut-off for making a virus call is stringent others have kept it at about % [ ] . we had kept it at % based on our earlier observation that the closely related viruses give high cross reactivity. in the earlier version of the chip, we used to get - % cross hybridization of probes between bhv and bhv and cav and cav . this has been brought down to about - % with the chip that was used in this study. the background intensity for identifying positive signal was arrived from intensity of random probes and was kept at th percentile of random probe signal intensity [ ] . the primer sequences used for amplification of bvd and bhv genes are listed in table . the amplification for bhv ge gene was carried out in ll reaction volume containing taq dna polymerase buffer, . mm mgcl , pmol of each primer, lm of dntps, % dmso, ll of amplified transcriptome, u taq polymerase (fermentas), and nuclease-free water to make up volume of ll. after initial denaturation at °c for min, the amplification was carried out for cycles each of °c- s, °c- s, and °c- min with final extension of min at °c. the amplification for bvd was carried out in ll reaction volume containing taq dna polymerase buffer, . mm mgcl , pmol of each primer, lm dntps, ll amplified transcriptome, u of taq dna polymerase (fermentas), and nucleasefree water to make ll. after initial denaturation at °c for min, the amplification was carried out for cycles each of °c- s, °c- s, and °c- min with final extension of min at °c. for nested pcr of bvd , the procedure was essentially the same except that the template was replaced by ll of primary pcr amplicon and primers of set b ( table ). the annealing temperature was kept at °c. of the many samples tested in one sample from cow, of the probes of bhv and of the probes of bvd gave positive signals ( table ) . a virus was called to be present if more than % probes for that virus gave signal above cut-off. according to this criterion, both the viruses were present in this particular sample. next virus for which we obtained some positive signal was bhv ( of the probes gave positive signal). bhv and bhv (formerly bhv . ) are closely related with more than % sequence similarity, and there is always some cross hybridization. we normally get this much cross hybridization with bhv when rna from bhv -infected cell culture lysate is hybridized with the chip (personal communication). we did not get any further significant signal for other viruses in this sample (fig. ) . the average signal intensity of bhv probes was consistently high as compared to bvd probes average signal intensity (table ) suggesting that this was probably not necessarily true, bhv was the major infection and bvd a minor infection. whole transcriptome pcr results (fig. , amplified product bp for bhv- and bp and bp for bvd , and bvd genotype, respectively) corroborated the microarray data. the unambiguous result in both the tests and clinical history (aborted fetus and fever) of the animal makes it almost a certainty that there was a mixed infection of bhv and bvd in the animal from which the sample was drawn. bhv , bvd, respiratory syncytial virus (rsv), bovine parainfluenza virus , bovine adenovirus, and coronavirus are the viruses found which are associated with the bovine respiratory disease complex [ ] . in india, cattle movement is frequent; cattle are moved across long distances under highly stressed conditions; shipping fever is known to exist; and, in most cases, it is bacteria, which are isolated from these cases [ ] ; the underlying virus cause of [ , ] , except india. they increase the complexity of the symptoms and economic losses [ ] . among bvd and bvd genotypes, it is the bvd genotype which is more virulent [ ] . among the few clinical samples tested, one sample was positive for bhv and bvd . in india, bvd is still considered as an exotic disease, and handling the virus is confined to a lab with high-security disease though serological evidence [ ] indicates otherwise. large-scale screening of clinical samples may give the actual extent of spread of mixed infections of these viruses. however, based on serological evidences [ , , ] , it can be assumed that mixed infection of these viruses could be present on a much larger extent and mostly go unreported due to want of extensive search. microarray chips for diagnosis have emerged as highly parallel diagnostic platforms, which that have the ability to detect many known, novel, and emerging pathogenic agents simultaneously. the virochip developed originally by palacios is one such chip [ ] , microbial detection array (mda) [ ] is even more comprehensive chip and has the capability to screen almost all the viruses currently known to exist. most of microarray chips developed and tested were for human pathogens though they contains probes for animal viruses also. the virochip was recently used for identifying pathogens in veterinary clinical samples [ , ] . we had also tested in-house designed chip for testing veterinary clinical samples [ ] . massive multiplexing ability of microarray as compared to other diagnostic techniques is advantageous in identifying multiple infections which may otherwise go unreported. disadvantage of microarray chip is its high cost which makes its applicability in routine diagnosis highly improbable. many lowdensity fda approved microarrays are now commercially available, e.g., xtag respiratory viral panel (luminex), filmarray (biofire), and tessarray rpm-flu . array (tessarae), resplex ii v . rvp (qiagen), they are now used regularly in many clinical microbiology labs. the use of high-density microarrays is limited for want of fda or other regulatory agencies' approval. their approval by regulatory agencies required testing against all the pathogens; they are capable of identifying, which is technically not feasible. current cost of using high-density array is high ( - usd). the cost is expected to go down substantially as the methodology gets widely adopted. high-cost microarray can still be used as an adjunct diagnostic method for screening of multiple infections, and in those cases where routine diagnostic methods fail to identify a pathogen from 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virus in karnataka note on serological evidence of viral abortion in cattle in orissa ruminant pestiviruses panmicrobial oligonucleotide array for diagnosis of infectious diseases effect of bovine viral diarrhea virus infection on the distribute on of infectious bovine rhinotracheitis virus in calves detection of respiratory viruses and subtype identification of influenza a viruses by greenchipresp oligonucleotide microarray association of bovine viral diarrhea virus with multiple viral infections in bovine respiratory disease outbreaks differentiation of types a, b and bovine viral diarrhoea virus (bvdv) by pcr studies on shipping fever of cattle. . comparison of pasteurella spp. isolated from shipping fever and other infectious processes isolation of newcastle disease virus from nonavian host sheep and its implications seroprevalence of bovine viral diarrhoea virus in india: a survey from - prevalence of bovine viral diarrhoea virus antibodies in india seroprevalence of infectious bovine rhinotracheitis in india e-predict: a computational strategy for species identification based on observed dna microarray hybridization patterns respiratory viruses in acute respiratory tract infection in western india acknowledgments the authors acknowledge and thank icar for funding and dr. umesh dimri for providing clinical samples from institute polyclinic. key: cord- - z skg n authors: senapati, abhishek; rana, sourav; das, tamalendu; chattopadhyay, joydev title: impact of intervention on the spread of covid- in india: a model based study date: - - journal: nan doi: nan sha: doc_id: cord_uid: z skg n the outbreak of corona virus disease (covid- ), caused by the virus severe acute respiratory syndrome coronavirus (sars-cov- ) has already created emergency situations in almost every country of the world. the disease spreads all over the world within a very short period of time after its first identification in wuhan, china in december, . in india, the outbreaks starts on $ ^{nd}$ march, and after that the cases are increasing exponentially. very high population density, the unavailability of specific medicines or vaccines, insufficient evidences regarding the transmission mechanism of the disease also make it difficult to fight against the disease properly in india. mathematical models have been used to predict the disease dynamics and also to assess the efficiency of the intervention strategies in reducing the disease burden. in this work, we propose a mathematical model to describe the disease transmission mechanism between the individuals. we consider the initial phase of the outbreak situation in india and our proposed model is fitted to the daily cumulative new reported cases during the period $ ^{nd}$ march, to $ ^{th}$ march, . we estimate the basic reproduction number $(r_ )$, effective reproduction number (r(t)) and epidemic doubling time from the incidence data for the above-mentioned period. we further assess the effect of preventive measures such as spread of awareness, lock-down, proper hand sanitization, etc. in reducing the new cases. two intervention scenarios are considered depending on the variability of the intervention strength over the period of implementation. our study suggests that higher intervention effort is required to control the disease outbreak within a shorter period of time in india. moreover, our analysis reveals that the strength of the intervention should be strengthened over the time to eradicate the disease effectively. human to human transmission is considerably growing almost everywhere in the world by means of the international movement [ ] and as soon as an area of a specific country is affected then covid- rapidly grows through local transmission. person infected with sars-cov- virus shows symptoms like fever, cough, and shortness of breath, muscle ache, confusion, headache, sore throat, rhinorrhea, chest pain, haemoptysis, diarrhoea, dyspnoea and nausea and vomiting [ , , ] . who situation report [ ] reveals that the covid- pandemic spread on the western pacific, european, south-east asia, eastern mediterranean, america and african region with their respective territories, causing a huge number of infected cases. the new cases are quickly growing in various countries like usa, spain, germany, france, italy, uk, iran, switzerland, india, netherlands, austria, etc. [ ] . in india, the first confirmed case of covid- was reported on th january, [ ] . government of india declared a countrywide lock-down for days as a preventive measure for the covid- outbreak on th march, [ ] . besides the lock-down, the ministry of health and family welfare (mohfw) of india, suggested various individual hygiene measures e.g. frequent hand washing, social distancing, use of mask, avoiding touching eyes, nose, or mouth, etc. [ , ] . the government also continuously using various media and social networking web sites to aware the citizen. however, the factors like very high population density, the unavailability of specific medicines or vaccines, insufficient evidences regarding the transmission mechanism of the disease also make it difficult to fight against the disease properly in india. mathematical models have been used to predict the disease dynamics and also to assess the efficiency of the intervention strategies in reducing the disease burden. in this context, several studies have been done using real incidence data of the affected countries and examined different characteristics of the outbreak as well as evaluated the effect of intervention strategies implemented to curb the outbreak in the respective countries [ , , , , , ] . in this work, we propose a deterministic compartmental model to describe the disease transmission mechanism between the individuals. we consider the situation of india during the initial outbreak period and fitted our model to the daily cumulative new cases reported between nd march, to th march, . we estimate the basic reproduction number, effective reproduction number and epidemic doubling time from the incidence data for the above-mentioned period. the efficiency of preventive measures in reducing the disease burden is also studied for different level of intervention strength. further, the impact of intervention in the situation where the strength of the intervention is varied over the implementation period. the rest of the paper is organized as follows. in section , we briefly describe our proposed model. section is devoted in describing the procedure of model fitting. the estimation of basic reproduction number, effective reproduction number and epidemic doubling time from actual incidence data is described in section . in section , the efficiency of the intervention is studied. finally we discuss the findings obtained from our study in section . we adopt deterministic compartmental modelling approach to describe the disease transmission mechanism. depending on the health status, the total human population is categorized into seven compartments: susceptible (s), exposed (e), symptomatic (i), asymptomatic (i a ), quarantined (i q ), hospitalized (h) and recovered (r). susceptible population becomes exposed with the disease after experiencing close contacts with the symptomatic as well as asymptomatic individuals. we assume that the rate of disease transmission from asymptomatic individuals to susceptible individuals is less than that of from symptomatic individuals. the rate of new infection is given by , where β denotes the transmission rate of the disease and η(< ) is the modification parameter that accounts the reduction in the transmission rate from the asymptomatic individuals. at any instant of time, the total population is given by n = s + e + i + i a + i q + h + r. since we consider the outbreak situation which usually persists for a shorter period of time, we do not incorporate any demographic factors (i.e birth, death, etc.) into the model. we assume that after the incubation period (σ − ), ρ fraction of the exposed individuals move to symptomatic compartment, ρ fraction move to the asymptomatic compartment and the remaining fraction, (ρ = −ρ −ρ ) move to the quarantined compartment. the individuals in the symptomatic compartment (i) show severe symptoms of the disease and after α − period of time they are hospitalized. on the other hand, the asymptomatic individuals who do not show any symptom of the disease get natural recovery at a rate γ a and move to the recovered class (r). the individuals in the quarantined compartment (i q ) are those individuals who exhibit mild symptoms and are advised to be quarantined. from quarantined class (i q ), individuals move to the hospitalized class (h) at a rate α q . they can also get natural recovery and move to the recovered class (r) at a rate γ q . individuals admitted in the hospitals move to recovered class at a rate γ. we also consider that the hospitalized individuals die due to the disease at a rate δ. the recovered population increases due to the recovery of asymptomatic, quarantined and hospitalized individuals at the rates γ a , γ q and γ respectively. the following set of ordinary differential equations represents the transmission dynamics of the disease: ( . ) the schematic diagram and the description of the parameters used in the model ( . ) is presented in fig. and table respectively. though the first confirmed case of covid- was reported on th january, [ ] , from nd march, onwards, the new cases are being reported continuously. therefore, we consider nd march, as the starting date of the outbreak in india. it is also to be noted that, government of india declared a countrywide lock-down from th march, for days [ ] . therefore, we assume that during the period nd march, to th march, no such preventive measures was taken by the government of india. since we do not incorporate any intervention in our model ( . ), we fit our model to the daily cumulative new reported covid- cases of india during the period nd march, to th march, . the daily cumulative cases data are obtained from [ ] . we estimate four unknown model parameters: (i.) the transmission rate (β), (ii.) modification parameter (η), (iii.) fraction of population move to symptomatic class from exposed class (ρ ) and (iv.) fraction of population move to asymptomatic class from exposed class (ρ ) by fitting the model to the cumulative reported cases data. the cumulative new reported cases from the model is given by where Θ = {β, η, ρ , ρ } and c( ) denotes the initial cumulative cases. we perform our model fitting by using in-built function lsqnonlin in mat-lab (mathworks, r a) to minimize the sum of square function. in our case, the sum of square function ss(Θ) is given by, where, c d (t i ) is the actual data at t th i day and n is the number of data points. the model fitting to the cumulative new reported cases is displayed in fig. . the values of the estimated parameters are given in table . basic reproduction number is a key quantity in epidemiology which quantifies the average number of secondary cases generated from a single primary cases during the his infectious period. this quantity can be calculated from a mathematical model by following next generation matrix approach. following [ ] , the new infection matrix f and the transmission matrix v are given by, the basic reproduction number, r is defined as the spectral radius of the matrix f v − , it is to be noted that, the first term is the number of new infection caused by symptomatic individual (i) whereas the second term is the number new infection due to the infection by asymptomatic individual (i a ). the basic reproduction number (r ) for communicable diseases can be estimated through the actual epidemic data by using various statistical as well as mathematical methods [ ] . in this study, we estimate r from the initial growth phase of the epidemics [ , , ] . at the early stage of the epidemic, there is a non-linear relationship between the cumulative number of cases c(t) and the force of infection Λ which can be mathematically written as c(t) ∝ exp(Λt). so the number of exposed, symptomatic and asymptomatic population progress in the following form, where e , i and i a are constants. further, the number of non-susceptible population can be assumed negligible i.e. s(t) = n. substituting the equation ( . ) into the model ( . ), we have using the expression of r from equation ( . ) and applying the above equations ( . ) we have determined relation between the r and the force of infection Λ as follows: here we first estimate the force of infection Λ and then estimate r by using equation ( . ) . following [ , ] , the relation between the number of new cases per day and the cumulative number of cases per day c(t) as: number of new cases ∼ Λc(t). the force of infection (Λ) can be calculated from the covid- incidence data in the following ways [ ] : step . we plot the number of new covid- cases (per day) in x−axis versus the cumulative number of covid- cases (per day) in y − axis. step . in the scatter plot, we point out the threshold of cumulative cases up to which new cases show the exponential growth. step . then we fit a linear regression model using the least square technique to this exponential growth data. step . the slope of the fitted line is considered as the force of infection (Λ). we obtain Λ = . ± . day − based on the slope shown in fig. . using the equation ( . ) along with the parameter values form table , we obtain the estimate of r = . with upper and lower bounds . and . respectively. this estimate of r indicates that the initial transmissibility of covid- is pretty much higher than , which in turns implies that it is essential to control the disease at the initial phase. the doubling time of an epidemic is a measure of the rate of spread of a disease. it is the required time to double the number of cases in the epidemic. there is an inverse relationship between epidemic strength and the doubling time i.e. if an epidemic declines, the doubling time increases and vice versa. following [ ] , we obtain the epidemic doubling time for our study is t = ln( ) Λ ≈ . days. therefore, it is necessary to apply some preventive measures else the epidemic appears in a large scale within a short time. study regarding the time span of an epidemic is very crucial and can be achieved to a certain extent through the estimation of r(t), the effective reproduction number. it is defined as the actual average number of secondary cases from a typical primary case at time t [ ] . the value of r(t) provides information about the severity of the disease over different time points and alert epidemiologists to suggest about the control measures [ ] . we estimate r(t) from the daily new infection curve of the infected covid- cases data by using the following equation derived from the renewal equation of a birth process: where, the term b(t) corresponds to the number of new cases in the day t and the term g() is the generation interval distribution for a disease [ ] . we derive the expression of the generation interval distribution g(t) from the model ( . ) by applying the method discussed in [ , ] . the rates of leaving the exposed and infectious compartments are indicated by b , b and b . these quantities are constant and extracted from the model ( . ) as b = σ, b = α and b = γ a . moreover, the generation interval distribution is the convolution of three exponential distributions with a mean t c = /b + /b + /b . following [ , ] , we have the following explicit expression for the convolution: with t ≥ . the validity of the above relation ( . ) holds for a minimum threshold value of the force of infection Λ, defined as Λ using the daily covid- incidence data and applying the expression of g(t) in equation ( . ), we estimate r(t) from equation ( . ). fig. shows the time evolution of the effective reproductive number r(t) to the covid- outbreak in india, from nd march, to th march, . the result is shown here for t ≥ , since, the method used here to derive the expression of r(t) is not applicable for lower values of t. here the value of r(t) lies between to most of the times. the low value of r(t) = appears on the second point (see fig. ) due to non occurrence of new cases at th march also the high value of r(t) ≈ . , . occurs on th , th day of the outbreak due to the high number of new cases found on these days. it implies that the disease continues to infect the more and more people during that period. it is worthy to remember that, at this point govt. of india announced a lock-down to break the chain of infection spread else it will be almost impossible to control the spread after a certain period of time. in this section, we study the effect of intervention strategies in reducing the new covid- cases through our model. intervention strategies includes the control measures such as lock-down, spreading awareness program through media, proper hand sanitization, etc. which results in slowing down the disease transmission process. in terms of model parameter, the implementation of intervention implies that there would be a reduction in the disease transmission rate β. this reduction in the transmission rate is considered as the strength of the intervention, k. in the presence of intervention, the parameter β is modified as ( − k)β throughout the period of implementation. staring from the initial date of outbreak, we consider a period of days (i.e months) and study the impact of intervention during that period. speaking in terms of actual date, we consider the time period nd , march, to th september, . we consider two types of intervention scenarios: (i.) the strength of the intervention (k) is fixed throughout the implementation period, (ii.) the strength of intervention is varied over the implementation period. in this intervention scenario, the strength of the intervention k is taken to be fixed over the implementation period. we first consider the situation without any intervention (i.e k = ). our model ( . ) is simulated for days to observe the dynamics of the disease in the absence of any intervention, using the in-built function ode in matlab (mathworks, r a). from fig. , we see that the number new cases grows exponentially and attains the maximum at the end of the june. it is also observed that maximum of . million new cases can occur in the absence of any intervention during the period (see table ). however, in the subsequent time, decreasing trend in the new cases is noted. now we study the efficiency of the intervention by varying the strength of the intervention (k). regarding the initiation of the control, we follow the same date when govt. of india implemented nation-wide lock down i.e th march, . throughout the study we consider this date as the initial date of implementing the intervention. for the low value of the intervention strength (i.e for k = . ), it is observed that the time for the occurrence of peak of the outbreak is slightly delayed than that of without intervention scenario (see fig. ). the peak of the outbreak is shifted to the end of the month july. in this case, maximum . million new cases can occur (see table ). if the strength of the intervention is increased further (for k = . ), the peak of the outbreak decreases and the occurrence of the peak shifted to the end of september (see fig. ). in this case, the maximum number new cases in a single day reduces to . million (see table ). now we consider the higher values of intervention strength. for k = . , the new cases tend to decrease within a week (see fig. ) from the date of implementation and in such a case maximum of new cases can occur (see table ). if the strength is increased further (i.e for k = . and . ) we see that the disease can be effectively eradicated within to months from the initial date of implementing intervention (see fig. ). table . next we evaluate the maximum number of new cases during the time period nd march, to th september, for different values of k (see fig. ). the actual number of maximum new cases for different values of k are tabulated in table . the percentage of relative reduction in the final cumulative new cases for different k is presented in fig. . it is observed that interventions having lower strengths(i.e for k ∈ [ . , . ]), can reduce up to . % final cumulative cases. however, if the strength of the intervention is considered to be higher then almost . % reduction in the final cumulative cases can be achieved. in this scenario, instead of considering the fixed value of k over the whole time interval after the initiation of intervention as in scenario , we vary the value of k over the implementation period. the implementation period i.e th march, to th september, is divided into three time windows. the first window consists of days whereas the second and third window consists of days and days respectively. we first decrease the value of k from first window to third window. the values of k taken in the three windows are . , . and . respectively. we observe from fig. that in this case, the new cases decreases in the first window and remains almost unchanged in the second window where the value of k is decreased slightly than first window. however, when the value of k is decreased further in the third window, the new cases tend to increase rapidly. this implies that the relaxation in the interventions strategy over the time does not end up with the disease eradication. next we consider the opposite case i.e we increase the value of k from first window to third window. the values of k are taken as . , . and . respectively in the respective time windows. it is observed from fig. that the new cases tends to increase in the first two windows. however, in the third window where the value of k is high enough, the new tend to decrease. this essentially implies that the intervention should be strengthened over the time to eradicate the disease effectively. the covid- outbreak in india is a potential threat to the country due to its rapid spread. mathematical models are very effective tools to predict the time span and pattern of the outbreak. moreover, mathematical models can also provide useful insights regarding the impact of intervention in lowering the disease incidence. in this study, we proposed a deterministic compartmental model to describe the disease transmission mechanism among the population. we considered the initial phase of outbreak of the disease covid- in india and fitted our proposed model to the cumulative new reported cases during the period nd march, to th march, . some model parameters are estimated by fitting our model to the cumulative new reported cases during the above mentioned period. by looking at the estimated parameters, it is observed that the rate of disease transmission is quite high which basically implies the high infectiousness of the disease. the percentage of the symptomatic individuals coming from exposed individuals is estimated to be more than %, whereas the percentage of the asymptomatic and quarantined individuals are estimated as more than % and % respectively. this indicates that the contribution of the asymptomatic population to covid- cases in india is not negligible. based on the estimated parameters and actual covid- incidence data, we estimated basic reproduction number, effective reproduction number and epidemic doubling time to get an overview of this initial phase of outbreak. we obtained the estimate of basic reproduction number r as . with upper and lower bounds are . and . respectively. this high value of r basically captures the outbreak scenario in india. the effective reproduction number (r(t)) provides information about the severity of covid- over different time points. in our study, the values of r(t) lie between and most of the time. this is also confirms high transmissibility of the disease. the epidemic doubling time is also estimated to be approximately . days. this suggests that the rate of disease transmission need to be controlled otherwise a large proportion will be affected within a very short period of time we studied the impact of intervention in reducing the disease burden. we basically considered the preventive measures such as lock-down, spreading of awareness program through media, proper hand sanitization, etc. which slow down the disease transmissibility. two intervention scenarios are considered depending on the variability of the intervention strength over the period of implementation. in the first scenario, we fixed the strength of the intervention throughout the period of implementation and studied the impact of intervention for different level of intervention efforts. in this scenario, our study reveals that higher intervention effort is required to control the disease outbreak within a shorter period of time. in the second scenario, the whole implementation time are divided into three time windows and in each of the window, the intervention strength is taken to be different. in such a scenario, our analysis shows that the strength of the intervention should not be relaxed over the time rather the intervention should be strengthened to eradicate the disease effectively. designing the efficient intervention strategy is one of the crucial factor to curb the disease spread in an outbreak situation. in this regard, our study suggests that strict intervention should be implemented by the government in the subsequent period of this outbreak. we believe that the findings obtained from this study can provide fruitful insights in framing policies regarding the control of covid- in india. genome structure, replication, and pathogenesis coronaviruses history and recent advances in coronavirus discovery middle east respiratory syndrome coronavirus transmission a comparative analysis of factors influencing two outbreaks of middle eastern respiratory syndrome (mers) in 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available online covid- : india imposes lockdown for days and cases rise available online all eyes on coronavirus -what do we need to know as ophthalmologists early dynamics of transmission and control of covid- : a mathematical modelling study phase-adjusted estimation of the number of coronavirus disease quantifying sars-cov- transmission suggests epidemic control with digital contact tracing estimating the unreported number of novel coronavirus ( -ncov) cases in china in the first half of january : a data-driven modelling analysis of the early outbreak preliminary estimation of the basic reproduction number of novel coronavirus ( -ncov) in china, from to : a data-driven analysis in the early phase of the outbreak coronavirus covid- global cases by the center for systems science and engineering. available online reproduction numbers and subthreshold endemic equilibria for compartmental models of disease transmission estimation of r from the initial phase of an outbreak of a vector-borne infection the risk of yellow fever in a dengue-infested area a generic model for a single strain mosquito-transmitted disease with memory on the host and the vector modelling the dynamics of dengue real epidemics early determination of the reproductive number for vector-borne diseases: the case of dengue in brazil the effective reproduction number as a prelude to statistical estimation of time-dependent epidemic trends how generation intervals shape the relationship between growth rates and reproductive numbers on the convolution of exponential distributions abhishek senapati is supported by the research fellowship from council of scientific & industrial research, india (grant no: / ( )/ /emr-i), government of india. the authors declare that there is no conflict of interest. key: cord- - ccgcrvd authors: nasta, amrit manik; goel, ramen; kanagavel, manickavasagam; easwaramoorthy, sundaram title: impact of covid- on general surgical practice in india date: - - journal: indian j surg doi: . /s - - - sha: doc_id: cord_uid: ccgcrvd the coronavirus disease (covid- ) pandemic is a global health crisis, and surgeons are at increased occupational risk of contracting covid- . the impact of the disease on prevalent general surgical practice is uncertain and continues to evolve. the study aimed to study the impact of covid- on general surgical practice in india and the future implications of the pandemic. a survey questionnaire was designed and electronically circulated month after india entered a national lockdown during covid- pandemic, amongst members of indian association of gastro-intestinal endo-surgeons (iages), a surgical association with nearly eight thousand members from across the country. survey questions pertaining to pre-covid era surgical practices, impact on current practice, and financial implications were asked. responses were collected and statistically analyzed. one hundred fifty-three surgeons completed the survey, of which only . % were women. majority ( %) were into practice for more than years; . % were into private practice at multiple hospitals (free-lancers). amongst the respondents, . % had mainly laparoscopic practice with mean outpatient consultation of patients/day and elective surgeries of cases/month prior to lockdown. post-lockdown, daily outpatient consults reduced to patients per day, and % had not performed a single elective procedure. hydroxychloroquine (hcq) chemoprophylaxis was reported by % surgeons. personal protective equipment (ppe) was used by % for all cases, while . % stated there are insufficient guidelines for future surgical practice in terms of safety. a drop of more than % of their monthly income was experienced by % surgeons, while % faced – % reduction. one third ( %) of respondents own a hospital and are expecting a monthly financial liability of . million rupees (nearly , us dollars). covid- has led to a drastic reduction in outpatient and elective surgical practices. there is a definite need for guidelines regarding safety for future surgical practices and solutions to overcome the financial liabilities in the near future. the novel coronavirus was declared a public health emergency of international concern (pheic) by the world health organization (who) on january , [ ] . in the first week on march, an unexpectedly high number of cases were detected worldwide and coronavirus disease (covid- ) was declared a pandemic on march , [ ] .the indian government announced a countrywide lockdown for weeks starting at midnight on march to slow the spread of covid- as the number of people testing positive in the country reached [ ] . however, this lockdown was further extended till may , . one month into lockdown, outpatient clinics and elective surgeries were likely to have taken a beating. majority of hospital resources were directed towards availing masks and personal protective equipment (ppe), minimizing staff movements and suspension of all elective work. aims the study aimed to study the impact of covid- on general surgical practice in india and the future implications of the pandemic. methods this survey was conducted at a tertiary-care hospital. the survey questionnaire was designed and electronically circulated month after india entered a national lockdown, amongst members of indian association of gastro-intestinal endo-surgeons (iages), nearly member strong association with surgeons having interest in general and laparoscopic surgery. survey questions pertaining to pre-covid era surgical practices, impact on current practice, and financial implications were asked. responses were collected, and chi square test was used for statistical analysis. the self-administered questionnaire consisted of twentyone questions with five part socio-demographic questions, questions on outpatient and surgical (emergency/elective) numbers in pre-lockdown and post-lockdown period, safety practices, and financial impact in the current period. results one hundred and fifty-three surgeons from across the country completed the survey, of which only . % were women. amongst the respondents, . % surgeons were more than years into practice, % for to years, and . % to years after completing their specialty degree. for place of practice, . % were into private practice at multiple hospitals (free-lancers), . % were full timers at a single corporate hospital, and . % were full timers at government hospitals. prior to lockdown amongst the respondents, % had mainly laparoscopic practice and . % had equal proportion of laparoscopic and open surgery (fig. ). surgeons reported a mean outpatient consultation of patients/day and elective surgeries cases/month prior to lockdown. post-lockdown since the beginning of lockdown, . % reported to have completely stopped outpatient services, . % surgeons had a reduction in their services, and % reported to have started online consultations. amongst those continuing consultations, average daily consults reduced to patients per day. all elective surgical work was stopped by . %, while . % had scaled down elective surgeries. no elective procedures were performed by %, while % performed less than surgeries during the lockdown period. no emergency surgeries were performed by % surgeons, and . % had reduced emergency services where feasible. average elective and emergency surgeries performed in the month of lockdown were merely one and five in number, respectively (fig. ) . the reduction in opd, elective, and emergency surgical practice was statistically significant (p < . ). safety practices hydroxychloroquine (hcq) was taken by % surgeons for chemoprophylaxis. it was felt by % surgeons that laparoscopic surgery and use of energy sources increased the risk of aerosol spread of the virus. for safe surgical practice, . % of surgeons said they would use ppe in all cases, . % would prefer open surgery, and . % would use filters for de-sufflation. more evidence was sought by . % of surgeons to understand safety practices in future (fig. ) . half the surgeons ( . %) claimed covid- rapid antigen test had false negative rate of up to %, while . % claimed high false negative antibody rates are seen in first week of infection. when asked to select top three areas where adequate information is lacking on covid- for surgeons, most surgeons selected future of surgery in covid era ( . %), safety in laparoscopy ( . %), and safety of staff ( . %) (fig. ) . for sources of covid- information, . % utilized internet as a medium, . % utilized television, while . % utilized directives given on government/national body sources. financial impact a drop of more than % of their monthly income was experienced by % surgeons, while % faced - % reduction. subgroup analysis revealed surgeons working in private hospitals had significantly (p = . ) greater reduction in income, compared to surgeon in government set up (fig. ) . one third ( %) of respondents owned a hospital and were expecting a monthly financial liability of . million rupees ( , us dollars). covid- has led to significant worldwide change in surgical practice. our survey showed that practice of majority of surgeons in india has been drastically affected by the covid- pandemic. as of april , at a.m., over , cases were confirmed positive cases in india [ ] . fig. distribution of open and laparoscopic surgical practice prior to lockdown outpatient consultations and non-emergency surgeries have declined from over cases/day and surgeries/ month to almost zero cases in this lockdown period. spinelli [ ] reported that most outpatient clinics were suspended in italy, and scheduled patients are called beforehand by hospital administration, asking for specific symptoms in the previous weeks (for example, fever or cough), or direct exposure to covid- -positive individuals. in such cases, the patient was asked not to come to the hospital and the visit was postponed. a survey on ophthalmology practice in india by nair et al. [ ] showed the . % of the practicing ophthalmologists in india were in total lockdown. while the clinicians themselves may be available, the unavailability of managerial, administrative, nursing, and other support staff may pose logistical and operational challenges in running a health care facility during covid- pandemic. surgeons are at dual risk of exposure in their practice, namely, both from the outpatient clinics and operating room. our survey showed that nearly % surgeons have taken hcq as chemoprophylaxis. a systematic review by shah et al. [ ] showed an absence of robust in vivo evidence to support the role of hcq in prevention of covid- . but the national task force for covid- constituted by indian council of medical research (icmr) on march , , recommended hcq for prophylactic use in asymptomatic healthcare workers (hcws) involved in care of suspected or confirmed patients of covid- (https://www.mohfw. gov.in/pdf/advisoryontheuseofhydroxychloroqu inasprophylaxisforsarscov infection.pdf). when hcq administration is considered for a covid- patient or suspect, efforts should be made to advise high-risk individuals to have a baseline ecg recording [ ] . after the pandemic is under control, it is unclear on the extent of precautions that would be required to be followed by surgical and operating room personnel. when asked about future concerns, most surgeons mentioned regarding the future of surgical practice in covid era ( %), safety in laparoscopy ( %), and safety of staff ( % fig. comparison of daily outpatient consultations (opd) and monthly elective and emergency surgeries prior and postlockdown need for national and international guidelines for addressing these issues. stahel [ ] has provided an algorithm based on elective surgical indications and predicted proper perioperative utilization of critical resources, including the consideration for intraoperative/postoperative blood product transfusions, estimated postoperative hospital length of stay, and the expected requirement for prolonged ventilation and need for postoperative icu admission. prior to covid- lockdown in india, . % surgeons in our survey mainly did laparoscopic practice. according to a study by tuech et al. [ ] , caution is required when performing laparoscopy because of the risk of aerosol release and subsequent risk of exposure to operating room personnel. the main risk comes from the possible presence of pathogens in the peritoneal cavity. the aerosol released into the theater during surgery from ports or after the operation (de-sufflation of abdomen) may contaminate personnel and equipment and surfaces in the room via airborne particles [ ] . in our survey, . % claimed they would use ppe in all cases, . % would prefer open surgery, and . % would use filters for de-sufflation, while . % stated more evidence was required. despite guidelines coming from various national and international surgical societies, there is still a major uncertainty about what safe practices are to be adopted. our survey reported that % of surgeons relied on internet as a premium source of covid- information. currently, the vast diversity of information available through the internet, including unverified malicious information, can spread quickly and can misguide healthcare workers (hcws). health authorities and scientists have warned that widespread misinformation about covid- is a serious concern causing xenophobia worldwide [ ] . another concern on surgical practice is the economic impact of the pandemic. our survey reported % surgeons experienced a % or more reduction in their income, and the duration of this scenario is uncertain. in a recent survey conducted by irish dental association (ida), which involved dentists, it was reported that one-fifth of the dentists have closed their practices (temporarily or permanently). in addition, around threefourth of the participants are expecting a financial loss of over % amid covid- outbreak [ ] . a limitation of the study was that covid has affected different cities and states in india with variable intensity; hence, the perceptions of the responders will be limited. our survey highlights the need for more information on future of surgical practices, to make surgery safe in the times of the pandemic. the existing lockdown has had a major impact on routine surgical practice and will require dedicated efforts for resumption of "new normal" in future of laparoscopic surgery. conflict of interest the authors declare that they have no conflict of interest. note from the editors: world health organization declares novel coronavirus ( -ncov) sixth public health emergency of international concern who director-general's opening remarks at the media briefing on covid covid- : india imposes lockdown for days and cases rise icmr testing update th covid- pandemic: perspectives on an unfolding crisis effect of covid- related lockdown on ophthalmic practice and patient care in india: results of a survey a systematic review of the prophylactic role of chloroquine and hydroxychloroquine in coronavirus disease- (covid- ) ) c a r d i o v a s c u l a r r i s k s o f hydroxychloroquine in treatment and prophylaxis of covid- patients: a scientific statement from the indian heart rhythm society how to risk-stratify elective surgery during the covid- pandemic? strategy for the practice of digestive and oncological surgery during the covid- epidemic severe acute respiratory syndrome coronavirus (sars-cov- ) and corona virus disease- (covid- ): the epidemic and the challenges scale of dental collapse highlighted in survey publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -gy f oyt authors: shetty, mamatha; brown, thelma alfonse; kotian, mohan; shivananda, p. g. title: viral diarrhoea in a rural coastal region of karnataka india date: - - journal: j trop pediatr doi: . /tropej/ . . sha: doc_id: cord_uid: gy f oyt abstract. a total of children below years of age admitted to the kasturba medical college hospital manipal karnataka (south india) were investigated over a period of months to determine the aetiologkal role of viruses in acute diarrhoea. viral aetiological agents isolated were rotaviruses in ( per cent) cases, adenoviruses in ( per cent) cases, corona virus and astroviruses in two ( per cent) cases each. non-viral isolates were cryptosporidium and salmonella typhimurium in two cases each, and entamoeba histolyticaand and shigella flexneri in one case each. in many developing countries nearly two-thirds of diarrhoea used to be of unknown aetiology. the introduction of electron microscopy for the examination of faecal samples led in the s to the discovery of a number of viruses which may cause diarrhoeal disease in man and animals. " in view of the recent recognition of some viral aetiological agents of acute infantile diarrhoea, we conducted the present study to identify viruses as the causative agents of infantile diarrhoea in manipal, a place in coastal karanataka (south india). one-hundred-and-six children aged below years, suffering from acute watery diarrhoea of less than days' duration who attended the out patient clinic of paediatric dept of the kasturba medical college hospital, karanataka, south india were included in the study. of the children, ( per cent) were less than years old, ( per cent) were below year, and the remaining five ( per cent) were between and years old. the stool specimens were also tested for cryptosporidium; other intestinal parasites, and for bacterial pathogens like salmonella, shigella, and vibrio cholerae by previously described methods. ' the stool samples were frozen and stored at - °c for viral testing by electron microscopy at the liverpool university, london. the stool samples were processed for the detection of cryptosporidium by modified ziehl-neelsen staining, sheathers sugar flotation technique, and also by phenol-auramine staining.* detection of rota virus was done by slide latex agglutination test as per the method advocated by the manufacturers (mercia diagnostic ltd, england). cultures showing typical biochemical reactions favouring salmonella, shigella, and vibrio cholerae were confirmed by agglutination with specific antisera. the specimens were also examined by both direct and concentration method for parasitic ova and for fungal isolation. of the total stool samples received, viruses were detected in samples ( per cent). they were identified as rotavirus in ( per cent) cases, coronavirus in two ( per cent) cases, adenovirus in three ( per cent) cases, and astrovirus in two ( per cent) cases each. fifty control infants, without diarrhoea during last weeks served as controls. among the control group, a single adenovirus was seen in the stool sample of a -year-old child. clinical picture of viral diarrhoea was characterized by a high frequency of vomiting, fever, and respiratory symptoms. in six infants, vomiting was the first symptom preceding diarrhoea (table ) . table shows the enteric pathogens (viral and non-viral) isolated from cases of suspected viral diarrhoea. in our study, rotavirus was isolated in children in the - -month age groups. coronavirus, adenovirus and astrovirus were isolated in children between and years of age group. salmonella typhimurium was isolated from two infants below months and a single isolate of shigella flexneri in a -year-old school-going child. frequency of detection of viruses in stool samples were high in winter months (december to february) or in the cold wet seasons than in the dry. diarrhoeal disease is perhaps one of the most important causes of sickness and death among infants and children in developing countries like india. seasonal characters such as prevalence in winter months supported the diagnosis of viral disease. rotaviruses are reported as the commonest cause of acute non-bacterial gastroenteritis. " rotavirus enteritis is generally a disease of infants and young children and appears to have a worldwide distribution. it is common in children of - months old with a peak incidence at - months. rotavirus is responsible for - per cent of all cases of severe watery diarrhoea in young children. in the past two decades, the importance of rotavirus as a cause of illness and mortality has been clearly documented and substantial progress has been made towards developing vaccines to control this agent. enteric adenoviruses are well established as respiratory viruses and are second to rotavirus as the most common cause of pediatric viral gastroenteritis. it is found to be common below years of age, particularly during the first year of life. serotypes of adenovirus responsible for diarrhoea are , , , , and . diarrhoea is often protracted, but vomiting and fever are less prominent than with rotavirus. astrovirus were first associated with gastroenteritis in in a report by macheley & cosgrove who visualized astroviruses on the electron microscope. astroviruses are found to produce clinical findings similar to those caused by rotavirus infection, but dehydration is uncommon here. the recent development of an enzyme-linked immunoassay using monoclonal antibodies has enabled the rapid detection of antigen common to all five serotypes in the stool. they have not been firmly established as a cause of gastroenteritis in humans because of the lack of controlled studies and the small number of patients studied. astroviral disease is most frequent in children from infancy to years of age." coronavirus have also been associated with diarrhoeal illness with the electron microscopic demonstration in faeces. the virus is seen both in ill and well patients. its causal relationship to ge is still questioned by many investigators. appreciation of role of viruses in childhood diarrhoea should lead to a decrease in the wasteful use of antibiotics and a greater emphasis being placed on oral rehydration in the management of the condition. viral diarrhoea is not uncommon in india, but very few reports have been published so far. this may be attributed to the fact that diagnostic centres possessing an electron microscope for detection of viral aetiological agents are very few in india. despite the large amount of investigative work carried out in viral gastroenteritis, an understanding of the natural history and epidemiology of this disease is still lacking. practically all the patients in our study are from rural areas where the people have been in close contact with nature and animals. moreover, this rural population is exposed to unprotected drinking water obtained from open wells, puddles, and streams. sporadic outbreaks of gastroenteritis and diarrhoea along with other water-borne diseases have been reported in this geographical area. ' as regards viral diarrhoea, no reports have been so far published from coastal karnataka in india, and further studies are indicated. shigellosis is one of the commonest causes of morbidity and mortality due to dysenteric illness in developing countries. it is evident from the epidemic of shigelia dysentry reported from west bengal, india. - the disease is worldwide in distribution and affects all the age groups. the reported incidence of shigellosis varies from - per cent. " sigmoidoscopic and histological features have been studied in adults, but not in the pediatric age group. epidemic viral gastroenteritis viral gastroenteritis identification of enterobacteriaceae manual for identification of medical bacteria comparison of sedimentation and floatation techniques for identification of cryptosporidium species oocytes in a large outbreak of human diarrhoea bacteria, parasitic agents and rotavirus associated with acute diarrhoea in hospital inpatient indonesian children viral diarrhoeas in childhood rotavirus, the first years importance of enteric adenovirus and in acute ge in infants and young children astrovirus as a cause of ge in children astrovirus associated ge in children human viral gastroenteritis viral diarrhoea rotavirus and bacterial enteropathogens causing acute diarrhoea an investigation of cholera outbreak in raipur district key: cord- -xad zht authors: kumaravel, santhosh kumar; subramani, ranjith kumar; jayaraj sivakumar, tharun kumar; madurai elavarasan, rajvikram; manavalanagar vetrichelvan, ajayragavan; annam, annapurna; subramaniam, umashankar title: investigation on the impacts of covid- quarantine on society and environment: preventive measures and supportive technologies date: - - journal: biotech doi: . /s - - - sha: doc_id: cord_uid: xad zht the present outbreak of the novel coronavirus sars‐cov‐ , epicentered in china in december , has spread to many other countries. the entire humanity has a vital responsibility to tackle this pandemic and the technologies are being helpful to them to a greater extent. the purpose of the work is to precisely bring scientific and general awareness to the people all around the world who are currently fighting the war against covid- . it's visible that the number of people infected is increasing day by day and the medical community is tirelessly working to maintain the situation under control. other than the negative effects caused by covid- , it is also equally important for the public to understand some of the positive impacts it has directly or indirectly given to society. this work emphasizes the various impacts that are created on society as well as the environment. as a special additive, some important key areas are highlighted namely, how the modernized technologies are aiding the people during the period of social distancing. some effective technological implications carried out by both information technology and educational institutions are highlighted. there are also several steps taken by the state government and central government in each country in adopting the complete lockdown rule. these steps are taken primarily to prevent the people from covid- impact. moreover, the teachings we need to learn from the quarantine situation created to prevent further spread of this global pandemic is discussed in brief and the importance of carrying them to the future. finally, the paper also elucidates the general preventive measures that have to be taken to prevent this deadly coronavirus, and the role of technology in this pandemic situation has also been discussed. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. an unprecedented outbreak of mysterious etiology pneumonia, which occurred in december , has taken the whole world to a state of sorrow and worry about the future. the novel coronavirus (covid- ) is a respiratory illness and its outbreak primarily originated from wuhan, china. the epidemic is found to be caused by a zoonotic transmission event associated with a wide seafood market and soon became transmission from human to human (zhou et al. ). mostly the virus affects animals only, but the covid- virus is able to mutate into new forms that are immune to the vaccine. despite various efforts taken by every country like global containment, travel restrictions, and treating the infected person, the incidence of covid- continues to rise at a tremendous rate. at the same time, the lockdown has also made some impacts on human society such as negative psychological effects due to quarantine, loss in the economy of the world. but there are also positive aspects like reduction in pollution due to less movement of vehicles and closure of many industries. covid- is identical to coronavirus with severe acute respiratory syndrome (sars) and coronavirus with middle east respiratory syndrome (mers). this is also known as coronavirus (sars-cov- ) severe acute respiratory syndrome pneumonia. it's confirmed that the sars-cov- ( fig. ) originated by nature itself by comparing the available genome of the coronavirus strains said by kristia andersen, ph.d., an associate professor of immunology and microbiology at scripps research (science daily a). coronavirus is a big family of severe respiratory illness, first it was found in at china as sars and its second outbreak occurred in in saudi arabia as mers (science daily a). the coronavirus with spike protein-rbd (receptor binding domain) portion is the important part of the virus that has been evolved and binds to the cells and then cleaves the site of contact where the virus enters the human cells (science daily a). the articles revealed that the covid- is a group of beta-coronavirus and this is mutated from bat coronavirus hku - which is the ancestor of covid- . this mutant virus interacts strongly with the human ace receptor. the researchers state that the sars-cov- shares less than % nucleotide identity and has . % similarity genes of the previous sars-cov (qamar et al. ) . the transmission of sars-cov- is presented as in (fig. ) . the genome of sars-cov- is . % similar to the bat cov ratg and shares its identity from sars-cov . it is known that the main cause of this virus has started from bats and the virus is mutated to affect the humans and it is identified that there are six coronaviruses which affect the human body and some of them are α-covs hcov- e and hcov-nl , which are of low pathogenicity and cause mild respiratory symptoms. the covid- is a respiratory disease that spreads at a maximum rate through droplets of the infected people through the air (world health organisation a). the coronavirus is mutant by the previous process; it has been continuously spreading between the humans, rapidly through many modes of transmission they are as follows: • cough or sneeze by the infected person. • through close contact with the victims by touching the nose, eyes, and mouth. • the transmission of droplets occurs within m. • the transmission can also happen by indirect means such as handling the instruments of the infected person, for example, stethoscope, thermometer (world health organisation a). the affected persons were observed with common symptoms like cough, fever and in addition to it, some were noticed by muscle soreness, headache, dyspnea, and fatigue. thoracic radiology and ct (computed tomography) are the best evaluations of the infection covid- (bernheim et al. ) . also, most of the positive cases are asymptomatic, they are not aware that they are carrying the virus to spread it on. the world statistics of infected cases increased to , , , total deaths climbed to , , , and recovered cases were , , by th july (worldometers a) . in india, the total number of cases was , , , death cases were , and the recovered cases were , , as on july th (worldometers, a) . the fatality rate on july th, was estimated to be . % and it is calculated by (total deaths/(death + active cases)) (qamar et al. ) . the observed spread of covid- is more rapid than the calculated values. the number of death cases all over the world increased about times from march th till march th from deaths to , death cases(see fig. ). covid- is a deadly disease that had no mercy on the pregnant women and even the infants inside the womb of the mothers during this pandemic. the who (world health organisation) has said that the covid- affected pregnant women may die due to the infection and may spread the disease directly to the foetus and neonate. after testing the affected women who gave birth to infants, the reports state that the babies were healthy and the women were tested negative for the virus after various effective treatments . the infected patients were given chloroquine phosphate to block the covid- infection in low micromolar concentrations. china has tested the safety and efficacy of the chloroquine that can be used to treat covid- in ten hospitals . the reproductive rate of covid- is ranging from . to . and the average reproductive rate is . and the estimates were calculated by different personnel in different methods (liu et al. a, b) and in india, the reproduction rate of coronavirus is estimated to be . (india's covid- ro value ). the purpose of this review is to convey the impacts on society due to the pandemic and also how to tackle this pandemic situation with the available technologies. this review shares the knowledge about the technologies that help out the industrialists, students, and doctors to fight against and run the routine life even during the lockdown. this review would also elucidate the environmental impacts that changed the world during the quarantine of the people and the preventive measures taken by the governments for the safety of the people in the world. in this review, the knowledge regarding the importance of quarantine and social distancing is gathered first. statistics obtained from who and worldometers is used for this review to demonstrate the quarantine effect. then, it discusses the social nature of the disease. statistics on the fatality incidence derived from standard research articles have also been used here. also, the environmental effects related to the epidemic were discussed in a detailed manner. data on the condition of air quality and bird status during the lockdown scenario is obtained from online reports and journal articles. the preventive measures for covid- were also discussed. data is also obtained based on the equipment used during the lockdown process. the knowledge obtained from academic or grey literatures were helpful to carry out this comprehensive analysis. a keyword search based method was used to collect the information along with a structured process of sorting the data. in the beginning, the keywords are made to be determined through detailed discussions. the keywords used for searching the data are covid- , environmental impacts, technologies, pollution, and quarantine. the academic literatures discussed in this work here comprises of regular papers and conferences while the grey literatures discussed here contain web sources and professional studies. this analysis took google scholar, scopus, and scopus indexed extended as the most important research sites for framing the important sections of the work. when gathering the data and details, we ensured that only the peer-reviewed publications and online sites to be referred to. for this review, about articles and official web resources were studied. the articles were further reviewed to identify the most suitable papers for this analysis. finally, references from scholarly journals and references from web resources, a total of references found to be the most suitable for this work, and those were included in this review analysis. when reviewing the relevant papers, a manual procedure is followed to determine the appropriateness of the papers for this study. the systematic framework for data collection adopted in this review paper is shown in (fig. ). the spread of covid- disease was announced by the world health organization (who) as a public health emergency of international concern on th january (world health organisation b). there are currently no appropriate treatments and vaccines for this virus (wilder-smith and freedman ). also, evidence shows that much of the human to human transmission occurs during covid- ′s asymptomatic incubation interval, which will be approximately between and days (rothe et al. ; sohrabi et al. ) . therefore we rely entirely on public health strategies such as quarantine to restrict the spread of this respiratory disease. quarantine essentially involves isolating or limiting the mobility of people who have come from other countries or have been exposed to this infectious disease. in this scenario, covid- infected persons are isolated from non-infected persons and this isolation usually takes place in the hospital. by quarantine, we can prevent the human-to-human spread of disease to break the chain of transmission (wilder-smith and freedman ). quarantine facilities must be provided to infected persons who do not have an appropriate homely environment (cetron and landwirth ) . but the infected patients would also be able to transmit the disease to another person before the symptoms appear to them. the incubation time for the covid- has a median of days . so quarantine is often too late to effectively stop the transmission and control this influenza pandemic (wilder-smith and freedman ). thus, it remains unknown when the transmissibility attains its peak and how frequently pre-symptomatic cases get transformed into secondary cases. quarantine was implemented successfully to halt the transmission during the sars epidemic in (goh and chew ) . it is one of the important steps in this pandemic disease plan. the quarantine can be done to an individual or at the group level and usually, it involves restriction to the home or a particular area. during the quarantine period, all the persons should be monitored regularly for the occurrence of any symptoms. if any symptoms occur, the infected individual must be immediately isolated in a designated place with all essential treating equipment. by quarantining, the detection of cases becomes easier, so that contacts can be listed and traced out within a short period of time frame (wilder-smith and freedman ). also, quarantine includes the following benefits: • the isolation of persons prone to reported cases will avoid a large proportion of diseases and deaths relative to those without control. • there was little impact of quarantining travelers from a country with a reported epidemic to prevent infection and death. • in addition, the incorporation of lockdown with other treatment and prevention measures such as school closures, travel restrictions, and social distancing has had a greater impact on spread prevention, cases requiring critical care beds, and deaths compared with quarantine alone. so in controlling the covid- outbreak, more systematic and early implementation of preventive and control measures may be more successful (science daily b). after an effective lockdown of months, the cases in china were reduced. this can be clearly viewed in fig. . it gives a clear overview of the covid- attack and how china resolved its pandemic situation. when covid- cases are increasing rapidly all over the world, china had got slowly relieved from this infectious disease with its severe methodologies and treatments. this also shows the effect of massive lockdown in mainland china. chinese health (worldometers b) authorities have declared that the country had passed the peak of coronavirus outbreak on march th, (impact of lockdown in china ). another component to prevent transmission is 'social distancing'. this must be introduced to minimize people-topeople communication in a larger population, where individuals may be contagious but have not yet been recognized as an infected person and therefore not isolated. so social distancing of people will effectively reduce the transmission of this kind of infectious disease (wilder-smith and freedman ). this involves avoiding unnecessary travel and social gatherings. there must always be a m gap between people in public, independent of viral transmission (social distancing in uk ). social distancing is useful where community spread is suspected to have occurred, but where the relationship between the infected persons are uncertain and restrictions imposed only on individuals known to be exposed are considered inadequate to prevent further disease transmission (centres for disease control and prevention ) . social distancing includes closure of schools or office buildings, public markets, and the cancellation of gatherings. community-wide isolation is an initiative extended to the entire city, town or area to restrict human interactions, except for limited interactions to ensure that vital resources reach human beings. in the absence of medicinal drugs for this covid- disease, the only solution is that by reducing the contact of affected people and the things used by affected people are to be totally avoided (lewnard and lo ) . but implementing community-wide containment is far more complex because it involves a large number of people (rothe et al. ) . it is important to use social media wisely during community-wide containment, which provides us with an opportunity to communicate the reasons for quarantine, to provide realistic advice, to avoid misinformation and getting panic. the implementation of the above mentioned public health initiatives also includes cooperation with law enforcement officials at local and state level, and it involves checkpoints and may need legal penalties if quarantine violations occur (rothe et al. ) . a community-wide containment is currently happening in america. quarantine is one of the unpleasant experiences for those who undergo it. since quarantine includes separation from loved ones, loss of rights, confusion about the status of disease and boredom can have drastic effects (brooks et al. ). this quarantine period can extend for an unpredictable long time. the possibility of psychological and mental problems increases due to quarantine (xiao ) . the psychological negative effects include symptoms of post-traumatic stress, uncertainty, irritation, disappointment, insufficient knowledge, financial loss, and stigma. studies show that post-traumatic stress in children who are quarantined is found to be four times higher than children who were not quarantined (brooks et al. ) . many who are quarantined often experience a great degree of psychological distress and signs of disease. also due to lockdown in several countries across the world, the production of several essential commodities has been decreased. consumer goods companies are facing various problems like the absence of labour, stranded trucks, and permissions for manufacturing products (drop in production of essential goods ). the government has taken several measures to make the people stress-free. they are arranging the markets to nearby places. they are allocating funds to the poor people who are depending on money for food. they are taking several actions to make this quarantine not affect people's minds. throughout the outbreak of communicable diseases such as covid- , the limitations placed on daily behaviours as part of social distancing requirements to avoid the disease spread. the immediate response should include maintaining community shelters and community kitchens, supplying other relief supplies, stressing the need for social isolation, reporting the cases of infected people, and adhering to guidelines for treating these cases. it is significant to remember that isolation doesn't just freeze your brain with boredom. when people like those kept in solitary confinement, know their sentence is nearly up, their mood lifts again in anticipation. those who experience social isolation because of covid- can no longer get it. open, clear, and reliable connectivity is what governments and organizations should achieve the most (prem et al. ) . protect yourself, and help other people. helping others in their time of need will benefit both the individual who receives assistance and the helper. managing your mental health, psychological, and social well-being during this period is just as essential as managing your physical health. keep regular routines and schedules including regular exercising, cleaning, daily chores, singing, painting or other activities. individual approach to each other can cause significant social disruption, it is necessary to know the degree of intervention which is required to minimize transmission and the burden of disease (lewnard and lo ) . people who are living together can share many ideas to prevent this disease and also they can care for each other during this quarantine. at the same time, they should also take care of elderly people. in joint families, people will share the financial burden during this situation. they can also play with the children and always keep them engaged without feeling their loneliness. people must be sanitized and should maintain hygiene by periodically washing their hands with soap and water for at least s. ensure that your home and workplaces are regularly cleaned and sprayed with a disinfectant, with particular attention to electronic devices. there is currently no vaccine or antiviral drug for coronavirus in humans and animals. so it is important to be healthy during the -ncov quarantine period (lu ) . symptoms of prodromal -ncov infection include nausea, dry cough and malaise are non-specific (wang et al. a, b, c) . through not exchanging personal things like food, water bottles, and utensils. families can implement these improvements now. people can also use a separate room in your home that can be used to isolate the affected member from the safer ones. affected people must use a separate bathroom. in case your caretaker is sick, it is important to have the one who is really very healthy. caregivers and their care recipients will be required to work closely and also ensure that they will not be affected by covid- . the caregiver will monitor the situation and regularly inquire about the wellbeing of the other tenants (rocklöv and sjödin ). the outbreak is predicted to spread among larger sections of the society than the mers-cov (yoo ) . in this period people must utilize their time to gain knowledge by reading books via the internet. because of the coronavirus outbreak, the technology and industry have become their new best friend for people hunkering down, with a number of lifestyle options that make "social distancing" easier. many of them wish to avoid crowds; they can have restaurant meals delivered, socialize online with friends, and work remotely. lifestyle approaches inspired by the latest technologies to gain momentum as more people are motivated to work from home, as more conferences and events are cancelled. many online streaming platforms have gained more users, as people are feeling very bored during this quarantine (increase of online usage ). internet usage has been increased; more people are using mobile phones to watch the news as it is very handy and portable. to make this quarantine useful online classes were launched, which has let students learn from home and gain information. nowadays, children are great at surfing and browsing the data. they are learning to play games and handle mobile phones at a younger age. this will be useful if they are acquiring knowledge but at the same time, many inappropriate content can misguide their path. so parents must watch their kid's daily activities (web safety for kids ). they love to play online games because they cannot play outside during this quarantine. children can use the same internet for their self-development. various videos are available on the internet platform to develop their skills (omar et al. ). the internet is a blessing to the present generation as it was not available to the previous generations. it is based on how people are using the internet whether it is to be treated as a blessing or curse. the same internet is considered as a blessing in disguise as it helps people. without the internet, people will get mentally weakened by facing the four walls during this quarantine. as a result of the covid- calamity, the trend in social media has grown, with more people going online to remain linked to families, friends, and colleagues. recent research from kantar's insights and advisory company shows just how many advantages those applications gain. according to a survey conducted between and th march with more than , customers in markets, whatsapp is the social media application that earned huge attraction from the covid- perspective (rapid increase in web usage ). people are continuously using whatsapp during this quarantine. as people are required to communicate with their relatives who are in distant places they are using different kinds of communication mediums. its handling capacity has risen from an initial % rise in the earlier days of the pandemic to % in the mid-phase. whatsapp handling has increased by % for countries now in the later phase of the pandemic (rapid increase in web usage ). fatality rates were calculated by dividing the total number of deaths in persons who tested positive for sars-cov- (numerator) by the total number of sars-cov- cases (denominator) and this is expressed as a percentile in both ( fig. ) and (fig. ) (outbreak of covid- ). when societies prepare for potential covid- diseases, regardless of underlying health problems, the risks of older people and those with weakened immune systems need to be remembered. from this figure, we come to the conclusion that people with greater than or equal to years of age had the highest fatality rate ( . %) than all the other age groups. such type of people are at higher risk of severe covid- infection or even death. since fatality and extent of illness have a connection with the age factor and comorbidities from (fig. ) and (fig. ) , we must make sure that these high-risk groups of people have sufficient protection from infections and they should be subjected to early access to medical care when infected. these measures are important for improving their chances of survival (outbreak of covid- ). fatality rates were calculated by evaluating n = , it was found that confirmed cases in mainland china in both ( fig. ) and (fig. ) as of february th, (outbreak of covid- ). patients with no comorbid conditions had just . % of mortality, whereas patients with comorbid conditions had much higher rates. so it is found that people, who are older, with higher sequential organ failure assessment (sofa) score and elevated d-dimer at admission, were at high risk for death due to covid- (zhou et al. ). the case fatality rate is considered as a great tool to express the fatality rate (spychalski et al. ) . covid- infected persons are identified by reverse transcriptase polymerase chain reaction (rt-pcr) testing. this method is used to test the patients on the throat swabs (onder et al. ). but it is reliable only in the first week of covid- disease because after the first week it slowly starts to disappear on the throat and begins to multiply in the lungs. after the second week, the suction catheter is used to collect samples from the deep air breath of the affected person. due to this pandemic covid- spread, this transition has brought some unforeseen consequences in the environment. compared to the last year, emission rates in many countries have fallen gradually. this shows how the environment is affected by regular day to day activities. this is considered as one of the best positive impacts of the quarantine during covid- . so the environmental impacts of covid- are seen in various forms of pollution, the condition of birds and animals, and the disposal of harmful medicinal waste. the coronavirus outbreak had led the world to shut down many cities, companies, and industries to ensure the safety of the workers. this had a great impact on the environmental changes in the quality of air, water bodies, etc. cleaner air has saved several lives in the last few months. there was a decline in the level of air pollution because of countries that are imposing strict quarantine and travel restrictions, the unintended decline in air quality from the virus outbreak is only temporary (british broadcasting council ). the long-term impact of the coronavirus pandemic on the world will depend on how countries respond to an economic crisis. at the end of november , delhi, a city in india was found to have a bad or unhealthy quality of air. data intelligence unit (diu) reviewed the central pollution control board (cpcb) and the aqi (air quality index) bulletin of delhi. the -h average aqi (november rd, pm to november th, pm) showed that jind in haryana had analysed the most polluted air in cities. the average aqi at jind was and aqi of delhi was at (polluted cities ). during the period of quarantine, the air quality of delhi increased drastically and the aqi dropped to from , this shows that the environment has a good impact due to the coronavirus outbreak (improvement of air quality ). as the vehicle's movement has reduced during this quarantine, horn usage also decreased. generally, unnecessary horn sounds will irritate people. this has reduced very much. birds' sounds are heard more than any other sound during this lockdown. birds are enjoying nature on their own by tweeting and chirping (natural effect on this pandemic ). sound which is unnecessary and higher than the audible frequency level is considered as noise. the entire city soundscapes are reduced, which may be pleasant to all the living creatures. the noise reduction helped the people who have high blood pressure and the disruption in sleep. many people started to recall their peaceful childhood days because at that time vehicles were less (natural effect on this pandemic ). due to the shutdown of industries, the noise level has reduced to a great extent. if we follow the standards of transportation and reduce unnecessary noise, we can make this globe a pleasant and peaceful place to live in the near future too. water pollution has also decreased much, this will lead to an improvement in the purity of freshwater sources. the famous water bodies such as ganga and yamuna in india have seen much improvement in freshness and its purity during the lockdown of the entire country (impact on water bodies). these rivers are the two important freshwater sources, these should be protected. freshness and purity should be maintained (water quality improvement during the lockdown ). due to the reduction in transportation of oil and goods via oceans, the chances of pollution of water like spilling of oils and waste into the ocean is reduced. (effects of water pollution ). many countries now have biomedical waste management regulations, the central pollution control board (cpcb) guidelines have been issued to ensure the scientific disposal of the waste generated while people research and treat covid- patients. biomedical waste is created during diagnosis, care, immunization of humans, animals or research, etc. (biomedical waste regulations ). biomedical waste disposal regulations show how the waste produced during human diagnosis, treatment or immunization should be disposed of (hegde et al. ). the waste consists of human skin, blood-contaminated products, body fat, and blood or body fluid pollution of the bedding. sacks of blood, needles, syringe or all other sharp items infected (hegde et al. ). for isolation wards in which covid- patients are quarantined, it is noted that double-layered bags can be used as a precaution to capture waste in addition to regulations on biomedical waste to ensure adequate intensity and no leakage (guidelines for waste disposal ). across a number of nations, when quarantine roll calls, people will spend more money on movies, social media, drama, and books. nonetheless, nature does its thing and the people are experiencing an unforeseen quarantine result. in countries such as japan, italy, and thailand, animals were observed roaming in the streets because of human absence. due to quarantine both the birds and animals are feeling free to roam outside, the roads are completely empty there is no rush as normal days. it is considered as the natural environmental change for both the birds and animals (freedom of animals ). manufacturing products use energy and natural resources which creates pollution and waste production, some wastes like plastic bags and bottles in rivers, lakes which lead to negative consequences for endangered species and other animals. now due to the covid- pandemic situation birds and animals are feeling completely happy (freedom of animals ). although there are no exact vaccines for treating covid- as of now, some methods of treatment or antiviral drugs have been effective in curing the patients. so to get rid of quarantine or to get discharged from hospital, the following conditions have to be met: • body temperature is supposed to be normal for longer than days. • it is important to strengthen the body and overcome respiratory symptoms. • the radiological abnormalities or acute exudative lesions on chest computed tomography (ct) images must be enhanced to a greater version. • two consecutive results of rt-pcr (reverse transcription-polymerase chain reaction) should be negative and these results must be at least h apart (lan et al. ; pan et al. ). no medicinal drugs have yet been proved safe and effective for the covid- diagnosis. a variety of medicinal products have been proposed as possible research therapies, some of which are currently being tested in clinical trials during this pandemic situation which are cosponsored by who and other participating countries (world health organisation b). (table ) provides common and potential antiviral drugs. in some countries, doctors are treating covid- patients with drugs that were not approved for this disease. the use of licensed drugs for indications that are not approved by a national regulatory authority for medicinal products is marked "off label" use. table represents some of the common and potent antiviral drugs used in clinical practice previously for some of the diseases. medicinal drugs prescribed by doctors for off label use may be subjected to national laws and regulations (world health organisation b). both healthcare staff should be aware of the laws and regulations regulating their practice and comply with them. in addition, the stipulation should be made on a case-by-case basis. it is necessary to avoid excessive stockpiling and creating shortages of approved medicines that are needed to treat diseases. based on the past experience of battling the sars-cov and mers-cov outbreaks, we have discussed certain prevention approaches against covid- . chloroquine is one of the drugs tested in china for covid- . it was reported on february th, , to inhibit sars-cov- in vitro. national health commission of the people's republic of china, included this drug in the covid- treatment guidelines on february th, . according to this guideline, the recommended dose for adults is about mg twice per day and it should not be continued for more than days (wong et al. ) . also, for adults, g of chloroquine becomes lethal (riou et al. ). chloroquine is a repurposed drug that is very effective in the treatment of covid- . chloroquine is previously used as an antimalarial and autoimmune disease drug. this drug has now been identified as a possible antiviral drug of broad range (wong et al. ). this drug acts as a novel class of autophagy inhibitor, which prevents further viral replication. also, a combination of remdesivir and chloroquine was found to be effective in the treatment of covid- . hydroxychloroquine which is an analogue of chloroquine has been found to have an anti-sars-cov activity. it is also found that azithromycin added to hydroxychloroquine was found to be more efficient for eliminating the virus. the study revealed a higher proportion of people diagnosed with hydroxychloroquine and azithromycin relative to patients treated with hydroxychloroquine alone (gautret et al. ). the kabasuraneer choornam is a siddha medicine that is used to cure many types of fever, flu, and respiratory illness (ayurveda benefits ). it is specially used when there is table common and potent antiviral drugs goldhill et al. ( ) fever associated with cold, cough, and difficulty in breathing as it is used for treating various cases of flu (ayurveda benefits ). the kabasuraneer choornam contains nearly types of medicinal herbs and they are chukku (dried ginger), thippili (piper longum), cirukancori ver (tragiainvolucrata), seenthil (tinospora cordifolia), karpooravalli (anisochilus carnosus), lavangam (syzygiumaromaticum), adathodai ver (root of justiciabeddomei), korai kizhangu (cyperus rotundus), kostam (costus speciosus), akkara (anacyclus pyrethrum), vatta tiruppur (sida acuta), mulliver (hygrophila auriculata), nilavembu (andrographis paniculata), kanduparangi (clerodendrum serratum) and kadukkaithol (terminaliachebula) is found to be efficient in prevention and treatment of swine flu (natural remedies to treat swine flu ). the kabasuraneer choornam is prepared from the extract of kabasura kudineer choornam, it is added to water and heated to about - ºc till the water reduces to / th of the volume. the kabasuraneer choornam is a siddha medicine practised in india and mostly in southern india which is prescribed to increase the immunity against swine flu in (saravanan et al. ) . atleast eight of the herbs used in the preparation of the kabasuraneer choornam could neglect the replication of the virus and gives protection for the human body from covid- , said by sanjeev biomedical research centre (benifits of kabasura kudineer ). phytocompounds bind to the coronavirus spike protein or surface protein and prevent it from binding to the human cell membrane receptors that serve as a barrier until it starts to replicate. if the kabasuraneer choornam is consumed before the virus is contracted, the phytocompounds will bind to the respiratory epithelial cells and strengthen the immune system and it also prevents the virus from linking with the human cells and replicating after the person gets affected by covid- . the benefits of kabasuraneer choornam includes several phytochemical components that are responsible for antiinflammatory, antipyretic, analgesic, antiviral, antifungal, antioxidant, hepato-protective, anti-diabetic, anti-asthmatic, immunomodulatory, anti-diarrhoeal activity (saravanan et al. ) . it is said that the kabasuraneer choornam can be used against the covid- virus by siddha practitioners in india because it is a preventive remedy against various types of fever, flu and also increases the immunity of the human body (ayurveda benefits ). however, a siddha practitioner, g. sivaraman director of arogya healthcare said that this drug cannot be used as treatment for covid- and this drug is used to treat pneumonia like diseases in siddha medicine (remedy given by siddha field ). astrazeneca has joined serum institute of india (sii), the world's biggest immunization makers by the number of portions created and sold, to deliver the possible antibody in india. the human trials of oxford covid- immunization have just begun in brazil. if any of these vaccines have proved its success, then we can slowly reduce this pandemic to a normal situation (research updates on the vaccine ). some of the developers of vaccines that are in the clinical evaluation stage as on th july, are shown in (fig. ). in this section, the preventive measures for both people and medical staff given by central governments from the world health organisation will be elucidated. preventive measures should be taken otherwise, the risk of disease transmission will be more. according to the english proverb "prevention is better than cure", prevention is the best thing that we can follow, until the proper medicine or vaccination is found. the preventive measures that can be adopted to prevent human from getting covid- infection, they are as follows: • hygiene should be maintained. • % alcohol-based hand rub, liquid soap can be used by people. • avoid touching each other and maintain social distancing for m. • stay home, seek medical attention if you have the symptoms of cold, fever, and problems in respiration. follow the guidelines of the local health authority. • personal protective equipment [ppe] such as sterile gloves, face shields, aprons, sterile gloves, gowns, protective goggles, scrubs, masks (n or ffp ) must be used by medical staff. (adams and walls ). • medical staff and paramedical workers should self-quarantine themselves for alternate weeks. • doctors should sterilize themselves before and after attending the patients. • reducing the contacts with the family members during the crisis. • screening people and risk assessment should be well planned and managed. • environmental cleaning and spraying disinfectant in local areas is a must. • spreading awareness among people through online videos can be done. • overcrowding in the areas of essential places such as markets should be strictly avoided (world health organisation, c). since the covid- pandemic has forced to close educational institutions and industries, we have to depend on cloud based technologies to connect students with educational institutions and also artificial intelligence-enabled robots can prove to be helpful for many industries to work during these pandemic. without these advancements in technologies, this lockdown would be hard for individuals to cope up. individuals will feel exhausted at their home. presently, they are engaged with their movies on online streaming platforms. if there was isolation during the olden days, people would fig. technologies used during covid- ). these technologies helped mankind to invent new products like face masks (developed by d printing), ir thermometer (bio sensors) to provide safety for human beings and for the front line workers feel stressed without cell phones and media transmission. but nowadays, individuals are getting occupied with these innovations. technologies also played a vital role in data collection (artificial intelligence and big data), online classes (virtual reality) etc. some of the other technologies were also used to tackle this pandemic condition as shown in (fig. ). artificial intelligence has a feasible contribution in fighting against covid- as well as existing constraints. in terms of life and economic destruction, the risk of a pandemic is terrible. improving artificial intelligence and data analytics technologies have evolved continuously over the last decades. because of the lack of evidence, artificial intelligence has not been impactful against covid- yet. overcoming these constraints requires careful consideration of data privacy and public health issues as well as the interaction between human artificial intelligence. it will be necessary to gather diagnostic data from infectious people to save lives and reduce the economic havoc due to containment (mccall ). the goal of artificial intelligence is to deploy decision support using predictive analysis. artificial intelligence can help people by predicting the case of covid- which helps them to identify persons affected and take actions in a faster manner. patients with confirmed n-cov infection suffer from respiratory illness, fever, and cough. incubation time ranges from days to weeks (carlos et al. ) . supervised training is a practice and learning process. accordingly, the computers are equipped with sample data and then used for predicting new sampling of the results. the vast collection of health data from a wide range of outlets types include genome screening, electronic health records (ehr), and wearables contributed to biomedical big data (elavarasan and pugazhendhi ) . artificial intelligence was praised for its possible contribution to the development of new medicines. artificial intelligence helps in finding new drugs and a covid- vaccine. artificial intelligence creates an aid clinical preliminaries which are ought to perceive the ailment in patients, distinguish the quality targets and foresee the impact of the particle structured just as the on-and off-target impacts (mak and pichika ) data is used to run artificial intelligence models; it helps to handle the pandemic more efficiently. early warning is a much better way to cure the pandemic. a basic urine test is expected to assist clinical experts in recognizing future decompensation of covid- disease (early warnings ). the case of the artificial intelligence model based in canada, blue dot, has already become legendary. this shows that blue dot, a fairly low-cost artificial intelligence platform. it can predict infectious disease outbreaks in humans (predetermining artificial intelligence ). blue dot predicted the outbreak of the infection by the end of , according to accounts, where it identified the top destination cities where wuhan passengers will arrive. this warned that those cities may be at the forefront of the disease's global spread. patients with suspected -ncov were admitted and quarantined, and samples of the throat swab were obtained and the same data is sent to the -ncov chinese centre for disease control and prevention using a quantitative polymerase chain reaction test and the surveyed data was very much useful for the analysis of the covid- disease (chang et al. ) . artificial intelligence can be used to monitor and predict how covid- will spread over the period of time. for instance, a dynamic neural network was built to predict its spread following a previous pandemic, zika-virus of . algorithms were formulated to predict seasonal flu are now being retrained on new covid- data at carnegie mellon university. the atypical case of pneumonia, caused by a novel coronavirus ( -ncov), was first documented and confirmed on st december in wuhan, china ). fast and accurate covid- diagnosis will save lives, limit disease spread, and generate data on which to train models of artificial intelligence. artificial intelligence may provide valuable feedback in this regard, in particular with a diagnosis based on images (predetermining artificial intelligence ). according to a recent study by researchers working with un global pulse of artificial intelligence applications against covid- , studies have shown that artificial intelligence can be as reliable as human beings, can save the time of radiologists and diagnose faster and cheaper than regular covid- tests (predetermining artificial intelligence ). the field of biology and modern medicine is making more tremendous upgraded technology which is becoming data-intensive, by using these data and the field of deep learning technology is more helpful in treating the patients (ching et al. ). deep learning is useful when a problem arises with a patient of a particular disease, the data which is input to the computer represents the disease in the patient, the computer analyses many logical symptoms in the patient and the treatment is given according to the results of the computer (hinton ) . machine learning has proved effective in many analytical areas of risk. machine learning probably matters in three major areas, with clear medical risk (machine learning in healthcare ). • danger of infection what is the risk of having covid- for a specific person or group? • risk of severity what is the risk of extreme covid- symptoms or complications requiring hospitalization or intensive care of a specific patient or group? • result probability what is the probability of the ineffectiveness of a medication for a specific person or group? theoretically, learning by computer can aid in detecting all three risks. although it is still too early to get some covid- -specific machine learning research completed and written, early findings are very positive. we can also understand how machine learning can be used in related fields and how it can assist with covid- risk prediction (machine learning in healthcare ). early statistics indicate that important risk factors that decide the probability of a person contracting covid- include: sex, pre-existing illnesses, general grooming practices, social behaviour, amount of interaction between individuals, duration of interactions, place, and climate, socioeconomic status(machine learning in healthcare ) (see fig. ). machine learning has the potential to support clinicians' work processing and management of large amounts of medical data contained in electronic health records and used in clinical applications which includes recognizing high-risk patients in need of icu, the identification of early signs of lung cancer, determination of patient's respiratory status from x-rays in the chest, such deep learning approaches employ neural networks to predict the input-output data relationship. another potential feature of ml is its ability to reduce the cost of operation and product, automate, and enhance customer support (elavarasan and pugazhendhi ) . deep learning works more similar to machine learning where it can be separated into two types as "supervised applications-where the predicted goal is achieved accurately and unsupervised applications-where the goal is to summarize the data outcomes and identify the patterns of the outcome data" (hinton ) . deep neural network (fig. ) is learned and trained over a large set of data and they work on the multiple layers for the specified results and they are more accurate because they are learning from the previous outcomes of the data obtained (healthit analytics ; hinton ). machine learning and the rapid advancement of deep learning based technologies have demonstrated their ability to transform these big data in biomedical applications to a functional form. in general, ai and ml are introduced at the healthcare has increased patient safety, and successful treatment, and healthcare costs also has got reduced (elavarasan and pugazhendhi ) . when data on covid- is collected and analysed by a deep learning network it would save as many lives as possible and the computers would suggest the doctors for the treatment. deep learning helps in the classification of each and every task by the use of multiple layer strategy in the patients with the risk abnormalities found earlier with the same symptoms and by means of medical imaging (table ) (switching healthcare ). deep learning is a key technology where predictive healthcare systems can be developed, which can have access to a billions of data of the patients for the next generation (hinton ) . table provides a list of deep learning data and its uses in diverse medical fields and where data can be gathered and therapies provided to patients. there are several applications used for helping the government. some of the important apps used in india to control the pandemic condition is shown in (table ) and some of the top applications used in the world to tackle the covid- is shown in (fig. ) . these applications give clear monitoring status, feedback and also give guidelines to be followed by the people. it gives several updates about contact tracing which will be very much useful to the people. these applications utilise the telephone's bluetooth and gps capacities. it will track the affected persons by utilizing bluetooth. (hinton ) types of data application references electronic health records • it helps in indicating different population subtypes and to differentiate symptoms of gout and acute leukemia from uric acid lasko et al. ( ) • assigns the diagnosis process for the patients by previous clinical status liang et al. ( ) • to know about heart failure and chronic pulmonary illness in advance cheng et al. ( ) • advanced treatments over the onset of diseases by predicting from lab results razavian et al. ( ) • end-to-end method for forecasting after discharge unplanned readmission nguyen et al. ( ) clinical imaging • advanced imaging using magnetic resonance imaging (mri) scan to detect alzheimer's disease brosch and tam ( ) • it is used to meet the requirement of people during this pandemic gizbot ( ) these applications will also utilize a gps to track the record of an individual. these data will be updated on the mobile application if any person is tested with positive covid- . this will be done on the basis of an appraisal review of every individual. in such infected cases, the records will be transferred to the servers (tracking apps for covid- ). table provides the information about the list of applications and their functionality developed by the indian government to handle the pandemic condition. the internet of things (iot) could be a well-defined platform of interconnected computing strategies, computerized, and mechanical gadgets having the capability for transmission of information over the defined network without having any human inclusion at any level (singh et al. ). in addition, no research in the current literature attempts to analyze the position of emerging technologies like iot. it is a well-developed scheme of interconnected computing techniques, physical and mechanical devices with data communication capabilities over the specified one. network without any degree of human involvement (singh et al. ) . iot is a way beyond concept which develops a general architectural history, which allows for integration and fig. top applications used in the world to control the pandemic (covid watch ), (central and eastern europe legalblog ) , (immuni ) , (covid- smartphone applications ) fig. working of iot in health care domains which minimizes the contact between the affected individuals and the frontline workers effective exchange of data between needy persons and service providers. in the latest problematic pandemic scenario, the number of globally infected patients are growing day by day, and there are a large number of the sufficient and well-organized facilities provided with the methodology of iot. in addition iot already is also used for the purposes being demanded in various domains in healthcare (mohammed et al. ) (see fig. ). plasma is the fluid piece of blood that is gathered from patients who have recouped from the covid- . this disease is brought about by the infection named sars-cov- . covid- patients create antibodies in the blood against the infection. antibodies are proteins that may help to fight against the contamination (food and drug administration ). individuals who have completely recuperated from covid- in the last days are urged to consider giving plasma, which may help the lives of different patients. covid- based healing plasma should possibly be gathered from recuperated people in the event that they are qualified to give blood. people should have an earlier analysis of covid- recorded by a research centre test and meet other contributor models. people must have a total goal of manifestations for the past days before plasma donation. a negative lab test for dynamic covid- ailment is not required for plasma donation (food and drug administration ). there are many technologies that are used to reduce the effect of this pandemic, some of them are as follows, big data investigation helps in studying the infected individuals very effectively. these frameworks can control the development of the pandemic and also aids in observing individuals who are isolated. it also keeps an eye on individuals to check whether they are infected or they have been in contact with a contaminated individual. (management during pandemic ). self-driving vehicles, automated drones, and robots would be able to avoid human interaction. automated vehicles can be used to move impaired people to and from the medical service offices, without bargaining individual's lives. robots can be utilized in the circulation of food, warming, medical clinic sanitization, and road watching. these technologies help people who are facing many difficulties during these lockdown period (management during pandemic ). currently, digital learning is gaining its popularity and also it the trend which is heading forward in modern educational activities, models, and processes. this will be the big moment for the online learning and educational approaches that will be re-planned much like the businesses that are going to operate remotely (work from home) because of the covid- . the present scenario has pushed scholars and educational institutions towards online learning plans and technology (online education ). e-learning training is very useful in this pandemic situation because it is instantly accessible and it also offers flexible scheduling for the training (computer aided elearning team ). since virtual classrooms are important for student-faculty interaction, video conferencing platforms like google meeting and webex are getting used extensively by many educational institutions. also, software like proctorio, a google chrome extension that monitors whether students take their online exams regularly, which has helped the educational institutions to keep track of the students, who take up their online exams regularly. so, the learning has become digitized and this will help us to get rid of the use of paper and costly textbooks (online education ). these online classes offer a highly effective learning atmosphere for students so that they can learn from their respective locations (computer-aided e-learning team ). such initiatives and steps taken by the educational institutions are important because extended school closure and home isolation during a pandemic could have negative effects on the physical and mental health of children (wang et al. a, b, c) . with more than million web clients, india is the second biggest online market among all countries, positioned distinctly behind china. it was evaluated that by , there would be more than million web clients in the nation. regardless of the huge base of web clients, the web entrance rate in the nation remained at around % in . this statistics imply that around half of the . billion indians started using internet accessibility that year. there has been a steady increase in web accessibility but it is contrasted with only the past years, when the web entrance rate was around % (statistical usage ). though india is the second biggest online market among all countries, some children in rural areas are lagging behind, without the internet facility. this would rule out a large proportion of children from rural areas in internet usage (online education ). since the confirmed cases and deaths due to covid- are rapidly increasing day by day, both medical staff and the public have been undergoing psychological problems, like depression, stress, and anxiety. also, the transmission of viruses takes place at a faster rate between people. this obstructs face-to-face psychological interventions. therefore, internet services and telecommunication helped health care professionals to provide mental health support online during the covid- outbreak (liu et al. a, b) . since epidemic contagious diseases mostly interrupt the movement of people, transportation systems, and mobility of commodity, the use of drones in this situation will relieve humanitarian aid. the use of drones and quadcopters will generally help to do certain things like (i) evaluate and analyse the infected area by aerial monitoring (ii) epidemic cargo and logistic delivery (estrada ) (iii) aerial spray and disinfection (drone technologies ). unmanned aerial vehicles are used to monitor the people, who were unnecessarily roaming in the streets. those people can be warned and sent back through this facility. disease transmission can be controlled to a greater extent and it is cost-efficient. by travelling, a high quantity of fuel will be wasted and it is not practically possible to monitor all the areas. aerial monitoring systems will be helpful for the reduction of covid- transmission (benefits of drones ). drones were used in china and dubai to spray disinfectant chemicals in public places and on vehicles for disease prevention so that the transmission mechanism gets reduced. justin gong, co-founder of an agricultural drone company said that spraying disinfecting chemicals using drones has been more effective in comparison with hand spray (drone technologies ). the use of drones is a great boon for the workers and it reduces the risk of being infected by the pandemic in the infected areas. in india, these drones are effectively used to control the spread of the disease. if the people are seen outside doing mischievous activities they would be spotted and punished or warned. drones are very much useful to monitor a highly populated country like india. otherwise, the disease transmission rate would be even higher. the covid- outbreak has shown the pathway of hygiene for people all over the world. we must learn from mother nature to give equal rights to all living beings in the world and we must uphold it as a superior sense. it is our duty to protect nature for ourselves and for future generations. the pandemic has demonstrated the world's best new technologies that can hold children up to date with lectures, courses, and more online learning and educational exams that have contributed to a landscape of modern interfacing within months. the advanced ai and machine learning systems tend to operate the industries while the whole planet is being shut down due to the epidemic and the industrial goods are already being processed by these systems. the lockdown of cities has reinforced the relationship within a family by obtaining more freedom to communicate with each other, and it has been found that the use of traditional medicines has a great influence on the society. also during the quarantine period, people have learnt a great lesson from the epidemic of a novel coronavirus, the sophisticated technology supports the community with drones disinfecting the cities, interfacing robots, and gathering data from the infected communities without transmitting the virus to the physicians. the risk of being affected is high to the workers in the frontline, also people who travelled from other countries can be quarantined for the safety of their family, and the surroundings. the people who ever recognize the symptoms can admit themselves to test them for the disease, rather than being detected at the final stage of the illness. the human race had faced many outbreaks of many contagious diseases and had 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quarantine, social distancing and community containment: pivotal role for old-style public health measures in the novel coronavirus ( -ncov) outbreak caution and clarity required in the use of chloroquine for covid- coronavirus cases daily new cases in china due to covid- world health organization (who) ( a) modes of transmission of virus causing covid- : implications for ipc precautions recommendations world health organization (who) ( b) coronavirus disease (covid- ) -events as they happen world health organization (who) ( c) prevention and control of covid- in prisons and other places of detention world health organization (who) ( d) draft landscape of covid- candidate vaccines a novel approach of consultation on novel coronavirus (covid ) related psychological and mental problems: structured letter therapy the fight against the -ncov outbreak: an arduous march has just begun preliminary estimation of the basic reproduction number of novel coronavirus ( -ncov) in china, from to : a data-driven analysis in the early phase of the outbreak clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study using deep learning for energy expenditure estimation with wearable sensors the authors thank dr.s.sivaramakrishnan ms ortho and dr. m. jayalalitha mbbs, shanthi ortho care hospital, tiruchirappalli, tamil nadu, india. they have helped us by suggesting some practical issues that are faced by the corona virus affected patients and the doctors working in the hospital during the covid- period. the inputs received has helped the authors in framing certain important sections of the paper. the authors declare that they have no conflict of interest. key: cord- -gykw nvt authors: yadav, mahendra pal; singh, raj kumar; malik, yashpal singh title: emerging and transboundary animal viral diseases: perspectives and preparedness date: - - journal: emerging and transboundary animal viruses doi: . / - - - - _ sha: doc_id: cord_uid: gykw nvt the epidemics and pandemics of a few infectious diseases during the past couple of decades have accentuated the significance of emerging infectious diseases (eids) due to their influence on public health. although asia region has been identified as the epicentre of many eids and upcoming infections, several new pathogens have also emerged in the past in other parts of the world. furthermore, the emergence of new viral diseases/infections, such as rift valley fever, west nile fever, sars coronavirus, hendra virus, avian influenza a (h n ), nipah virus, zika virus and swine influenza a (h n ) virus, from time to time is a glaring example threatening adversely both animal and public health globally. infectious diseases are dynamic and concerning due to their epidemiology and aetiological agents, which is manifested within a host, pathogen and environment continuum involving domestic animals, wildlife and human populations. the complex relationship among host populations and other environmental factors creates conditions for the emergence of diseases. the factors driving the emergence of different emerging infectious disease (eid) interfaces include global travel, urbanisation and biomedical manipulations for human eids; agricultural intensification for domestic animal eids; translocation for wildlife eids; human encroachment, ex situ contact and ecological manipulation for wildlife–human eids; encroachment, new introductions and ‘spill-over’ and ‘spill-back’; and technology and industry for domestic animal–human eids. the concepts of sanitary and phytosanitary (sps) measures and biosecurity have gained recognition globally in almost all the realms of human activities, including livestock health and production management. this chapter provides the experience gained in the control and management of a few important tads and eids along with the successes, constraints, limitations and future research needs for developing better control approaches. for wildlife-human eids; encroachment, new introductions and 'spill-over ' and 'spill-back'; and technology and industry for domestic animal-human eids. the term 'emerging disease' is used to refer to changes in the disease dynamics in the population. emerging infectious diseases (eids) are those which have moved recently into a new host or have enhanced incidences or geographic range or are caused by evolving pathogens (lederberg et al. ; daszak et al. ) . this general definition covers a range of infectious diseases of man and animals which pose a significant threat to both medical and veterinary public health. among the oie-listed diseases of viral aetiology, major changes have been experienced in the occurrence of rinderpest, peste-des-petits ruminants (ppr), foot-and-mouth disease (fmd), african swine fever (asf), lumpy skin disease and rift valley fever (rvf). of these, rinderpest presents a success story from the s to as a result of fao, oie, eu and iaea (international atomic energy agency) guided and coordinated programmes including the pan african rinderpest campaign (parc), npre and nrep in india (yadav ) , global rinderpest eradication program (grep) of the fao and other national governments where the disease was endemic. these exemplary efforts led to the historic declaration of global rinderpest eradication by the fao on june , . the terms 'exotic disease' and transboundary animal diseases (tads) are often used interchangeably. though all transboundary diseases are of exotic origin, all exotic diseases are not included in tad listing. many eids are also transboundary diseases. the tads are defined as highly contagious and transmissible epidemic diseases of livestock which have the capability for rapid spread to new areas and regions regardless of national borders and have serious socio-economic and public health consequences. nearly all diseases affect livestock, poultry, fishes and other animals and adversely impact the quality and quantity of food and other products, such as hides and skins, bones, fibres, wool and animal draft power for tilling, transport and traction. the reduction in animal production, productivity and profitability due to tads affect the human livelihood. in the present scenario of fast-increasing globalisation, tads represent a serious threat to the economy and welfare of the public and affected nations as they drastically reduce production and productivity; disrupt trade and travel and local and national economies; and also threaten human health through inferior food quality and zoonotic diseases/infections. as such, consequences of tads could have a significant detrimental effect on the economy and public health of not only the affected nations but also the whole of the world. possibly the infectious agents which cause emerging and transboundary diseases are already present in the environment and get the opportunity to cause disease under certain altered circumstances. the transmission of the infectious agent could occur between animal and human; between wildlife, human and domestic animals; or between wildlife, domestic animal(s) and human. however, the main source for maintenance and transmission of the infectious agents in nature is determined by the zoonotic pool and spill-over and spill-back mechanisms. tads have become of great concern due to the risk for national security on account of their economic significance, zoonotic nature and ever-growing threat of newer tads in future. among the tads having zoonotic manifestations, a number of infectious diseases, such as highly pathogenic avian influenza (hpai), bse (mad cow disease caused by prion), west nile fever, rift valley fever, sars coronavirus, hendra virus, nipah virus, ebola virus, zika virus and cchf, to name a few, adversely affecting animal and human health have been in the news in recent times (malik and dhama ; munjal et al. ; singh et al. singh et al. , . the direct and indirect costs due to the fmd outbreak in the uk in were assessed to be over us$ billion. over million chicken died or were destroyed in southeast asia in to control hpai (h n ). the netherlands suffered an economic loss of $ . billion due to classical swine fever in [ ] [ ] . as per the estimates of fao nearly one-third of the world meat trade was facing import bans on account of bse, hpai and other animal diseases. there is evidence to suggest that threats from tads have increased over the years. the risk of animal disease outbreaks is likely to further grow in future as the higher incomes of people in developing countries will generate more demand for animal protein and products (milk, meat, egg, chicken and fish). the number of animals raised for meat is growing rapidly. during s poultry production in east asia has increased by about % per year to double every - years. similar to tads, new human viral diseases have emerged like ebola, sars, zika, cchf, nipah and bse as well as there is the emergence of new antigenic forms or new biotypes of the existing infectious diseases, such as a hypervirulent strain of ibd in poultry in europe and highly virulent strain of newcastle disease in the usa (riemenschneider ; singh et al. ) . vector-borne pathogens, namely, bluetongue, african horse sickness, rift valley fever and west nile fever, have the potential to spread in epidemic forms. riemenschneider ( ) has deliberated over several issues relevant in the control of tads as proposed in the institute of medicine (iom) report (anonymous ) . some of the points which could be responsible for the increased threat of tads are briefly discussed below. in the present-day world, higher quantitative levels of animal origin foods, as well as faster trade, new trade routes and air travel, have led to higher risks for contracting new infections and diseases. as it is now possible to reach any part of the world within h which is less than the incubation period of most of the infectious diseases, animals or people carrying the infectious agents go undetected in want of clinical disease/symptoms. fresh commodities vis-à-vis processed foods that have witnessed an increased trade are more likely to carry the pathogens to distant parts of the world-countries and continents. recent decades are witnessing higher demands for animal protein and other nutrients through meat and meat products, milk and milk products, eggs, and fish and fish products as a result of rising incomes in the developing countries and elsewhere which leads to the intensification of production systems and overcrowding of animals. this increased production is often required in peri-urban areas, having large human populations, under suboptimal husbandry practices. in such high-production areas, disease outbreaks affect a greater number of animals at a faster rate and speed, leading to heavy economic losses. drastic control measures are taken, such as the slaughter of infected and in-contact animals followed by burning or burial is not acceptable to the society at large. for example, the mass slaughter of pigs in the netherlands in - for the control of csf virus led to objection from the non-farm population which might influence the application of the stamping-out policy as a disease control approach in future. exposure of the domestic animals to forest niches due to deforestation and transformation of tropical rainforests for livestock grazing exposes the domestic livestock to a completely new range of pathogens and vectors which previously circulated in wildlife reservoir niches only. with the domestic livestock being fully susceptible and naïve to these infectious agents, the disease spreads more rapidly and severely in want of lack of diagnostic tests and vaccines against these new pathogens resulting in heavy morbidity, mortality, trade restrictions and economic losses. nowadays many countries face prolonged civil unrests besides inter-and intracountry conflicts, which may lead to enhanced threat of tads. civil disorders are known to disrupt enforcement of quarantine and other control measures due to refugee and army deployments/movements. breakdown in the institutional support for quarantine and difficulty in gaining access to border area due to landmines make disease surveillance more difficult. inflows of more food aids for such areas also pose additional risks as the food items may have contaminants. climate change and global warming seem to be altering rainfall and weather patterns. rising temperatures in the northern hemisphere are likely to shift the distribution of insect vectors of bluetongue, african horse sickness, rift valley fever and similar vector-borne diseases. the bluetongue virus (btv) having serotypes occurs in many parts of the world. however, until recently it was never reported from europe. the sudden incursions of some serotypes into spain, italy, greece, portugal and the balkan countries since , followed by germany, and the recent incursion of btv serotype in several farms in the netherlands, germany and belgium since august as well as serotype are also believed to be due to climate change as european weather has become hotter in recent decades. the btv serotype revealed that this serotype is closest to the nigerian strain. the incursion is believed to have been caused by the importation of an infected zoo animal or an infected midge. an upsurge of rift valley fever was observed in east and west africa due to climatic changes. many factors discussed above make the tads as a serious threat to national and international security. the developing countries are usually the worst sufferers. among other factors, veterinary public health services in developing countries are usually much behind than the medical public health services. moreover, unlike human disease reporting, animal disease reporting systems are usually based on passive reporting rather than active disease surveillance. a few other factors are also responsible for greater threat due to tads, namely ( ) lack of awareness of the farmers about the high-threat epizootic animal diseases; ( ) lack of diagnostic facilities for exotic diseases, and under-reporting of animal diseases like hpai due to the fear of loss of internal and export market till the country gets infection-free status as per oie-laid-down criteria; and ( ) poor and faulty compensation schemes. in the technological advances made in today's world, there is always a real risk of deliberate misuse of certain infectious agents/pathogens by terrorists as a means of biowarfare between nations to harm the people and/or livestock, poultry and other animals. potential for pathogenic disease agents not reported previously in a country and being misused or mishandled for bioterrorism is likely to threaten the ecosystem on a large scale. even new pathogens can be engineered as novel infectious agents. the animal diseases could even be a greater threat than human diseases as these may result in significant economic disruptions, besides causing food poisoning and deterioration, and zoonotic diseases in human beings. as animal diseases get less priority than human infections/diseases in undertaking immediate disease control measures, the threat scenario with the use of animal pathogens for bioterrorism or biowarfare will have many serious consequences. some of the viruses having significant bioterror potential for humans and or animals include hpai (h n ), when an exotic viral disease strikes a country for the first time, it may initially affect one animal, few animals or a large number of animals. the strategy to be adopted for containing the outbreak will depend on the nature of the virus, speed of its spread, role of vectors, risk assessment, communication and management, response time and country legislation on disease control and prevention. thus, there is a need to develop strategic plans for the prevention and control of exotic and tad on a case-to-case basis. examples of such viral diseases from indian perspective include african swine fever (asf)‚ transmissible gastroenteritis (tge)‚ and swine vesicular disease in pigs, rift valley fever, african horse sickness (ahs), west nile fever, eastern equine encephalomyelitis (eee), western equine encephalomyelitis (wee), and venezuelan equine encephalomyelitis (vee), fmd virus types 'c', 'sat i', 'sat ii' and 'sat iii', nipah virus, hendra virus, sars coronavirus, and prion diseases-bovine spongiform encephalopathy (bse), and scrapie. institution of appropriate and timely biosecurity measures is an important instrument for the protection and improvement of animal health. breach in biosecurity due to ignorance and avoidable lapses in the adoption of timely biosecurity and biosafety measures in the management of livestock, poultry and fish minimise the risks from infectious diseases including eids and tads. breach in biosecurity in livestock management is often an important reason for the high incidence of zoonotic and other infectious diseases of animals. this is more so in case of the viral diseases of livestock and poultry. closer contact between wildlife, animals and humans and rearing of livestock and poultry in close association with people promote spread of viral and other infectious diseases which have the potential for threatening health, economies and food security around the world. the emergence of new viral diseases/infections, such as rift valley fever, west nile fever, sars coronavirus, hendra virus, avian influenza a (h n ), nipah virus, zika virus and swine influenza a (h n ) virus, from time to time is a glaring example of zoonotic disease threats adversely affecting both animal health and public health, national economies and food and nutrition security globally. due to a lacuna in the biosecurity, viral diseases like the fmd had reoccurred in countries where these had not been reported for many decades, including the uk, a developed country. biosafety and biosecurity are interrelated terms but used in different contexts. the guidelines are developed by who, fao and oie. biosafety aims at the protection of person(s) at work and the facilities which are dealing with the biological agents, against their exposure to a disease agent, and prevents unintentional exposure to pathogens/toxins or their accidental release. thus, biosafety is the application of knowledge, techniques and equipment to prevent personal, laboratory and environmental exposure to potentially infectious agents or biohazards. biosecurity, unlike biosafety, has divergent meanings in different contexts in which it is used. it deals with the protection of microbiological assets from spill-over, theft, loss, diversion or intentional release from laboratories, preventing the import of certain organisms/ toxins. biosecurity is a set of preventive measures designed to reduce the risk of intentional transmission of infectious diseases to safeguard the facilities containing sensitive biological materials with the potential of a biological weapon. in brief, biosecurity means bio-risk management. once a disease is eradicated globally, the policy for keeping the wild and vaccine strains of the virus along with vaccine stocks for emergency use and their subsequent destruction is decided by international agencies like fao, who and oie based on the recommendations of experts in the area. these include risk assessment; communication and management; quarantine of imported animals at seaports, dry ports and farm; establishment of check posts and vaccination stations at international and interstate borders for clinical surveillance; creation of immune belts at international borders; and planning and conducting structured disease surveillance including clinical surveillance and serosurveillance. biosafety and biosecurity need to be observed at all levels beginning from farm to national and international levels. for handling the most dangerous transboundary disease pathogens, bsl iii and bsl iv laboratories are required to ensure biosafety, biosecurity and biocontainment. proper zoo sanitary measures, such as quarantine; rodent and vector control; disinfection of animal sheds and premises; proper disposal of dung, urine, feed and fodder wastes; and proper carcass disposal, need to be adopted religiously for effective management of eids and tads. every country needs strict and foolproof biosecurity mechanism at its international borders as a safeguard against the entry of exotic infectious agents/diseases from abroad along with the import of livestock and other animals and their products. for example, india has contiguous and porous borders with countries like nepal, bhutan, pakistan and bangladesh, besides free trade with nepal and bhutan. since all these countries are vulnerable to tads, there is a need for regional biosecurity plan to ensure a biosecure region. it would never be possible to have a biosecure country if the bordering countries do not have effective biosecurity in place. different countries are at risk for a number of tads like anthrax, plague, glanders, lyme disease, contagious equine metritis, salmonella abortus equi, hpai virus, fmd virus (sat - ), lyssavirus, rabies, hendra and nipah viruses, west nile virus, highly pathogenic nd virus, rabbit haemorrhagic disease virus, bovine spongiform encephalopathy (bse), african horse sickness (ahs), equine encephalomyelitis (eee, vee, wee), equine infectious anaemia, chicken infectious anaemia, equine influenza, vesicular stomatitis, rift valley fever, malignant catarrhal fever (mcf) and other tses of sheep, goat and deer. biosecurity measures are required for preventing and containing the ingress of these diseases through international trade. the oie has facilitated safe trade in animals and animal products by developing effective standards to prevent the spread of animal diseases across the globe. prevention of transmission of pathogens across intra-and inter-country borders warrants devising of biosecurity measures at par with international standards. adequate infrastructure comprising check posts and quarantine facilities at seaports, airports and porous international land border are must to check the ingress of viral and other pathogens from across the borders. diagnostic facilities with trained human resource, and well equipped with instruments and pen-side diagnostic tests/kits, should be in place for ensuring the pathogen-free status of imported livestock and livestock products. biosecurity measures at national level incorporate the components of 'external biosecurity' preventing the ingress of exotic and transboundary animal diseases and 'internal biosecurity' within the country encompassing zonal, compartmental and farm-level biosecurity. regulations for animal movement through interstate borders in india are in place but need strict implementation. modern detection systems can be used for identification and tracking of animals and animal products to provide information regarding the origin of the animal, and environmental practices used in production and food safety. for effective disease prevention and control, integration of biosecurity into every operation at the farm is essential. farm biosecurity should be inclusive of both 'bioexclusion' (measures for preventing a pathogen from being introduced to a herd/ flock) and 'biocontainment'. the latter addresses the events after the introduction of the pathogen and its ability to spread among susceptible groups of animals at the farm or further spill-over to other farms. strict implementation of biosecurity at farm level has played a crucial role in preventing the spread of diseases. a suitable plan addressing important issues, such as location and layout of the farm, animal health practices in place and general management on the farm, needs to be chalked out. it should be flexible to include new knowledge, concepts and technology. a wide range of biosecurity practices have been recommended for different livestock species and production systems, both for specific infection risks or for disease prevention in general. biosecurity practices have been recommended for cattle, sheep, pig, poultry and fish production systems. general biosecurity practices and interventions that can be applicable across species and farms include: . maintaining a closed herd procurement/purchase of animals from known sources . minimising the number of animals purchased/transferred/exchanged and the number of herds from which the animals are introduced . avoiding purchases from markets or dealers . appropriate quarantine and testing of animals upon introduction or reintroduction in farm premises . discouraging farming practices such as hiring a bull or stallion and returning it after the breeding season . avoiding the introduction of biological material of uncertain health status . health and vaccination records should be obtained for all the newly introduced animals isolation/quarantine of such animals for - weeks in a separate quarantine facility should be practiced and the animals during this period should be observed for illness/symptoms and screened for important diseases before mixing with other stock at the farm. laboratory testing of appropriate samples collected during quarantine against important infectious diseases is recommended. the incoming stock can also be given vaccine against the endemic disease prevalent in the area at least weeks before release from quarantine to boost their protective immunity. animal diseases can spread from farm to farm resulting in animal sickness, death and economic losses. visitors to the livestock farm, disease laboratory, birds, rodents, vehicles, feed and fodder and other inanimate objects are often a source of infection. in addition to adverse effects on the economy, there can be negative effects on the environment and human health. the best designs are to implement effective biosecurity practices. baths by the laboratory workers after and before visiting animal farm or laboratory and putting on gum boots, disposable overall, head gear and gloves should be a mandatory requirement. all effluent from the laboratory should be pre-treated to ensure freedom from pathogens before their disposal to the environment. disinfectant foot bath for the workers and vehicles entering the farm at the gate, exclusive separate dress and shoes for laboratory and farm workers, minimum movement of the people and animals within the farm during the outbreak period, and personal health and hygiene of the staff are some of the minimum guidelines to strengthen farm biosecurity. timely, rapid and accurate disease reporting based on oie-approved diagnostic tests is a must for effective detection of the pathogen and instituting early response without giving much time for the disease to spread further. to face the new exotic diseases, it is recommended to have a standard sop in place along with technical guidelines, decision-taking levels along with adequate provision for funds and legal backup. it has been observed that lack or inadequate compensation for culling the diseased and in-contact animals and poultry and negative effect on the sale, sale price and exports deter the farmers from reporting animal diseases in time which eventually leads to the spread of tads. for example, due to bse cattle producers in the usa lost over $ billion in exports to japan. similarly, hpai resulted in over $ billion loss in poultry exports for thailand. trade concerns also discourage the use of preventive vaccinations for some diseases such as hpai and fmd. disease-free countries are generally reluctant to import animals or animal products from the countries practicing preventive vaccinations. with these adverse trade considerations, stamping-out policy was adopted by the uk over the vaccination for fmd in outbreak. from a public health point of view, a vaccination programme might reduce the viral load circulating in a country and thus reduce the risk of hpai spreading to humans. however, stamping out rather than vaccination is preferred by most of the countries to declare themselves free from disease/infection at the earliest possible to regain access to exports. to ensure the cooperation of livestock farmers, it is essential to provide adequate and timely compensations to reduce the losses suffered by them on account of culling and closing the units for a few months. the failure of timely disease reporting hastens the spread of tads within the country as well as between countries. it is believed that the hpai (h n ) avian influenza virus might have been circulating in the poultry for months in the affected region before it was reported to the international authorities in leading to the wide spread of the disease/infection. an ex ante study of the fmd outbreak of the uk suggested that the fmd virus was probably introduced - weeks before it was reported and followed by a ban on livestock movements. earlier reporting and ban on animal movements would have cut the spread of the disease by about %. it is believed that the eids and tads will continue to remain an ever-growing threat to animal and human health, economic sustenance of the world and global environment well-being. however, it is difficult to predict the number of these diseases which could rapidly escalate in a country or region threatening the animal and human life as well as the economy of that region or nation. the rising global demands for meat, particularly in east and south asia, have put humans and animals together in numbers never seen before in the world. the fact is that the farm biosecurity in these countries where meat production is growing most rapidly is often poor. this scenario creates a great scope for animal diseases to jump species to create human health problems. some of these issues were thoroughly described in the iom report, , and further debated and discussed by riemenschneider ( ) . the steps suggested include early detection and early response, preparedness plans, decentralisation of government structure, international coordination, understanding of ecology, microbial evolution and viral traffic, expanded surveillance system, disease intelligence, preparedness, collaboration and cooperation among government agencies and cross-field partnerships. in developing countries, the preparedness plans for animal diseases are often unsatisfactory. incentives such as adequate compensation should be provided to the affected farmers as an impetus for reporting animal diseases. the level of preparedness should be assessed by conducting mock drills. this will help in confidence building for rapid detection and response to both eids and tads that appear suddenly and are capable of spreading to large areas in a short time. import bans in response to an animal disease outbreak must be based on sound scientific evidence to ensure that the concerned countries also have the incentive to report the disease to international agencies, namely oie, fao and who. deficiencies in national veterinary services have been attributed for inability in early detection of the disease and response as investigation, and diagnostic services have deteriorated in many regions. a continuing structural upgradation programme for national veterinary services will have to be taken into account for their transformation from providers of services, such as diagnosis, vaccinations and treatment of sick animals to inspection and quality assurance services. disease surveillance, early warning and emergency preparedness need to be pursued more vigorously in africa, the middle east and southeast asia as vital components of national veterinary services. though public health and national security are under the perspective of national governments, the decentralised government structure and improved international coordination are essential to address the threat of tads effectively as they do not respect local, regional or national boundaries. nevertheless, government support at the administrative level is essential to assure sufficient and timely response to avoid the spread of disease through livestock movement controls, closing of live markets, sharing of diagnostic services, expertise, funding, etc. technical support and guidance of international agencies, such as fao, who and oie, are key in the formulation and timely implementation of the plans and modalities for the control and management of eids and tads. the fao in established the global framework for the control of tads (gf-tad) through the emergency centre for transboundary animal disease (ectad) operations and emergency prevention system (empres) for transboundary animal and plant pests and disease initiatives for early warning and response to disease threats, following a collaborative approach to investigation at animal-human-ecosystem interface. these mechanisms have proved to be of immense help and use in the control, prevention and eradication of disease(s). microbial evolution, particularly viral evolution, is a continuous process. it is, therefore, necessary to conduct basic research on emerging infectious diseases, both viral and another microbial origin, for providing new insights about the factors responsible for the emergence of new microbes. for understanding the ecology of disease, social factors, viral and microbial traffic and spread, ecological and demographic changes in human and animal populations due to migration and other factors work in tandem leading to precipitation of emerging infections. these signals for viral and microbial traffic should be seen as warning signs. biodiversity should include microbes and viruses, and environmental impact assessment should include health aspects into account in development planning. enhancing surveillance systems by establishing laboratory response network at national, regional and international level is important for which adequate funds should be provided. by linking the laboratories in public and private domains, such networks are expected to enhance the capabilities at all levels to detect and prevent the spread of eids, transmitted naturally or intentionally (anonymous ) . a network of more than laboratories world over by who for a constant survey of influenza viruses is one of the best examples of networking of laboratories for eids and tads. these laboratories should have multidisciplinary teams involving veterinarians, physicians, ecologists, entomologists, vaccinologists, epidemiologists, molecular biologists, immunologists and possibly other specialists. state-of-the art disease surveillance is required having the capability to forecast when and where a particular disease is likely to occur for more targeted surveillance. such actionable intelligence may derive from the analysis of changes in climatic conditions, vegetation, wildlife demographics, trade pattern or vector demographics and distribution (anonymous ). the disease-producing microbes, particularly viruses and bacterial agents, often change their antigenic make-up as a result of spontaneous mutations, and immune pressure when the wild strains of the infectious agent persist in the host in the presence of vaccinal antibodies. rna viruses having segmented genome are more prone to such antigenic changes as a result of recombination, gene deletion, etc. influenza a viruses of human and animals continuously evolve new virulent variants by exchanging haemagglutinin (h) and neuraminidase (n) genes of various h and n types circulating in human, birds, pigs and other species including equines. with the change in antigenic make-up, the current vaccine strains do not provide protection against the new types of the virus. similar situations occur in fmd virus having seven types and further subtypes, clades and genotypes: ppr virus and newcastle disease virus, to name a few. new antigenic types of a virus or pathogen may also be introduced from abroad through imported livestock and poultry. hence, there is a need to have a plan in place to upgrade the vaccine by incorporating the current strains of the pathogen which induce strong and lasting immunity. this will require the setting of repositories of field strains isolated from disease outbreaks, particularly the ones from vaccine failure cases. such updates of vaccines are routinely followed for influenza vaccines for poultry, equines and human, and fmd and csf vaccine for livestock. vaccination is a valuable and well-tested method in preventive veterinary medicine for promoting animal health and welfare and reducing the risk of human exposure to several zoonotic pathogens. prophylactic immunisation practices, principles and vaccination protocols have helped in significantly reducing the prevalence of many life-threatening viral and bacterial diseases. the risks of not vaccinating their stock on account of lack of awareness among the stakeholders, non-availability of costeffective diagnostics and vaccines, and poor delivery of veterinary services to the livestock farmers can have serious consequences on livelihoods of rural livestock producers. effective vaccination programmes if implemented properly with a broader perspective are likely to reduce the need for antimicrobials, which in turn can help reduce the risk of emergent antimicrobial resistance. the world veterinary association (wva) and health for animals believe that it is essential for the global veterinary profession to educate the public, particularly animal keepers and producers, about the benefits of vaccination for animals and humans. the major objectives and motive of veterinary vaccines are to protect, improve and promote the health and welfare of companion and food animals; increase the production of livestock in a cost-effective manner; and prevent animal-to-human transmission of infectious diseases from domestic animals and wildlife to humans through animal-origin food, close contact and other mechanisms. these diverse aims have led to different approaches to the development of veterinary vaccines from crude but effective whole-pathogen preparations to molecularly defined subunit vaccines, genetically engineered organisms or chimeras, vectored antigen formulations and naked dna injections for immunisation of animals. the final successful outcome of vaccine research and development is the generation of a product that will be available in the marketplace on demand and suitable to be used in the field to achieve desired outcomes. successful veterinary vaccines have been produced against major bacterial, viral, protozoan and multicellular pathogens, which led to successful field application and adaptation of novel technologies. these veterinary vaccines have had, and continue to have, a major impact not only on animal health and production but also on human health through increasing safe food supplies, namely milk, meat, eggs and fish, and preventing animal-to-human transmission of infectious diseases. the continued interaction between the researchers from veterinary and medical streams and health professionals will be a major impetus for adapting new technologies, providing animal models of human diseases and confronting new and emerging infectious diseases. over different veterinary vaccines are currently commercially available (meeusen et al. ). multivalent (bivalent, trivalent and polyvalent) vaccines should be given preference over monovalent vaccines to cover more than one disease prevalent during control programmes to save money, time and other expenses and also to reduce the burden on implementing agencies, such as veterinarians and para-health livestock workers. there should be a system in place to conduct post-vaccination sero-monitoring in the field by appropriate agencies for finding evidence for adequate seroconversion in the randomly collected samples as per standard procedure preferably using diva tests to differentiate between vaccine-induced immune response and the one induced by the virulent virus. the application of risk analysis concerning the spread of disease on account of international trade in live animals and their products, namely, import risk analysis (ira), has been largely driven by the sanitary and phytosanitary (sps) agreement of the world trade organization (wto). the ira standard established by the world organisation for animal health (oie), and associated guidance, meets the needs of the sps agreement. the use of scenario trees is the core modelling approach adopted to represent the steps necessary for the hazard to occur. there is scope to elaborate scenario trees for commodity ira so that the quantity of hazard at each step is assessed (peeler et al. ) . the dependence between exposure and establishment of the hazard suggests that they should fall within the same subcomponent. ira undertaken for trade reasons must include an assessment of consequences to meet sps criteria. the integration of epidemiological and economic modelling may open a path for better methods. matrices have been used in qualitative ira to combine estimates of entry and exposure, and consequences with likelihood, but this approach has flaws, and better methods are needed. ira standards and guidance provided by oie indicate that the volume of trade should be taken into account. some published qualitative iras have assumed current levels and patterns of trade without specifying the volume of trade, which constrains the use of ira to determine mitigation measures (to reduce risk to an acceptable level) and whether the principle of equivalence, fundamental to the sps agreement, has been observed. it is questionable whether qualitative ira can meet all the criteria set out in the sps agreement. nevertheless, scope exists to elaborate the current standards and guidance, so that they better serve the principle of science-based decision-making. options for trade from disease-free zones and disease-free compartments and trading in safe commodities are now available to have a positive mechanism for facilitating international trade. in india, fmd-control program (fmd-cp) is already in operation intending to create fmd-free zones. similar zones can be created for other diseases like hs, bluetongue, sheep pox, goat pox, ppr and other important diseases. compartmental biosecurity is the new concept for the management of biosecurity in a compartment through a single set of biosecurity measures. creation of zones/compartments will ensure a boost in international trade of livestock and poultry products. in india, legislation regarding the movement of animals across these zones and compartments are required by the central and state governments. the tads are a threat to animal health and production and cause huge losses to the economy of nations. recent outbreaks of bovine spongiform encephalopathy (bse), foot-and-mouth disease (fmd) and highly pathogenic avian influenza (hpai) have unfolded the real and growing global threat that animal diseases pose to livestock systems and to human health and welfare. the tads adversely affect the trade in live animals and their products. the detection of one bse-positive animal in in the usa led to an % drop in beef exports during [ ] [ ] . similarly, the losses in the uk were estimated to be over us$ billion during the ill-fated fmd outbreak. the economic losses due to hpai (h n ) avian influenza have been estimated from . % to . % of gdp in thailand and vietnam by rushton et al. ( ) . the outbreak of avian influenza due to h n strain in the netherlands destroyed as many as million birds. direct losses due to fmd in india have been estimated to the extent of inr , million per annum (anonymous - ) . ppr has been estimated to cause global losses between us$ . billion and $ . availability of adequate financial support for animal health r&d, especially in developing countries, is not always readily ensured. as the livestock keepers in these countries are mostly socio-economically poor, the local and national governments should come forward to support these programmes, particularly for the landless and marginal farmers keeping pigs, sheep, goats, backyard poultry and low-producing bovine stocks by providing incentives or subsidies for diagnostics and vaccines. raising venture fund for emergency disease control through public and private partnership could be considered to meet the urgent requirements, besides farmer-friendly insurance policies for livestock health protection. for important tads, such as avian influenza, ppr and fmd, multinational, regional or global programmes under the supervision of fao, who and oie under 'one health' concept are suggested for better coordination and results. the 'one world-one health' (owoh) concept steered by fao, who and oie has its roots in the interaction between living beings including humans, animals and pathogens, and the environment is considered as a unique dynamic system in which the health of each component is interconnected and dependent with other components. nowadays, a newly integrated 'one health one medicine' approach reflects this interdependence with a holistic view of the ecological system. the owoh can be defined as a collaborative and a multidisciplinary effort at the local, national and global level to guarantee an optimal healthy status for humans, animals and environment. the control of infectious diseases, which have influenced the course of human history, is to be considered strictly related to the one health concept. after its first occurrence in in china, the highly pathogenic avian influenza (hpai) a virus (h n ) has affected more than countries in asia, europe, africa and north america. the virus affected wild birds as well as domestic poultry. sporadic cases of transmission to humans in close contact of infected birds with sizeable mortality raised the pandemic concern of 'bird flu'. after the first report of the h n virus from india and bangladesh in and , respectively, both these countries are experiencing outbreaks almost every year. between february-march and february , india incurred an expenditure of more than inr . million, including inr . million for compensation and inr million on the culling of . million birds (anonymous - ) . avian influenza viruses (aivs) have become a continued threat to global health and economy. after its first outbreak in , the h n hpai serotype disseminated very fast from korea to other parts of asia, europe and north america, a feature not observed in case of other highly pathogenic aivs. however, the pathobiological features of the virus that favoured its global translocation are not known. results of simulation studies undertaken in migratory birds to identify pathobiological features supporting aiv intercontinental dissemination risk suggest that characteristic differences exist among h n and other aiv subtypes, e.g. h n and h n that have not spread as rapidly. lower infection recovery and mortality rates and migration recovery rates also favour translocation in migratory bird populations. although india has been reporting h n aiv since , the h n virus was first time reported in from migratory birds and poultry in the states of delhi, madhya pradesh, kerala, karnataka, punjab and haryana. studies undertaken on comparative epidemiology of influenza viruses h n and h n among human and bird populations to find out similarities and differences between the two viruses in their genetic characteristics, distribution patterns in human and bird populations and postulated mechanisms of global spread (bui et al. ) indicated that h n viruses are diversifying at a much greater rate than h n viruses. analyses of certain h n strains demonstrated similarities with engineered transmissible h n viruses, which make it more adaptable to the human respiratory tract. these differences in the epidemiology of h n and h n viruses in human and birds raise further questions as to how h n has spread at a greater rate than the h n virus. african swine fever (asf) is a highly contagious, deadly emerging disease of pigs in many countries. although first described in and it affected more than countries in africa, europe and south america, several key issues about its pathogenesis, immune evasion and epidemiology remain uncertain (arias et al. ). in the absence of a vaccine, the disease causes greater sanitary, social and economic impacts on swine herds compared to many other swine diseases. currently, asf is present in sub-saharan africa, sardinia, the trans-caucasus, the russian federation and central and eastern states of the european union. the disease continues to spread, with first reports in china (august ), bulgaria (august ), belgium (september ) and vietnam (february ) highlighting the increasing threat of asf to the global pig industry (netherton et al. ) . ongoing outbreaks have also been reported in hungary, latvia, moldova, poland, romania, russia, south africa, ukraine, cambodia, north korea, vietnam and laos. the disease was rampant in china during , and about half of china's breeding pigs died or were slaughtered. the threat of asf looms large as presently no licensed vaccine is available against this disease, and further research is desired in this area for the development of live attenuated vaccines for asfv. it has been possible to generate pigs resistant to classical swine fever virus and prrs virus (burkard et al. ) by using genetic modification of the host species. genetic modification can be attempted as a viable solution to increase the host resistance to asfv. wild suids, namely warthog or bush pig, sequences could be engineered into the domestic pig genome to produce animals in which replication of asf virus and/or disease burden after asfv infection is reduced. however, to generate pigs fully resistant to asfv infection, a more effective strategy such as targeting the virus receptors on the host cell to block the entry of virus and viral replication may be attempted. different clinical courses of asfv infection in pigs have been described based on the virulence of the virus isolates, and sequencing the genomes of isolates of reduced virulence has identified virus genes associated with this phenotype. targeted gene modifications and deletions and testing of the genetically modified viruses in macrophages and pigs have contributed to an understanding of virulence factors and how the virus modulates host responses. in the absence of a vaccine and rapid spread of asf in europe and asia, the main emphasis should be on strict customs and border protection to keep the negative countries free from asf virus infection/ disease. research is required on priority to explore the virulence genes and genes related to host protection and immune evasion, role of multigene families in antigenic variability, mechanism of evasion of the immune response, factors determining viral persistence and infection outcomes, and interactions between asfv and wild african suids, which are tolerant to asfv infection. such studies will provide a complete understanding of the pathogenesis of asf. the specific role of different hosts including wild suids, vectors and environmental factors in disease propagation needs to be elucidated for understanding different epidemiological scenarios. in this regard, the northern european scenario in which infected wild boars drive disease transmission and maintenance needs to be investigated further. presently, asf has become of great significance in china and a real threat to the pig and pork production. the affected countries are planning to compensate for the losses in pork production by increasing broiler poultry production. gaps in sanitary control of wild boar populations make asf control difficult. raising awareness among veterinarians, hunters and farmers should be the priorities for asf control. advances in non-invasive sampling are required to facilitate surveillance in affected areas. current and future tests need to be optimised for noninvasive matrices. the availability of a confirmatory serological test and cell lines for replacing primary cell cultures should be the priorities for future work. availability of safe and potent vaccine against asf could benefit disease control and prevention substantially, but despite some advances such vaccine is still lacking (arias et al. ). after the successful eradication of rinderpest from the globe in , foot-andmouth disease (fmd) of cloven-footed animals is another oie-listed important viral disease inflicting heavy economic losses and adversely affecting the trade of livestock and livestock products from endemic countries to fmd-free nations/ regions. knight-jones et al. ( ) have given a detailed account of global fmd research update along with gaps and an overview of global status and research needs. the conclusions are drawn to highlight that currently available vaccines and control tools have enabled fmd eradication from many countries of the developed world. however, in many developing countries, fmd remains uncontrolled. the main reason given is that biosecurity measures that have been fundamental to successful fmd control in the developed country are difficult to be implemented effectively in developing countries due to obvious reasons. in the present scenario, improved vaccines, with longer lasting protection against a wider range of fmdv strains and lower production costs, could be the single most important development to enhance our ability to control fmd. although encouraging progress has been made with several novel vaccine candidates, addressing key limitations of the current inactivated vaccines, a commercial vaccine is yet awaited. while new discoveries are crucial, current vaccines have been used to effectively control fmd on numerous occasions. however, for imparting better immunity, fmd vaccines should be subjected to adequate quality assurance and be made available in sufficient quantity to provide desired coverage following appropriate strategy. there is also a need for better training and support in the design and execution of vaccine-based fmd control programmes. another area of research is genetic and molecular studies on the virus to elucidate host-virus interactions. more powerful tools and analyses are increasing our understanding of various aspects of fmdv evolution, ecology and epidemiology. this, in turn, should benefit many areas of fmd research, from basic virology to the vaccine and diagnostic development. furthermore, improved genetic technologies have the potential to reveal information crucial for control, such as transmission chains, vaccine match and level of virus circulation. fmd control has been prioritised by many governments around the world. besides traditional bastions of established research institutes in europe and north and south america, notable work is being conducted in china, india and africa. experiences in south america and europe have shown that through decades of sustained investment fmd can be controlled, even in regions where once it was rampant and control was seemingly impossible. however, if improved and more widespread fmd control is to be achieved, continued investment in fmd research at the local and international level is a must. improved diva diagnostics increase our ability to detect infected animals in vaccinated populations. greater confidence in the ascertainment of fmd status of animals and products has, in turn, opened the way for international standards for trade and disease control that are more efficient and less restrictive. rigorous licensing procedures increase the time taken for new technologies for diagnostic kits and vaccines to reach the market. however, if authorisation is less rigorous, substandard products may be released onto the market. hence, there is a need to balance these two requirements. relaxation should be provided for necessary changes to the existing technologies, such as changing vaccine strains, particularly when the need is urgent (knight-jones et al. ). rinderpest, also known as 'cattle plague', was once a deadly serious threat to the livestock industry and agriculture economy in several regions of the globe, particularly in asia, africa, europe and the americas. it periodically swept through old world, resulting in devastating epizootics and huge economic losses. the disease could be successfully eliminated from the globe with mass vaccination programmes, zoo sanitary measures, policy support, international cooperation and political will. the morbidity and mortality rates in newly exposed naïve populations could be as high as - % leading to enormous economic losses. in india mortality rate of about , animals were recorded among the affected bovine population of , per annum during the first half of the s, indicating average mortality of %. throughout the history of humankind, the social, economic and ecological consequences due to rinderpest had been more catastrophic, even changing the history of nations and empires. in india, the presence of rinderpest was confirmed by the cattle plague commission (hallen et al. ) . this disease has been conquered successfully by following mass vaccination along with zoo sanitary measures. the fao declared the global eradication of rinderpest on june , marking it the first ever viral disease of animals eradicated globally about three decades after the eradication of smallpox, a viral disease of humans in (yadav et al. ) . constraints of availability of quality vaccine in sufficient quality, freeze-drying of vaccines and maintenance of cold chain for a vaccine in tropical countries, lack of infrastructure for structured clinical surveillance and sero-surveillance were some of the limitations in executing the mass vaccination programmes. in india, dividing the country into four zones based on the epidemiological picture of the disease and adopting strategic and focused vaccinations at interstate and international borders and migration routes of bovines and caprine for creating immune belts, coupled with rigorous clinical and sero-surveillance, were of great help in achieving freedom from the infection. the financial support and/or technical guidance from fao, oie, eu and iaea were the driving forces in achieving infection-free status for india in the year . with the successful eradication of rinderpest, the livestock sector across the globe became safer, and consequently the living standard of livestock farmers improved. the success of rinderpest control and eradication proved a rewarding experience and landmark for the veterinary services in india, providing capacity building and confidence among field veterinarians, researchers, policy planners and donor agencies and other stakeholders to undertake a successful control programme of livestock diseases at the national level. the freedom of the country from rinderpest not only enabled the growth of the dairy industry in india but has also boosted the export of meat and other dairy products in the recent decade. today india tops not only in milk production in the world but is also the largest exporter of buffalo meat. cost-benefit analyses indicated that every dollar spent on rinderpest control programme gained about $ to the indian dairy industry through more milk, meat and draft power for better agricultural productivity (uppal ). in the fate of rampant threat due to eids and tads, a diverse, dynamic and wellplanned structured disease surveillance and monitoring approach would be the key for the sustainability and welfare of healthy livestock production systems of any country. preparedness for combating the prevailing, emerging, re-emerging eids and tads requires robust monitoring and precision detection systems that are flexible, feasible and adaptable under field conditions. in this regard, pen-side diagnostic tests/lab-on-the chip tools are the need of the hour. the hurdles of sampling need to be curtailed opting non-invasive methods for sample collection from different animal species and wildlife. transparency in disease reporting needs to be adhered to and reported to oie. because of trading in animals and animal products, the international obligation for oie reportable diseases of high importance must be followed by all member countries of wto. it is high time to apply developed diagnostics and molecular detection tools in the field to ensure fast detection and confirmation of pathogens capable of causing diseases in humans and animals. this must be accompanied by national-level disease surveillance, monitoring and networking to enable an early warning system for infectious diseases based on forecasting (saminathan et al. ) . due priority is also required for development and application of new potent, safe and affordable vaccines and vaccine delivery systems and adopting innovative vaccination programmes and immunomodulatory and effective therapeutic modalities, which would help in devising timely prevention and control strategies against viral and other infectious diseases. besides these, good manage-ment and standard biosecurity and biosafety measures/practices and appropriate hygienic and zoo sanitary and quarantine measures should be observed. moreover, on-the-spot control and checking of the spread of pathogens and adequate trade restrictions as envisaged under the sps agreement of wto also need to be followed. a holistic vision and approaches are required for timely implementation of these concepts and strategies along with the strengthening of various multidimensional research and development programmes supported by appropriate funding resources. these measures will greatly help to minimise disease incidences and outbreaks, and lessen economic burdens due to infectious animal diseases and boost livestock and poultry health, reproduction and production to strengthen sustainable growth of livestock and poultry industry. reduction in pandemic threats and public health concerns eventually lead to an improvement in the socioeconomic status and welfare of the society at large under 'one health' umbrella. application of artificial intelligence (ai), gps, remote sensing and traceability in disease detection and management needs priority attention in developing countries. similarly, the latest techniques of gene editing, base editing, nanotechnologies, electronic nose, etc. should be applied for efficient disease diagnosis and drug delivery. while planning the breeding policies for livestock and poultry, both higher production performance and health of the progeny should be given equal weightage. modern techniques should be used for developing disease resistance (absolute or partial) in livestock and poultry using indigenous germplasm. institute of medicine (iom) report - ) annual report, icar-directorate of foot-and-mouth disease - ) annual report, department of animal husbandry, dairying and fisheries, ministry of agriculture and farmers welfare, govt. of india gaps in african swine fever: analysis and priorities a systematic review of the comparative epidemiology of avian and human influenza a h n and h n -lessons and unanswered questions pigs lacking the scavenger receptor cysteine-rich domain of cd are resistant to porcine reproductive and respiratory syndrome virus infection emerging infectious diseases of wildlife-threats to biodiversity and human health allijan mm ( ) the cattle plague commission report to government of india global foot-and-mouth disease research update and gap analysis: -overview of global status and research needs emerging infections: microbial threats to health in the united states zika virus-an imminent risk to the world current status of veterinary vaccines advances in developing therapies to combat zika virus: current knowledge and future perspectives the genetics of life and death: virus-host interactions underpinning resistance to african swine fever, a viral hemorrhagic disease animal disease import risk analysis-a review of current methods and practice: open access article avian influenza and other transboundary animal diseases, director, liaison office for north america, food and agriculture organization of the united nations. presentation at "health in foreign policy forum impact of avian influenza outbreaks in the poultry sectors of five south east asian countries prevalence, diagnosis, management and control of important diseases of ruminants with special reference to indian scenario ebola virus-epidemiology, diagnosis and control: threat to humans, lessons learnt and preparedness plans-an update on its year's journey nipah virus: epidemiology, pathology, immunobiology and advances in diagnosis, vaccine designing and control strategies-a comprehensive review peste des petits ruminants: sheep and goat plague. today and tomorrow's printers and publishers fao sponsored final project report "national testimonies" under the global rinderpest eradication programme (grep)-(gcp/glo/ /ec) fao sponsored final project report on "laboratory contributions for rinderpest eradication in india" under the global rinderpest eradication programme (grep)-(gcp/ glo/ /ec) animal sciences. in: singh rb (ed) years of agricultural sciences in india acknowledgements all the authors of the manuscript thank and acknowledge their respective universities and institutes. there is no conflict of interest. key: cord- -kmj hj authors: babbar, s. title: battle with covid- under partial to zero lockdowns in india date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: kmj hj the cumulative records of covid- are rapidly increasing day by day in india. the key question prevailing in minds of all is when will it get over? there have been several attempts in literature to address this question using time series, machine learning, epidemiological and statistical models. however due to high level of uncertainty in the domain and lack of big historical data, the performance of these models suffer. in this work, we present an intuitive model that uses a combination of epidemiological model (seir) and mathematical curve fitting method to forecast spread of covid- in india in future. by using the combination model, we get characteristics benefits of these models under limited knowledge and historical data about the novel coronavirus. instead of fixing parameters of the standard seir model before simulation, we propose to learn them from the real data set consisting of progression of corona spread in india. the learning of model is carefully designed by understanding that available data set consist of records of cases under full, partial to zero lockdown phases in india. hence, we make two separate predictions by our propose model. one under the situation of full lockdown in india and, other with partial to zero restrictions in india. with continued strict lockdown after may , , our model predicted may , as the date of peak of coronavirus in india. however, in current scenario of partial to zero lockdown phase in india, the peak of coronavirus cases is predicted to be july , . these two predictions presented in this work provide awareness among citizens of india on importance of control measures such as full, partial and zero lockdown and the spread of corona disease infection rate. in addition to this, it is a beneficial study for the government of india to plan the things ahead. india reported the first confirmed case of the coronavirus infection on january , in the state of kerala. the affected had a travel history from wuhan, china. as of now, june , , confirmed cases stand at . lakhs with more than , deaths in the country. the top states with the highest number of cases include maharashtra, delhi, tamil nadu, gujarat, and uttar pradesh. to protect . billion population of india from getting infection, world's biggest lockdown in history was imposed in four phases by the government of india. the motive was to flatten the curve of the infection and slow the spread of this deadly virus. during full lockdown started from march , , india witnessed a surge in confirmed coronavirus cases due to tablighi jamaat religious congregation event held in delhi in mid march. the meeting was estimated to have been attended by more than , members including foreigners. it was an exceptional and undesirable event occurred under the toughest restrictions executed in india. with no doubt continued full lockdown after may, , might have resulted in controlled spread of disease in india. but at the same time, extending it for several more weeks was not a solution either. the four phases of serious lockdown in india has brought millions below the poverty line struggling for basic needs like food and shelter. the issue of migrant workers was one of the most crucial and highlighted issue in this pandemic where millions were rendered unemployed and stranded without money, and basic needs contributing to further growth of disease in india. it has been more than months to the prevailing situation of deadly coronavirus hounding india with rapid growth of cases. medical researchers all over the world are busy experimenting right vaccine for the virus, academic researchers are making predictions based on machine learning and time series models and astrologers are forecasting the end of disease based on planetary position and more. the key finding everyone is trying to uncover is: when this pandemic will get over?. it is a challenging task to be addressed for the reasons that there are several time variant factors that influence spread of coronavirus disease. this includes social distancing, population and density, public awareness, corona testing facility, lockdown and restrictions, medical facility, nature of virus and more. consider the factor of "social distancing" which is one way to reduce the speed of the spread of the infection through the population. social distancing not only helps in slowing the spread of infection, but also support by keeping the peak number of cases below the capacity of the medical system. consider figure from [ ] . where two curves of different shapes are shown. the curve on the left is a steep curve indicating exponential increase in the virus spread. with such infection rate, the local health care system gets overloaded beyond its capacity to treat people. whereas, the curve on the right is flatter showing a slower infection rate over longer period of time. under this situation, health care system is less stressed and the required medical attention can be given to the patients. the second curve is the output of maintaining adequate social distancing and lockdowns whereas, first curve is result of zero precautions. hence, following social distancing and lockdowns restrictions are the key to slow the spread of the virus. in this work, we show impact of full and partial to zero lockdowns in predicting likely end of coronavirus in india. from full lockdown we mean the phase starting from march , to may , . where the government of india imposed strict restrictions. whereas, partial to zero lockdown indicates the time period from may , to current date. where restrictions are lighten and india is moving from locking to unlocking stage. we used a combination of epidemiological model (seir) and mathematical curve fitting method to forecast spread of covid- in india in future. the key motivation to integrate two methods for the predictive task is to use benefits of seir model by making its key parameters learn using historical data of confirmed cases under full and partial to zero lockdowns in india. fundamentally, seir model works by fixing the parameters such as n (population of the country/state under study), β (expected amount of people an infected person infects), γ (the proportion of infected recovery), δ(the length of incubation period) and r o (computed as β n to identify lockdown scale of country/state under study) before simulation. however, we suggest that keeping these parameters fixed may affect the prediction capability of the model. consider the parameter r o . r o is a indicator of reproduction rate of disease. a r o < means that an outbreak is subsiding since each infected person is transmitting the virus to fewer than one other person. whereas, r > one means the virus is spreading exponentially. the scale at which virus is spreading cannot be same for every country/state. it depends upon several factors such as population and density, lockdown restrictions, rules and regulations, corona virus testing facility and more. hence, setting it fixed for predicting task is not a realistic solution. we propose to learn it from the data instead of keeping it fixed. on way to do is to use logistic function to learn r o . where function is learnt from the data. since this study is related to india so the data considered for the learning task is only meant for india. for robust learning of r o parameter the data set is carefully used so as the right values are learnt under full and partial to zero lockdowns phases in india. the learnt r o value is further used to evaluate parameter β. once the parameters are learned, seir model is simulated to produce two predictions under full and partial to zero lockdown states in india. more clearly, we show end of corona virus if the full lockdown was extended by government of india after may, , and, the prediction of date of peak of coronavirus under partial to zero lockdown in india. we also show similar predictions for capital of india, new delhi. our propose approach has resulted in a good performance giving mean absolute log error (male) of . and . on fitting india's and delhi's full lockdown data respectively. the rest of the paper is organized as follows. section reviews trendy models such as time series, machine learning and deep learning for predicting coronavirus spread in india. the summary of standard seir model, details on curve fitting model and our propose algorithms are presented in section . the data sets used in this work are detailed in section . results achieved by our proposed algorithms are summarized in section . finally, we conclude in section . the key contributions of this work is as follows: . we propose a novel algorithm that is integration of standard seir model and mathematical curve fitting to make predictions of coronavirus in india . predict and analyze confirmed infected cases of coronavirus in india under strict and partial to zero lockdowns. . to predict likely number of population to be affected in india and new delhi by the coronavrius. in work by t. hiteshi et. al. [ ] used various time series model such as, arima, single and double exponential methods and moving average to forecast future of corona virus cases in india. the data taken for study was from january , to may , . where, observations till april , were used for training the models and rest were used for the evaluation purpose. it was concluded that arima outperformed remaining time series models giving mean absolute percentage error of . . it was summarized in the paper that coronavirus cases with continue to grow in india for coming days. the study is not extended to show the prediction of arima in future beyond april , . the work is related to fitting arima on the available data and showcasing closeness of model performance with actual data. authors in [ ] used autoregressive time series models based on two-piece scale mixture normal distributions, called tp-smn-ar models to analyze the real world time series data of confirmed and recovered covid- cases. the data set comprising of confirmed and recovered corona cases from february, , t april, , were considered for experimentation purpose. model was trained on observations till april , and tested on remaining days. the performance of model was evaluated using mean absolute percentage error (mape). the reported mape were . % and . % for confirmed and recovery coronavirus cases respectively. low mape indicated better fitting of model to the existing data. however, future predictions on development of corona virus globally were not studied in the work. similar work has been proposed by [ ] where authors used arima model on johns hopkins epidemiological data to predict the corona epidemic trend of prevalence and incidence of covid- . arima( , , ) and arima( , , ) were discovered as best performing models to address prevalence and incidence of covid- on data set used till february, , . authors used to these models to forecast for next two days, i.e., february , and february , . the time series models arima and sarima have also been used in study [ ] on coronavirus data set for countries italy, spain and turkey. these authors also measured the performance of their model using mape. in addition to this, they extended their model to forecast new cases of coronavirus in the mentioned countries. it was revealed in their work . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . that likely decline of new cases in italy and spain is in july whereas; turkey will see the decline by september . machine learning models such as, linear regression, support vector regressor, deep neural network, recurrent neural network and long short-term memory have also been studied to predict coronavirus cases globally. in [ ] , authors used linear regression model to forecast growth of confirmed corona cases in india for weeks from march, , . where linear regression model was trained on data set of the disease before march , . the trained model was evaluated by root mean square log error metric, which resulted in . error. it was concluded in the work that india will see growth by - cases during the first two weeks of april, . authors in [ ] used support vector regressor, recurrent neural network and long short-term memory for predicting task. models were trained till observations dated april, , and, forecasted results were shown for next days. in work proposed by a. sina et.al. [ ] , machine learning and soft computing models were used to make extended prediction of days using corona virus data for countries usa, iran and germany. the predicted result revealed continuous progression of the outbreak in these countries. in another work by y. novanto [ ] long short-term memory model was used. the available global data set on coronavirus was divided in to sets namely, training ( february, , -march, , ) and test set (march, , to january, , ). where training set was used to learn long short-term memory model and its performance was tested on the test set. the root mean square error was reported to be . . authors did not use the trained model to forecast possible decline of coronavirus cases. authors in [ ] proposed machine learning and cloud computing based model to effectively to track the disease, predict growth of the epidemic and design strategies and policies to manage its spread. they fitted the available data on coronavirus using generalized inverse weibull distribution to develop a prediction framework that resulted in a statistically better performance than the baseline model ( by jianxi luo from singapore university of technology and design (sutd)) considered in the work. their model makes details country-wise predictions on growth and decline of coronavirus cases. in addition to this, they have deployed their model on a cloud computing platform for more accurate and real-time prediction of the growth behavior of the epidemic. the baseline model by jianxi luo used in their work proposed in [ ] was based on standard seir model. this work also presents countywise predictions on coronavirus cases. however, their published results on predictions do not match with current situation of coronavirus cases globally. for example, it was forecasted by their model that covid- may end in india by may, , but, it does not stand true. the key reason to the failure is that the uncertainty and changes are continuously evolving real-world scenarios affecting the affect the distribution of cases and hence to the curve parameters of any model. the models discussed in section are intuitive enough to predict the pattern of corona. however, they fail on revealing the likely date of maximum infected cases, the possible decline and importantly when will the pandemic ends. probable reason to their failure is poor training of model due to lack of historical data. in addition to this, every country is different in population, diversity, density, rules and regulations and geographic structure. data set of one country may not represent dynamics of some another country. it is not possible to have one standard training data set for a model to learn that suffice these constraints. with covid- occurring globally for the first time, these time series models fails to provide desired insights. by the end of covid- globally this time, each country will have enough historical data to learn and make future remedies to prevent further occurrence of this disease. in current situation, mathematical model namely seir is a good choice to analyze the spread and the control of corona infectious disease. the model categorizes each individual in the population into one of the following four groups: . susceptible (s) -people who have not yet been infected and could potentially catch the infection . exposed (e) -people who are exposed, but not yet infectious . infectious (i) -people who are currently infected (active cases) and could potentially infect others they come in contact with . recovered (r) -people who have recovered (or have died) from the disease and are thereby immune to further infections . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . these groups contain a certain number of people on each day. however, that number changes from day to day, as individuals move from one phase to another. for instance, individuals in compartment s will move to the compartment e, if they are exposed. similarly, exposed people will move to the recovered i group once they catch infection. from this stage people may move to recovery (r phase) or die from the disease. the total population n across the four groups (s+ e+ i+r) is assumed to remain the same at all times. where n is the total population of the country (or state/region) considered in the study. since, people move from one phase to other over time, the groups s,e,i,r are functioned of time t, represented by s(t): number of people susceptible on day t, e(t): number of people exposed on day t, i(t): number of people infected on day t and r(t): number of people recovered on day t as shown in figure . based on the chain between groups, goal is to find out how the number of people in each phase changes with time. seir model make three simple hypotheses on what drives the movement of people between these groups. first hypothesis controls the transmission from group s to e using parameter β. it defines expected amount of people an infected person infects per day. second hypothesis responsible for change from e to i is controlled by parameter δ. it represents the incubation period of the disease, which is the time between exposure to the virus and symptom onset. in case of coronavirus disease it is average of - days and can be up to days. lastly, the third hypothesis, controlled by parameter γ is responsible is defining proportion of infected recovery per day. in summary, seir model consist of system of nonlinear ordinary differential equations(ode's) in the time domain with three parameters namely, β, δ and γ. equation below represents the change in people susceptible to the disease and is moderated by the number of infected people and their contact with the infected. equation gives the people who have been exposed to the disease with time. it grows based on the contact rate and decreases based on the incubation period whereby people then become infected. the change in the infected people based on the exposed population and the incubation period is addressed by equation . it decreases based on the infectious period, so the higher γ is, the more quickly people die/recover and move on the final stage in equation . besides three fundamental parameters in seir model, there is one more important variable that is important to discuss, r o value. it is the total number of people an infected person infects. to calculate r o value, we use the formula = β γ . r is a indicator of reproduction rate of disease. a r o < means that an outbreak is subsiding since each infected person is transmitting the virus to fewer than one other person. whereas, r > one means the virus is spreading exponentially. r for corona virus is estimated by many gropus. the imperial college group has estimated r o to be somewhere between . and . . most modeling simulations that project future cases are using r in that range for predictive task. given r o and γ values from literature, β can be computed for corona virus disease and equations , , and are solved. one major limitation of standard seir model is the user sets the parameters that control this change often based on expert knowledge and, hence remains constant during modeling. this makes the model unrealistic to capture the real trend of development of the disease. consider the parameter r that controls the reproduction rate of . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . the disease. keeping this parameter constant while modeling seir may not be a good choice since it is influenced by several external factors. population density, divergent demographic regions, mitigation efforts, such as social distancing, school, business , malls closures, and wearing of face masks all contribute in driving the r o number down. in addition to this, the characteristics of corona virus itself majorly influences on the r o rate. in this work, we present a modified seir model wherein, we make the model learn seir specific parameters from the data instead of keeping them constant for the realistic performance. under our proposed model, we consider actual corona virus data related to india that details date wise confirmed, recovery and death cases. using this data, our proposed algorithm learns parameters over time t such as: r o , β(t), s(t),e(t), i(t), r(t). this brings change in standard equations of seir model represented by equations , , and as equations , , and respectively. the key intuition behind learning the parameters r o and thus β(t) as, r o = β γ from the data is to get the real change in reproductive rate over time. as discussed earlier, the key factors influencing reproductive rate are population, lockdown controls, rule and regulations. population of india is well known. what is unknown is how reproductive rate has grown since the first case india on january , . with increasing number of confirmed cases after january , , india imposed several lockdowns to control the effect of disease. the four lockdown phases were: march, , -april, , , april, , -may, , , may, , to may, , and may, , to mat, , . where first two lockdowns were very strict whereas, some relaxations were allowed in the last two lockdowns phases. the imposition of these strict and relaxing lockdowns has majorly contributed in forming the trend of confirmed corona infected cases in india. the main idea of this paper is to automatically learn the shift in r o value under zero, strict and relaxed lockdown phases in india and predict likely decline of covid- in india. as r o continuously changes when social distancing measures are loosened and tightened again. one choice that is adopted in this paper to capture r o is using the logistic function as discussed in [ ] . the function is defined as in equation . the summary of all those parameters that are learned and fixed in our proposed algorithm are defined in table r using equations , , , and we apply curve fitting using coronavirus data to generate a model. curve fitting is a process of constructing a mathematical function or a curve that best captures the series of data points given. ideally, a good model "best fit" by capturing the underlying trend governing the data for us to make predictions of how the given data series will behave in the future. the mathematical function used in this work to learn the function f(x) from the data was "least-square". where the idea is to choose the parameters of the function so as to minimize the fitting error, i.e., the distance between the data values y i and the y-values f(x i ) on the fitted curve. the "least-square" method uses root-mean-square error method to compute the difference between actual and fitted value as represented by equation . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . we now detail our approach of curve fitting over seir model using coronavirus data in form of algorithm. for simplicity, whole process in divided into algorithms. the first algorithm which we call as "seir derivation" is responsible in computing derivatives of s, e, i and r over time. to compute r o using equation , we used algorithm called "r o derivation" . the third algorithm named "model derivation" describes model building by providing initial parameters and computation of β using "r o derivation" function. lastly, "curve fitting " algorithm fits the inputted coronavirus data using algorithms "seir derivation", "r o derivation" and "model derivation" . in this work, we used to real data set of india hosted on website [ ] . as stated earlier, the aim of this work to predict confirmed corona cases. so, we only considered data set containing date wise total confirmed, recovery, and deceased cases of individual states of india. the data set included observations from dates january, , to may, , making instances. where, january , marked the first case of corona in state kerala of india. as a first step to data preprocessing, we only kept features namely, date, total confirmed cases and state and deleted remaining features from the data set. the next step was to create two data sets from this main data set representing exclusive total confirmed cases of india and delhi respectively. this step was required since the aim was to develop predictive modeling for india and delhi separately on covid- confirmed cases. in this present . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . study, we considered india and delhi to showcase predictive results. however, our propose model is robust enough to be deployed on data set on other states for the predictive task. the above preprocessing steps resulted in two main data sets. one data set containing date wise cumulative confirmed cases in india starting from january , to may, , . second data set represents delhi from february , to may , with records. figures representes tend of daily-confirmed cases in india and delhi for and days respectively. for each data set, we performed two main predictive analyses considering strict and partial to zero lockdown. during the time period from march , to may, , , india was under strict lockdown phase. however, after may , , government of india reduced the strictness and eventually it became situation of zero lockdown. this gap between strict lockdown to almost zero lockdown has given rise to several fluctuations in corona confirmed cases. considering these fluctuations and to provide model the true behavior of confirmed cases under strict and zero lockdowns, we divided each data set in two parts. the period from till may, , in each data set was considered as strict lockdown whereas, remaining data from may, , was considered to be relaxing period. under strict predictive analysis, we made the model learn the trend of confirmed till may , and forecasted its performance for the next days. this analysis revealed the peak of confirmed corona cases conditioned on continued strict lockdown by the government. in case of relaxed lockdown, we made the model learn from the remaining time period left in the data set and discovered the peak of corona cases. in this section, we present experimental results on predicting peak of coronavirus cases in india and delhi under two main situations: (a) under strict lockdown and, (b) partial to zero lockdown. under strict lockdown phase, observations till may , were considered for all different data sets used in this work for model learning. and, predictions were made for next days using the learned model. the outcome of this experiment revealed situation of virus spread in india under continued strict lockdown beyond may , . besides extended predictions of days under strict lockdown situation, we also present the outcome of model fitting on strict lockdown data set using algorithms discussed in section . figures and represents fitting of learned model over actual new cases of coronavirus data set of india and delhi respectively. the curve fitting outcome on data set of india in figure shows similar trend of actual increase in new cases of coronavirus infection till may , . we notice, steep increase in cases from start of april . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . figure shows outcome on data set of delhi. the actual cases till may , in delhi were whereas, model predicted it be . the msle for this data set was computed to be . . we now present predictions on trend of new cases of coronavirus for continued strict lockdown beyond may , to discover its peak and decline. the fitting of real data set on our propose algorithm revealed that predicted peak in india was on may , and thereby was decline in new cases. in delhi peak predicted was may, , . figure and figure shows the peak and decline trend of new cases in india and delhi respectively. the % of corona virus effect was expected to vanish by early, july conditioned on continued strict lockdown. table summarizes values of parameters r ostart , r o end , k and x o learnt by the model on data sets of india, delhi and haryana. as per the results, peak of new cases were predicted on th day from start of spread of disease in india and th day in delhi. the above-presented results were to stand true if there was a situation of extended strict lockdown after may , in india. however, it is well known that relaxation in lockdown have been eased steadily after may , and, has reached to partial to zero lockdown stage in india. considering this, data available till today may not be a good choice for a model to learn since it is the combination corona cases occurred during of strict and zero lockdown phases in india. hence, to predict the situation of new cases of coronavirus in india, it was important to discard the records before may , . the key assumption made by the model to make new forecast for india was to consider relaxed lockdown. we made predictions for days by our proposed model with values of key parameters r ostart and r o end set manually instead of learning them from data. the results of prediction are shown in figure and figure for india and delhi respectively. as per the predictions by the model, the peak of coronavirus is expected to hit the nation on july , with over cases and thereby declining. the % cases are forecasted to vanish by september, . in delhi the disease will be at peak on july , . the model was fiited with r ostart of . , for india and . for delhi. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint the study done in this work indicated that india is yet to achieve the peak in the spread of coronavirus disease. the predictive model proposed revealed that it is unlikely to get rid of covid- before end of october in india. it is ofcourse not good news, but has to be accepted to meet the basic survival. referring to the model development, it used combination of epidemiological model (seir) and mathematical curve fitting method to forecast the impact of the covid- in india. for conventional seir to begin simulation, the basic parameters such as, β, r o ,γ, δ, population are to be fixed. however, in reality these parameters may vary depending on several factors like country, states, lockdown strictness, rules and regulations and social distancing. keeping them fixed may affect the prediction accuracy of the model. while the factor population of can be easily be identified for the country, the other variable parameters are not easily retrievable. hence, approximating them through process of "curve fitting" proposed in this work is a good choice. to provide robust learning to the model, the historical data of coronavirus confirmed cases in india till may , was used. the key reason to choose the data till may , was because till this date india was under strict lockdown phase. extending the historical data beyond this time for the purpose of learning may have affected the curve parameters. the parameters β and r o were learnt through the method of "least-square" deployed on seir model. this fitting of historical data on seir model discovered the possible peak of corona, i.e., may , in india. however, situation in india was different after may , . people in india were given relaxation in movement, migration of labourers, change in diagnostic facilities and many such factors contributed in further progressive spread of the disease. to predict new peak of coronavirus under this situation is a challenging task since many variable factors influence the coronavirus infection rate from person to person. considering this, it was sensible to make the model relearn the situation of spread under partial to zero lockdown phase. this revised learning discovered new peak at july , to be the date of maximum confirmed cases to reach in india. similar predictions were also done for the capital of india, new delhi. the new predictions made for india under partial to zero lockdown are again under assumptions that things will move the way they are currently moving with no variations. however, the predictions for the future may change rapidly with time. where, different mobility patterns of indian people, social distancing, corona testing facility, ban on international travel and group activities will play a key role in increasing or decreasing the infection rate in india. another factor, which may influence the predictions and affect the distribution of infected cases in future is the virus mutation. however, a study like presented in this work will enable citizens of india, government and medical staff to plan their way forward. in addition to this, contribution of study provides insights on situation of virus spread under full, partial and zero lockdowns. it is the now the awareness of citizens of india to act and behave responsibly to bring life back to normal and mitigate affect of virus from the country. coronavirus (covid- ): arima based time-series analysis to forecast near future time series modelling to forecast the confirmed and recovered cases of covid- application of the arima model on the covid- epidemic dataset. data in brief forecasting of covid- cases and deaths using arima models seir and regression model based covid- outbreak predictions in india covid- epidemic analysis using covid- outbreak prediction with machine learning covid- growth prediction using multivariate long short term memory predicting the growth and trend of covid- pandemic using machine learning and cloud computing predictive monitoring of covid- . white paper covid- in india infectious disease modelling: fit your model to coronavirus data social distancing key to slowing covid- spread key: cord- -j mvulr authors: prasad, rabinder kumar; sarmah, rosy; chakraborty, subrata title: changing clusters of indian states with respect to number of cases of covid- using incrementalkmn method date: - - journal: nan doi: nan sha: doc_id: cord_uid: j mvulr the novel coronavirus (covid- ) incidence in india is currently experiencing exponential rise but with apparent spatial variation in growth rate and doubling time rate. we classify the states into five clusters with low to the high-risk category and study how the different states moved from one cluster to the other since the onset of the first case on $ ^{th}$ january till the end of unlock that is $ ^{th}$ june . we have implemented a new clustering technique called the incrementalkmn (prasad, r. k., sarmah, r., chakraborty, s.( )) a severe acute respiratory disease, caused by a novel coronavirus, has spread in the month of november-december throughout china and received worldwide attention. the world health organization (who) officially declared the novel coronavirus (covid- ) epidemic on th january as a public health emergency of international concern. in india, the first case of novel coronavirus was detected on th january in the state of kerala (ward, a. ( , march ) ). as the number of confirmed novel coronavirus positive cases closed , the govt. of india introduced "janta curfew" on th march and after that govt. of india enforced days lockdown phase-i nationwide from th march - th april, nearly all services and factories were suspended (singh, k. d., goel, v., kumar, h., gettleman, j. ( , march ) ). due to the number of confirmed cases of covid- increased, on th april , govt. of india extended the lockdown phase-i period till rd may i.e. lockdown phase-ii, with certain relaxations (bhaskar, u. ( , april ) , dutta, p. k. ( , april ) ). in methodology in order to define data clustering, let d = {x , x , . . . . . . ., x n }, be a data set with n number of data elements, and each data element characterized with m number of features : x i = {x i, , x i, , . . . . . . ..x i,m }. the main objective of clustering is to group these data elements into homogeneous sub-groups such that the intra-cluster similarities are high while inter-cluster similarities are low. the data elements in each sub-group are called a cluster, and the union of all sub-groups is equal to the dataset d. clustering methods have been classified into five different categories, i.e., partition-based, density-based, hierarchical-based, grid-based and model-based (han, jiawei, jian pei, and micheline kamber ( ) ). in the last few decades, clustering algorithms have been extensively used to solve the problem of data-mining. in this research, we have used incrementalkmn (prasad, r. k., sarmah, r., chakraborty, s.,( ) ) clustering method on novel coronavirus (covid- ) data set of india based on confirmed cases, which produced the k desired number of group of states of india i.e. divide the data set into k number of group of states. and apply the growth rate and doubling time from equation . and equation . on desired k number of clusters produced by incrementalkmn (prasad, r. k., sarmah, r., chakraborty, s.,( )) clustering method. the steps of incrementalkmn method is given below: step : select the value of k and dataset d step : set i = and c = φ, where c is empty centroid list. step : select first centroid i.e. c i as mean of a given dataset d. step : update the centroid list c = c ∪ {c i }. step : assign each data objects to its nearest centroid. step : compute the sse of each cluster. step : select i th center i.e. (i ∈ , , ..., k) is selected from maximum sse of a cluster. the i th center is a maximum distance from the data object and the centroid of maximum sse cluster. step : repeat the step until it reaches k number of centroids and finally formed k number of clusters. . compound growth rate (murphy, c. b. ( , may )): in this paper, we have used compound growth rate over regular time intervals of confirmed case for each state phase wise. the growth rate of each state is computed as: growth rate = p resent conf irmed case p ast conf irmed case where, p resent conf irmed case is a ending value, p ast conf irmed case is a beginning value and n is a the number of periods(in days). . doubling time (manias, m. ( , january )): doubling time is a time it takes for a confirmed case to double in size. the doubling time of confirmed case for each cluster is computed with the help of equation . , which is described as: doubling t ime = ln( ) ln( + growth rate) ( . ) the complete flowchart of the methodology adopted is given in fig . in fig , the proposed method start with input data set d and value of k, in this paper, we have considered the value of k is five. in the next step, we have applied the incrementalkmn clustering method using data set d and value of k that produced k number of clusters. in the next phase of the flowchart, it computes the growth rate and doubling time of clusters produced by the incrementalkmn clustering method. the data set of novel coronavirus (covid- ) daily confirmed cases state-wise is collected form (https://api.covid india.org/).in this data set, the total number of confirmed cases in india was , , from th january to th june . in novel coronavirus dataset, we have considered the following states and uts, as an ( we have considered five different clusters (subgroups) of states namely (i) high risk, (ii) moderate-high, (iii) moderate, (iv) moderate-low, and (v) low-risk states with respect to the daily incidence of covid- positive cases. as such the value of k is taken as five in lockdown: the first confirmed case of novel coronavirus in india was reported on th january in the state of kerala (ward, a. ( , march ) ). the number of confirmed covid- positive cases reached close to on th march and by th march that is before lockdown the positive case reached . in fig which depicts the situation prior to the start of the lockdown based on the number of confirmed cases, the states {mh and kl} were on the high-risk state, {hr and up} were on moderate-high risk state, union territory dl and the state ka were on moderate risk state, {gj, la, pb, rj, tg} were on moderate-low risk states and the remaining states and uts were on the low-risk states. in table , the growth rate and doubling time(in days) of each cluster of states are shown. the growth rate of clusters i, ii, and iii states i.e. {gj, la, pb, rj, tg}, {kl, mh}, {dl, ka} were approximately same and doubling time was - days (approximate). whereas, the growth rate of cluster iv i.e. the states {hr and up} were much lees that the top cluster but close to that of cluster v, and doubling time of days(approximately)was nearly time that of the top clusters. the rest of the states and uts before lockdown, the growth rate was low, and the doubling time was approximately - days. down phase-i: table . accordingly, the growth rate of the state of mh before the lockdown was high and in lockdown phase-i, the growth rate decreased considerably from % to %. similarly, the days doubling time before the lock down climbed up to days after lockdown phase-i. on the contrary, the average growth rate of cluster ii i.e. {dl, tn} has increased, and doubling time in lockdown phase-i was decreased as compared to before lockdown. similarly, the average growth rate and doubling time of cluster iii and iv i.e. states {ap, gj, kl, mp, rj, tg, up} and states {hr, jk, ka, pb, wb} have improved in lockdown phase-i. but in cluster v i.e. states and uts {an, ar, as, br, ch, ct, dn, ga, hp, jh, la, mn, ml, mz, nl, or, py, sk, tr, ut}, the average growth rate has increased and doubling time also decreased in lockdown phase-i as compared to before lockdown. in phase-ii, the lockdown was extended nationwide up to rd may with certain relaxations (bhaskar, u. ( , april ) , dutta, p. k. ( , april ) ). in fig based table shows the growth of the rate and doubling time of each cluster of states and uts. the growth rate for both the cluster i that is {mh} and cluster ii i.e. {dl and gj} reported as % is a substantial decrease from their % and % in lockdown phase-i third phase of lockdown started from th - th may, with some more relaxations ( online, e. t. ( , may ), newsworld . ( , may )). the country was divided into zones: red zones, orange zones, and green zones (thacker, t. ( , may )). in fig , again the state mh was in a high-risk category, and dl, gj, and tn formed the moderate-high risk category. the states {mp, rj, up} were in moderate risk, {ap, jk, ka, pb, tg, wb} were in moderate-low risk state, and the rest of the states and uts were in the low-risk category. in phase-iii the growth rate of confirmed cases of all clusters except cluster v in lockdown have decreased and the doubling time of all clusters increased except for cluster v which shows in table in phase-iv, the lockdown was extended for another two weeks from th − th may with some additional relaxations. here, red zones were further divided into to containment and buffer zones ( may ) ). in fig , table . the phase v (or unlock-i) of lockdown started from th − th june with only limited restrictions (sharma, n., ghosh, d. ( , may ) ) . in our study, we have considered the novel coronavirus (covid- ) data set till th june . the state mh was in the high-risk state based on the number of confirmed cases and {dl, tn} was in moderate-high risk state which shows in figure . similarly, the state gj was in moderate risk state, and {mp, rj, up, wb} were in moderate-low risk state, and the rest of the states and uts were in the low-risk state. from table , the growth rate of all clusters has decreased or remained the same in lockdown phase-v as compared to previous phases. similarly, the doubling time of all clusters has increased or remained the same. the doubling time of cluster i i.e. the state mh is in days(approximate). similarly, cluster ii i.e. the states {dl, tn} is required - days(approximate) to double and cluster iii i.e. the state gj is required days to double. the cluster iv and v have days(approximate) and days(approximate) to doubling time. from what we have found it was expected that some of the states/uts lying in the category v will soon move to the category iv in the next weak or so starting th june . in order to verify this, we have then extended our study covering data up to th june to cover the full unlock i period to see how the cluster changed in the last days of this phase. the result is shown in figure . as expected the some of the states {ap, as, br, hr, jk, ka, or, pb, tg} which were in category v moved to category iv. in fact from figure where we have demarcated instead of clusters to reveal hidden groups with the cluster v gave a clear indication of the tendency of the above state towards the next higher risk category (see also table ). ii. lockdown seemingly had its impact on two other states hr(haryana) and up(uttar pradesh) as these states improved down to low risk and moderate low-risk category. iii. based on that we observed that some of the states like ap (andhra pradesh), as (assan), br (bihar), hr (haryana), jk (jammu and kashmir), ka (karnataka), or (odisha), pb (punjab), and tg (telangana) will move up the ladder towards higher risk level in weeks to come. iv. also it appears that some of the states/uts where the onset was late might show surge in coming days to move to a higher category of risk. v. the current study is based on the number of confirmed cases and subject to reporting biases if any in the data source. we have not considered other relevant factors, co-variate and non-pharmaceutical interventions which might completely alter the picture favorably. vi. number of confirmed cases alone can not give a true picture of the prevalence of the disease as it is proportional to the number of tests conducted. in this study, we used incrementalkmn (prasad, r. k., sarmah, r., chakraborty, s.,( )) clustering method to classify the indian states and uts in five different stages of risk on the basis of the number of confirmed cases of novel coronavirus . then evaluated the growth rate and doubling time of confirmed cases of each cluster. as on th june , the state mh (maharastra) in on high-risk category with the doubling time of confirmed cases is - days(approximate). similarly, the union territory of dl (delhi) and the state tn (tamil nadu) are in moderate-high risk state and is expected to join mh in the high-risk state soon as the doubling time of these set of states is - days(approximate). the state gj(gujarat) is in moderate risk sate and has decreased their growth rate during the lockdown phases and the doubling time of this state is days(approximate). moreover, the states mp (madhya pradesh), rj (rajasthan), up (uttar pradesh), and wb (west bengal) are in moderate-low risk state and the growth rate and doubling time are same as the state of mh. rest of the states are in the low-risk cluster but some of the states namely ap (andhra pradesh), as (assam), br (bihar), hr (haryana), jk (jammu and kashmir), ka (karnataka), or (odisha), pb (punjab), and the tg (telangana) are expected to reach next level of risk soon. our aim in this work is not to prove or disprove anything but present the pattern for everyone to see and realize that the situation we are in still remains critical. there is no room to rejoice now by saying we are in low risk compared to mh. yes! mh is ahead of us but not in terms of numbers but we are behind them in time scale and it is a matter of time before we reach and experience that stage. incremental k-means method. lecture notes in computer science pattern recognition and machine intelligence india's coronavirus lockdown and its looming crisis, explained india, day : world's largest coronavirus lockdown begins india to remain closed till may, economy to open up gradually in lockdown . . retrieved in coronavirus lockdown extension, modi wields stick, offers carrot on exit route all major cities named covid- 'red zone' hotspots lockdown extended by weeks, india split into red, green and orange zones centre issues state-wise division of covid- red, orange green zones coronavirus lockdown extended till may, says ndma india lockdown . guidelines: what's allowed and what's not? lockdown . guidelines: nationwide lockdown extended till may , with considerable relaxations unlock ": malls, restaurants, places of worship to reopen data mining: concepts and techniques understanding the compound annual growth rate -cagr doubling time calculator clustering analysis of countries using the covid- cases dataset monitoring novel corona virus (covid- ) infections in india by cluster analysis a review of modern technologies for tackling covid- pandemic machine learning can help get covid- aid to those who need it most automated detection of covid- cases using deep neural networks with x-ray images industry . technologies and their applications in fighting covid- pandemic automatic x-ray covid- lung image classification system based on multi-level thresholding and support vector machine key: cord- -k vzcbca authors: padhi, a.; pradhan, s.; sahoo, p. p.; suresh, k.; behera, b. k.; panigrahi, p. k. title: studying the effect of lockdown using epidemiological modelling of covid- and a quantum computational approach using the ising spin interaction date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: k vzcbca covid- is a respiratory tract infection that can range from being mild to fatal. in india, the countrywide lockdown has been imposed since th march, , and has got multiple extensions with different guidelines for each phase. among various models of epidemiology, we use the sir(d) model to analyze the extent to which this multi-phased lockdown has been active in `flattening the curve' and lower the threat. analyzing the effect of lockdown on the infection may give us a better insight into the evolution of epidemic while implementing the quarantine procedures as well as improving the healthcare facilities. for accurate modelling, incorporating various parameters along with sophisticated computational facilities, are required. parallel to sird modelling, we tend to compare it with the ising model and derive a quantum circuit that incorporates the rate of infection and rate of recovery, etc as its parameters. the probabilistic plots obtained from the circuit qualitatively resemble the shape of the curve for the spread of coronavirus. we also demonstrate how the curve flattens when the lockdown is imposed. this kind of quantum computational approach can be useful in reducing space and time complexities of a huge amount of information related to the epidemic. covid- (coronavirus disease ) is a disease caused by the virus strain known as sars-cov- (severe acute respiratory syndrome coronavirus ii). it has widespread implications on the human body in the form of respiratory issues, septic shock, co-morbidity arising from multiple-organ failure, and even death [ ] . routing back to its emergence in mainland china around the end of , till may , it has spread to over countries resulting in a total of around lakh cases with almost lakh deaths due to the same. the world health organisation (who) declared it as a global pandemic on th march , observing the rate it transmits. various countries, including india, put forward extensive mea- * anshuman.padhi@niser.ac.in; @ those are the first authors and have equally contributed to this work † su @iiserbpr.ac.in; @ those are the first authors and have equally contributed to this work ‡ pragna @iiserbpr.ac.in; @ those are the first authors and have equally contributed to this work § kalyanisuresh @gmail.com; @ those are the first authors and have equally contributed to this work ¶ bikash@bikashsquantum.com * * pprasanta@iiserkol.ac.in sures to curb the viral epidemic, by extensive tracing, testing and isolating the suspected ones while improving healthcare systems and imposing lockdowns. govt. of india declared the countrywide lockdown on th march to reduce the virus's rate of transmission. to tackle this global pandemic, the extent of spread and the time taken by the epidemic to reach its peak and other details must be well predicted so that the state can plan accordingly and fight against it. mathematical modeling can come handy in these processes, as they can predict how the epidemics evolve while analyzing the current set of available data. any such prediction system requires a set of assumptions and considerations, which helps to formulate the necessary equations that can later project the regular convolutions. precise consideration of networks within a population while the model is being formulated yields an accurate prediction. later, the prediction can be informed to the healthcare sector and the stakeholders for necessary implementations. here, we use a time-dependent sird (susceptible-infected-recovered-deceased) model to predict the evolution of this epidemic in india. the sird model is one among several compartmental studies in epidemiology [ ] such as seir, where e stands for exposed and rest staying the same; seird, sir, sis model, etc. they have its origin from the kermack-mckendrick theory of infection spread, a very rigorous statistical analysis performed in . here, the population is divided into various compartments, and their interactions are studied further. it is a simple yet an instrumental model of epidemiology since it takes into account various factors such as the rate at which infection spreads, the rate at which the active cases recover, etc. in this current study, we use the data present at the crowd-sourced covid- tracker [ ] . we use classical computation to demonstrate how a change in spread rates might stabilize figures related to infection, recovery, and death. several studies have been done with the available set of data of covid- spread in india and other countries. some of the notable works have used several other statistical approaches while some have used compartmental studies to model and predict the viral spread [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . in our study, we focus on breaking the time scale into smaller intervals (a period of ten days) and analyzing them individually to determine the value of the parameters specified in these periods. we demonstrate how step-wise constraints on such systems have effectively reduced infection spread over time. here, we introduce two possibilities concerning a set of parameters, one which depicts a situation with no lockdowns and another with controlled movement of people. we discuss and analyze the curves obtained from the simulation in terms of rates of infection spread, as they are mostly dependent on the interaction network of subjects in a concerned system explicitly. as we study this parameter, we aim to establish a pattern in their evolution based on data obtained and extrapolate them to obtain a specific value in the timeline towards the end of the multi-phased lockdown (supposedly on th may). further, this set of predicted parameters is used to deduce the progress of the system in the near future with a fixed population. these deductions with current constraints on the system are put up with a system with no such constraints to demonstrate the efficacy of multi-phased lockdown in widening and delaying the peak of infection reporting. quantum computation can be useful in the assessment of such systems since an accurate prediction of a viral spread needs to encompass various factors that might pose complexity challenges in classical computation. factors like quarantine measures, social distancing, population networking, self-protection actions, etc, can give rise to a complex set of problems, challenging for a classical computer to solve. assuming such factors could be easily fitted into quantum computation facilities, given its intrinsic ability to hold substantial information and parallelly process them, underlies this project's hypothesis. parallel to the sird modelling in the study, we form an analogy to the ising model of magnetic lattice to form a hamiltonian. then we build a quantum circuit to demonstrate how they are efficient enough to qualitatively show the nature of the epidemic through the obtained graphs as outputs. we also demonstrate how the considered parameters must be varied to reduce the number of infec-tions when at its peak and also to delay the time by which viral spread peaks in the country. this delay of the peak with lowering of its height is given a term called 'flattening the curve' and this becomes crucial, as the affected population is more spread out for a given time interval. hence, this might not flood the country's healthcare facilities, unlike otherwise. the reduction of the number of cases at its peak also ensures that the current healthcare facility faces a shortage of resources while treating the patients. to build the quantum circuit, we have used the ibm quantum experience platform. various prototypes of quantum operators have been designed and have been made available through ibm quantum experience, a freeweb based platform. researchers have used it to their strength to experiment with circuits and also to simulate results which have furthered their research [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . we organize this paper as follows. section ii discusses the theoretical backgrounds of the sird compartmental model and the quantum computational approach. section iii proposes how both of them have been implemented and what results were obtained from them. section iv is dedicated to a general discussion on the obtained results, including the drawbacks. furthermore, at last, we conclude this article by citing the future implications of the proposal in section v. for additional references, an appendix has been attached at vi. as already mentioned, the sird model is one of the compartmental models used in epidemiology. it divides the whole population into categories where s stands for the part of the population which is susceptible to being infected by the virus. i is the population that has been infected and has the potential to spread the infection. r is the group which has successfully recovered from the disease. d stands for the portion which has been deceased after getting infected due to it. n, the country's total population assumed to be time-independent, is the sum of the susceptible, infected, recovered and the deceased. to develop the operating mathematical model equations, some assumptions have been made here to keep the model computationally simple. they are • the average birth rate and mortality rate of india have not been considered. • the mode of transmission has been considered to be from person to person. • once a person has recovered from the disease, he/she has attained the immunity for infection, hence does not fall back to the category of susceptibles. here α is the rate at which the infection is transmitted to the susceptibles due to possible contact between infected and susceptible ones. β indicates the rate at which the infected individuals recover, which is the reciprocal of the number of days in the treatment period. γ describes the fatality of the virus as the rate at which infected individuals lose their life due to the virus. in this article, we have assumed that the incubation period of the virus is days for patients in india. from the chart presented above, we describe the sird modeling of the virus by the time rate of change of the different compartments of the population using coupled ordinary differential equations. the much talked about r value of a viral epidemic is the number of individuals to whom one infected person can transmit the virus in a day. it can be calculated by using the expression r = α x incubation period (incubation period= β , if appropriate unit is used). if r values become less than , then we can think that the situation will be under control as the disease now will eventually die down. it is so because the number of people infected per day would become less than the number of people recovering during that period. we present the plot of the cumulative data of i, r, and d, obtain the parameters, α, β, and γ by the curves for fixed time intervals with multiple iterations. later, we solve the mentioned differential equations for the multiple sets of parameters, and their corresponding time intervals, which nearly fits the data. once the phase-wise plotting is done, we note down two sets of parameters, one corresponding to a no-lockdown/constraint system and another with some constraints. it must also be noted that this analysis assumes the occurrence of both extremities, and the period of the analysis is from fourth march to th may . on the other hand, we use the ising model [ ] to build a quantum circuit to demonstrate the effect of 'curve flattening'. the ising model of atomic spin discusses the spin interaction of an individual atom in the lattice with its neighboring lattice points and how the spins behave in the presence of a magnetic field. each can have an atomic spin of + or − . the model describes the spin-spin coupling and the exchange interaction between the lattice points and the associated energy value to them. interaction matrix depicts the fashion in which two lattice points interact with each other. here, squillante et al. [ ] , attempted to study the covid- spread by comparing it with the ising model, with the analogy of each atom as an individual. the spin of each lattice point (individual) describes whether the person is infected with the virus or not. a spin of + (p=probability of getting infected [success]) depicts that the person is infected with the virus and the spin of − (q= -p, probability of not being infected [failure]) indicates otherwise, while considering the total population = n. hence, just like the ising model, here also the spins (infected or susceptible individuals) interact with each other. the effect of magnetic field has not been considered since it doesn't carry in relevance in the analogy to the viral spread. since, in the case of viral epidemics, the infection is spread through 'contact' between individuals [ , ] , we assume in a population of n, out of which 's' are susceptible 'r' people are infected. here, we consider when two infected people interact, the net interaction is or no effect. so a general probability distribution can be obtained from the bernoulli's equation as follows- from the previous sird model, we get a reproduction rate (r o = α β ) which also tells about the average number of secondary cases arising from primary cases in an entirely susceptible population, so we can consider p = ro s or ps = r o . the resultant equation turns out to be on using stirling approximation ?? formula and further solving ( ) we get a poisson distribution (for further details, refer appendix vi), as analysed, new cases per day rise nearly exponentially to maximum value and then decrease, which shows the trend of a peak function, from which the equation could be derived ( ) . we can derive its time evolution factor with the probability of cases by implementing hamiltonian operator of its function dependent on time. the spin systems interact with each other by the exchange interaction. it is defined by a hamiltonian operator as-. cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . where, a n , b n and c n are the probability functions. the strength of the exchange interaction decreases as the distance between these particles increases (which can also deduce that if people maintain distance, the spread of infection may decrease). in the neighboring region, we can almost assume that the interaction of one particle is almost similar to all of the neighbors, and the interaction is followed in all three directions, and thus the exchange interaction takes place; the stronger the exchange interaction more will be its infection rate. hence to find its co-relation with the time evolution operator and deriving it into quantum circuits here, for n= , we get a more straightforward form i.e. we apply the time evolution unitary operator on our hamiltonian operator by taking h π = and putting the hamiltonian of ( ) in unitary operator of ( ) we deduce. on solving the equation ( ) which follows the condition of where i is the identity matrix and a is of same order of the identity matrix. here, a=σ x ⊗ σ x , which follow the identity rule and has a order and we break down it to hence, solving the matrix and comparing with the u matrix we derive a following circuit : similarly, working for the equation we get a reduced matrix format where the equivalent matrix is reduced in the form of circuit as, the derived circuit has a combination of a cnot gate, control u gate, anti-control u gate and a cnot gate, where θ = b n (r)t, φ = −π/ and λ = π/ and θ = b n (r)t, φ = π/ and λ = −π/ . similarly, working for the equation we get a reduced matrix format u (t) = cos(c n (r)t)i − isin(c n (r)t)σ z ⊗ σ z . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. finding the average value helps us find the energy eigenstate of the operator, which we can relate to the number of infected people at a particular time. where, <> = shows average value and < σ x σ x >= p − p − p − p which is determined by putting hadamard gates at the end of the equivalent circuit, which is useful for moving information between the x and z bases, which is shown in the following diagram ( ). similarly, < σ y σ y > can be represented by putting a inverse s gate followed by a h gate in each qubit as it moves information from y to z bases, which is shown in the following diagram ( ). and for < σ z σ z >, we only measure the qubits in zz basis, which is shown in the following diagram ( ). a n (r), b n (r) and c n (r), all three functions are taken to be p(r) which we have derived in the above. hence the hamiltonian, whose time evolution we study for covid- spread now turns- . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . the first covid- case was reported in india on th january . considering it as day , on th march (the rd day), the number of cases jumped suddenly from to . so, in this study, we start analyzing the data from march th onwards. for solving the differential equations, we use the odeint module from scipy, which uses the lsoda algorithm to solve the system of coupled odes. as rajesh et al. [ ] pointed out in their sird model prediction of covid- in india, that there is no reported error in the database, so we cannot use reduced chi-sq fitting for the above data. so, we employed the approach mentioned to carry out our analysis i.e., the method of eye-approximation for the best fit. as per this fitting, in fig. , the peak of the infection curve suggests that a maximum of people will get infected for a particular set of parameters. however, data plotting suggests a change in the concavity of the curve it follows periodically, hence in its slope. thus taking a single fitting for the whole period might not be a well scientific method. hence, we tried to break the time interval into smaller legs (here ten days) as per table i and record the values of the parameters (table ii) in the respective leg. the simulated curves are thus made to nearly fit the data points in fig. . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . by obtaining values of parameters, we proceed to make the curves for infection, recovery, and deaths that approximately match the data points available. furthermore, thus we obtain alpha and beta as for each period i.e., α(t) and β(t). here, our only concern remains α(t), and how it evolves in time as it is dependent on interactions between components of the population that's being curbed and regulated during a lockdown [ ] . β(t) and, on the other hand, is dependent on various other factors like the efficacy of treatment, the capacity of the healthcare system, and demographics of the individual population, which is not the point of discussion in this paper, hence not given much importance. also, changes in their values are in the order of − if any were made during the fitting and duly presented. in india, many cases start exhibiting the symptoms after completing their -day quarantine. hence, for safety purposes, many state governments have extended their quarantine period to days. so it might be unsafe to assume any incubation period of fewer than days. hence we consider it to be exactly days. moreover, that makes the r value for the rd leg (march -april ) . , which falls to . by the end of the th leg. hence, the lockdown has been able to contain the spread to some extent, but it should continue until it reaches a value closer to . if we go on plotting the evolution of α(t) from the above data, we can see that a lockdown can successfully reduce the infection rate. to know the future of α under the lockdown, we consider the rate of infections of the several smaller periods under lockdown while excluding the first data points for day - and - (since the lockdown nearly began on the day of the arrival of the virus in india) and do an exponential decay fit. we later go on extrapolating the curve to know the estimated alpha values in the few next legs. as shown in figure , we later use a straight-line fitting to extrapolate beta for subsequent legs. here, we can interpret that the recovery rates have increased in a pretty uniform manner. it can be attributed to various aspects, such as improvement in the healthcare scenario, change in the demography of the infected individuals, or a boost in the quality and quantity of available treatment methods. further studies and accurate models might be able to justify this trend (fig. ) . we use the obtained values of α and β for the next legs and simulate the sird curve and present it cumulatively. we have tried to analyze how the future numbers might be if the lockdown continues as it is until the disease is entirely null. after - legs further, the change in α would have started becoming negligible (and r value . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint slowly tending to ). the recovery rate also would have become nearly constant, we have taken the values of the parameters at the end of the leg of period - to be constant throughout, for the time to come. we extrapolated the curve to obtain a trend (fig. ) . parallelly, we have studied the effect of the current lockdown being lifted. if the lockdown is lifted on may , we had assumed the other extreme that the infection rate might well reach the value it had before the imposition, but certainly not anything greater than that and plotted the curves. fig . : analysis of number of infections upon various scenarios of lockdown. the time axis is segmented by using green lines, which signify the start and (probable) end of lockdown. it can be observed that the number of cases at the peak almost halves with a distinct shift in the abscissa of peak, when the lockdown continues. when lockdown is removed all of a sudden (and assumed that the α= . , just like the value before lockdown), there is less decline in the number of cases at the peak with a subtle shift in the abscissa of peak. from equation ( ) from the previous section, we have a hamiltonian for the covid- spread when compared to the ising model. we were able to find a function which, when fed into the quantum circuit, qualitatively depicts the shape of the curve for the infected individuals, as we also obtained in the sird modeling. while trying out various functions, we finally found that a poisson probability distribution function gives a considerable resemblance to an actual graph and also the type obtained from sird modelling (fig. ) . in the function, the parameter r signifies the ratio of α to that of β. we can observe that when r is decreased while keeping other variables and parameters constant, we can observe that the peak of the curve shifts forward in the time axis with a reduction in its height and making it broader. from these, we can easily derive that a decline in the rate of infection (α) will infect lesser people than before, thus flattening the curve. also, an increase in the rate of recovery (β) will imply an improvement in healthcare facilities, changing demographics of the infected patients, etc. and show a change in the height and position of the peak. using proper parameters and constants, this can be a novel way to simulate approximate curves for given values. an analysis of epidemic spreads can be carried out with the inclusion of more and more factors that otherwise gets difficult for classical computers. the three graphs, with i, r, d, show two trends post lockdown-one set of parameters without any distancing (constraints), and their respective carrier limits, and time is taken to attain them. the latter case depicts another set of parameters that have a few constraints imposed on them, as in the last phase of lockdown. so latter case parameters postponed the attainment of carrier limits and are not as rapidly growing as the former case. also, the no lockdown case is started from the day of data collection, along with lockdown trends and post lockdown trends growing by two parameters to give an effective picture of what would have been the picture without a lockdown and how it would evolve once a lockdown is lifted off considering the extreme case scenario too. it is evident that the lockdown shouldn't be lifted all of a sudden, as it will lead to a massive upsurge in the number of cases (nearly same as that of no-lockdown case) with a very narrow delaying of the peak. the sird model discussed here has its own set of limitations pertaining to the assumptions made and the methods adopted while formulating it. the first limitation of this analysis is the use of the slope-estimation of data plotted curves to find the simulated curve in the lockdown period while obtaining a periodic split up of parameters. this might account for errors in the analysis. the assumptions like not considering birth and mortality rates, the permanent immunization of a recovered patient, unavoidable migration and interactions, etc. make the model lose its precision. here, the susceptible are considered to be the entire population except the infected, recovered, and deceased individuals, initially at a time t. no considerations have been made to distinguish the exposed individuals out of the susceptible and model them accordingly. this might be a significant drawback of the model. the trend in recovery and its rate also is incomprehensible due to the lack of data on the demographics of the recovered patients in terms of their age, sex, etc. in this model, the number of tests performed and their rate has not been considered, but they might play a significant role in reporting the cases, hence the α(t). . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . our n (the total population) has been assumed constant, but immigration, new birth, and deaths might vary the n, thus making us compromise on its accuracy. more efficient models like the seird (susceptible-exposed-infected-recovered-deceased), and higher compartmental models can be implemented for better prediction and analysis. the quantum circuit design only gives the qualitative shape of a 'usual' curve of an epidemic infection spread with the proper use of the parameters and some constants, this can be used to simulate the curves for respective regions. adding various complexities, out of which some are discussed in the above, is a matter of time. with better and smarter use of quantum gates, efficient circuits can be made to minimize the space and time complexities. here, we have assumed only two parameters, the rate of infection and the rate of recovery. this can be intricately designed to accommodate various other detailed parameters that encompass factors like the number of tests, the age group of infected individuals, government measures in curbing the epidemic, etc. moreover, this can give us a more accurate simulation of the epidemics as significant as covid- . covid- has turned out to be a global crisis, affecting all the countries. the current model study report hints at a frightening upsurge of the viral epidemic in the times to come. measures like quarantine and lockdown have been successful enough to reduce their impact, yet a lot needs to be taken care of. however, the current prolonged lockdown has started worrying national as well as global economies, pushing them into a tremendous crisis; hence the lockdown cannot be sustained forever. but as per our analysis, the lifting of lockdown shouldn't be all of a sudden, and be more gradual in the approach. we must start practicing the concept of social distancing and personal hygiene to keep the viral spread at bay. in desperate times like these, researchers of all fields must come together and contribute towards finding more information regarding the virus through experiments and data analysis. this shall let us be more aware and help us in tackling the risk. we sincerely hope that, just like previous global pandemics, we can pass through this with the advent of science and technology. acknowledgments s.p., a.p., p.s. and k.s. would like to thank bikash's quantum (opc) pvt. ltd. for providing hospitality during the course of this project. a.p. would like to thank dr. victor roy, sps, niser for clearing some of the doubts and sharing valuable resources in the initial phase of the project. b.k.b. acknowledges the prestigious prime minister's research fellowship awarded by dst, govt. india. the authors acknowledge the support of ibm quantum experience for producing the basic circuits. the views expressed are those of the authors and do not reflect the official policy of ibm or ibm quantum . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint vi. appendix p is the probability of getting infected. q is the probability of not getting infected,i.e.,q= -p. so, p (x = r) = c s r * p r * q s−r p (x = r)= s! (s−r)!r! assuming the susceptible to be infinite,r is a constant. is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint covid- infection: origin, transmission, and characteristics of human coronaviruses attacking the covid- with the ising-model and the fermi-dirac distribution function a time-dependent seir model to analyse the evolution of the sars-cov- epidemic outbreak in portugal prediction of new coronavirus infection based on a modified seir model predictions for covid- outbreak in india using epidemiological models age-structured impact of social distancing on the covid- epidemic in india trend analysis and forecasting of covid- outbreak in india a critique of the covid- analysis for india by singh and adhikari covid- prediction for india from the existing data and sir(d) model study modeling and predictions for covid spread in india epidemic landscape and forecasting of sars-cov- in india discrete epidemic models with arbitrary stage distributions and applications to disease control generalized markov models of infectious disease spread: a novel framework for developing dynamic health policies stirling's approximation for central extended binomial coefficients quantum locker using a novel verification algorithm and its experimental realization efficient quantum algorithm for solving travelling salesman problem: an ibm quantum experience exact search algorithm to factorize large biprimes and a triprime on ibm quantum computer nondestructive discrimination of a new family of highly entangled states in ibm quantum computer a novel quantum n-queens solver algorithm and its simulation and application to satellite communication using ibm quantum experience design of quantum circuits to play chess in a a quantum computer designing quantum router in ibm quantum computer, quantum inf. process experimental demonstration of non-local controlled-unitary quantum gates using a five-qubit quantum computer, quantum inf experimental realization of quantum violation of entropic noncontextual inequality in four dimension using ibm quantum computer demonstration of entanglement purification and swapping protocol to design quantum repeater in ibm quantum computer design and simulation of an autonomous quantum flying robot vehicle: an ibm quantum experience generalization and demonstration of an entanglement-based deutsch-jozsa-like algorithm using a -qubit quantum computer simulating quantum synchronization of atomic spin model on ibm q experience a simulational model for witnessing quantum effects of gravity using ibm quantum computer quantum artificial life in an ibm quantum computer quantum simulation of klein gordon equation and observation of klein paradox in ibm quantum computer covid- data key: cord- -wp z lok authors: kannan, k. p.; hari, k. s. title: revisiting kerala’s gulf connection: half a century of emigration, remittances and their macroeconomic impact, – date: - - journal: indian j labour econ doi: . /s - - -z sha: doc_id: cord_uid: wp z lok in the literature on development studies, the state of kerala in india is known for its high human and social development despite its low-income status. however, there has been a turnaround in its growth performance and has now come to occupy a high rank in terms of per capita income among indian states. this has been largely through a high growth performance facilitated by significant remittances from abroad. however, there have not been consistent time-series data on annual remittances. this paper is an attempt to fulfil this gap by estimating foreign remittances to kerala for a period of years that is close to half a century. using these data, the paper has presented a modified state income for kerala and calculated its impact on consumption and savings. the significance of the sizeable emigration to the labour market situation has also been highlighted. given the fact that remittances come as household income confined to a small segment of the total households, the impact of annual remittances on income and consumption inequality has also been highlighted. the results show an increasing trend in inequality. despite a high growth performance aided by remittances, kerala has not been able to address its longstanding problem of educated unemployment, especially for its women. in this context, the state’s inability to take advantage of the enhanced per capita income to maintain its tax–income ratio, let alone enhance it, assumes great significance as an area of concern. during the last decade, india has emerged as the single largest recipient of private remittances from abroad. the state of kerala has been a star performer in this followed by punjab and gujarat. the role of foreign remittances in the economy of the state of kerala in the form of money sent by its workers is now widely acknowledged. as of , kerala emigrants abroad at . million, who have an identifiable household to report in kerala, works out to a little more than % of the population but to % of its workforce. six countries in the arabian peninsula, called gulf countries (bahrain, kuwait, oman, qatar, saudi arabia and the united arab emirates), accounted for . % of the total emigrants in ; it came down to . % in (sunny et al. : ) . however, reliable estimates of the quantum of such remittances over time have been difficult to obtain for a regional economy like kerala because balance of payments accounts are prepared at the national level. the revival of growth in the kerala economy since the late s, after more than a decade of economic stagnation, brought into prominence the role of remittances. it is in this context that we attempted an estimation of remittances to kerala for a period of years from - to - and spelled out its importance to the macroeconomy of kerala (kannan and hari ) . given the resilience of remittances-despite two wars in the gulf region and the global financial crisis-and its continuing influence on the macroeconomy of kerala, we decided to revisit our earlier paper to construct a long-term series of remittances, from - to - , covering a period of years that is close to half a century and to highlight the macroeconomic impact. the main conclusions of our revisit are: (a) an impressive increase in the number of kerala emigrants from one lakh in to . lakhs by and . lakhs by reaching a peak of lakhs by and then a decline to . lakhs by , (b) an equally impressive increase in total remittances, (c) an increase in per capita remittances despite a recent decline in total emigrants and (d) an impressive increase although kerala's history of international migration, in any significant sense, can be traced to only about years or so, the migration to gulf countries since the oil price boom of became a watershed and constitutes its single largest stream of international migration so far. as such, this provoked a large number of studies on the various socio-economic aspects of migration and its probable impact on certain aspects of the economy. some of these studies are gulati and mody ( ) , nair ( ) , saith ( ) , krishnan ( ) and issac ( ) . the kerala migration survey (kms) started in under the leadership of k.c. zachariah contributed to a measurement of the migration flows along with the socio-economic characteristics and dynamics of the emigrant households through periodic household surveys. several papers and books were produced based on these surveys. these are summarised in zachariah et al. ( ) , and irudaya rajan and zachariah ( ). kerala's remarkable recovery, after a long period of stagnation in income, was highlighted in a study of the growth performance of indian states by ahluwalia ( ) . in a study of the growth performance of the industrial sector, subrahmanian and azeez ( ) underlined the continuing high growth performance of the kerala economy since the late s. kannan reported the recovery from the slow growth 'since the late s that marked the beginning of economic liberalisation process in the country' ( : l- ) but did not pursue this finding further in that study. this was done later in kannan ( ; revised in ). in consumption and savings making kerala one of the high-income and consumption states in india. however, a downside of this has been an increase in income inequality. from a public finance point of view, this increase in consumption has not been accompanied by even maintaining the tax-to-state income ratio, let alone increase it, due to a manifest decline in tax collection efficiency. there have been several attempts to estimate the remittances to kerala, but they are either limited by methodology or an absence of reliable database and/or limited period of coverage (for details, see kannan and hari ) . our method is a direct estimate of the remittances to the economy. in the balance of payments statistics published by the reserve bank of india (rbi), remittances can be identified as credits in current account as 'net private transfers' and also as 'net nri deposits' in the capital account. from these figures, we have estimated region-wise remittances to the indian economy in terms of middle east countries and other countries. the method we have adopted to estimate the remittances to the kerala economy is as follows: where r kt is the remittance to kerala in year t; r it (me) is the remittance to india from the middle east countries; k t is the share of persons from kerala in the stock of indians in the middle east; r it (ome) is the remittance to india from countries other than the middle east; k t (a) is the assumed share of remittance to kerala from countries other than the middle east; nre kt represents the non-resident external (foreign exchange) deposits in banks located in kerala; and r kt (k) represents the money equivalent of remittance in kind to kerala. the details of the method adopted and the data sources are given in "appendix". the important aspects of our method are the following. (a) we have been able to generate an year-wise stock of keralites in gulf/middle east countries as well as the rest of the world from the results of the kerala migration surveys (kms) for seven time points between and (see irudaya rajan and zachariah : ). these figures were used to work out the share of kerala in the total stock of indian emigrants that were collected separately. a time series of the stock of kerala emigrants were constructed for the period to through interpolation and extrapolation (for details, see "appendix"). this share is taken as the share of kerala out of the total remittances to india. these were worked out separately for the middle east countries and rest of the world since the former accounts for an overwhelming share of kerala emigrants as well as remittances in the total. (b) we have assigned a share of remittances in kind to total remittances to kerala. this was . % of the total remittances during the s obtained from the survey of . for the period up to , we have taken twice this rate since the temptation for bringing electronic and other valuable goods was much greater prior to the liberalisation of the indian economy. from from - from to from - we applied this rate. the kerala migration surveys of and have reported a decline in remittance in kind as a percentage of total remittances, and these have been applied to the period since - (see "appendix"). (c) since the data on nri deposits in banks located in kerala are published as 'outstanding deposits as on march', we have taken the annual change as the net inflow on this account. based on the above method, we have constructed time-series data on foreign remittances to kerala from kerala from - kerala from to kerala from - . the relevant figures are given in table . what comes out clearly from these estimates is that the magnitude of annual foreign remittances to kerala started acquiring significance (i.e. equivalent to % of the annual state income) by the early s when international labour migration began to acquire momentum. it reached a high of close to % in - followed by a decline before recovering to close to % in - . but since then, it has been a decline once again. since our estimation of remittances depends crucially on the estimation of emigrants, it is important to see the trend. figure shows that there has been a secular trend till followed by a slow decline. the periodic fluctuations in remittances would get smoothened if we take the annual average flows for every years. what this shows is that the decline in remittances in some years is getting more than compensated by increases in remittances in other years within these -year blocks. in terms of absolute magnitudes, -year average annual remittances ranged from rs. crores during - and rs. , crores during . it jumped to rs. , crores during - and rs. , crores during - . as a percentage of the net state domestic product (nsdp) remittances, equivalence constituted, on an average, around % for the whole -year period. it was around % since the early s to the early s (till the end of the fixed exchange rate system). between and , it doubled to around %. it declined to % equivalent to state income during - . this relative decline in remittance, despite an increase in absolute the central statistical organisation of the government of india changed the base year of india's gdp calculation from - to - along with a change in methodology of estimation. it gave rise to a debate among economists which is yet to arrive at a consensus (see, for a critical view, subramaniam and nagaraj ). it also affected kerala's nsdp that jumped by % between - and - . however, remittances also increased by %, thereby minimising the relative decline from . to . % of nsdp in equivalence. however, the remittances continued to grow faster reaching . % of nsdp by - . since then, it has declined to . % of nsdp in equivalence. hence, the change in the estimation of nsdp has not been the main factor in the relative decline of remittances to kerala. table given in the appendix levels, is due to a much higher growth in annual state income than in rupee remittances (table ) . this is an interesting development about which we comment briefly in the last section. smoothening the annual fluctuations in remittances by taking the averages for -year blocks, we summarise the overall picture in table . first, the remittances increased secularly in both rupee terms and us dollars. neither the two gulf wars nor the financial crisis seems to have affected the flow of remittances. remittance relative to state income (nsdp) also increased secularly till the end of the twentieth century but then started declining. since - , there has been a decline in the growth rate of remittances to a significant extent (table ). this is partly due to the net decline in kerala emigration to the extent of % between and ( fig. ). but this has not affected the average annual flow when a block of years is taken. this is also the case when we take the remittances in us dollars (fig. ). it is also interesting to note that the per capita per emigrant remittances for kerala are higher by to % when compared with the all india (columns and in table ). we shall comment on the per capita per remittance-receiving household (column ), later. the net decline in the number of kerala emigrants (close to % of whom are concentrated in the gulf countries) has been the result of changes in both demand and supply factors. from the demand side, there has been an increasing push for absorbing its citizens into the workforce in many gulf countries in addition to a change in the structure of demand for labour in the gulf countries in favour of the more educated category. from the supply side in kerala, the major factors seem to be the advanced stage of demographic transition leading to a situation of close to a zero rate of growth of population, increasing wage rates of casual male workers and the increasing levels of educational attainments of the younger population. a good part of the increase in remittance per emigrant is due to the depreciation of the indian rupee. however, since , there has been a real increase in remittance per emigrant measured in dollar terms (table , column ). we attribute the reasons for this to the compositional changes in the emigrant population in favour of the higher educated. recent work based on the computation of unit-level data five rounds of the kerala migration survey (kms) data (see sunny et al. ) has brought out the educational attainments of emigrants, which are summarised table annual average flow of remittances to kerala for every block of years remt stands for remittances; rrhh stands for remittance-receiving household. source: column computed from data given in table in table . it is quite evident that the educational composition of emigrants has undergone a sharp change within a period of two decades from . by , the share of the higher educated (higher secondary and above) increased from . to % ( . times). the period around coincides with the start of the rise in remittance per emigrant in us dollars (table , column ). by , those with higher education-taken as those with at least a higher secondary level-formed as much as %. this is reflected in the occupational categorisation of emigrants that has also been reported in the recent study mentioned above. we summarise it in table . those with secondary education have been referred as 'up to secondary education', and hence, only a part of them could have successfully completed secondary education. even if half of them is assumed to have a secondary level, then the share of educated increases to %. this of course is reflected in the occupational distribution. the less skilled manual labour-oriented jobs in the last two categories in table which were close to half the emigrant workers in got reduced to % in and then to just % by . the largest group is described as professionals in the private sector, and the self employed could also be included in that category. in terms of wages, government employees would ages: - to - (base year - = ) . source: computed on the basis of data in table , columns and also be close to the private sector professionals of the kind described in table . such a picture of compositional change in terms of education and occupation suggests that kerala emigration has undergone a transformation in favour of the higher educated and hence higher earnings than before. this explains the reason for the secular increase in remittance per emigrant since . the remittance per remittance-receiving household (rrhh) based on the proportion of households with current emigration and the proportion of such households actually receiving remittances (see sunny et al. ) tells us about the skewed distribution of the remittance income with implications for income inequality, discussed later. kerala benefited substantially as a result of exchange rate liberalisation in moving from a fixed exchange rate to a floating (though managed) exchange rate system. this, in our opinion, should be reckoned as the single most gain of kerala as a result of economic reforms introduced in . we have quantified this gain by estimating the difference between actual exchange rate since and the expected exchange rate without liberalisation. this may be represented as where g rt = gain in rupees as a result of exchange rate liberalisation, r t = actual remittance in us dollars, r at = actual exchange rate, r et = expected exchange rate and t = time point. the expected exchange rate was calculated by projecting the growth rates under the fixed exchange rate system that the government of india followed including our remittance period to . since the exchange rate liberalisation in , kerala has gained a 'windfall' that works out to rs. , , crores in indian rupee (in nominal terms) for a period covering years since - . this comes to an annual average of rs. crores. as a percentage equivalent of nsdp, this works out to . % for the -year period combined. taken as an average annual flow for every -year period, the windfall gain increased from rs. . crores during - to - to rs. , . crores during - to - . crores per annum for the last years. expressed as a percentage of total remittances that conveys a more meaningful measure of the relative gain, the gain works out to more than % except for a decade from to (fig. ) . the macroeconomic impact of the remittances on the regional economy was evaluated by estimating the impact of the remittances on income, consumption and savings. as mentioned in the beginning, a modified nsdp, called modified state income (msi), for kerala was estimated by adding the series of total remittances with the nsdp. this shows that the per capita income in kerala, when the annual flow of direct remittance is added, is significantly higher than the reported official per capita income. until , it was less than % but rose to - % between (fig. ) . this msi is, however, not a substitute for calculating the net income of a regional economy by factoring 'net payments from abroad' as in the case of calculating the gross or net national product of a country. remittances to the kerala economy started assuming significance from the early s when it was equivalent to % of the nsdp. we have seen (table ) how it reached an equivalence of - % on an average during the quarter century beginning with the early s. since , it started declining as a percentage of the nsdp and currently stands at %. once again, we must caution that the share for the s might be an underestimation due to the administered exchange rate system and the consequent incentive for sending remittances through illegal channels. if this argument is a plausible one, then the share of remittances in the nsdp during the s might have been higher than what is reported in table . we have also worked out the relationship between the per capita consumption, per capita nsdp and msi through the estimation of the average propensity to consume out of nsdp and msi. the results are given in table . the propensity to consume remained well above % of the msi and % of the nsdp till the early s. given an increasing trend in income, the average propensity to consume has declined to half of the per capita nsdp (psdp) and less than half of the per capita msi (pmsi). it reached as low as and % out of the nsdp and msi, respectively, by - . since then, the only detailed consumer expenditure survey carried out by the national sample survey organization in - was not released by the government of india. by deducting the apc from per capita income (pnsdp and pmsi), we have also reported the average propensity to save (aps) that shows a high rate of gross savings in kerala. however, we must point out here that there has been a controversy over the disparity in consumer expenditure as reported through household surveys of nss and that estimated in the national accounts statistics (nas). even if we modify the apc based on nss by a certain margin say, %, due to the underrepresentation of very-high-income groups in the sample, the aps of kerala shows a very high rate of saving. a media report that secured a copy of the report on consumer expenditure reported in decline in the per capita consumption expenditure in the country and that could have motivated the government to withhold and later reject the report (see jha ). scholars such as sundaram and tendulkar ( ) have examined the differences between nss and nas consumption data in great detail and came to the conclusion that nss data are preferable 'because they are based on direct observations relating to the survey period and because, unlike nas, they avoid recourse to adjustments based on arbitrary assumptions'. the savings rate in the kerala economy seems to have increased tremendously since the early s. what is not consumed is savings, and these are held as either financial or non-financial assets. in the kerala context, much of the savings have gone into house construction, investment in gold and in financial assets. an indirect test of reliability of our estimates of remittances and consequently of modified state income (msi) is possible by examining the trend in per capita consumer expenditure and income in kerala relative to all india. the relevant figures are given in table . the annual average per capita consumer expenditure (apce) in kerala was below the national average till - . but the per capita nsdp matched that of all india only in - . but when we take the msi that includes the annual remittances, the per capita msi matched with that of all india by - . this mismatch is perhaps due to the illegal remittances until the liberalisation of the foreign exchange rate of the rupee. since the turn of the twenty-first century, it is the pmsi that matches more with the per capita consumption (apce) for kerala than the pnsdp suggesting the role of remittances in filling the gap between consumption and state income (nsdp) in kerala. we have omitted the year - in the growth rate calculations in table since that year witnessed a sudden decline in remittances due to the iraq war. *the period - to - could not be calculated since the data for - were not released by the government of india. for the earlier periods, the time series for per capita consumption was generated through interpolation based on the data for the different rounds as indicated in the years in table . **only commercial bank deposits. kerala has a vibrant cooperative banking sector, but time-series data for our periods were hard to obtain variable variable - variable to variable - variable variable - variable to variable - variable variable - to - there is no doubt that by the s, remittance income has emerged as a major macroeconomic variable in the kerala economy. the relevant figures are given in table . by the early s, remittances reached % in equivalence to the state income but considerably less than the total government expenditure or value added in agriculture or industry. the situation changed dramatically by the end of s when remittances equalled % of the state income and exceeded the total government expenditure as well as the value added in agriculture and industry. by , the gap widened while the relative size of remittances remained constant. what is interesting is that since , the importance of remittance has started declining as a percentage of nsdp, government expenditure and value added in industry. however, it continues to be much higher than the value added in manufacturing by % that shows the catching-up process by the manufacturing sector in kerala. a small part of it could be due to the change in methodology of estimation of national income in india by changing to a new base to - (that affects the computation of state income as well). however, as shown in table , the growth rate in remittances decelerated to . % since - , while the state income continued to grow over % in nominal terms. this declining share of remittances in relation to crucial macroeconomic variables in kerala needs some elaboration and perhaps shows the signs of a new phase of growth in the kerala economy. we comment on this in the last section. apart from the monetary value of remittances and its contribution to the kerala economy, another important dimension of emigration is the impact on kerala's labour market. since % of emigrants were reported to be in employment, working emigrants constituted % of kerala's workforce within the state in - that almost doubled to . % in . % in - . % in . by . % in - . % in , it increased to . % and to . % in . % in - it is interesting to note that by - , the total number of working emigrants is close to total employment in kerala's organised or formal sector estimated at . million. the relative importance of remittances can also be represented in dynamic terms to show the importance of remittance to the economy ( reflected in the per capita growth in these variables. this has also contributed to maintaining a high growth in consumption. growth in total outstanding bank deposits was marginally higher perhaps reflecting the multiplier effects of remittance in the economy. what is significant to note is the continuing resilience in growth in nsdp and msi as well as bank deposits despite a steep decline in the rate of growth in remittances. the higher growth rate in nre deposits during - and - seems to be a sign of higher per capita per emigrant earnings leading to a higher rate of saving. as a result of the high growth rate of the economy assisted by international remittances and an early demographic transition, kerala's per capita income surpassed all india. in an international perspective, kerala's per capita income at the turn of this century ( ) ( ) was us$ and us$ as measured by nsdp and msi, respectively. two decades later ( - ), they stood at us$ and us$ , respectively. for all india, the per capita net domestic product (ndp) in these two time points was us$ and us$ , respectively. if kerala is to be treated as a country, its status is now close to the definition of a 'middle-income country' (us$ to us$ , ). however, this achievement, while impressive in the south asian context, is not as impressive as some of the south east asian economies such as indonesia (us$ ), thailand (us$ ) or malaysia (us$ , ) but well above vietnam (us$ ) with a comparable human development ranking. but given its commendable achievement in reducing multidimensional poverty and enhanced human development, kerala presents itself well in a developmentalist perspective. for example, the most recent estimate of multidimensional poverty for indian states (see ophi ) shows kerala at the top with . % of the population as multidimensionally poor as against . % for india. it also compares well with such countries as thailand ( . %) and better than indonesia ( . %) and vietnam ( . %). in fact, kerala's performance is one of the best among all global regions and close to europe and central asian average ( . %) (see undp and ophi : ). however, despite the significance of remittances in powering and transforming the kerala economy, there are some crucial issues that should worry both the state and the society. a brief comment is made here on three such problem areas. (i) increasing income inequality: remittances constitute 'outside money' in the case of a regional economy like kerala that is not counted in the official estimate of annual income (nsdp). it is entirely a private transfer because it is the households that are the recipients of this outside money. when such a private transfer takes place only to a small segment of the total households, it creates inequality in income table gini ratios of income inequality for kerala ce stands for consumption expenditure. and are based on the decile-wise distribution of consumption expenditure. is based on state income by taking the distribution as in . is based on modified state income (nsdp plus remittances). is based on nsdp based on consumption distribution and remittance distribution based on consumption decile-wise distribution as obtained from the nsso th round and given in table inequality based on the distribution of - - - as between those households (and population) receiving remittances and those who do not. these are shown as per capita income in table for three time points. these are statistical averages and do not reveal the distribution of income. to understand inequality, we need to know the distribution of the income. in india, this is usually carried out on the basis of consumption expenditure data. we have taken the distribution of consumption expenditure data and applied it to the nsdp. however, there is a problem in distributing the remittances as per the distribution of nsdp because only a segment of the households reported emigration. fortunately, the th round of nss included information on remittances receiving households as well as the remittances (in rs) received. we have applied this distribution of remittances for the three selected years to compute the income inequality based on msi (table ). the results (as gini ratios) are given in table . however, this distribution takes into account only those remittances that are homebound. the nre remittances through bank deposits are not reflected here. here, we make some assumptions on distribution of nre-type remittances in the sense that emigrants belonging to poorer and lower middle classes are unlikely to have any significant nre deposits say the first five consumption deciles from the bottom. therefore, the nre remittances are distributed to the top five deciles in the same proportion as home-bound remittances. the resultant inequality ratios are also reported in table . an interesting insight from the th round of the nss is that close to % of the remittances accrue to households belonging to the four deciles from the bottom. that is to say, direct remittances to the poorer houses might have eased their poverty to some extent. our results on inequality show that kerala has gone through a period of rapid growth in inequality in income since the onset of economic reforms. and this has been exacerbated by the unequal distribution of emigration and the resultant remittance income to the households. however, we must keep in mind that inequality (expressed as gini ratio) for the selected years is influenced by the impact of remittances during the previous years through consumption and investment multipliers. if our assumption on the distribution of nre deposit is a reasonable one, then the inequality due to the total remittance income gets further skewed in favour of the richer classes in the society. this constitutes a further challenge to kerala's development trajectory given its earlier record of social justice and human development to the less fortunate members of the society. (ii) high educated unemployment: there is no doubt that the uninterrupted and increasing remittances, in both absolute and relative terms, were a factor in pulling kerala out of its stagnant growth bootstraps. ever since the turnaround in growth in - , kerala economy has been on a high growth path. the sustainability of this high growth path was the result of a historic conjunction in the form of initial investment in human and social development that enabled the large-scale emigration of people in search of jobs resulting in sizeable remittances, and a specific national economic policy reform in liberalising the foreign exchange rate of the indian rupee. despite the impressive success in the growth front, there has not been a reasonable resolution of the problem of educated unemployment. the situation for the last quarter century is summarised in table . with increasing levels of education and falling incidence of poverty, there has been a steady withdrawal of both men and women from much of manual work (most visibly in agriculture and construction) that led to an increase in wages for casual work. this has effectively resolved the problem of 'less educated unemployment' for men and women. but the problem of 'educated unemployed' persisted. given the steady increase in emigrants till , educated unemployment for men declined significantly between and but resurfaced in - given the 'jobloss growth' in kerala and all india during the latter period (see raveendran , ) . for women, the problem of 'educated unemployed' has been persistent at a very high level. without the safety valve of national or international migration (except for a very small segment of specialised professionals such as nurses) and a continuing trend in acquiring higher educational levels, the educated unemployment rates among women have remained at unacceptably high levels. this is despite the withdrawal of a significant number of women from the labour force (see kannan and raveendran ) . a similar picture of higher unemployment rate among men and women compared to the less educated is also seen at the all india level (table ) , but the kerala rates for women are double that of all india. there is no doubt that the persistence of educated unemployment has been a central failure in kerala's development experience characterised by an early demographic transition followed by a process of growth and structural transformation in both income and employment away from the primary sector. (iii) declining tax collection efficiency: while aggregate economic growth increased, it was largely, if not only, first led by construction (part of the secondary sector) followed by the service sector (see pushpangadan ) . what is important to remember is that remittances are additional income accruing to the household economy and that the state government's benefit in terms of additional income is through tax revenue on consumption of goods and services. we do not have evidence to suggest that the kerala government has been efficient enough in this respect. for example, the tax-to-state income ratio shows a declining trend (fig. ) in terms of nsdp as well as msi. since it is the msi that constitutes the basis for consumption, it is this ratio that is of relevance. this ratio comes down by . to . % points when compared to the nsdp-based ratio although a narrowing down to a little more than % is visible for the last years. what should be more worrying for the government, from a public finance point of view, is the declining trend in tax collection efficiency whether measured by nsdp or msi. since - to the present, the growth rate in remittances declined considerably to as low as . % per annum, but the economy continued to register a growth rate of over % in nominal terms (table ) . what this means is that the earlier flow of remittances helped the kerala economy to grow faster than otherwise. and that raised the state income that constitutes the new denominator to calculate the equivalence of subsequent remittances to the state income. in sum, a stage has now reached such that the kerala economy seems to have picked up enough resilience even as it enters a phase of a relative decline in remittances. however, the positive gain in the form of a higher-income base of the kerala economy (along with other positive gains such as enhanced educational and health standards, especially of the younger population) could prove to be inadequate and even lead to a crisis, if the sharp decline in economic activity arising out of the covid- pandemic that started in march continues for the rest of the year. that, of course, will be part of a generalised crisis in india as well as the rest of the world. it could spell a turning point in terms of a sharp phase down in kerala's large-scale labour migration to the gulf - - - - - - - * countries. alternatively, it could set off a beginning of a change in the composition of emigration if the demand for healthcare personnel increases in the gulf as well as in other countries. in these uncertain times, kerala economy as well as society and polity will be facing unprecedented challenges further complicated by the environmental disasters such as floods (already experienced in and ). it could well be an opportunity to chart a new developmental path within a framework of environmental sustainability and employment creation, especially for the educated adults. the national context on these objectives is certainly not an enabling one, let alone an encouraging one, despite rhetorical declarations, to put it modestly. but the big question here is the ability of kerala's polity to provide the required visionary political leadership. having estimated the share of npt to india from middle east and other regions, respectively, the next task is to estimate a share for kerala from these two regions. for middle east, we estimated the share of persons from kerala in the stock of indians in gulf countries. this share was applied to the remittances from middle east countries. the share of keralites in gulf countries was estimated as follows. first, we have the data on stock of indians for some time points as given in table for the period up to - till - . using the information, we have constructed timeseries data by interpolation and extrapolation. the share of kerala in the total stock of indians in gulf countries has been applied to the total npt to india from middle east countries to obtain kerala's share in npt. for kerala, we have been able to obtain the actual stock of kerala emigrants for the period to in gulf countries from the data of study of . these relate to ( country-wise data for kerala emigrants are available in kms for years , , , , and (zachariah and irudaya rajan , , and irudaya rajan and zachariah . country-wise data for indian emigrants are available in un population database provided by population division, department of economic and social affairs of united nations. these data are available for years , , and . for the period and , world bank also gives bilateral migration matrix. we have corroborated the stock of emigrants from india in different countries from various sources and found only marginal differences across the sources. intermediary year figures were extrapolated using logarithmic growth having thus obtained the share of npt of kerala, from middle east, the next task is to find out kerala's share in npt from countries other than middle east. for this, we applied a share of % for the period - to - . this is somewhat higher than kerala's population share ( . %) to reflect the higher emigrating propensity of keralites. for the subsequent period (i.e. - to - ) , kerala's share is taken at . %. this is obtained from the kerala migration study conducted by zachariah et al. ( ) wherein the source of remittances was obtained from the sample households. post- period, we have used the actual proportions based on subsequent kms household surveys. computation of nri deposits in banks in kerala: data relating to nri deposits in banks located in kerala are published in the annual economic review published by the state planning board, government of kerala. these deposits are of three types: fcnr (b) is repatriable deposits in foreign currency, nr(e)ra is repatriable deposits in indian rupees and nr(nr)rd is in non-repatriable deposits in indian rupees. the net difference between each year's deposit and previous year's deposit stock has been taken as the net remittances through direct deposits to bank accounts. for the year - , we have projected this number based on previous trend. computation of remittances in kind: the kerala migration study ) estimated the share of remittances in kind and this works out to . % of total remittances. for the s, we have applied this share. for the period before - , we have doubled this share to reflect the greater temptation to bring valuable electronic and other consumer durable goods. subsequent surveys revealed that remittance in kind declined to . % of total remittances in and . % in . these proportions are assigned for the periods to - and - to , respectively. from to , it has been taken as . % since the trend in bringing commodities has decreased drastically (irudaya rajan and zachariah ). source: data sources as detailed in the text in the appendix economic performance of states in post-reform period international migration and the development in the arab region remittances of indian migrants to the middle east: an assessment with special reference to migrants from kerala. centre for development studies emigration and remittances: new evidences from the kerala migration survey economic consequences of gulf migration consumer spending falls after decades. business standard political economy of labour and development in kerala kerala's turnaround in growth from human development to economic growth: kerala's turnaround in growth powered by human development, remittances, and reform. in institutions and markets in india's development: essays for from jobless to job-loss growth india's employment and labour market dynamics. study carried out for the ilo decent work team south asia sub-regional office emigration, remittances and their macro economic impact. centre for development studies foreign remittances, consumption and income. thiruvananthapuram: akg centre for research and studies is india overestimating its economic growth? the hindu incidence, impact and implications of migration to the middle east from kerala (india) migration, remittances and capital flows: the indian experience ophi (oxford poverty and human development initiative). . global mpi country briefing : india (south asia). retrieved from remittances, consumption and economic growth in kerala invisibles in india's balance of payments invisibles in india's balance of payments: an analysis of trade in services, remittances and income. reserve bank of india bulletin absorbing external shocks, the gulf crisis: international migration linkages and the indian economy, (with special reference to kerala) manpower and international labour migration in the middle east and north africa india's gdp mis-estimation: likelihood, magnitudes, mechanisms, and implications. cid faculty working paper no. industrial growth in kerala: trends and explanations. working paper no. , centre for development studies nas-nss estimates of private consumption for poverty estimation: a further comparative examination . remittances, investment and new emigration trends in kerala united nations development programme and oxford poverty and human development initiative). . charting pathways out of multidimensional poverty: achieving the sdgs return emigrants in kerala: rehabilitation problems and development potential migration mosaic in kerala: trends and determinants gulf revisited: economic consequences of emigration from kerala: emigration and unemployment. working paper , centre for development studies emigration and remittances in the context of the surge in oil prices dynamics of emigration and remittances in kerala: results from the kms dynamics of migration in kerala: dimensions, determinants and consequences. hyderabad: orient longmans socio-economic and demoigraphic consequences of migration in kerala we would like to place on record our thanks to k.c. zachariah and s.l. shetty for their comments on an earlier version of the paper and to jan breman, gerry rodgers, d. narasimha reddy, j. krishnamurty and k. pushpangadan for their comments and views on the current version. the authors alone are responsible for errors, if any. for estimating remittances to the kerala economy, we have computed the following: (i) the share of kerala in the net private transfers (npts) in the current account of the balance of payments of india, (ii) the non-resident indian (nri) deposits in banks located in kerala and (iii) the money equivalent of remittance in kind.computation of net private transfers: data relating to net private transfers to india are available according to currency areas (such as sterling area, dollar area, oecd area and rest of non-sterling area), but not according to countries or geographic regions such as the middle east till . however, it is well known that an overwhelming share of kerala emigrants is in the middle east countries. therefore, the first task is to estimate the npt to india from middle east countries and all other countries. based on the distribution of indians abroad, nayyar ( ) made certain assumptions for calculating the share of remittances to india from the middle east countries. they are given in table .for the period - to - , there was a modification in the data presentation of the reserve bank of india (rbi) in its reporting of private transfers key: cord- -d vbnjff authors: jha, vishwajeet title: forecasting the transmission of covid- in india using a data driven seird model date: - - journal: nan doi: nan sha: doc_id: cord_uid: d vbnjff the infections and fatalities due to sars-cov- virus for cases specific to india have been studied using a deterministic susceptible-exposed-infected-recovered-dead (seird) compartmental model. one of the most significant epidemiological parameter, namely the effective reproduction number of the infection is extracted from the daily growth rate data of reported infections and it is included in the model with a time variation. we evaluate the effect of control interventions implemented till now and estimate the case numbers for infections and deaths averted by these restrictive measures. we further provide a forecast on the extent of the future covid- transmission in india and predict the probable numbers of infections and fatalities under various potential scenarios. the infections and fatalities due to sars-cov- virus for cases specific to india have been studied using a deterministic susceptible-exposed-infected-recovered-dead (seird) compartmental model. one of the most significant epidemiological parameter, namely the effective reproduction number of the infection is extracted from the daily growth rate data of reported infections and it is included in the model with a time variation. we evaluate the effect of control interventions implemented till now and estimate the case numbers for infections and deaths averted by these restrictive measures. we further provide a forecast on the extent of the future covid- transmission in india and predict the probable numbers of infections and fatalities under various potential scenarios. almost every continent of the planet is grappling with a large number of infections arising due to virus called coronavirus , sars-cov- [ ] . these infections that may result in a mild to severe symptomatic disease called coronavirus disease or covid- were first detected in wuhan, a city in central china [ , ] . later the infections spread across the globe and it has forced nations to undertake drastic measures to minimize the loss of precious human lives [ , ] . for a populous country like india, which has a dense and large population (≈ . billion), the cause of concern is quite high. therefore, it is of special importance to study the spread of covid- in india, and make reliable predictions which can help in mitigation of its ensuing effects. these timely critical information may be crucial for devising strategies for containment of infections and estimating the requirements of medical facilities. in india an early complete nation-wide lock-down was imposed from th march when the number of cumulative sars-cov- infections were around . these strict measures prevented any large scale disaster and slowed down the rate of infections in the initial stages and helped in geographical containment of the epidemic. however, recent days have seen no real decrease perhaps due to gradual weakening of restrictive measures owing to pragmatic social and economic reasons. from june st india continues to have a complete lock-down only in the defined containment zones where the infection rates are high. these steps of gradual easing of lock-down have been necessitated as the balance between life and livelihoods are intertwined, which calls for invoking more intelligent strategies because a complete extended lockdown cannot be sustained for very long time without other competing collateral losses to the most vulnerable sections of society. alternative steps based on isolation of infected patients through the lock-down in the containment zones and more widespread testing and contacttracing are being followed for controlling the rate of infection. this represents the transition from suppression to mitigation strategy for the resolution of any potential outbreak but efficacy of these steps remains to be seen as the execution of these policies on ground level are challenging. the transmission dynamics of viral epidemics in any population is an interplay of various factors related to viral, immunologic, environmental and sociological conditions. a number of mathematical and physical models have been proposed in general to understand the evolution of epidemics, aiming to make reliable predictions so that to help governments to formulate proper policies and response plans for effective control of the disease [ ] [ ] [ ] . simple deterministic mathematical models based on the formulation of differential equations have been extensively used to provide information on the transmission mechanism of various viral epidemics. the sir model is a one of the simplest epidemiological models that is based on dividing the population among three compartments, the susceptible, the infected and the recovered (or deceased) populations and determining their time evolution [ ] . the seir [ ] model is a simple extension of the sir model, where an additional compartment of exposed population with a latency period is introduced which is more appropriate for covid- like epidemic which has an inherent latency and asymptomatic transmission [ ] . extended models have been employed that use several separate compartments for various sub-populations such as, asymptomatic, quarantined, hospitalized or components based on the variations for example, according to age, gender etc. [ , ] . however, this entails incorporation of many unknown parameters and uncertain initial conditions about which the information is either not available or there are large associated uncertainties. in the present article, we employ a dynamic seird model with the inclusion of population of deaths as a separate compartment in the seir model. several works have been already performed in the indian context to explain the covid- dynamics in the initial phase of its transmission [ ] [ ] [ ] [ ] [ ] . we incorporate the crucial parameter of contact period with a time variation connecting its value at the beginning of the epidemic to the current reduced value. the reduction in the values of contact rate has been achieved due to many isolation measures, primarily the imposed nation-wide lock-down. the time variation in the contact rate β(t) is determined through arxiv: . v [q-bio.pe] jun the effective reproduction number r(t) that is in turn related to the doubling time of the rate of infection growth [ ] [ ] [ ] . we integrate this parameter in the seird model calculations and estimate the role of interventions in preventing the number of probable infections and death till now. further, we consider different potential scenarios for the rate of growth of infections for making projections of sars-cov- transmission. we make a forecast for the probable numbers of infections and fatalities in the coming times. the projections provide information for the extent of suppression and containment strategies that need to be employed to mitigate the impact of covid- in coming times. it is to be mentioned that results obtained in this work are to be used for the research purposes only. the data for the present studies are collected from the repository hosted at website https://www.worldometers.info/coronavirus [ ] for cases specific to india. the epidemiology of the covid- outbreak using a deterministic seird model is studied with five compartments governed by a set of ordinary differential equations where, s(t) is the susceptible population, e(t) is the exposed population, i(t) is the infectious population, r(t) is the recovered population and d(t) is the number of deaths at any instant t and n = s + e + i + r + d is the total population. we have not included separate compartments for the number of asymptomatic, quarantined, hospitalized populations or the variations according to age or gender, as these lead to increase in number of unknown parameters and therefore lead to large uncertainties in the predictions. in any case, these numbers can be estimated in an average way with their relations to populations that have been considered. in addition, assumption about the no re-infection of the recovered population is made as there is no evidence to the contrary. the parameters of the above set of equations are the latent period of being exposed a = /φ that is related to the incubation period of the virus, the contact period b of infection = /β, the period of being free from being infected g = /γ commonly known as the recovery time , the parameter corresponding to death d = /δ of the infected population. these parameters determine the transitions that occur across the compartments as the time evolves. here, the parameters a, g and d are specific to characteristics of sars-cov- and only weakly correlated to the health responses of the country and therefore expected to have similar values across countries. the parameter b represents the strength (speed) of the virus transmission which is intimately related to the prevailing conditions of containment measures undertaken by specific countries. apart from these parameters, the fraction of the susceptible population at the beginning to the total population α = s( )/n is a very important parameter. taking total population of the region as s( ) may lead to gross overestimation of case numbers, because the part of population may be inherently immune or less affected by the virus or live in isolated conditions. furthermore, the extent of initial exposed latent population defined by = e( )/i( ), parameter, may also be an important parameter that indicates the presence of a number of undetected or asymptomatic exposed individuals at the beginning. one of the most significant parameters that describes the pandemic is the basic reproduction number of infection r , which is defined as the number of individuals that are infected from the uninfected, susceptible population by one infected individual under normal conditions [ , ] . there are challenges in determining r in terms of the parameters of deterministic model as one requires estimates of included parameters that are uncertain [ ] . during the spread of the epidemic one can define an effective reproduction number r i (t), which is a time dependent quantity that changes because of control measures and depletion of susceptible population. it provides the dynamic information on the strength of the epidemic transmission as the time evolves. in general, the infection continues to expand if r i (t) has values greater than , while the epidemic stops eventually if r i (t) is persistently less than . the estimation of the effective reproduction number is complicated and many models have been proposed for its determination [ , ] from the data. here we use a simple method based on fitting the incidence data growth rate by a distribution with gaussian shape to determine the behaviour of r i (t). it must be mentioned however, that reported data has an inherent delay as compared to the instantaneous population numbers that are required for the estimation of its actual value. in the sir -type models or their simple extensions, such as one described above r i (t) can be expressed as in the initial stages of the infection, s(t) ∼ n and r i = β γ , since (γ δ). the r i (t) value can be estimated using the initial doubling time t d of the number of infections [ ] the t d value can be determined by fitting the reported growth in the cases of infection, which shows an exponential growth at the beginning of the epidemic, where, the daily growth rate r(t) is determined from the data of reported cases of infections. at smaller values of the values of r(t) are extracted from the reported data of daily growth rate of infections starting from th march to th may (day ) with a -day moving average. it is fitted with a function in the following form where a, b, σ and t are fit parameters. these parameters are determined from the best fit approach through the local minimization of the sum of squares of the error. the resulting fit to the daily growth rate is shown in fig. a along with the band with standard error on fit parameters. in addition, the projections for next days after th may are also shown for various probable scenarios by the straight lines that are used for the extrapolations of infection growth rate. it is seen from the figure that india had a peak daily growth rate of ∼ % at the beginning of the epidemic which reduced to ∼ % after one month of imposition of lock-down. it is to be noted that the nationwide lock-down imposed on th march has been continually relaxed in phased manner and exists now only in the containment zones from st june. however, after the decrease in growth rate in infections in the initial phase following the lock-down, the cases of infection have continued to grow at somewhat constant rate for a while. the extrapolations for next days that define various probable scenarios are approximated as a linear reduction or increase from the present value of infection growth rate. the quantity r(t) determined from the data is also used to study the evolution of r i (t) in time as shown in fig. b . it must be noted that r i (t) also depends on the period of infection for which, we present the result for values g = . days and g = days. the r i (t) values have been extracted from the r(t) of the reported cases and also obtained through fitted value of r(t). these values are seen to decrease from a peak value of ∼ to a value of ∼ . for g = . days, which is still substantially higher than the value that is required for the spontaneous disappearance of the infection. the t d (t) value that is directly extracted from the data and also from the fit shows a constant value of ∼ days. the value of r i (t) and t d values are also shown for one probable scenario where the rate reduces by one-half of the present value in a linear manner. this shows a moderate reduction in the value of r i (t). in addition, the rate decrease leads to a significant increase in t d values. the seird model calculations using eqn. have been performed to make comparisons with the data aggregated for india using the reported cases of infected, recovered and dead populations up to th may and to make forecasts about the future scenarios. the contact rate parameter β(t) is taken to be time dependent with the parameters β and β c fixed in accordance of equation . the parameter a is taken as . days, which is the mean incubation period and bit larger than the latency period. the value of parameter δ = . is taken, which determines the death population and very weakly affects populations in other compartments. the parameter γ(t) is taken in the following form the time variation in this parameter with γ = . corresponding to period of . days and κ= . takes into account the larger value of g ≈ days that is needed to explain the behaviour of data in the initial stages. as the time elapses, a reduction in the recovery period is seen and γ approaches γ value. the model was applied from the day of the epidemic when cumulative number of infections were ∼ as on th march. the fraction of the population at day in compartments are set as follows : i = / . e , r = / . e and d = / . e as provided by the reported data. other initial conditions, defined by α and are the unknowns in the model. we take α= . which is similar to value of α= . extracted for european countries in ref. [ ] . the parameter = . a, is important for the initial description of data but it does not affect long time dynamics of the epidemic as predicted by the model. the results of calculations with these parameters that use the time varying β(t) parameter as determined above provide a good description of the evolution in the case numbers of reported infected, recovered and death population as shown in fig. a . in addition, the calculations have also been performed for constant β = . value, which is obtained from the best fit to the exponential distribution according to eqn. . while the model results as shown in fig. b provide a good description in initial days, it grossly over-predicts the case numbers as compared to the reported cases. it is quite evident from the figure that the time dependence of β(t) is necessary to understand the dynamics of infection spread for cases in india. the period of infection related to the recovery time of the infected individuals is also taken with a time variation. this parameter is primarily the characteristic of the epidemic and it is only mildly dependent on the responses of the health-care systems. in absence of any effective therapy or cure that may shorten the length of the infection it is relatively well known and it is taken as ∼ . days. however, larger value is required to explain the reported data both with constant β-value [ ] or even when time variation in β-value is taken into account as it has been found in the present study. the recovery rates are continually improving, a feature also reflected in the reported recovery data. therefore, a time dependence in the parameter γ(t) is introduced to account for this observation. we show the calculations in fig. to study the role of interventions we perform calculations with different values for the contact rate β. the interventions have led to a decrease in the daily growth rate of infections which is intimately related to the β value. we use the constant values of β = . and . , which correspond to the peak rate of growth and half its value. the peak β-rate is expected to have prevailed in the early stages of infection spread in the absence of any interventions such as, the lock-down or the conditions of no enhanced public awareness. in addition, we also give results obtained from the β = . , β = . and time varying β-value. the infected, recovered and death populations for these β-values are shown in fig. a, fig. b and fig. c , respectively. from the comparison it is evident that the lock-down and other interventions have prevented any large spread of infections and kept the death numbers particularly low. these interventions could have prevented around million peak infections and , deaths at the day mark. the lower growth rate also means that number of active infections are low at any instant which helps to optimize the response of health care systems. the rate of infections in india have remained approximately constant after the initial reduction for last several days. after an extended lock-down slowly the restrictions have been loosened up. we extrapolate values of β(t) to predict the outcomes of various probable scenarios. the β(t) values corresponding to growth rate value r pr as on th may are varied so as to attain a given value at the end of next days assuming a time variation with constant slope. these scenarios are named as the best case, the optimistic case, the most likely, current, problematic and alarming scenarios respectively. the time evolution of the epidemic is studied with these time variations for the future. the resulting predictions for the populations of infected, recovered and dead are shown in fig. a, fig. b and fig. c respectively. the growth rate same as r pr may lead to a high number of total infections (∼ million) with fatalities in excess of , . in the scenario that we term as the most likely scenario, we can have a total of . million infected cases with almost , fatalities over the course of pandemic. this will correspond to a in this case, the death figures can be kept substantially low in the range of , - , . in contrast, if the rate of growth were to increase from the present values due to pre-mature lifting of the lock-down in the affected zones and other lapses, the death numbers can be , with a rather alarming number of infected individuals in short time. higher rates of growth also mean the large number of active infected cases appearing early and that may stretch the health care systems to the brink. we have made detailed comparison of model predictions with the real data using the important parameter of contact rate and infection rate derived from the data itself from the first principles. it must be noted that there is an inherent delay in the reported rate and instantaneous rate of the infection. in addition, the effect of any restrictive measures undertaken appears with a delay in the reported rate, which is estimated by the fit parameter t ∼ days in the present case. the model calculations are able to describe very well the case number of infected and recovered populations of reported data till now. the imposed restrictions have led to a reduction in the r i (t) and an increase in the t d values as the time elapses. the quantitative measure of the intensity of the imposed lockdown that reduced the growth rate r(t) to almost half its value is given by the fit parameter σ = days. it is seen from the calculations that a large number of infections and fatalities have been averted due to imposition of the lock-down. some part of this reduction may be ascribed to the enhanced public awareness, and growing disease monitoring and testing capabilities with the passage of time. however, effect of complete lock-down in reducing the infection rate has been quite significant. after the initial period of days following the complete lock-down, there has not been much gain in the reduction of infection spread rate in last days. it is probable that the gradual weakening of the lock-down due to socio-economic reasons might have offset the gains due to restrictive measures. nevertheless, the continued restrictions have prevented any rise in the rate of growth of infections, which in absence of any such measures is expected to rise again. even the growth rate of ∼ − % attained so far implies an exponential growth and it is seen that the epidemic in india is still in early stages. current estimates of future trends in new infections in the weeks after th may suggest that more severe outbreak may occur in coming times leading to high number of infections. with the estimates from the most likely scenario, over , would be clinically diagnosed at the maximum resulting in ∼ , total fatalities. impact of the severity of the disease outbreak is quantified through the case fatality ratio (cfr). it is defined as the ratio of fatality rate d(t) to the cumulative number of infections c(t). the cfr values have varied from ∼ . - . as on april to the present day which is less than the global average of ∼ . . however, some doubts remain about the estimations of cfr because it is possi- ble that both the number of fatalities and infections may be underestimated. it is more likely that c(t) may be underestimated more due to the presence of large number of asymptomatic or non-critical infected cases which leads to the overestimation of cfr, assuming reported d(t) cases to be true. cfr remains low as long as the health facilities are able to cope with the rate of patients requiring critical care. in the scenarios if the number of active infected cases is large as predicted by multiple scenarios described above, requirements of hospitalizations and critical care resources may increase sharply. in such a situation, the health care system is going to be severely challenged in providing the critical care facilities for prevention of fatalities. the cfr in these conditions may rise to higher values. therefore, imposing stricter measures inside the containment zones and more extensive testing and contact-tracing seems to be only viable logical preventive option that can lead to a manageable reduction in infected cases and casualties in absence of any therapies or large-scale immunity. there are limitations of the simplistic model employed here and therefore the exact quantitative numbers presented in the work are only indicative. in the present model, the asymptomatic populations are taken only in an indirect way at the start of the epidemic through the introduction of the parameter . inclusion of this population as a separate compartment however would lead to introduction of extra set of unknown parameters. further, we have not considered the regional and age specific heterogeneities in the model. while we have made a reasonable assumption for the parameter α = . , implying a % of the total population as the susceptible population, the overall numbers presented in this work may differ if it has a significantly different value. this number is going to be affected as the country has seen large scale migration from the infected areas to the other areas in recent times which may increase the pool of susceptible population. further, we have made forecasts in this work based on probable daily growth rates. the determination of contact rate parameter through the measured rate in the simple way is uncertain due to stochastic fluctuations in the early stages and inaccuracies and time delay of the reported data. further, there are challenges on designing the control mechanisms based on the basis of the numbers of daily growth as discussed in ref. [ ] . however, this work shows the operational use of the r i (t) calculated from the instantaneous infection rate to provide a reasonable description of the transmission dynamics. in this article, we have presented results of seird model calculations to study the role of interventions and make future projections in the covid- spread in india. to make reliable forecast we have determined the time dependent reproduction number r i (t) and contact rate parameter β(t) from the data for the daily rate of increase of infections. it is shown that timely imposition of lock-down and other public health interventions have led to a substantial reduction in the effective reproduction number which decreased to a present value of ≈ . from the peak value of ≈ . corresponding to an increase in the doubling time of the infections. calculations performed using the time dependent contact rate parameter β(t) in the seird model provide a good description of the case numbers of infections, recovered and deaths. we further make the projections for different probable scenarios. in the most likely scenario the model predicts a peak of active infections around the month of september with significant number of fatalities over the course of the epidemic around end of november. the results show the impending critical challenges for health care systems due to prospective high number of people with infections. the salient feature of the simple model employed in this work is the use of minimal uncertain parameters and therefore in our opinion it makes reliable predictions of the infections and fatalities. the projections of peak infections suggest big challenges for the available critical care health facilities in the management of pandemic. new innovative solutions have to be continuously found and intelligent measures have to be effectively implemented if the covid- infections have to be contained with a moderate number and the ensuing fatalities have to be minimized. the most important extension of this study will be to incorporate the regional variability and apply this model by considering the state wise infection data and make predictions accordingly. situation report infectious diseases of humans cal epidemiology of infectious diseases: model building, analysis and interpretation mathematical models in population biology and epidemiology nd edn seasonality and perioddoubling bifurcation in an epidemic model swarnajit chatterjee, mintu karmakar and raja paul medarxiv we thank v. v. parkar, d. k. mishra and g. chaudhuri for useful discussions and their interest in the work. key: cord- -awv sp m authors: iyengar, karthikeyan p.; ish, pranav; upadhyaya, gaurav kumar; malhotra, nipun; vaishya, raju; jain, vijay k. title: covid- and mortality in doctors date: - - journal: diabetes metab syndr doi: . /j.dsx. . . sha: doc_id: cord_uid: awv sp m background and aims: covid- disease appear to have been associated with significant mortality amongst doctors and health care workers globally. we explore the various risk factors associated with this occupational risk, especially focusing on india. this may elucidate lessons to protect these frontline workers during the covid- pandemic. methods: we carried out a comprehensive review of the literature using suitable keywords such as ‘covid- ’, ‘pandemics’, ‘physicians’ ‘mortality’ and ‘health personnel’ on the search engines of pubmed, scopus, google scholar and researchgate in the month of july during the current covid- pandemic and assessed mortality data. results: mortality in health care professionals has been on the rise. the countries which faced the pandemic in the early months of have had a huge surge in mortality amongst doctors due to covid- . india continues to show a rising trend in covid- cases, however although compared to the western world india has seen a comparatively favourable statistic. male gender, elderly doctors and those belonging to black, asian, and minority ethnic (bame) community seem to be predisposing factors in the western world. conclusion: covid- has been associated with an increased mortality in doctors and health care workers. until an effective cure/vaccine is developed, risk assessments at work, mitigating confounding factors, adequate supply of personal protective equipment (ppe) and enhanced protection against infection are necessary to protect health care professionals on the coronavirus frontline. otherwise this occupational risk can lead to further untimely mortality and become another unintended consequence of the covid- pandemic. the novel coronavirus sars-cov- outbreak has created a significant impact on the daily life and health care systems across the world including india [ ] [ ] [ ] . covid- has caused a huge burden and loss to the world with doctors bearing the brunt of physical burnout, mental stress, occupational risk of infection with increased risk of morbidity and mortality, being the front-line workers. currently india is the third worst affected country in the world with more than million confirmed cases and above , deaths attributed to covid- [ ] . it has been observed that covid- related mortality in the general population has been slightly lower in the south asian subcontinent. [ ] concerns have been raised since nearly doctors have succumbed to covid- so far with a significant number of healthcare professionals affected as well. [ ] the mortality of these doctors has made a dent in an already compromised health care system due to poor doctor patient ratio. the indian medical association (ima) national covid- registry data suggests more than doctors have been infected with sars-cov- virus, where % of them are above the age of years. [ ] doctors face multiple challenges while dealing with this pandemic-specially limited personal protective equipment (ppe), training, rest, and rotation but worst of all loss of life due to coronavirus infection [ , ] . ima has issued a 'red alert' and requested the health authorities to ensure adequate safety of all doctors along with support from state sponsored medical and life insurance facilities to all involved in the coronavirus containment efforts. [ ] we aim to explore the burden, the risk factors and lessons that can be learnt to protect these frontline workers. as on date april ; countries with the most reported physician deaths were from italy %, iran %, philippines %, indonesia %, china %, spain %, usa %, and uk ( / ; %) [ ] . even though there is no global platform for assessing the mortality among doctors due to covid- , reported literature in the national media has raised concern (table ). doctors account for . per cent of the total deaths in india due to covid- .there have been reported deaths among doctors in india due to covid- as reported by ima over the last months until august after reporting of the first covid- case on january [ , ] . developed nations in europe, however, have had worse figures. italy reported its th covid- casualty amongst doctors back in april [ ] . the reasons could be unpreparedness of these countries in terms of ppe, delayed implementation of social j o u r n a l p r e -p r o o f distancing and infection prevention strategies, and late lockdown in the early phase of the pandemic. we have identified several risk factors that are associated with increased mortality amongst the healthcare workers and doctors. . age and gender-yoshida reported deaths of medical doctors up to april in the early months of covid- [ ] . out of them were between - years of age with a median age of years and were males. no reason for this disparity has been described in the article. the results of other meta-analysis showed that % of the covid- patients were male [ ] . the reason for a disproportionate mortality in the male gender is unclear. lack of hand hygiene may be a causative factor for increased prevalence of covid- infection in males. social roles of females in asian countries like india such as cooking, house cleaning etc may sensitize females to having a different perspective towards hand hygiene. higher rates of tobacco consumption, increased concentration of angiotensin-converting enzyme (ace- ) in males as compared to females, a reluctance to seek proper and timely medical care and even lower rates of handwashing absolutely has been quoted to be few of the reasons [ ] . as observed about the deaths amongst the general population most of fatality were seen among elderly male doctors [ ] . the reasons postulated are these senior physicians had re-started to work during the earlier part of the pandemic when protection may have been insufficient, or they had associated co-morbidities. covid- [ ] . frontline doctors that deal with covid- patients seem to bear the brunt of mortality rates. deaths were noted to be more common among general practitioners or physicians, suggesting a higher risk of deaths among doctors who may have repeated encounters with covid- patients [ ] . physicians from certain fields of medicine such as anaesthesiology, dentistry and otorhinolaryngology are more prone to acquire covid- as their work involves intubation, oral/nasal or other aerosol generating procedures, which may place them at an increased risk and table seems to suggest that. preventive strategy against covid- is a stringent and effective use of personal protective equipment (ppe). in early april, when the outbreak was exponentially increasing in magnitude in europe, concerns regarding a lack of ppe were voiced by health care professionals across multiple countries in the continent [ , ] . soon, the lack of numbers of ppe was managed by development of effective reuse methods and an increase in the production capacity of ppe. shown to have a significant bearing on the course of covid- disease. it has been acknowledged that there is disproportionate mortality and morbidity amongst black, asian and minority ethnic (bame) people, including our national health service (nhs) staff, who have contracted covid- [ , ] . a large proportion of bame healthcare workers were more severely affected by covid- at the beginning of the pandemic succumbed to the disease. % of doctors who lost their lives were of a bame background [ ] . a multitude of confounding reasons including individual patient factors, genetic susceptibility, socio-economic factors, associated comorbidities have been postulated to suggest higher disease burden in bame people including doctors with calls for urgent public health research priority in this discrepancy [ ] . include lack of adequate ppe, inadequate technique of donning and doffing, nondisclosure by patients of their exposure to possible covid- excessive working hours and poor doctor-patient ratio. certain comorbidities including advancing age, diabetes mellitus, cardiovascular diseases, chronic lung disease or immunocompromised states are also contributory [ ] . • india is a country with a large population where most of the patients seek treatment in government hospitals. the outpatients of these hospitals have been flooded with patients even during the lockdown period. it has been difficult to organise testing for covid- of all patients visiting these hospitals. this could be another cause of exposure to the doctors from these patients. most of the elderly doctors having comorbidities continued to do private practice without taking proper precautions succumbs to death in various states across india. in bihar, the percentage of doctors' death is . per cent, which is nine times more than the national average. one of the reasons for more doctors' death in the bihar state was doctor's work for more than j o u r n a l p r e -p r o o f longer days than the other states as the quarantine protocol of days was not followed in managing covid patient and due to large number of vacant post of doctors; the elderly and comorbid doctors were forced to perform duty and got no relief. [ ] • as such lack of covid- safe facilities, resources, availability of appropriate ppe and lack of uniform application of infection prevention strategies remain cause of concerns and an occupational risk for health care professionals in india. • however, cues have been taken with a stringent lockdown, creation of dedicated covid facilities, indigenous production of ppe and sanitisers, enforced central health guidelines and protocols. training of the health care workers on use of ppe and prevention of spread of infection has been carried out [ ] . • by the time india saw a substantial growth in covid- patients, the production and import of ppe had already been ramped up in the country. however, even with this increased capacity, a shortage of ppe was expected in the country considering the population. the country's premier medical institute (all india institute of medical science (aiims) delhi, issued timely guidelines on the reuse of ppe [ ] . these measures may have contributed significantly towards reducing the effect of ppe shortfall. • current data from the ima (table ) suggests general practitioners, primary care physicians and emergency doctors dealing acute or active covid- cases seem to be disproportionately affected. the ima national registry is a good step forward and initiatives such by nhs england to launch an enquiry into excess bame nhs deaths will help the world community to understand the mitigating factors leading to hcp deaths and take steps to protect them. [ ] • all the health care workers and doctors should screen for tuberculosis and a major comorbidity such as diabetes before start practicing or doing covid- duties. as history of latent or active tuberculosis is an important risk factor for acquiring covid- infection. [ , ] limitation of the study covid- is an evolving disease. there is lack of uniform database on morbidity and mortality statistics due to covid- amongst doctors and health care workers globally. this effects of covid pandemic in daily life the rise and impact of covid- in india covid- : challenges and its consequences for rural health care in india differential mortality in covid- patients from india and western countries times of india. ima says nearly doctors in india have succumbed to covid at least doctors succumbed, , infected in india: ima gaps in india's preparedness for covid- control indian response to covid- : expertise and transparency the economic times. ima says doctors succumbed to covid- , issues 'red alert' for medicos physician deaths from corona virus (covid- ) disease ima says nearly doctors in india have succumbed to covid- so far: requests pm's attention coronavirus in india: how the covid- could impact the fast-growing economy on the death of + italian doctors from covid- . infection ( ) may ; - characteristics of doctors' fatality due to covid- in western europe and asia-pacific countries covid- patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis why are so many more men dying from coronavirus? available at covid- -a very visible pandemic covid- mortality in italian doctors guidance on supply and use of ppe tribute to health workers in china: a group of respectable population during the outbreak of the covid- lacking beds, masks and doctors, europe's health services struggle to cope with the coronavirus personal protective equipment and covid -a risk to healthcare staff? covid- hospitalization and death by race/ethnicity. available at addressing impact of covid- on bame staff in the nhs deaths in healthcare workers due to covid- : the need for robust data and analysis ethnicity and covid- : an urgent public health research priority covid- : risk factors for severe disease and death hindustan times, patna. death rate among doctors due to covid far more in bihar, says ima official concerns of frontline doctors in india during covid- : a cross-sectional survey appropriate use of various types of personal protective equipment (ppe triple layer masks, n masks, gowns, goggles, gloves, kits etc) at aiims as part of covid- preparedness supporting our bame nhs people during and beyond covid- : an update tuberculosis in the era of covid- in india tuberculosis and covid- in india-double trouble! indian j tuberc key: cord- -deu ma authors: prabhu, shreekanth m.; subramaniam, natarajan title: surveillance of covid- pandemic using hidden markov model date: - - journal: nan doi: nan sha: doc_id: cord_uid: deu ma covid- pandemic has brought the whole world to a stand-still over the last few months. in particular the pace at which pandemic has spread has taken everybody off-guard. the governments across the world have responded by imposing lock-downs, stopping/restricting travel and mandating social distancing. on the positive side there is wide availability of information on active cases, recoveries and deaths collected daily across regions. however, what has been particularly challenging is to track the spread of the disease by asymptomatic carriers termed as super-spreaders. in this paper we look at applying hidden markov model to get a better assessment of extent of spread. the outcome of such analysis can be useful to governments to design the required interventions/responses in a calibrated manner. the data we have chosen to analyze pertains to indian scenario. covid- is the name given by who to the disease caused by sars cov- virus. whereas the death rates of earlier sars virus were higher than cov- virus, as a pandemic covid- has spread far more speedily infecting lakhs of people. over the last few decades and centuries there has been incidence of pandemics and losses of human lives on large scale from time to time. however, the terminology around pandemic can be confusing. an endemic is something that happens to a particular people or region. for example, malaria is endemic to certain countries. an outbreak is a greater-than-anticipated increase in the number of endemic cases. it can also be a single case in a new area. thus, an outbreak can happen in regions where a given disease is endemic or in totally new regions. if it's not quickly controlled, an outbreak can become an epidemic. an epidemic is often localized to a region, but the number of those infected in that region is significantly higher than normal. when an epidemic spread world-wide due to travel or other reasons it is termed pandemic. it is the geographic spread that is vital to spread of pandemic [ ] . naturally the first response to arrest covid- spread should have been ban of travel from and to regions where the disease was endemic. however due to complex factors which played out that did not happen in a timely manner and the pandemic has been spreading since early january when it was publicly acknowledged world-wide. on top of that people travelling in from only certain countries were screened while infection had already spread to lot more countries. the travellers who did not display symptoms were asked to be in isolation and those who displayed symptoms were quarantined. this again did not happen to the degree that was needed. once an outbreak happens in a new region, expected response was to arrest further spread to more people. this however could only be done retroactively by tracing contacts a newly detected person may have encountered and testing them. the governments had limited capacity to test and they needed to manage them judiciously. this resulted in continued spread of the disease in a latent manner. the covid- spread from person to person via droplets that got dispersed when a person was coughing, sneezing or even talking. it was also suspected that the virus spread through surfaces and on certain surfaces the virus lasted for couple of days or more. many of these conclusions were based on simulation studies and not necessarily attested from field studies. in addition to pervasive mode of spreading another challenge with covid- is that many infected people do not display any symptoms for long periods. table below compares covid- with other viruses [ ] . you can see that covid- has the longest incubation period during which virus can be contagious i.e. even before the symptoms start. a person will continue to be contagious with onset of symptoms and may be for some more time even after recovery. it was also seen that those with pre-existing health problems were more vulnerable. on an average the disease impacted the elderly lot more. in the case of any new virus, medical communities take a few months in the least to come up with a vaccine that can build immunity among people. further, vaccines are of no use to people already sick. to treat them suitable antiviral drugs are needed which can shorten the time people are unwell. they may need to be taken early on and may not work in every case. there has been vocal community of experts urging governments to test, test and test. but considering the size of populations involved and the scale of effort required it has proved impractical. at the same time, it is worthwhile to test only in regions and among communities where there is a possible outbreak. inviting people to common testing facilities can itself expose them to chance of infection. even though there has been debates about herd immunity by allowing the virus to spread among healthier people, making such calls has been rather highly risky. finally, it is not health experts but the politicians and governments who have to take responsibility for their actions. general information on covid- is presented in a lucid manner by robert roy britt [ ] . currently india as of early may , is possibly able to flatten the curve but yet to see a dip in infections [ ] . the situation can change unpredictably as more people are allowed to travel back to india or across india. we hope that this work can help governments calibrate interventions/responses using a relatively simple model. we also outline strategies for building more complex models to deliver fine-grained analysis. the remaining part of the paper is structured as follows. section , covers literature survey where we cover literature on surveillance of past pandemics followed by literature related to covid- . section covers the proposed methodology for covid- pandemic surveillance using hidden markov model. section presents results on application of the proposed methodology to indian context. in section , we make a list of recommendations for better surveillance of covid- pandemic in india. section concludes the paper. the three pandemics in the twentieth century killed between and million people and the h n "swine flu" exposed vulnerabilities that we still have to influenza epidemics. david hutton [ ] has done a review of operations research tools and techniques used for influenza pandemic planning. he covers instances where simulation modelling is used in as a way of representing the real world and being able to estimate the impact of interventions and to improve their performance. among the simulation models, system dynamics approach can capture how the changing level of infection and immunity in the population affects the spread of future infections in the population. system dynamics modelling techniques have been applied to pandemic influenza preparedness problems as varied as social distancing, vaccination, antiviral treatment, and portfolio analysis of interventions. larsen [ ] showed with his simple model that the people with high rates of contact drove the initial growth of the epidemic and that targeting social distancing (reducing contact rates) to the correct subpopulations with high contact rates can prevent the epidemic with limited disruption to the remaining population. nigmatulina and larson [ ] built off that simple dynamic compartmental model of influenza to include multiple interconnected communities. each community has citizens that interact with each other and is connected to other communities by a few travellers each day. this might represent towns near each other. they used this model to compare the impact of vaccination and travel restrictions. they also find that travel restrictions will not be effective: only a complete % travel restriction would stop or significantly slow transmission between communities. the above analysis [ ] and the one by larson alone [ ] use very simple models that can be implemented in spreadsheets, but they provide very powerful policy insights. system dynamics models also have been used to evaluate antiviral use [ ] as well as vaccine delivery mechanisms [ ] and optimal allocation of health-care resources. discrete event simulations are used to manage distribution systems. agent based models have been used where more elaborate data is available to decide on policy choices such as who should be vaccinated first [ ] . vaccine selection problem can be formulated as optimization problem when one has to choose between releasing an available vaccine or waiting for better vaccine. along the same lines, hutton refers to cases where decision analysis, game theory and supply chain analysis are used to manage health-care resources. rath et al. [ ] made use of hidden markov model for automated detection of influenza epidemic. he builds on serfling's method that is commonly used for influenza surveillance. the method uses cyclic regression (to address cyclical data owing to seasonality of epidemics) to model the weekly proportion of deaths from pneumonia and influenza and to define an epidemic threshold that is adjusted for seasonal effects. that approach however suffers from several shortcomings, such as the need for non-epidemic data to model the baseline distribution, and the fact that observations are treated as independent and identically distributed. this can be handled by modeling the data as time series and use hidden markov model to segment it as non-epidemic and epidemic phases. rath et al. in their paper have used exponential distribution for non-epidemic phase and gaussian distribution for epidemic phase. this is a refinement over the work done by le strat & carrat [ ] who made use of only gaussian distributions. covid- pandemic has been an active area of research last few months. there have also been large number of articles in main-stream, social media and as part of professional health-care literature. here we cover literature related to testing procedures and pharmaceutical interventions, non-pharmaceutical interventions followed by mathematical analysis of forecasts globally and in india. finally, we look at aspects related to surveillance and social implications. nandini sethuraman et al. [ ] emphasize on importance of timing to get the correct results in real time reverse transcription-polymerase chain reaction (rt-pcr) tests that are used to detect sars-cov- rna as illustrated in figure below. thus, there is a very real possibility that a sizable number of covid- cases are not detected on testing. as shown in figure above, the negative results do not preclude sars-cov- infection. on top of this, administering rt-pcr tests for the identification of sars-cov- rna is complex and needs specifically trained man-power [ ] . the sars-cov- rna is generally detectable in respiratory specimens during the acute phase of infection. positive results need to be clinically correlated with patient history and other diagnostic information, after ruling out bacterial infection or co-infection with other viruses. according to wikramaratna et al. [ ] , rt-pcr tests are highly specific and the probability of false positives is low but false negatives can also occur if the sample contains insufficient quantities of the virus to be successfully amplified and detected. xu et al. [ ] propose alternative diagnosis via ct scans in combination with deep learning techniques to address relatively low positive rate of rt-pcr tests in the early stage to determine covid- . there is similar work which makes use of x-rays and cnn [ ] . feng shi et al. [ ] made use of random forest algorithms along with ct-scans. they claim detection of rt-pcr tests is only - percent, requiring repeated tests. as far as other pharmaceutical interventions go, there is work that recommends antibody-based therapies [ ] and discovery of potential drugs using deep learning methods [ ] . there were studies on effectiveness of hydroxychloroquine and azithromycin, which concluded that for serious patients they did not affect mortality outcomes [ ] . more studies may be needed here. k. kang et al. [ ] talk about repurposing existing drugs by making use of ai to predict drug-target interactions. w, zhang p [ ] have studied herd immunity and vaccination game. they inform that herd immunity can be achieved by voluntary, private vaccination. as of now, research is yet to establish long-term post-infection immunity from covid- [ ] . ferguson et al. [ ] from imperial college london classified possible non-pharmaceutic interventions to tackle covid- under mitigation with focus on slowing the epidemic spread and suppression with objective of reversing the epidemic growth. whereas mitigation included detection, isolation and quarantine of suspect cases, suppression required lock-down of large regions save for bare essentials. they concluded that mitigation is unlikely to be a viable option without overwhelming healthcare systems, suppression is likely necessary in countries able to implement the intensive controls required. some authors [ ] suggested strategies to come out of lock-downs by combining green zones and allowing movements in disconnected zones. there has been flurry of response by mobile app developers to tackle issues related to surveillance with privacy, health and well-being in the context of covid- [ ] . yanfang ye et al. [ ] worked on risk assessment of communities by looking at combination of disease-related, demographic, mobility and social media data. there is also research work [ ] on monitoring covid- social distancing using person detection. kathakali biswas and parongama sen [ ] analyzed the space-time dependence of novel corona virus outbreak using sir model and data from china. their research showed inverse-square law dependence of number of cases against distance from the epicenter. kathakali biswas et al. [ ] also predicted exponential growth of cases based on sir model. their model could also predict how long the disease may last. however. research by anna l ziff and robert m ziff [ ] pointed to exponential growth in death-rates followed by power-law behavior when epidemic peaks and only then exponential decline in death rates. tim k tsang et al. [ ] did a study on how changing case definitions impacted analysis of disease spread in china, leading to overestimation of basic reproductive numbers. some studies [ ] concluded even after the lockdown of wuhan on january , , the number of patients with serious covid- cases continued to rise, exceeding local hospitalization and icu capacities for at least a month. fotios petropoulos et al. [ ] conclude that not only the covid- numbers will grow but also uncertainty about forecasts will also grow. plos editors [ ] are vocal in decrying uncertainty in predicting the manifestation of virus in different countries and difficulties in reconciling potentially contradictory data and advice from models and researchers in managing conflicting political, economic and health priorities. vivek verma et al. [ ] made use of time-to-death periods/lethal periods to predict the morality rates. vishwesha guttal [ ] in their paper covered risk assessment via layered mobile tracing. eksin et al. [ ] have made modifications to standard sir/seir epidemiological models to account for social distancing to arrive at more realistic predictions. some countries have been more successful than others in surveillance of the pandemic. rapid identification and isolation of cases, quarantine of close contacts, and active monitoring of other contacts have been effective in suppressing expansion of the outbreak in singapore [ ] . south korea as widely reported in the press, was successful in containing the disease by using anti-body testing. in india however anti-body test setups imported from china failed to work reliably. the paper [ ] covered the details of french surveillance system and early experience with covid- . kissler et al. [ ] have analyzed the potential transmission dynamics through the pandemic period and beyond. they expect the disease to be around at least till may be with a break. there are many studies that predicted the growth of covid- cases in india. the very first wellknown study [ ] hidden markov model has great promise in the surveillance of covid- pandemic. this is because certain transitions happening in the progression of virus in the larger society have an association with time series data on confirmed/active cases, recoveries and deaths reported from hospitals. a generic hidden markov model is illustrated in figure , where the xi represent the hidden state sequence. the markov process which is hidden behind the dashed line is determined by the current state and state-transition probability matrix a. we are only able to observe the oi, which are related to the (hidden) states of the markov process by the observation probability matrix b. both the matrices a and b are row-stochastic as well as π which contains initial probabilities of hidden states. a, b and π together constitute the hidden markov model. we propose to make use of hidden markov model to perform surveillance of covid- spread. in our model, with each region we associate a state. thus, we define hidden states which should model majority of situations namely healthy, infected, symptomatic and detected. in addition, we define additional states that may seldom get used namely catastrophe- and catastrophe- . table below describes the hidden states. healthy this is the state a region is in prior to the first outbreak of disease and when the region is moving towards normalcy (or non-epidemic phase) h infected people are at different points in incubation phase of - period. general awareness is low and degree of complacency prevails about the disease due to low cases. this is the state of a region when a region is clearly in epidemic phase and patients come to know about their disease after onset of symptoms, typically in later part of incubation phase. this is the state of a region when region is in epidemic phase and patients come to know about their disease before the onset of symptoms during early part of incubation phase. the dynamics of spread suddenly alters due to large number of outward migrations of infected people. the dynamics of spread suddenly alters due to large number of deaths may be due to health sector capacity issues. the above states are aptly considered hidden as in the absence of exhaustive, expensive and repeated testing it is hard to know what state a given region is in at a given point in time. table below represents observations. these observations pertain to reportage on a given day as far as net additions are concerned. dead these observations pertain to additional deaths reported on a given day. total number of deaths reported is generally expected to monotonically increase over time. in these cases, patients could not recover from the disease and expire during the treatment or brought dead to hospitals/reported dead to the authorities. inactive (or active complement) these observations pertain to reduction in the active number of cases. here capacity to treat patients in hospital is freed up due to reduction in active number of cases. the cumulative count of above cases is reported under confirmed. welfare, government of india on their website [ ] . india related data is also available in greater detail on kaggle platform [ ] . for our work, we make use of the former, as it is adequate and convenient. on each day, the public health authorities report aggregate information on confirmed cases, active cases, deaths and recoveries. a, b, π) that best fit the training data where a is state-transition probability matrix, b is visible symbol probability matrix and π is probability distribution of hidden states at the initial stage. for the covid- surveillance scenario, we propose the following alternative solution approach to learning problem instead of standard baum-welch forward-backward em algorithm. . choose a vector of observation sequences catering to different region. each region on a given day can generate a, d, r and a-symbols in different numbers that account for change of observed states of patients on a given day. based on the visible symbols generated above we infer state symbols for that day as follows. thus, at the end of steps to , we have a hidden markov model comprising of a, b and π. the model can then be used for evaluation problem and decoding problem. the state distributions arrived using this model on a given day can be used by governments to design interventions in a calibrated manner. we can further refine the model by using numeric values for probability for b from the model in step and arrive at more refined values of a. we made use of the data on covid- published on daily basis by the ministry of health and family welfare [ ] , government of india to train the hmm. the approach we chose was to make reasonable assumptions about mapping between data reported by hospitals and state of infection in regions as shown in table . then by making use of inferred states we derive state transitions. we followed this approach for data between th april and may th , which is detailed in tables a and b. then based on the derived state transitions we arrive at state transition matrix(a). the computation of which is described in table . now based on our knowledge of states inferred, we compute the observation probability matrix b as shown in table . thus, based on analysis of data between april th and may th we have a refined model parameter b with quantitative values compared to qualitative inferences we started with. we also have learnt the hmm parameter a i.e state transition matrix. now the model learnt is described in table . to enable regional analysis, we provide table that lists the states/uts based on their hidden states and table that reports hidden state sequences for last one week for each of the states and uts. we have chosen to use the model in table only for prospective data (and not retrospectively). we believe this is an appropriate decision as we are primarily looking at sequential data figure illustrates state transitions and figure depicts corresponding mapping between observations and inferred states. figure shows the distribution of inferred states. in all these cases we have used our initial approach for data between april th and may th and then use the learnt model for data between may th to th the approach we recommend is to recompute and refine the hmm every two weeks and apply for the prospective data. we made use of the refined model as of may th for the period may to and data as of june th . the hidden state sequences region-wise along with active cases all the way to june , are shown in table . figure illustrate hidden state transition probabilities of states(regions) of concern compared to similar states(regions). here we assume that the transition sequence leads us towards normalization and hence benign. these transitions are represented clock-wise and with solid-lines. the transitions in opposite sequence are considered as matter of concern and they are represented using dashed-lines and/or in anti-clockwise manner. transition back to the same state is considered benign in case of healthy states as well as detected states. the latter ensures timely detection of pandemic spread. transition back to the same state is considered a matter of concern in case of symptomatic as well as infected states. as earlier benign transitions are marked using solid lines and others using dashd lines. further after a gap of a month we reviewed the data on covid- spread in india on july th and arrived at the hidden states with june th as the base date. the status of states as on july th is given in table . then again, we assessed the incremental spread on july th relative to data on the th and the inferred hidden states of different states and union territories are given in table . in this section we analyse the results we have obtained in order to make policy/process recommendations. we can make the following observations regarding covid- pandemic surveillance in india. it is to be noted that because of inter-state movements of migrants there was some impact on the covid- scenario where certain states may have reported surge in the number of cases due to influx of migrants. here figure , table and table illustrate the data as of may th and figure - illustrate the data as of june th . as shown in figure , the number of healthy states has remained around the same and new infections seem to be still breaking out. on the positive side there seems to be steady reduction in the symptomatic states and increase in the number of detected states. this means there is early detection of the cases to greater degree than earlier. . table overall while things continue to be of concern in delhi, they most probably will normalize much sooner than maharashtra provided new outbreaks of infection are prevented. in case of haryana we can broadly say that percent of the cases it is in healthy state and percent of the cases it is in symptomatic state. here the focus should be on active cases and how to get them cured fast. . figure in summary, we make the following recommendations. • states/uts/zones which predominantly maintain healthy state, should strictly regulate migrations in and out of the region. • for states/uts/zones which show off and on, infected status, focus should be on those who may potentially get infected. these may be health workers or people who typically interact with large number of people or move around a lot. • for states/uts/zones which maintain symptomatic status, the focus should be on nonpharmaceutical interventions such as social distance and containment. • state/uts which maintain detected status yet may have high mortality the focus should be on pharmaceutical interventions and on improving the health infrastructure. table a : covid- progression in india between - - and - - table b : covid- progression in india between - - and - - the main issue unique to covid- spread is that the infected may remain asymptomatic between to days i.e. through the incubation period. during that period, they may be unknowingly spreading the disease. some detections may also get missed if tests return false negatives. we have proposed an approach that takes as input data reported from hospitals in regard to active cases, recoveries and deaths and infers the latent state of regions as far as spread of covid- is concerned. to that end we categorized regions as healthy, infected, symptomatic and detected (before onset of symptoms). we modeled the state of regions as hidden states and reportage from hospitals as observations. we proposed a simpler approach to tackle the hmm learning problem in lieu of baum welch em algorithm. we have also provided a set of recommendations to better manage the surveillance of covid- . we believe our approach can help governments have a better assessment of spread of epidemic in different regions and enable them to plan appropriate interventions/responses. • this paper has made use of hidden markov model (hmm) to assess the state of spread covid- pandemic in regions based on reportage from hospitals. • the hmm states are categorized as healthy, infected, symptomatic and detected. • policy recommendations suggested for each of the above states can be calibrated further by governments. the model can be continually refined to handle prospective and future data. domain experts can contribute towards validating/refining the underlying assumptions in this research. what's the difference between a pandemic, an epidemic, endemic, and an outbreak? how to tell if you have flu, coronavirus or something else the latest coronavirus q&a: everything you need to know now curve flattened but no dip is a concern: aiims chief dr randeep guleria 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(a preprint from www modelling and simulation of covid- propagation in a large population with specific reference to india modeling epidemics spreading on social contact networks covid- and racial/ethnic disparities information as of am ist, ministry of health and family welfare covod- in india, dataset on novel corona virus disease in india karnataka fares better than high prevalence states in covid- fight coronavirus: bengaluru to go under complete lockdown from july to as cases surge key: cord- -e c zubo authors: pinder, adrian c.; raghavan, rajeev; britton, j. robert; cooke, steven j. title: covid‐ and biodiversity: the paradox of cleaner rivers and elevated extinction risk to iconic fish species date: - - journal: aquat conserv doi: . /aqc. sha: doc_id: cord_uid: e c zubo nan notwithstanding the human suffering caused by covid- , the response (e.g. shelter-in-place orders) has yielded some tangible environmental benefits such as substantial improvements in air and water quality (corlett et al., ) . in india, this has manifested as heavily polluted rivers now running clear for the first time in decades with, for example, reports suggesting that the quality of the river ganges has improved sufficiently to support safe bathing. hidden beneath these brighter stories however, covid- is also intensifying pressure on india's aquatic wildlife. in an already povertystricken country, an additional million are predicted to face extreme poverty as a result of covid- (world bank, ) . lacking social security, % of india's workforce are entirely dependent on daily wages, and are heavily reliant on food supply chains (reardon et al., ) that have been severely disrupted across rural india. with fish (farmed as well as marine-sourced) and meat forming a primary source of protein for many, its sudden unavailability has resulted in local communities exploiting wild populations, especially freshwater fish. as most newly recruited fishers lack knowledge on responsible and regulated capture techniques, illegal, indiscriminate and destructive methods are being used that have impacts on all aquatic fauna (e.g. dynamite, poisons). this also includes harvesting species of high extinction risk, exemplified by the endemic hump-backed mahseer (tor remadevii, figure ) , an iconic and critically endangered member of the freshwater megafauna (pinder, raghavan, & britton, in press) symbolic of india's extraordinarily diverse aquatic life. there is increasing evidence that their last remaining giant specimens are being removed from south india's river cauvery by illegal fishers using a variety of capture methods (deccan herald, ), pushing them a step closer to extinction. this demonstrates that to understand fully f i g u r e youths with a critically endangered hump-backed mahseer, tor remadevii, caught from the harangi reservoir in kodagu, karnataka, india [photo credit: star of mysore] impacts of the coronavirus pandemic on biodiversity conservation youth in a fix for catching mahseer fish, equipment seized from scientific obscurity to conservation priority: research on angler catch rates is the catalyst for saving the hump-backed mahseer tor remadevii from extinction. aquatic conservation: marine and freshwater ecosystems rapid transformation of food systems in developing regions: highlighting the role of agricultural research & innovations covid- and biodiversity: the paradox of cleaner rivers and elevated extinction risk to iconic fish species key: cord- -yi n nc authors: singh, k.; agarwal, a. title: impact of weather indicators on the covid- outbreak: a multi-state study in india date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: yi n nc the present study examines the impact of weather indicators on the covid- outbreak in the majorly affected states of india. in this study, we hypothesize that the weather indicators could significantly influence the impact of the corona virus. the kendall and spearman rank correlation tests were chosen to conduct the statistical analysis. in this regard, we compiled a daily dataset including confirmed case counts, recovered case counts, deceased cases, average temperature, maximum relative humidity, maximum wind speed for six most affected states of india during the period of march , to april , . we investigated that the average humidity and average temperature seven days ago play a significant role in the recovery of coronavirus cases. the rise in average temperature will improve the recovery rate in the days to come. the cities with very high humidity levels or dry weather conditions have high probabilities of recovery from covid- . the findings of this research will help the policymakers to identify risky geographic areas and enforce timely preventive measures. coronavirus disease (covid- ) is an infectious disease which initially detected in wuhan, china, has now spread all over the world, and if not well dealt, it could even lead to the worldwide economic crisis. this virus exhibits high human-to-human transmissibility, that is the reason it has spread all across the world in a very short span of time. the world health organization (who) reported , , covid- confirmed cases and , deaths worldwide until april , [ ] . the deadly virus has affected more than countries had been affected where united states (us) alone contributed approximately onefourth of the total cases. other major countries having a significant impact are spain, italy, iran, france, germany, uk, turkey, china, and many more. the situation in india has started worsening day by day. the first covid- case in india was reported on january , and as on april , india has covid- confirmed cases, including deaths [ ] . as per who, india has not entered into the state of the community transmission, still it has clusters of cases. india had enforced nationwide lockdown from march , to april , and further extended it till may , . the lockdown might have lowered the transmission rate of the covid- pandemic. figure shows the overall picture of confirmed cases of covid- across the states of india. many geographical, social, political, and environmental factors might influence the impact of this deadly virus. earlier studies have suggested that the meteorological parameters might be active factors in the transmission of viruses and disease emergence. yuan et al. investigated that the peak spread of sars occurred in a particular range of temperature, relative humidity, and wind velocity [ ] . variations of absolute humidity correlate with the onset and seasonal cycle of influenza viral in the us. [ ] . recently, various studies have been conducted to analyze the impact of weather conditions on the spread and effect of covid- . we have summarized the outcome of these studies conducted worldwide in the table . the independent effect of weather indicators on the transmission of covid- has not been studied systemically in the indian context. the main objective of this study is to investigate the association between weather indicators and the covid- outbreak in india. to the best . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint of our knowledge, this is the first study to explore the effects of weather indicators on covid- outbreak for india. since every state has a different geographical and political environment, we have considered different states of india rather than on state or city. the primary weather indicators i.e. temperature (°c), wind speed (mph), and humidity (%) are considered as independent variables for finding the correlation with affected cases of covid- . the majority of the related recent studies have considered the metrological indicators of the same day, which could present a false picture in terms of the correlation with covid- cases. since the incubation period of the covid- virus varies from day to days, we have evaluated one-week old weather indicators. the data of covid- cases of india corresponding to the six most impacted states maharashtra, delhi, rajasthan, gujarat, tamilnadu, and madhya pradesh was retrieved from a publicly available repository and accessible through this link: https://www.covid india.org/. this is a volunteer-driven, crowd-sourced database being collected and homogenized from multiple official and private web sources. the . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint the weather and covid- data collected are not normally distributed; therefore kendall [ ] and spearman rank correlation [ ] tests are considered in this study to investigate the correlation between weather indicators and covid- cases. both of these methods are accepted measures of non-parametric rank correlations. a null hypothesis corresponding to each weather indicator is formulated that there is no association between individual indicators and the three case statistics considered in this study. for all the hypothesis testing, statistical significance was set at p-value < . . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint the bold values show moderate or strong correlations among the variables with % significance level. the significant findings of this study are the strong correlation between average temperature days ago and average relative humidity days ago with the recovered cases. the average . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint temperature days ago has shown moderate correlation ( . < r < . ) with recovered cases in four states i.e. delhi, rajasthan, gujarat, and madhya pradesh for both kendall and spearman correlation test. the rise in average temperature might improve the recovery rate in the days to come. in rajasthan and gujarat, average temperature days ago parameter is also associated with new confirmed cases and deceased cases. similarly, the average temperature same day has shown some associations with confirmed and recovered cases as posited by [ ] . these outcomes might be due to a certain profile of the temperature in these states. [ ] also reported similar findings that warm weather would play an important role in suppressing the virus. in this study, it has been analyzed that the states having different humidity profiles exhibit different recovery response from covid- . the results show that average relative humidity days ago has a conclusive association with recovered cases in all the states. the two states tamilnadu and maharashtra, where the average relative humidity is in range ~ - % are positively correlated with recovered cases, which implies that recovery chances are higher in the humid environment. however, the other states where humidity levels are comparatively low and range approximately between % to % has a negative correlation between relative humidity days ago with the recovered cases. it can be concluded that the cities with very high humidity levels or very low humidity levels have high probabilities of recovery from covid- . by and large, the maximum relative humidity on the same day doesn't exhibit a significant association with the covid- cases in the duration of this study, which contradicts the study in iran [ ] . in the time interval of this study, we observed that the wind speed does not affect the viral spread or recovery in all the states considered. this study has shown evidence of weather indicators correlation with covid- cases; however, there are various limitations under which this study has been conducted. the . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint variables such as lockdown measures, people's individual immunity, migration index, and other climate indicators can impact the results presented in this study. the weather indicators can play a crucial role in the fight against coronavirus. to the best of our knowledge, this is the first study to investigate the impact of weather indicators on covid- incidences. this study investigates that average temperature and average relative humidity seven days ago are significantly correlated with the covid- outbreak and will be useful in suppressing covid- . in conclusion, weather indicators influence the covid- pandemic, potentially hot, and humid environment that can help in the recovery of the infected patients. the present study can be further enhanced by including other parameters such as demographic variations, healthcare infrastructure, and social policies like lockdowns to provide better insight into the fight against covid- . coronavirus disease (covid- ) situation report - a climatologic investigation of the sars-cov outbreak in beijing, china absolute humidity and pandemic versus epidemic influenza correlation between climate indicators and covid- pandemic a spatio-temporal analysis for exploring the effect of temperature on covid- early evolution in spain covid- transmission in mainland china is associated with temperature and humidity: a time-series analysis effect of weather on covid- spread in the us: a prediction model for india in effects of temperature variation and humidity on the death of covid- in wuhan, china impact of meteorological factors on the covid- transmission: a multi-city study in china impact of temperature on the dynamics of the covid- outbreak in china impact of weather on covid- pandemic in turkey investigation of effective climatology parameters on covid- outbreak in iran role of temperature and humidity in the modulation of the doubling time of covid- cases a new measure of rank correlation the proof and measurement of association between two things correlation between weather and covid- pandemic in jakarta, indonesia unique epidemiological and clinical features of the emerging novel coronavirus pneumonia (covid- ) implicate special control measures this research was supported partially by the research grant scheme of teqip-iii, mnit jaipur. key: cord- - p bkcnt authors: ghosh, abhishek; choudhury, shinjini; basu, aniruddha; mahintamani, tathagata; sharma, kshitiz; pillai, renjith r; basu, debasish; mattoo, s.k. title: extended lockdown and india's alcohol policy: a qualitative analysis of newspaper articles date: - - journal: int j drug policy doi: . /j.drugpo. . sha: doc_id: cord_uid: p bkcnt objectives: : since th march india went into a complete and extended lockdown. alcohol production, sales, and purchase were barred with this overnight prohibition order. we conducted a qualitative analysis of the media reports published within the first month of the nationwide lockdown with the objectives (a) using the media reports as indications of possible public health impact and population response of a sudden alcohol prohibition in india, (b) suggesting areas for future research. methods: : we performed thematic and content analysis of articles published online in national newspapers between the th march, and th april, . initial inductive, followed by deductive coding was done in this exploratory thematic analysis. results: the thematic analysis revealed four main themes: the beneficial aspects of the policy, the harmful aspects of the policy, non-compliance and attempts to change and / or subvert the policy, popularity and level of public buy-in of the policy. we generated relevant sub-themes under main themes. two additional themes, not directly related to the sudden prohibition, were use of stigmatizing language and ethical concerns. the content analysis showed the frequency of the appearance of the main themes and proportions of sub-themes and codes under those main themes. conclusion: : the harms, perceived from the media reports, should be balanced against the potential benefits. absence of a national-level alcohol policy was made apparent by the reflexive, disconnected , and conflictual measures. future research could systematically examine the potential ramifications of alcohol prohibition on public health, social, and economic aspects. according to the nation-wide survey published last year, an estimated million ( . percent) people in india consume alcohol and million ( . percent) were dependent on it (ambekar et al., ) . in addition to the number of people who are dependent on alcohol an additional million ( percent) experience hazardous consumption. more than % of alcohol consumed consisted of "spirits" (i.e. indian made foreign liquor and country-made liquor) (ambekar et al., ; benegal, ; gaunekar et al., ; mohan, chopra, ray, & sethi, ) . among the sear countries, india had the highest yearly per capita alcohol consumption of . litres (world health organization, ) . all these three factors together pose a serious public health threat. the proportion of young drinkers rose from % to % in the last two decades, and the age of initiation declined from years to years (prasad, ). the threat is multiplied by an added concern of a powerful alcohol lobby, led by multinational corporations, which targets india's emerging market of young drinkers (schess, jambhale, bhatia, velleman, & nadkarni, ) . the enthusiasm of the corporations is fuelled by a steady change in the level of acceptance and attitude towards alcohol from a culture of abstinence to ambivalence to covertly permissive (benegal, ; prasad, ). india needed a national level alcohol policy to minimize the public health impact of the aforementioned factors. however, india's alcohol policy is governed by the states. the three main pillars of the policy aresupply reduction to prohibition; taxation; and tertiary prevention (schess et al., ) . presently, alcohol sales and consumption is illegal in five of the states and union territories of the country, whereas for a large majority of other states alcohol sales-tax constitutes - % of their total revenues (benegal, ) . the government of india does not receive any taxation revenue from alcohol. taxation, although used successfully elsewhere, has not been effective in india to reduce consumption because of easy access to unrecorded alcohol (e.g. illicit or tax evaded). as per the global status report ( ) nearly half of the total alcohol consumed in the country fell in the unrecorded category (world health organization, ) . preventive services such as community-based, school or college-based prevention programs, brief intervention at primary care, and emergency services are mostly nonexistent in india. to this backdrop of a population vulnerable to serious public health impact, ineffectual policy, and a motivated third-party, since th march with overnight notice, india went into a complete and extended lockdown, with the intention to contain the spread of sars-cov- . alcohol being a non-essential commodity, all production, sales, and purchase were prohibited akin to an overnight prohibition order, enforced by the government of india. there was, however, an inherent contradiction to the enforcement of a national level policy because alcohol policy was a state-subject until that point. in normal times, the constitutional scheme ensures the autonomy of the states with regard to the spheres of activities earmarked for the states in the constitution. however, exceptions can be made during emergencies (arora, ). the main arguments behind the government of india's prohibition were: alcohol's potential harmful effect on the immune system, possible flouting of physical distancing and hand hygiene under the influence of alcohol, the possibility that alcohol may contribute to the domestic violence which was on the rise during the pandemic, and finally to reduce the healthcare burden resulting from alcohol-related accidents and violence (nadkarni, ) . we read several newspaper reports of suicide, consumption of illicit and harmful liquor or non-alcoholic beverages within a week of the lockdown. a research report from a tertiary care hospital in southern india showed a significant increase in the number of patients with complicated alcohol withdrawal (narasimha et al., ; pulla, ) . india was not the only country to impose a nation-wide prohibition during the covid- pandemic. south africa, sri lanka, thailand, and greenland, have also forced similar restrictions (french, ) . results of prohibition from south africa portrayed a beneficial effect. an article from the washington post quoted the director of alcohol research at the south african medical research council, reporting fewer admissions to the trauma units following the week of prohibition. the modelling of data by the council showed at least people are being saved every single day, who would have otherwise died from alcohol-related traumas (mogotsi and bearak, ; council, ) . sri lankan media, on the other hand, reported the proliferation of home-breweries and illicit distilleries across the country, and the availability of high-price alcohol in the grey market (rakshit, ) . hence, prohibition seems to have different effects across countries. there were still other countries such as canada, the us and the uk which designated alcohol as an essential commodity and continued the supply during the pandemic. several commentators have discussed the harmful effects of such policies-encouraging the general population to drink and sending a message that alcohol is essential for lives (hobin & smith, ; neufeld, lachenmeier, ferreira-borges & rehm, ) . a direct population survey, which would have been ideal to understand the effect of prohibition, was not possible under the present circumstances. therefore, alternative data sources can be explored. researchers so far have used alcohol sales data or isolated media reports (nadkarni, kapoor & pathare, ; borges & rehm, ) . we wanted to systematically explore the scope of the media reports, using the media as an indicator of potential harms and benefits. at the same time we acknowledge that media as a data source can be biased, and there are issues with accurate factual reporting and reliability. therefore, the result of this paper should be read with these caveats in mind. we conducted a qualitative analysis of the media reports published within the first month of the nationwide lockdown with the objectives of (a) using the media reports as indications of possible public health impact and population response to a sudden alcohol prohibition in india, (b) suggesting areas for future research. the study had an exploratory design which systematically looked at the response of individuals, public and society at large, government and non-government organizations which primarily deal with public health and related aspects of alcohol by studying newspaper reports. by a consensus among the authors, the following search words were selected. type of news-items was only in english, published between th march to th april with the search words: "alcohol", "alcohol policy", "state", "alcohol treatment", "illicit liquor", "alcohol ban", "alcohol revenue", "alcohol suicide", "alcohol lobby", "alcohol e-marketing", "alcohol withdrawal", "alcoholics", "chief minister alcohol", "isopropyl alcohol", "alcohol revenue" "alcohol poisoning", "alcohol price" "alcohol home-delivery". the search was made on google news (india). the rationale for using google news india was as follows: a large majority of the best selling newspapers in india have a digital version (e-paper). hence, an online search on google news india, in addition to the exclusively online media reports, was likely to uncover the reports of the online editions of the print media. besides, there were two other reasons for screening the media reports through google news-(a) the covid- pandemic resulted in nearly percent decline in the print newspaper sales in different cities india (gonews desk, ), (b) india has a growing number of internet users and it is second largest in the world. more than percent of internet users use google as their search engine (mishra & chanchani, ) , (c) the lockdown, travel restrictions, and closure of libraries, and outlets selling newspapers had made it impossible to check the print editions. the choice of only english papers was determined given that (a) the eighth schedule of the indian constitution recognized languages and english was (and still is) one of the official languages across indian states. therefore, a search of english media reports was likely to be more generalizable than searching in different regional languages; and (b) most widely circulated english newspapers (e.g. times of india, hindustan times, the indian express) have versions in hindi and other regional languages. the period includes the most intensive phase of lockdown between th march and th april when there was a virtual clampdown on all activities and people were not allowed to step out of their homes. only emergency and essential activities like purchasing essential food, attending hospital, and attending pharmacies were allowed during this period. after th april there was some relaxation in some of the states but mostly all states were in lockdown with heavy restrictions on nonessential activities. qualitative thematic analysis was done by the coding, categorization and theme generation which was done after meticulous data immersion. a comprehensive coding frame with definitions and examples for each item was designed by peer debriefing and researcher triangulation to guide the coder in identifying the main four themes and subthemes. the codes were generated inductively under the broad domains of 'impact of alcohol prohibition policy among various stakeholders' and 'response to the prohibition policy' for the newspaper reports of the initial two weeks that is till th april. for the remaining weeks a deductive approach was taken for coding. however, any additional codes, discovered were documented and discussed. two of the authors (ag and ab) independently undertook the coding. ag and ab are both qualified addiction psychiatrists and have been working in the field of addiction medicine for more than six years. all the coding was done manually. each characteristic was coded as being either present ( ) or absent ( ). we did not force concordance between the investigators in order to explore multiple perspectives. in case of any additional code generation by one of them (ab or ag), it was taken into account by mutual consensus. once all the codes were finalized, themes and sub-themes were generated by triangulation. a diagramming approach was taken to understand the connections between the themes and subthemes. the themes were labelled tentatively with the objective of finalizing the names following the third team meeting. three team meetings and peer debriefings were done during this period. the first meeting aimed to (a) document theoretical and reflexive thoughts; (b) share thoughts about potential codes. the second meeting was held following the inductive code generation and creation of the coding framework. the third meeting was held with the objectives of (a) ratifying any additional codes; (b) discussing the main themes and sub-themes and vetting by the team members. the overarching flow of ideas was noted. in sum we assumed a factist epistemological paradigm, the emerging categories/sub-themes and themes led us to an overall understanding of the response of all the stakeholders to this sudden prohibition the themes, sub-themes, and codes retrieved from each article were entered into an excel sheet by tm and these were cross-checked by ag. the frequencies were mentioned in the content analysis we followed the methodology by göbekli et al., and nowell et al., . ethical clearance was obtained from the all india institute of medical sciences, rishikesh, india-ethics committee (ref: / /psy/ - ). a total of news articles from newspapers were accessed for the study. for further details please see the article selection flow diagram ( fig. ) . ……the three major newspapers contributing to these media reports were: times of india ( . %), the hindu ( . %), and the indian express ( . %). for other mastheads please see supplementary table . all articles were published between th of march, and th of april, . among them, articles had only online publication and the rest ( ) had both print and online versions. the news articles from national and regional news were ( . %) and ( . %), respectively. regional articles were from states and union territories. kerala ( . %), karnataka ( . %), telangana ( %), tamilnadu ( . %), and west bengal ( . %) were the first five states represented in the regional news. the types of articles and their states of origin are depicted in supplementary table . fig. gives a detailed distribution of the states represented in the analysis. ………four main themes emerged when all the articles were analysed: (a) "the beneficial aspects of the policy," (b) "the harmful aspects of the policy," (c) "non-compliance and attempts to change and/ or subvert the policy," and (d) "popularity and level of public buyin of the policy." we could identify two additional themes, which could not be considered as direct repercussions of the sudden prohibition, nevertheless were important markers of societal attitudes towards individuals who use alcohol. these themes are "use of stigmatising language" and "ethical concerns". table gives an example of the coding schemes, and generation of sub-themes and themes. fig. depicts the themes and sub-themes in a nutshell. the main theme "beneficial aspects of the policy" is represented by the following codes: several medical practitioners described the lockdown as "an opportunity for treatment" of persons with alcohol dependence. as per a newspaper report, a document generated by the national drug dependence treatment centre, all india institute of medical sciences (aiims), referred to the lockdown situation as a blessing in disguise for some people who could use this opportunity to quit drinking altogether (phull, ) . media reports indicated that the number of people presenting with alcohol withdrawal to functioning outpatient services and emergency departments of general and psychiatric hospitals, and addiction treatment centres showed a sharp rise in the weeks following the enforcement of the lockdown. the articles reflected similar news coming largely from the southern parts of the country (kerala, telangana, tamilnadu) both from the cities and the rural districts. one news report quoted the superintendent of the institute of mental health in erragadda, hyderabad saying -"we have received to patients today who are suffering from withdrawal symptoms. close to per cent of them are dealing with the withdrawal of alcohol.." (mojumder, ) reports from addiction treatment centres under the department of excise in kerala, "vimukthi", read-"according to the officials of vimukthi, ever since then, in just a week's time, people were admitted to the deaddiction centres under vimukthi alone. "this is not the usual pattern. not more than - people usually get admitted to the vimukthi centres in a week…." (mithun & joseph, ) calls to the national helpline numbers as well as different state helplines for alcohol and other substance use saw an unprecedented rise. a title of one news article read -"coronavirus lockdown: helpline for drug addicts, alcoholics reports % surge in calls" (businesstoday.in, a) a hospital from tamilnadu, too, reported within the first week of the ban -"we have been getting at least five to six calls per day from places like chennai and hyderabad in the past week, and the number is sure to go up as the lockdown progresses" (nainar n, ) a. ghosh, et al. international journal of drug policy ( ) involvement of the self-help groups alcoholics anonymous (aa) arranged for telephonic communication as part of a pan india initiative to continue their meetings during the time of lockdown severely restricting movement. with the use of conference calls and different slots for better coordination, these meetings are being held. the reports were from both southern and north-eastern states namely from kerala, karnataka, and meghalaya. reports read-"in a pan india initiative, aa is using telephonic communication where callers are put on a conference call -since people are working from home, different slots are provided. regional meetings are also held separately. the addicts' families can participate in the conference calls. only addicts will be allowed to speak," said a member of karnataka area committee, aa….." (de'sousa, ) telemedicine and tele-counselling services were initiated in different parts across the country. in one of the states, a free online counselling platform was launched. in several places, counsellors worked from home, attending calls from patients or their family members (mithun & joseph, ) . one of the opinion types of article indicated a possible beneficial aspect of the alcohol prohibition could be a reduction in domestic violence (agarwal & srivas, ) . their assumption was based on a study conducted in the slums of mumbai, which revealed women whose husbands consumed alcohol were two times more likely to experience intimate partner violence than those whose husbands did not consume alcohol (begum, donta, nair & prakasam, ) . this report assumed significance in the background of increased complaints of domestic violence received by the national commission for women, within the first one week of lockdown (khandekar, ) . (srivastava, ) inclusion of alcohol in the list of essential commodities a. ghosh, et al. international journal of drug policy ( ) the harmful aspects of the policy as a recent study estimated, an approximate million people in india had problematic use of alcohol, almost half of whom consumed alcohol in a dependent pattern (ambekar et al., ) . the newspaper reports possibly indicated the distress experienced by this population, reflected by the following codes. this was perhaps the most tragic and extreme fallout of the sudden unavailability of alcohol and one of the first news topics related to the ban on alcohol which came to light. the southern state of kerala reported the death of people by suicide within the first days of lockdown (jayakumar, ) . as per the news reports, all such deaths could be attributed to severe distress from marked withdrawal symptoms in these persons with alcohol dependence. in addition to kerala, suicide deaths or attempts allegedly due to non-availability of alcohol were reported from assam, meghalaya, karnataka, chattisgarh, telangana, and tamil nadu. although the media predominantly observed these deaths by suicide as a fall-out of distress due to non-availability of alcohol some did report alternative or additional perspectives of mental health problems and depression (swamy, ) . a. ghosh, et al. international journal of drug policy ( ) consumption of non-consumable alcohol according to the media reports, as people resorted to desperate measures to access alcohol, some people drank non-consumable forms of alcohol such as paint varnish, after-shave lotions or hand sanitisers. within the first couple of weeks of lockdown, several such incidents were reported from tamil nadu where people died after drinking hand sanitisers or paint varnish and soft drinks mixed with after-shave lotion (dhns, ). one such case was also reported from kerala, and nine from uttar pradesh (swamy, ) . media reported that sales of illicit liquor shot up rapidly following a. ghosh, et al. international journal of drug policy ( ) the ban. although the prices were several times higher than usual, stocks of illegally bought liquor were clearing at a very rapid pace. few people could afford such high prices. those not having enough money, looked for cheaper alternatives and often ended up consuming spurious liquor, risking their health. reports of illicit and spurious liquor consumption and resultant deaths and hospitalizations were reported from uttar pradesh and tamil nadu (siddiqui, ) . in the slums of hyderabad, one newspaper report noted that this significant population of teenage children of poor migrant workers with alcohol dependence, began to experience symptoms of marked alcohol withdrawal. the article quoted the head of a non-profit organisation running shelter camps in the city saying -"at least minors in the camps sheltering over a hundred migrant workers and homeless persons have been showing moderate to severe withdrawal symptoms." (menon, ) the high demand for treatment was not always met with a corresponding increase in the treatment provisions. media reports suggested that most of the private de-addiction centres decided to remain closed or function only with the admitted patients, due to the lockdown. all new patients were referred to government hospitals for management. due to most centres refusing new admissions and referring patients to government hospitals, people seeking treatment remained unattended. however, such reports came only from tamil nadu (lakshmanan, ) . we could identify the following three sub-themes under this main theme-non-compliance at the state level, at the individual level, and illicit or criminal activities. the states of kerala and punjab had initially included alcohol among the list of essential commodities, to continue its sale even post lockdown. in kerala, while private liquor stores were closed, the staterun kerala state beverages (manufacturing and marketing) corporation limited (bevco) remained open. however, both states had to stop following directives from the government of india. the government of punjab had requested government of indiato allow the sale to address the significant loss of revenue which followed banning the sale of alcohol. in tune with this, the international spirits and wine association of india, lobbied the government of india to classify alcohol as an 'essential item'. the northeastern states of assam and meghalaya allowed the sale of alcohol for limited hours on permitted days while under strict enforcement of social distancing and other precautionary measures (ani correspondent, ). in assam, the state government allowed the opening of liquor shops, from am to pm. distilleries, breweries, bottling plants were also allowed to open (additional commissioner of excise, ). in meghalaya, liquor stores opened from am to pm from th to th april. only a single member from each household would be permitted to buy, along with measures restricting movements between the districts. meghalaya also permitted home delivery of alcohol in areas without liquor shops. however, following a second directive from the government of india refusing any relaxation to alcohol sale or production, both states had to withdraw their orders. as per times of india th april report, the excise department of govt of karnataka made a proposal to allow sale of liquor between am and pm. the newspaper reported that this may improve excise earning and state revenue but on the flip side of it sale for only a few hours a day may lead to huge rush thereby violating guidelines to prevent the virus (gejji, ) . however, later it was withdrawn by the karnataka government. in kerala, the state government formulated plans to supply alcohol upon certification by a government medical practitioner that the person was experiencing symptoms of alcohol withdrawal. the government cited the recent suicides among those experiencing alcohol withdrawal as the primary reason for initiating this unprecedented step. it decided to issue special "liquor passes" from the state excise department on the production of such certification (government of kerala, ) they placed a limit of litres of alcohol per person for a week and plans were to supply the alcohol to the homes of the applicants (pti, a). the state of west bengal had started making plans to enable online home delivery of alcohol, ensuring that the norms of social distancing were maintained while attempting to generate revenue from the sales. the state of west bengal saw a discrepancy between the messages conveyed by police and excise departments regarding the same piece of information, again suggesting inter-department incoordination (fpj webdesk, a). kerala had planned doorstep delivery so that crowding at liquor outlets could be avoided. however, none of the plans could be enacted. in those areas without liquor shops, meghalaya has allowed home delivery (team latestly, ). there have been various whatsapp groups forwarding numbers of people selling alcohol in metro cities like mumbai at escalated rates (fpj webdesk, b). as mentioned in the press trust of india and corroborated from the notice issued by the revenue department of the government of west bengal, the state government attempted to make up for the loss in revenues by imposing a sales tax of % of the mrp in addition to the existing excise and additional taxes (pti, b; government of west bengal, ) however, for alcohol users who were forced to pay up to % more than the usual price as per different newspaper reports (tnn, ). when the government of kerala decided to provide special "liquor passes" through the state excise department, to persons experiencing signs and symptoms of alcohol withdrawal upon certification by a government medical practitioner, a large number of fake prescriptions were detected. most lacked the doctor's seal while some were from retired doctors, private doctors or ayurvedic practitioners all of which led to the rejection of their applications. a newspaper report read, "an excise officer said most of the prescriptions did not have the seal of the doctors and were fake. some brought prescriptions from retired and private doctors (express news service, a)." another way that people responded to the situation was trying to brew alcohol at home. an article read, "some social media users are also trying to brew and share recipes for home-made alcohol (de sousa, )." another newspaper reported an incident of selling illicit home-made liquor by a "socially connected" person from kerala, "a covid volunteer was arrested by the varkala police on saturday for selling alcohol made using various components, including sanitisers, and for selling it to clients to whom he delivered it on his bike (express news service, b)." people were also using free rice given in ration shops a. ghosh, et al. international journal of drug policy ( ) for the preparation of country liquor -this has been reported from assam (g plus news, ). in some parts of west bengal previously banned liquors were again found to be brewed. an example: 'rakshi, a traditional distilled nepali beverage banned in bengal, has suddenly outstripped illicit country liquor in demand in several parts of barrackpore police commissionerate during the lockdown. police have found out that a few nepali families, who sell momos and other chinese fast food, at khardah are behind the revival of the strong drink that is usually made from rice, barley or millet' (chaudhury, ) good samaritan response a newspaper article reported on one of the most circulated viral videos showing a man distributing alcohol to daily wage workers in hyderabad, prompting varying comments of "crazy", "fame-seeking", "dev-maanush (godsent)" and also sparked debates on the pros and cons of the ban (khandekar, ) . this one month period saw a spate of illegal activities related to the consumption of alcohol. while some struggled to cope with the sudden stoppage of alcohol, others saw opportunities to make money through illegal means, often leading to disruption and arrests. the following codes illustrate such activities. amidst the unavailability of alcohol, there have also been a growing number of thefts and robberies of bars and liquor stores. the majority of such reports came in from the states of karnataka, maharashtra, tamil nadu, telangana, chhattisgarh and andhra pradesh along with capital delhi (shekhar, ) . while the sale of alcohol from legal outlets remained closed, there was an increase in smuggling illicit and spurious liquor. there were frequent reports of seizures of large amounts of illicit liquor by the authorities. innovative means of smuggling were seen such as hiding alcohol in milk cans or sale from authorised milk booths, while reports came in of a stash of cartons of liquor in an ambulance in delhi (pti, c) . grey market sellers during this time charged double the price and even hooch was expensive (reuters, ) . alcohol was sold under the garb of essential items and medications -it was found to be smuggled in milk cans by a person posing as a milkman or as homeopathic medications (joshi, ; team newsable, ) . as people continued to search for alcohol, several reports of online scams came to the fore. most of these gangs established contacts through social media, promising online delivery of alcohol, usually charging exorbitant rates, meanwhile getting access to bank account details and often making away with large sums amounting to lakhs of rupees. while authorities cautioned against such fraudulent activities, people's desperate search for alcohol often led them to these traps. news of such frauds were reported in different parts of the country with the cities of kolkata, mumbai, bengaluru, hyderabad, gurugram, mangalore witnessing many such cases. social media has also been used as a tool by online fraudsters claiming to sell alcohol and people selling illicit liquor or home-brewed liquor to access their target population, with anonymity inherent in this medium of communication undoubtedly promoting such use. as an example, several residents have been cheated online by making payment through e-wallet or other upi platforms, as reported by the media outlet, hindustan times (dhankhar, ) . newspapers have also reported details about the modus operandi of such illegal transactions of alcohol, such as: the masterminds "would never meet the buyer anticipating that he would get caught. he would cross-check the name of buyers on true caller before processing the deal," said an official. after stashing the liquor bottle at the designated spot, he would call the buyer and give the location. he would hide and watch from a distance to ensure that the liquor reached the right person' (the hindu correspondent, b). the prohibition of alcohol enforced by the government of india received a mixed response from the stakeholders, as detailed in the media analysed herein. while a large number of states, organizations of alcohol manufacturers and sellers, and a few celebrities opposed the ban, a few other states, health professionals, and the judiciary supported or upheld the prohibition (pti, d). the different sellers' bodies repeatedly tried to draw the focus towards the loss of revenue and rise in black market sales of alcohol while trying to persuade the government of india and state governments to relax the ban on alcohol. one newspaper report quoted the international spirits and wines association of india (iswai) chairman saying -"states are strapped for cash. - percent of a state's revenue comes from alcohol. this is a significant revenue stream that comes directly to state coffers and can help in these cash-strapped times particularly when there is pressure to provide a safety net" (businesstoday.in, b) . the sellers' body -confederation of indian alcoholic beverage companies (ciabc) made recommendations to the commerce minister of the government of india, health minister and chief ministers of all states to allow home delivery of alcoholic beverages. they also focussed on the sudden lack of employment of the workers in the huge alcohol industry while urging the government to resume the sale of liquor. the ciabc and international spirits and wines association of india (iswai) requested phased re-openings of liquor stores outside the hotspot areas, for a longer duration to reduce crowding. they also suggested providing licenses to the shops for - home delivery workers through which the government could control the frequency and the amount of liquor being delivered. the sellers' bodies also advocated for online alcohol delivery or etailing of alcohol. they had recommended this to minimise the gathering in front of liquor shops. they also suggested identity proof for age verification during applications made online or through phone calls. there were widely varying reactions of the medical fraternity and other sources of help to the different situations which arose in the country in relation to the ban on alcohol. the following two codes provide an illustration. as discussed, when kerala decided to issue special "liquor passes" to those suffering from alcohol withdrawal upon such certification by government medical practitioners, the medical professionals in the state as well as across the country criticised the move, calling it "unethical". the kerala government medical officers association (kgmoa) protested by observing a black day and wearing black badges and bands to work. news reports quoted a kgmoa office-bearer saying -"there are scientific methods of treating people with withdrawal a. ghosh, et al. international journal of drug policy ( ) symptoms and that's the medical protocol. this is something which will affect our morale and numerous side effects will surface. we will not be doing this." (ians, ) other medical bodies such as the ima (indian medical association) and indian society of gastroenterology's kerala chapter refused to prescribe it, saying it was against medical ethics. the kgmoa and the ima then filed petitions in the kerala high court to stop the government from proceeding further with provision of "liquor passes." however, not all medical professionals were aligned to the policy of prohibition. the director of the centre for mental health law and policy in pune expressed his belief that the current alcohol crisis was a result of the states' contradictory approach to alcohol which was both puritanical and pragmatic (hamid & harigovind, ) . a psychiatrist in karnataka also filed a public interest litigation against the sudden ban and advocated for allowing the liquor shops to open. this plea was turned down by karnataka high court (the hindu correspondent, a). the high courts of kerala and karnataka were primarily involved in this scenario for differing reasons. in kerala, as mentioned above, the kgmoa and ima filed petitions to stop the government's decision to provide alcohol, based on certifications by doctors. the kerala high court stayed the move for three weeks (prathapan tn vs state of kerala and others, ). a newspaper report quoted the bench as saying -"we are concerned that the state government has taken a unilateral decision to administer more alcohol to persons suffering from alcohol withdrawal syndrome. this is a recipe for disaster." (swamy, ) in karnataka, following a pil filed by a private psychiatrist requesting reopening of liquor shops, the karnataka high court ordered the psychiatrist to contribute rs , to the prime minister's fund. the loss of revenue was cited as one of the major reasons for the states to oppose the alcohol prohibition. the estimated daily revenue loss due to stoppage of alcohol sales was around usd . million daily in india, and most of the states earned around - % of their revenue from alcohol. the worst-hit states were maharashtra, uttar pradesh, telangana and karnataka, which earned approximately usd million, usd million, usd million and usd million respectively during the financial year - . we did not conduct a qualitative analysis of the social media but the thematic analysis of the newspaper reports identified a particular subtheme with the response from the social media. in an age of digitisation and ubiquitous social networking through the internet, social media has quickly become the source of information of dubious authenticity, often acting as a tool for rumour-mongering. it has also evolved as a platform for expression of opinions of a significant portion of the population. consequently, in the present scenario, social media platforms have been used in diverse ways. the social media platform twitter saw trends of #liquorfreeindia doing the rounds which drew a lot of reactions, both light-hearted and those with serious overtones (saxena, ) . a viral video depicted a political leader of the ruling party in the newly enforced prohibitionist state of bihar, in an inebriated state and led to significant public shaming and political mudslinging. celebrities from different fields had their own take on the situation. while some advocated for the ban, there were others including a famous movie director who urged the state governments to relax the ban and allow alcohol sales for limited hours. newspaper article mentioned veteran bollywood actor's tweet: "think. government should for some time in the evening open all licensed liquor stores. don't get me wrong. man will be at home only what with all this depression, uncertainty around. cops, doctors, civilians etc... need some release (bangalore mirror bureau, ). the following themes were not directly related to the alcohol prohibition but were relevant for understanding the socio-cultural milieu and newspaper reporting standards. a common theme that featured in most of the news articles that were analysed was the use of stigmatizing language in the context of alcohol use and dependence. terms such as "tipplers", "addicts", "boozers" and "drunkards" used to refer to persons with alcohol dependence is a reflection of this stigma. many of these words were used in the title of the news article (indulekha, ; nidheesh, ) . one of the other noticeable themes that emerged from the news reports was the lack of privacy of the affected individuals, with articles on reported suicide or isopropanol (methanol) poisoning providing detailed personal identification data. we performed a content analysis to determine the frequency of the themes, sub-themes and codes. there was coexistence of different themes, sub-themes and codes within a single article. the most prevalent theme was 'non-compliance and attempts to change and or subvert the policy' which was found around times in the articles. there were various state-driven endeavours to subvert this ban-like 'distribution of liquor pass' (n= , . %), 'plans for online and doorstep delivery' (n= , . %), 'limited hours sale of alcohol' (n= , . %), 'inclusion of alcohol in the list of essential commodities' (n= , . %) and 'tax hikes' (n= , . %). non-compliance at the individual level consisted of 'attempts to brew alcohol at home' (n= , . %), 'forging prescription to obtain liquor pass' (n= , . %) and 'good samaritan response' (n= , . %). there were various reports of illegal activities non-complying with this ban, like 'smuggling of illicit and spurious liquor' (n= , . %), 'online scams' (n= , . %) and 'thefts/robberies of bars, liquor shops and hotels' (n= , . %). the 'popularity and level of public buy-in' was the next most common theme, which appeared times in our search. the main subthemes were 'view of healthcare professionals' which was found times in our search. 'doctors' protest against the "liquor pass" '(n= , %). some doctors also expressed their views against the national policy (n= , . %) as a result the judiciary had passed decisions (n= , . %). another subtheme was 'views of the alcohol sellers and manufacturers' that appeared times. the alcohol sellers recommended for the resumption of business to the governments (n= , %) through phased reopening of the liquor shops or online delivery. the most frequent cause proposed for these recommendations was revenue loss' (n= , . %). there was considerable 'social media response' both for and against the ban (n= , . %). celebrities (n= , . %) also expressed their opinions regarding the ban. there were accounts of the 'harmful effects' of the abrupt alcohol ban. it included several reports of suicide (n= , . %), fatal or near-fatal consequences of consumption of non-consumable alcohol like aftershave lotion or hand sanitizer (n= , . %), and consumption of spurious liquor (n= , . %). the other aspects of the harm were the 'closure of private de-addiction centres' (n= , . %) and alcohol withdrawal in migrant adolescents (n= , . %). a. ghosh, et al. international journal of drug policy ( ) although many news reports focussed on the negative and subversive aspects of the ban, there were accounts of the beneficial effects of the ban. on the part of the patients, this led to increased treatment-seeking (n= , . %) for alcohol use. the service providers were also viewing this ban as an 'opportunity for treatment' of patients with alcohol use disorder (n= , %). as in-person consultation was not a viable treatment option, the teleconsultation services flourished as an alternative treatment platform (n= , . %), and self-help groups like 'alcoholics anonymous' also played their role in helping those in need of treatment (n= , . %). the ban on alcohol has presumably led to a relative reduction in domestic violence during the lockdown period (n= , . %). we found the use of stigmatizing languages (like 'drunkard', 'tippler', 'alcoholic') in articles and contents with ethical concern (like a. ghosh, et al. international journal of drug policy ( ) exposing the names and other personal details of suicide victims) in articles. the distribution of frequency of the themes, sub-themes, and codes are presented in fig. . we conducted thematic analyses of articles, published over a span of one month in a wide-range of english dailies and online-only newspapers. we followed a predetermined and systematic approach to retrieve the newspaper articles, to do the thematic analysis and extraction of themes and sub-themes. we believe this was a relatively novel, feasible, resource-friendly and time-saving strategy to indicate the possible effects of this sudden national policy. . one basic premise of the rigour of this study has been the trustworthiness and reflexivity as reflected by the authors by clarifying their own perspective as addiction psychiatry professionals (lincoln, guba, & pilotta, ) . credibility has been established by peer scrutiny of the coding process and data triangulation by a discussion of the results amongst the authors. we also carried out a content analysis of the themes to quantify the relative dominance of the themes and to make the qualitative research transparent and replicable. both thematic and content analysis added to the methodological triangulation and the overall robustness of the qualitative study. however, the authors acknowledge that the dynamic nature of qualitative results is variable based upon the epistemological and ontological paradigms assumed (silverman, ) . drawing a causal inference (as was done by the media reports) would have been an oversimplification for several reasons-(a) the covid- pandemic itself might increase the risk of suicide by enhancing the risk of mental illness, loss of employment, financial hardships, and bereavement (gunnel et al., ), (b) some media reports had actually suggested a possibility of underlying depression in many of these individuals (swamy, ) . a psychological autopsy could have been a scientifically valid way to discern the possible causes. countries such as the usa, where alcohol sale was not banned during the pandemic, had witnessed several cases of methanol poisoning due to consumption of alcohol-based hand rubs (yip et al, ) . similar cases, on a large scale, were also reported from iran, which is otherwise a dry country (haghdoost, ) .these instances were likely to be driven by the myth that consumption of alcohol-hand rubs will kill the sars-cov . therefore, the events of consumption of non-alcoholic beverages, reported by the indian newspapers could also be a result of similar myths. the content analysis revealed media reports focussed more on the harmful aspects of the policy than the potential benefits of prohibition. nevertheless, this result was not an evidence of harms outweighing the benefits because media reports were not done with scientific rigor and there was financial, political, and ideological bias inherent to the reporting. in sum, the qualitative analysis of newspaper reports indicated potential public health-related benefits and harms of the sudden alcohol prohibition in india. future research could systematically explore issues flagged by the media reports. our study results showed a few limitations in india's alcohol policy: firstly, alcohol policy in india was a state-matter. therefore, ban imposed by the government of india on alcohol unmasked the incoordination between the government of india and the states, between the states, and even within departments of a state. the disconcerted attempts to subvert the national level policy resulted in confusion among the public and medical professionals. the judiciary had to intervene in one particular case. all these were reflective of the incoordination in the planning and implementation of alcohol policy. secondly, alcohol is a huge revenue generating commodity for the states and therefore, the alcohol policy is largely driven by financial incentives rather than a focus towards public health (benegal, ) . thirdly, states' attempt to subvert the policy by the government of india by alcohol home delivery and online delivery was potentially harmful for several reasons-(a) evidence from russia showed percent stockpiled alcohol at home and only a very small proportion intended to use it as hand sanitizer (neufeld, ) . commentators also raised the possibility of overcompensated drinking-at home in the absence of social inhibitions (neufeld, ) ; (b) the boredom, stress, and social isolation during the pandemic could contribute to increase in alcohol use (the lancet gastroenterology hepatology ; hoblin & smith, ); (c) economically disadvantaged group of individuals with alcohol use disorders would not be able to afford either online or home delivery of alcohol. importantly, they are more vulnerable to alcoholrelated harms as opposed to the group, which could afford such services (katikireddi et al., ) ; (d) easier access to alcohol might give a wrong message to the non-using population that alcohol is an essential commodity and reduce the public perception of harm (hoblin & smith, ). all these factors together suggested that home or online delivery of alcohol was likely to produce more harm than benefit. firstly, the lockdown, prohibition, and consequent response from the stakeholders indicated a need for national alcohol policy in india. the disconnected attempts of states to restore 'normalcy,' discrepancies between state departments, conflicts with the government of india, and the resultant confusion among the public could have been averted by national-level policy. secondly, the indian alcohol policy requires a public health reorientation, i.e. policy aimed at reducing the harms of alcohol, both at the individual and the societal level (babor et al., ) . beginning with the abrupt prohibition and to recurrent themes of the compulsion for the states to compensate for the excise-related revenue loss, the involvement of commercial entities in decision making (even remotely), an under-equipped health care infrastructure, and desperate measures of state to "prescribe alcohol" to alleviate suffering were some glaring examples of a lack of public-health oriented decision making. a comparison of alcohol control policies among countries, across the globe, showed an inverse relationship between alcohol harms and the strength of policy measures (brand, saisana, rynn, pennoni, & lowenfels, ) . the strength was defined by the "alcohol policy index," with public health as the basic common denominator. thirdly, the "suddenness" of the prohibition might have been responsible for most of the potential harms and confusion between the states and the government of india . a discussion with the states and other stakeholders prior to the enforcement of the prohibition could have resulted in a more coordinated implementation of the policy. fourthly, the harmful aspects of the prohibition were largely applicable to individuals with alcohol dependence. our analysis revealed the need for improving the availability and access to treatment, and enhancing public awareness for the same. finally, use of stigmatizing words to describe people with alcohol use-related problems and direct breach of privacy indicated that there is a need for media reporting guidelines to use neutral language and to monitor the level of adherence with the existing guidelines. this study has several limitations. firstly, the analysis was based on the english newspapers with online access. news reports published in regional languages were not reviewed for the content analysis. nevertheless, a majority of the news items accessed and analysed were from the regional-section of national newspapers or regional newspapers. secondly, our narrative was solely based on news reports, which might be biased because of its political predilections and financial conflicts of interest. however, we conducted an extensive newspaper survey and included all news items retrieved by our search. thirdly, newspaper reports are not peer-reviewed literature and no causal inference should be drawn from the reports, such as an increase a. ghosh, et al. international journal of drug policy ( ) in the incidence of death by suicide might also be contributed by the financial burden, stress of the outbreak, or underlying mental illness. however, these reports suggested a trend, which should be subjected to scientific scrutiny in the future. fourthly, by design, we reviewed the first one month of post-lockdown prohibition. in india, prohibition continued even after that. although our thematic analysis captured the immediate effect of prohibition on public health and on other stakeholders it might have missed some delayed responses such as permitting alcohol sale through food-delivery mobile applications in a few states or opening of shops for limited hours in a few others. the newspaper analysis indicated beneficial and harmful aspects of an unplanned and unprecedented alcohol prohibition during the lockdown. the absence of a national-level alcohol policy was made apparent by the reflexive, disconnected, and conflictual policy measures. the lack of a public health orientation to the policy augmented the harm. the sudden alcohol prohibition was, perhaps, a learning lesson for countries like india, which are yet to have a strong public healthoriented national alcohol policy and emphasized the need for a balanced approach aiming at the reduction of alcohol-related harm. nevertheless, the harms, perceived from the media reports, should be balanced against the potential benefits of prohibition such as reduction of domestic violence and increased treatment seeking. besides, one should exercise caution in drawing any firm conclusion from media reports, which are not considered to be a source of scientific evidence. a disproportionately higher reporting of harmful effects of alcohol prohibition could result from visibility or presentation bias of media reporting. having said that, we believe, the analysis of newspaper reports underlined the possible areas for future research. supplementary material associated with this article can be found, in the online version, at doi: . /j.drugpo. . . magnitude of substance use in india people follow social distancing norms while queuing outside liquor shops in assam's dibrugarh. business standard administrative powers between center and states in india alcohol: no ordinary commodity: research and public policy a case for reopening liquor vends with all the adequate safe socio-demographic factors associated with domestic violence in urban slums india: alcohol and public health comparative analysis of alcohol control policies in countries coronavirus lockdown: helpline for drug addicts, alcoholics reports % surge in calls industry body seeks alcohol home delivery amid coronavirus lockdown nepali liquor brews again in bengal. the telegraph online reports on weekly deaths in south africa should karnataka go kerala way. the indian express retrieved st gurugram: illegal sale of liquor online, fake promises of doorstep delivery annoy vend owners, residents. hindustan times from aftershave to paint varnish: alcoholics take desperate measures to get their daily dose. retrieved th tipplers tap excise offices across kerala for daily fix. the new indian express covid volunteer arrested for selling 'home-made' liquor in kerala. the new indian express assam government permits opening of liquor shops from am to pm amidst coronavirus lockdown chennai during lockdown . ? full list of states and union territories which are allowing liquor sale craving a drink in mumbai? alcohol body writes to maha cm requesting 'phased reopening' of wine shops the countries that have banned alcohol sales due to coronavirus puzzled' excise department mulls opening wine shops by april . guwahati plus drinking patterns of hazardous drinkers. moonshine markets: issues in unrecorded alcohol beverage production and consumfreeon karnataka may allow liquor sell for hours if curbs extended thematic analysis of the organ transplantation news in turkish press issuing liquor pass for providing liquor to persons showing alcohol withdrawal symptom, due to unavailability of liquor further to the closure of liquor shops as part of measures for the containment of spread of covid- -guidelines. go(rt)no. / /td suicide risk and prevention during the covid- pandemic. the lancet alcohol poisoning kills iranians seeking virus protection on the rocks: ever since the lockdown, reports of deaths and suicides related to alcohol withdrawal have been rising. the hindu. retrieved th is another public health crisis brewing beneath the covid- pandemic? lockdown: home delivery of liquor in kerala announced covid: tipplers tackle acute withdrawal symptoms as defacto a. ghosh, et al the economic times. retrieved st alcohol non-availability kills more than coronavirus in kerala; foreign liquor served as 'medicine the delhi police caught a man trying to smuggle alcohol in milk cans. the vice socioeconomic status as an effect modifier of alcohol consumption and harm: analysis of linked cohort data. the lancet is an alcohol ban necessary during the lockdown? tamil nadu in low spirits as lockdown shuts tasmac outlets; deaddiction experts see opportunity for ban. news, . retrieved st naturalistic inquiry california hyderabad: as lockdown turns off booze tap, addicted migrant kids struggle for the first time, india has more rural net users than urban. times of india. retrieved rd alcohol withdrawal symptoms during lockdown: telangana, kerala tackle spike in cases. the news minute. retrieved st south africa's alcohol ban during lockdown reveals its deadly drinking habits alcohol consumption in india: a crosssectional study. surveys of drinking patterns and problems in seven developing countries lockdown effect: alcoholics turn up at hyderabad's erragadda hospital covid- and forced alcohol abstinence in india: the dilemmas around ethics and rights lockdown hits those battling alcohol addiction the hardest. the hindu retrieved st complicated alcohol withdrawal-an unintended consequence of covid- lockdown is alcohol an "essential good" during covid- ? yes, but only as a disinfectant!. alcoholism hyderabad man arrested for distributing free alcohol amid coronavirus lockdown hc stays kerala govt's decision to allow liquor for addicts amid lockdown. live mint thematic analysis: striving to meet the trustworthiness criteria covid- lockdown hangs heavy on boozers in himachal alcohol use on the rise in india state of kerala and others, general secretary government medical officers' association v. state of kerala and others, jossey matthew vs state of kerala and others tipplers in kerala with withdrawal symptoms to get special passes to buy liquor west bengal imposes per cent sales tax on liquor liquor stash in ambulance; milkman. cop among several held in delhi in crackdown on bootlegging no bars, no 'thekas', no alcohol, lockout sobering experience for tipplers covid- : india imposes lockdown for days and cases rise stay on liquor supply based on doctor's prescription in kerala amid covid alcohol ban. sri lankans are brewing moonshine lockdown sends grey-market booze prices soaring. the times of india daarunahi re baba. dawaiihai': twitterati reacts as #liquorfreeindia trends amidst countrywide liquor ban policy environment impacting the societal harm caused by alcohol in india: protocol for a scoping review besides coronavirus, protection of liquor bottles in state-run stores is another task for tamil nadu authorities. outlook india. retrieved st spurious liquor claims two lives, six ill amid lockdown in uttar pradesh. the times of india. retrieved st doing qualitative research kerala cm directs excise dept to provide liquor to those with doctor's prescription after surge in suicides west bengal government to allow home delivery of alcohol amid covid- lockdown. retrieved on th kerala hc stays govt order to provide liquor on prescription, calls it 'recipe for disaster liquor sellers seek permission for online, on-call sale of alcohol during coronavirus lockdown illegal liquor sellers find a new way to run their business during coronavirus lockdown psychiatrist withdraws plea for opening liquor shops after high court warning. the hindu man arrested for selling liquor by advertising on social media. the hindu after dry weeks, offloading of liquor set to start at ware. the times of india global status report on road safety : summary. retrieved from the world health organization serious adverse health events, including death, associated with ingesting alcohol-based hand sanitizers containing methanol -arizona and new mexico key: cord- -o ilxqo authors: sharma, v. k.; nigam, u. title: modelling of covid- cases in india using regression and time series models date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: o ilxqo in this article, we analyze the growth pattern of covid- pandemic in india from march th to may th using regression analysis (exponential and polynomial), auto-regressive integrated moving averages (arima) model as well as exponential smoothing and holt-winters models. we found that the growth of covid- cases follows a power regime of (t ,t..)after the exponential growth. we have found the optimal change points from where the covid- cases shifts their course of growth from exponential to quadratic and then quadratic to linear. we have also found the best fitted regression models using the various criteria like- significant p-values, coefficients of determination r values and anova etc. further, we have searched the best fitting arima model for the data using the aic (akaike information criterion) and caic (consistent akaike information criterion) and forecasted the number of cases for future days. we have used the usual exponential smoothing and holt-winters models for the data. we further found that the arima( , , ) model is the best-fitting model for covid- cases in india. the covid- pandemic has created a lot of havoc in the world. it is caused by a virus called sars-cov- , which comes from the family of coronaviruses and is believed to be originated from the unhygienic wet seafood market in wuhan, china but it has now infected more than countries of the world. with around million people affected around the world (as of th may, , *to be updated*), it has forced people to stay in their homes and has caused huge devastation in the world economy. (ref [ ] , [ ] ). in india, the first case of covid- was reported on th january, which is linked to the wuhan city of china (as the patient has travel history to the city). on th march, india saw a sudden hike in the number of cases and since then, the numbers are increasing day by day. as of th may (*to be updated*), india has more than , cases with more than deaths. (ref [ ] ). since the outbreak of the pandemic, scientists across the world have been indulged in the studies regarding the spread of the virus. lin et al. [ ] suggested the use of the seir (susceptible-exposed-infectious-removed) model for the spread in china and studied the importance of governmentimplemented restrictions on containing the infection. as the disease grew further, ivorra et al. [ ] suggested a θ -seihrd model that took into account various special features of the disease. it also included asymptomatic cases into account (around %) in order to forecast the total cases in china (around ). giordano et al. [ ] also suggested an extended sir model called sidharthe model for cases in italy which was more customized for covid- in order to effectively model the course of the pandemic to help plan a better control strategy. apart from the epidemiological models, various timeseries models were also suggested in order to model the cases and predict future cases. ceylan [ ] suggested the use of auto-regressive integrated moving average (arima) model to develop and predict the epidemiological trend of covid- for better allocation of resources and proper containment of the virus in italy, spain and france. chintalapudi et al. [ ] suggested its use for predicting the number of cases and deaths post -days lockdown in italy. petropoulos and makridakis [ ] suggested the use of exponential smoothing method to model the trend of the virus, globally. kumar et al. [ ] gave a review on the various aspects of modern technology used to fight against covid- crisis. since the spread of the virus started to grow in india, various measures were taken by the indian government in order to contain it. a nationwide lockdown was announced on march th to april th , which was later extended to may rd . the whole country was divided into containment zones (where large number of cases were observed from a relatively smaller region), red zones (districts where risk of transmission was high and had higher doubling rates), green zones (districts with no confirmed case from last days) and orange zones (which didn't fall into the above three zones). after the further extension of the lockdown till may th , various economic activities were allowed to start (with high surveillance) in areas of less transmission. further, the lockdown is now extended to may st and some more economic activities have been allowed as per the transmission rates, which are the rates at which infectious cases cause new cases in the population, i.e. the rate of spread of the disease. on the other hand, indian scientists and researchers are also working on addressing the issues arising from the pandemic, including production of ppe kits and tests kits as well as studying the behaviour of spread of the disease and other aspects of management. various mathematical and statistical methods have been used for predicting the possible spread of covid- . the classical sir model by ranjan [ ] , seir model by ranjan [ ] and siqr model by tiwari [ ] suggested the increasing trend of the virus and predicted the peaks of the pandemic. early researches showed the pandemic to reach its peak by mid-may. they also showed that the basic reproduction number r and the doubling rates are lower in india, with comparison to european nations and usa. a tree-based model was proposed by m.k. & bhatnagar [ ] and bhatnagar [ ] in order to study and predict the trends. they suggest that lockdown and socialdistancing in india has played a significant role to control the infection rates. kumar et al. [ ] suggested the use of arima and richard models for the same and have used them to predict the cases and deaths in future days. chatterjee et al. [ ] suggests growth of the pandemic through power law and its saturation at the later stages. due to the complexities in the epidemic models of covid- , various researchers have been focusing on the data in order to forecast the future cases. chatterjee et al. [ , ] and ziff & ziff [ ] suggest that after exponential growth, the total count follows a power regime of t , t , t and t . before flattening out, where t refers to time. it can therefore be realized that there is an urgent need to model and forecast the growth of covid- in india as the virus is in the growing stage here. in india, the most affected states are maharashtra with over , cases (as of th may, *need to be updated*), tamil nadu (over , cases) and gujarat (over , cases). the greatest number of cases per million have been seen in the national capital of delhi ( . cases per million). (refer [ ] for population estimates). various states such as arunachal pradesh, goa, mizoram and manipur have been declared covid- free states as they have treated all their cases since more than days. states of nagaland and sikkim and union territories of lakshwadeep islands and daman and diu are yet to report a single case. these large variations suggest the effectiveness of lockdown and sealing of state borders in containing the virus. in the latest research. singh & jadaun [ ] studied the significance of lockdown in india and suggested that the new covid- cases would stop by the end of august in india with around , total cases. while some states may see an early stopping of new cases such as telangana (mid-june), uttar pradesh and west bengal (july-end) etc., the badly affected states of maharashtra, tamil nadu and gujarat will achieve this by august-end. since a proven vaccine and medication is yet to be developed by the researchers then in such a scenario, modelling the present situation and forecasting the future outcome becomes crucially important in order to utilize our resources in the most optimal way. therefore, the article aims to study the growth curve of covid- cases in india and forecast its future observations. since the disease is still in its growing age and very dynamic in nature, no model remains perfectly valid for future. we need to develop the understanding of the present situation of the pandemic. in this article, we first study the growth curve using regression methods (exponential, linear and polynomial etc.) and propose an optimal model for fitting the cases till may th . further, we propose the use of time-series models for forecasting the future observations on covid- cases. here we reach the best-fitted arima model for forecasting the covid- cases. we also compare these results with exponential smoothing (holt-winters) model. this study will help us to understand the course of spread of sars-cov- in india better and help the government and the people to optimally use the resources available to them. in this section, we briefly present the statistical techniques used for analyzing the covid- cases in india. here, we used usual regression (exponential, polynomial), times series (arima and garch) and exponential smoothing models. regression is a statistical technique that attempts to estimate the strength and nature of relationship between a dependent variable and a series of independent variables. regression analyses may be linear and non-linear. a regression is called linear when it is linear in parameters e.g. where ‫ݕ‬ is response variable, a non-linear regression is a regression when it is non-linear in its parameters e.g. in the beginning of the spread of a disease, we see that the new cases are directly proportional to the existing infected cases and may be represented by is the proportionality constant. solving this differential equation, we get that, at the beginning of a pandemic, thus, at the beginning of a disease, the growth curve of the cases grows exponentially. as the disease spreads in a region, governments start to take action and people start becoming conscious about the disease. thus, after some time, the disease starts to follow a polynomial growth rather than continuing to grow exponentially. in order to fit an exponential regression to our data, we linearize the equation by taking the natural logarithm of the equation and convert it to a linear regression in first order. we estimate the parameters of a linear regression of order ݊ as following-let the model of linear regression of order ‫‬ be: represent the residual sum of square (rss). all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . by minimizing the rss, we get the best estimates of these coefficients by solving the following normal equations; this technique is referred to as the ordinary least squares (ols). we will use this technique of the ols in order to estimate the coefficients of our proposed model. (refer montgomery et al. [ ] ) since we know that the growth curve of the disease changes after some time point, exponential to polynomial, we propose to use the following joint regression model with change point ߤ , where we take is the order of the polynomial regression model and ‫ݐ‬ stands for the time (an independent variable). during the analysis, we found that a suitable choice of is a quadratic or cubic model. one the order of the polynomial is kept fixed, as optimum values of the change point can be easily obtained. we can obtain the ols of the parameters of the model ( ) as given below. the least square estimates (lses) of the parameters, can be obtained by minimizing the residual sum of squares as given by where, are the estimates value of ‫ݕ‬ from the exponential and polynomial regression models, respectively and ܰ is the size of the data set. the lses of can be obtained as the simultaneous solution of the following normal equations, solution to these equations is difficult since the parameter ߤ is decenter time point. we suggest to use the following algorithm while ߤ is kept fixed. algorithm : as an optimum value of the parameter ߤ in order to find the optimal value of µ, i.e. the turning point between the exponential and polynomial growth, we will use the technique of minimizing the residual sum squares in section . the auto-regressive integrated moving averages method gauges the strength of one dependent variable relative to other changing variables. an arima model can be understood by outlining each of its components as follows: autoregression (ar) refers to a model that shows a changing variable that regresses on its own lagged, or prior values. integrated (i) represents the differencing of raw observations to allow for the time series to become stationary, i.e., data values are replaced by the difference between the data values and the previous values. moving average (ma) incorporates the dependency between an observation and a residual error from a moving average model applied to lagged observations. here, we may refer the reader to follow box et al. [ ] and box et al. [ ] for more details on arima model, estimation and its application arima is a joint model of two models, autoregressive ar p and moving average ma q and is integrated using the difference variable, d. the mathematical model for arima can be expressed as follows; let us consider a backshift operator b, which causes the back shifting of the observation by interval. for any time-series {y t }, we have: the general model for arima/seasonal arima can be expressed as: since we are using arima only, the components of sarima, i.e. p=d=q=s= for our model. so, our model becomes: where the parameters (p, d and q) represents the lag order, degree of differencing and the order of moving average, respectively. we obtain the optimal values of p, d and q by using the aic (akaike information criterion) and caic ( . these information criteria may be used for selecting the best fitting models. lower the values of criteria, higher will be its relative quality. the aic, caic and bic are given by where k=number of model parameters, and n=no. of data points. exponential smoothing is one of the simple techniques to model time-series data where the past observations are assigned weights that are exponentially decreasing over time. we propose the following models, for modelling of covid- cases (see holt [ ] and winters [ ] ). all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. for this study, we have used the data available at github, provided by john hopkins university (see [ ] ). we have used the data from march th to may th (*to be updated later*) for continuity of the data. we know that at the beginning of the spread of the disease in india, the growth was exponential and after some time, it was shifted to polynomial. we first obtain optimum turning point of the growth, i.e. when did the growth rate of the disease shifted to polynomial regime from the exponential. we consider both quadratic and cubic regression model for second part of the data. we will also discuss the types of polynomial growth (with their equations) in india. in order to find the turning point of the growth curve, we follow the algorithm , given in the previous section. using that, we evaluate the rss for all the days (from march th ) and find the date on which it is minimum. the change points of growth curve for cubic and quadratic regressions are presented in figure depending upon the size of the data set. from figure (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . table . we see that after the exponential regime (till april th ), the growth curve follows a polynomial growth till may nd . after this, we again see a change in the behavior of the growth curve. in tables - , we try to model these growth curves through regression analysis. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. having evaluated the coefficients for various models (i.e. linear, quadratic and cubic) as well as the important statistics (i.e. r values, p-values of the models as well as individual coefficients and fstatistic), we will select the best fitting models. in order to select the best fitting models for region ii (april th to may nd ) and iii (may rd to may th ), we have the following steps. we select that model which has high r values, significant p-value, high f-statistic and where the p-values of all the variables are significant. we see for region ii, from table both the anova tables for region ii and iii suggest significant p-values for its coefficients and suggest that the models fit well the respective regions. thus, according to our study, the growth of the virus was exponentially increasing from march th to april th . then after, the virus grew by following a quadratic rate from april th to may nd . since may rd , we have been experiencing a linear growth, see table for best fitted regression models. figure shows the best fitted regression models to the daily cumulative cases of covid- in india till may. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . first, we obtain the optimal arima parameters (p, d, q) by using the aic and caic criteria. we take various possible combinations of (p, d, q) and compute the aic and caic criteria. then, select the best fitted arima model that has the lowest aic and caic among all considered models. according to the aic and caic, the arima ( , , ) is the best fitted models for the covid- cases, india. estimates of arima ( , , ) parameters and mape are shown in table . estimates of the holt-winters exponential smoothing and exponential smoothing models are given in table . according to the mape and accuracy measures, the arima ( , , ) is a better model than the holt-winters exponential smoothing and exponential smoothing models. from this, we can conclude that the arima model is the best fit for the cases of covid- , followed by holt-winters model. the forecasting are shown in table and figure . we observe that the arima model captures the trend well but it underestimates the actual covid- cases. we therefore suggest to update the arima model in future or to use some generalized versions of the arima models in future studies. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . from the regression analysis, we conclude that the spread of convi- disease grew exponentially from march rd to april th . further, from april th to may nd , the cases followed a quadratic regression. from may rd to may th , we see a linear growth of the virus with average daily cases of . verma et al. [ ] showed the four stages of the epidemic, s : exponential, s : power law, s : linear and s : flat. therefore, covid- pandemic in india has entered in stage s of linear growth. in the days to come, it is highly likely that the total cases may start to follow a square root equation, i.e. in time series analysis, we conclude that the arima ( , , ) is the best fitting model for the cases of covid- with an accuracy of . %. this is also suggested by the exponential smoothing and holt-winters models. the basic exponential smoothing is not very accurate for our case but we see that the holt-winters model is around . % accurate. both arima ( , , ) and holt-winters models suggest a rise in the number of cases in the coming days. we also observed that the arima model underestimates the actual observations. therefore we suggest updating the arima model time to time or using some generalized arima models. we may also conclude that the cases of covid- will rise in the coming days and but slowly, we may head towards the reduction in the daily number of cases. but this should be accompanied by following of proper safety measures and following the guidelines of the government of india. with the gradual relaxation of lockdown measures, if proper precautions are not taken, we may see an increase in the daily cases. we must learn to lead our lives by following all the precautions once the lockdown measures are relaxed. a conceptual model for the coronavirus disease (covid- ) outbreak in wuhan, china with individual reaction and governmental action mathematical modeling of the spread of the coronavirus disease (covid- ) considering its particular characteristics. the case of china a sidarthe model of covid- epidemic in italy estimation of covid- prevalence in italy, spain, and france, the total environment science of the total environment covid- virus outbreak forecasting of registered and recovered cases after sixty daylockdown in italy: a data driven model approach forecasting the novel coronavirus covid- predictions for covid- outbreak in india using epidemiological models estimating the final epidemic size for covid- outbreak using epidemiological models modelling and analysis of covid- epidemic in india medrxiv modeling and predictions for covid spread in india covid- : mathematical modeling and predictions forecasting covid- impact in india using pandemic waves nonlinear growth models evolution of covid- pandemic: power law growth and saturation covid- pandemic: power law spread and flattening of the curve fractal kinetics of covid- pandemic time series analysis: forecasting and control r: language and environment for statistical computing. r foundation for statistical computing introduction to time series and forecasting forecasting seasonals and trends by exponentially weighted averages forecasting sales by exponentially weighted moving averages modeling tempo of covid- pandemic in india and significance of lockdown covid- ) outbreak in india: a perspective so far a review of modern technologies for tackling covid- pandemic m a y m a y m a y m a y key: cord- -oz x a s authors: agrawal, shubhada; bhandari, siddharth; bhattacharjee, anirban; deo, anand; dixit, narendra m.; harsha, prahladh; juneja, sandeep; kesarwani, poonam; swamy, aditya krishna; patil, preetam; rathod, nihesh; saptharishi, ramprasad; shriram, sharad; srivastava, piyush; sundaresan, rajesh; vaidhiyan, nidhin koshy; yasodharan, sarath title: city-scale agent-based simulators for the study of non-pharmaceutical interventions in the context of the covid- epidemic date: - - journal: nan doi: nan sha: doc_id: cord_uid: oz x a s we highlight the usefulness of city-scale agent-based simulators in studying various non-pharmaceutical interventions to manage an evolving pandemic. we ground our studies in the context of the covid- pandemic and demonstrate the power of the simulator via several exploratory case studies in two metropolises, bengaluru and mumbai. such tools become common-place in any city administration's tool kit in our march towards digital health. : timeline of covid- cases, recoveries and fatalities in india taken from [ ] . see [ ] and [ ] for detailed information on how covid- progressed in india. covid- is an ongoing pandemic that began in december . the first case in india was reported on january . the number of cases and fatalities have been on the rise since then. as on august , there are , , cases (of which , , have recovered) and , fatalities [ ] ; see figure for a timeline of covid- cases, recoveries and fatalities in india. while medicines/vaccines for treating the disease remained under development at the time of writing this paper, many countries implemented non-pharmaceutical interventions such as testing, tracing, tracking and isolation, and broader approaches such as quarantining of suspected cases, containment zones, social distancing, lockdown, etc. to control the spread of the disease. for instance, the government of india imposed a nationwide lockdown from march to april , and subsequently extended it until may to break the chain of transmission and also to mobilise resources (increase healthcare facilities and streamline procedures). to evaluate various such interventions and decide which route to take to manage the pandemic, epidemiologists resort to models that predict the total number of cases and fatalities in both the immediate and the distant futures. the models used should have enough features to enable the evaluation of the impact of various kinds of non-pharmaceutical interventions. broadly three kinds of models have been used to study this epidemic. the first set of models takes a curve-fitting approach. they rely on simple parametric function classes. the parameters of the model are fit via regression to match observed trends. the second set of models addresses the physical dynamics of the spread at a macroscopic level. these are meanfield ordinary differential equations (odes) based compartmental models (e.g. susceptible-exposed-infected-recovered (seir) model and its extensions) based on the classical work of kermack and mckendrick [ ] . here the population is divided into various compartments such as susceptible, exposed, infected, recovered, etc., based on the characteristics of the epidemic. one then solves a system of odes that captures the evolution of the epidemic at a macroscopic scale . localised versions of these are spatio-temporal mean-field models that lead to partial differential equations . the third set of models, and the focus of this work, are agent-based models . a very detailed model of the society under consideration, with as many agents as the population, is constructed using census and other data. the agents interact in various interaction spaces such as households, schools, workplaces, marketplaces, transport spaces, etc. see figure for a schematic representation of an agent-based model with the aforementioned interaction spaces. these interaction spaces are the primary contexts for the spread of infection. a susceptible individual can potentially get infected from an interaction in one of these spaces upon contact with an infected individual. once an individual is exposed to the virus, this person goes through various stages of the disease, may infect others, and eventually, either recovers or dies. other models work at an intermediate level by modelling the social network of interactions, e.g., [ ] , but we shall focus more on agent based models. there are several advantages of using agent-based models. first, since modelling is performed at a microscopic level unlike the macroscopic level in compartmental models, agentbased models are well suited to capture heterogeneity at various levels. for instance, the agedependent progression of covid- in individuals (severity, the need for hospital care, intensive care, etc.) can be incorporated in agent-based models. second, individual behavioural changes, known to be important in certain diseases such as aids, can be easily modelled. third, agent-based models are well suited to study the impact of various non-pharmaceutical interventions, such as "lockdown for a certain number of days", "offices operating using the see [ ] for a state-level epidemiological model for india and [ ] for a combination of the two approaches. for a paper in the indian context see [ ] . there are other agent-based simulators that have informed policy decisions. see [ ] for uk and usa related studies specific to covid- , see [ ] for a covid- study on sweden, see [ ] and references therein for many agent-based models and their comparisons, and see [ ] for a taxonomy of agent-based models. (so-called) odd-even strategy", "social distancing of the elderly", "voluntary home quarantine", "closure of schools and colleges", etc. explicit modelling of these contexts of infection spread also enables studies of control measures targeting the interaction spaces. fourth, there is an important difference between the actual infected number in the population, which is what the differential equations-based models predict, and the reported cases. the latter is invariably based on those that come to hospitals/clinics seeking health care, or those that are identified due to random testing, followed by contact tracing of such index cases. as a consequence, reported cases provide a biased estimate of the actual infected number in the population. agent-based simulators have the capability to track such biased estimates of prevalence. in this work, we describe our city-scale agent-based simulator to study the epidemic spread in two indian cities and demonstrate how digital computational capabilities can help us assess the impact of various interventions and manage a pandemic. we now provide sample outcomes for bengaluru and mumbai for covid- under various interventions. these outcomes have been generated using our city-scale agent-based simulator. bengaluru and mumbai have estimated populations of . and . crore people respec- the census figure for bengaluru is . crore and for mumbai is . crore (mumbai city only, not the mumbai urban area whose census estimate is . crore). bengaluru's population is estimated to be . crore. reliable data is not available for mumbai city's population. we have used estimated population for bengaluru and census estimate for mumbai. social distancing of the elderly, closure of schools and colleges, % occupancy at workplaces, and case isolation. this is the fourth shaded region in the plots. • from may onwards, continued contact tracing (following the indian council of medical research (icmr) guidelines as much as possible) and associated quarantining and case isolations, but otherwise an unlocked bengaluru. soft ward containment continues to be in force. by soft ward containment, see figure , we mean linearlyvarying mobility control that turns an open ward into a locked ward when the number of hospitalised cases become . % of the ward's population; in the latter locked scenario, only % mobility is allowed for essential services. • past studies [ ] - [ ] have indicated that masks have been effective in reducing the spread of influenza. anecdotal evidence seems to suggest that masks are effective for covid- . the ministry of home affairs (mha) order of april [ , annexure ] made the wearing of masks in public places compulsory. this was reemphasised in the mha order of may [ ] . we assume that masks are mandatory from april onwards. • it is often the case that when there are several restrictions in place, only a fraction of the population complies with these restrictions. getting the entire population to comply is often a big challenge and requires significant and persistent messaging (including communication, rewards, punitive measures). we assume a compliance factor of . up to may , which means that percent of the population adheres to the government guidelines like social distancing, wearing masks in public places, etc., and . thereafter. the reduction could be attributed to behavioural changes due to lockdown fatigue. • a brief lockdown during - july was implemented in bengaluru. we compare two scenarios, one with this lockdown and one without this lockdown. as one can anticipate, simulation of the above scenarios requires a significant level of sophistication in the modelling and implementation. we describe how we do these in the coming sections, but now focus only on the outcomes. the trend for the reported cases is roughly captured, but fatalities are over-predicted. this is surprising since the reported cases continued to be high in the third week of july. for a more detailed study of these plots, we refer the reader to section iii-a. at this stage, we only observe that the public health benefit of the lockdown is clear from the pictures, reduced peak at the expense of a brief second wave. armed with these predicted outcomes under the two scenarios, public health officials can now weigh the benefits of the lockdown against its economic consequences. ) mumbai: for mumbai, we simulate the following scenario. • workplaces open with a small strength of % during - may , as per government of maharashtra directions. this is the fifth shaded region. during this period, social distancing of the elderly and school and college closures remain in force. • workplace strengths increase to % in june, to % in july, and to % in august, with commensurate capacity increases in the local trains. social distancing of the elderly and school and college closures remain in force. in addition voluntary home quarantine and case isolation come into play. • throughout the simulations, soft ward containment is in force. • it is often difficult to comply with social distancing directives in high population density areas, like in slums, with many common essential facilities. in mumbai, we model compliance to be . in high density areas and . in other areas. • throughout the simulations, contact tracing, associated quarantining, testing, and further tracing are enabled. • we will compare the above scenario, with local trains enabled, and will contrast it with another hypothetical scenario having no local trains. is our hope that such tools become common place in a city administration's tool kit, and are used to the fullest extent before drastic interventions with wide-scale impact, e.g., lockdown, are imposed. with additional modelling of activity, mobility, and behaviour, and use of high quality data on the migrant labour force in urban areas, we speculate that we could have anticipated certain behavioural outcomes seen in india after the lockdown announcement (e.g., migrant population movement). broadly, the steps involved in agent-based modelling are the following: build the simulator, calibrate it, validate it, and use it for estimating how the pandemic will evolve. . simulator. the simulator itself consists of four parts. synthetic city. a synthetic city generator builds a synthetic city with individuals and various interaction spaces. individuals are assigned to various interaction spaces such as households, schools/workplaces, communities and transport spaces. in doing this we capture the demographics of the city, the school size distributions, the workplace size distributions, the commute distances, the neighbourhood and friends' interaction networks, the transport interaction spaces, etc. these fix the "social networks" on which individuals interact and transmit the virus. table i for some examples. many of these involve reduction in changes in contact rates as a consequence of the interventions. the values to set could be based on observed mobility patterns. for example, according to the covid- community mobility report for india in april [ ] in table ii, prepared by google based on data from google account users who have "opted-in" to location history, there was significant reduction in mobility during the lockdown period compared to the baseline period of january to february . this informs the nominal contact rate choices in the interventions' definitions in table i and later in other tables. . calibration. once the simulator is ready there are still unknown parameters that need to be identified. these include the contact rates at various interaction spaces, the number of infections to seed, the time at which these infections should be seeded, the compliance parameters, etc. the purpose of the calibration step is to identify these parameters to capture the city specific trends and contact rates. we do this by choosing the initial number to seed, the time at which these are seeded, and the contact rates so that the initial trend of the disease is matched. once calibrated, we can run our simulator for a certain number of days and understand how the epidemic spreads. . validation. we next have to validate our simulator, so that we can understand the predictive power of the simulator. for this, we look for phenomena in the real data that have not been explicitly modelled and we check if the simulator is able to capture these phenomena. for specific details, see section iv. . use of the simulator in an evolving pandemic. it is often the case that in evolving pandemics, predictions do not match reality as time unfolds. models are often gross oversimplifications of the underlying complex reality and assumptions are often wrong or may need updating as the pandemic evolves. the purpose of models in an evolving pandemic is not merely to predict numbers, in which task they will likely fail, but more to enable principled decision making on intervention strategies. they enable a study of the public health outcomes of one strategy versus another. armed with these comparisons, public health officials can make more informed decisions. needless to say, these are often more complex and involve several aspects beyond just public health, e.g. economy, psychology, education, political climate, to name a few . for a proposal on how to simulate economic and public-health aspects together, see [ ] . one of the powerful features of the agent-based simulator is its ability to explicitly control various interaction spaces and study the outcomes. we demonstrate this feature via the case studies for bengaluru and mumbai listed in table iii . we compare the following three scenarios in bengaluru: • no intervention other than contact tracing, testing and associated case isolation. • indefinite lockdown starting from march onwards. this naturally will have enormous economic and societal cost, but we focus only on the direct covid- public health outcomes. • scenario- in table iv: soft ward containment, case isolation with testing and contact tracing, and a one-week lockdown during - july . we assume a compliance of % until may (i.e. during the initial karnataka-wide lockdown followed by the nation-wide lockdown) and a compliance of % starting may , for all these scenarios. that is, % (resp. %) of the population comply with the restrictions in place until may (resp. starting may ). under these scenarios, we plot the following: daily cases (figure ), daily fatalities ( figure ), cumulative cases ( figure ), cumulative fatalities ( figure ) and estimated hospital beds and critical care beds ( figure ). we make the following observations. • as one would expect, the least number of cases, fatalities and hospital beds requirements correspond to the "indefinite lockdown" scenario. however this scenario has serious impact on the economy, livelihoods, etc. • in terms of the daily number of cases, the no intervention scenario had a peak around june (with roughly , cases), whereas the present scenario in bengaluru (i.e. scenario- in table iv ) had a much lower peak around july (with around cases), followed by another peak around end of august. similar trends can be seen in the fatalities estimates as well as the hospital bed estimates. our health care system would have struggled with the no intervention scenario, and the present scenario in bengaluru helped mitigate and delay the peak of the epidemic. • the second predicted peak in scenario- in table iv is due to the one-week lockdown during - july . • towards the end of july, we overpredict the number of daily fatalities and underpredict the number of daily cases. this could be because of two reasons: ) the number of tests has increased significantly during mid-july due to which there is a likely surge in the number of asymptomatic cases. as a consequence, a reduction in the number of daily cases due to the one-week lockdown during - july is not observed in the reported number of daily cases; such a reduction is visible in our estimates because the testing regime is assumed constant through the period in our simulator. ) there is a delay in reporting the fatalities. as the reported number of daily cases follow an exponential trend during early-mid july, one would expect a similar trend in the reported daily fatalities during end-july, as shown in our prediction of the daily fatalities under scenario- . however, we see a reduction in the reported number of daily fatalities during after july . this could be due to a possible delay in reporting the daily fatalities, or an effective use of the rapid point-of-care antigen test kits, or a combination of both. testing of these hypotheses require further investigation. b. case study b: impact of opening offices at % capacity with higher compliance versus lockdown at lower compliance the degree of compliance among the population to public health directions/guidelines is an important factor that affects the epidemic. to understand the importance of compliance, we compare the following scenarios for bengaluru: the present bengaluru (i.e. scenario- in table iv ), an unlocked bengaluru (i.e. scenario- in table iv) , and an unlocked bengaluru with a higher compliance of % starting may (i.e. scenario- in table iv with % compliance during march - may and % compliance starting may ). as before, we plot the following: daily cases (figure ), daily fatalities ( figure ), cumulative cases ( figure ), cumulative fatalities ( figure ) and estimated hospital beds and critical care beds ( figure ). we make two important observations: • in terms of the number of cases and fatalities, the present bengaluru (i.e. scenario- in the general populace on the public health impact of their actions, to induce more prosocial behaviour, and to ensure greater compliance. this was the approach taken by sweden, a country with a population of about crore. • comparing scenario- and scenario- , we see that the effect of the one-week lockdown during - july is very minimal in the long term as far as the cumulative number of cases and fatalities are concerned. however, there is a significant difference in the cumulative number of cases and fatalities between scenario- and scenario- with a higher compliance of % starting may . this suggests that, given that vaccines for covid- are not yet available, short-term lockdowns' benefit is restricted to mobilising resources and preparing the healthcare system in the short term. on the other hand, higher compliance has a greater impact in reducing cases and fatalities. • trains-off: suburban trains are not operational throughout. as indicated in table v , we assume a compliance factor of % in non-slums and % in slums. we plot our results in figures - . • from the plots, we see that the phased opening of suburban trains starting june gives a marginal increase in the number of cases, fatalities and hospital beds compared to the trains-off scenario. this suggests that trains can be operated with enforcement • although we match the daily fatalities curve very well, we over-predict the daily number of cases. we believe that this is due to the limitation on the testing capacity on the ground. because of this, the test results of many people arrive late and cases get reported with a certain delay. it is also worth mentioning that, although we overpredict the daily number of cases, we correctly capture the growth rate of the daily number of cases as well as the cumulative number of cases. we study the impact of two containment strategies for bengaluru: soft ward containment (i.e., linearly-varying mobility control that turns an open ward into a locked ward when the number of hospitalised cases become . % of the wards population; in the latter locked scenario, only % mobility is allowed for essential services, see figure ) and neighbourhood containment (i.e., when an individual is hospitalised, everyone living in a m surrounding area undergoes home quarantine). soft ward containment is a more feasible strategy than strict ward containment since the average ward population in bengaluru is about , . as we use a corrected version of the reported number of daily fatalities from brihanmumbai municipal corporation (bmc). the initial reported daily fatalities curve from bmc had a very large peak at june . the corrected data adjusts the daily fatalities curve until june so that the peak on june gets re-distributed to the previous days in a suitable way. the number of hospitalised cases in the ward increases, more public health wardens could be deployed and help reduce mobility and interaction in the ward. in figures - , we plot these two scenarios. we observe that neighbourhood containment is more effective than soft ward containment, in terms of cases and fatalities. to compare various levels of strictness with which policies are enforced, we now consider the opening scenario indicated in table v we now study the impact of opening schools. in figures - , we compare the following two scenarios: • schools-closed: the present scenario in bengaluru, i.e., scenario- in table iv, • schools-open: scenario- in table iv with schools open from september . as expected, both these scenarios follow the same trend until about mid-september, after which the disease spread increases in the latter. around early november, we observe a between - % increase in the cumulative number of cases and the cumulative number the first step in our agent-based model is to model a synthetic city that respects the demographics of the city that we want to study. our city generator uses the following data as input: • geo-spatial data that provides information on the wards of a city (components) along with boundaries. (if this is not available, one could feed in ward centre locations and ward areas). • population in each ward, with break up on those living in high density and low density areas. • age distribution in the population. • household size distribution (in high and low density areas) and some information on the age composition of the houses (e.g., generation gaps, etc.) • the number of employed individuals in the city. • distribution of the number of students in schools and colleges. • distribution of the workplace sizes. • distribution of commute distances. • origin-destination densities that quantify movement patterns within the city. taking the above data into account, individuals, households, workplaces, schools, transport spaces, and community spaces are instantiated. individuals are then assigned to households, workplaces or schools, transport and community spaces, see figure for a schematic representation. the algorithms for the assignments do a coarse matching. the matching may be refined as better data becomes available. the interaction spaces -households, workplaces or schools, transport and community spaces -reflect different social networks and transmission happens along their edges. there is interaction among these graphs because the nodes are common across the graphs, see figure for various interaction spaces and figure for a bipartite graph abstractions of these interaction spaces. an individual of school-going age who is exposed to the infection at school may expose others at home. this reflects an interaction between the school graph and the household graph. similarly other graphs interact. we now describe how individuals are assigned to interaction spaces. the households are then assigned to wards so that the total number of individuals in the ward is in proportion to population density in the ward, taken from census data. a population density map is given in figure in past works, given the structure of educational institutions elsewhere, educational institutions have been divided into primary schools, secondary schools, higher secondary schools, and universities. the norm in indian urban areas is that schools handle primary to higher secondary students and then colleges handle undergraduates. we view all such entities as schools. we assign students to schools on a ward-by-ward basis. in each ward, we have a certain number of students. we pick a school size from a given school size distribution and instantiate the unemployed fraction in bengaluru, from the census data, is just over %, even after taking into account employment in the unorganised sector. similar is the case with mumbai. this may have some bearing on the epidemic spread. a school of this size and place it randomly in that ward. students who live in that ward are picked randomly and assigned to this school until that school is filled to its capacity. we repeat this procedure until all students in that ward gets assigned to a school, and then we repeat this procedure for all wards. this procedure could lead to at most one school per ward whose capacity is more than its sampled capacity. assignment of workplaces: workplace interactions can enable the spread of an epidemic. in principle, bengaluru's and mumbai's land-use data could be used to locate office spaces. the assignment of individuals to workplaces is done in two steps. in the first step, for each individual who goes to work, we decide the ward where his/her office is located. this assignment of a "working ward" is based on an origin-destination (od) matrix. an od matrix is a square matrix whose number of rows equals the number of wards, and its (i, j)th entry tells us the fraction of people who travel from ward i to ward j for work. in the second step, for each ward, we sample a workplace size from a workplace size distribution, create a workplace of this capacity and place it uniformly-at-random in that ward. we then randomly assign individuals who work in that ward to this workplace. similar to assignment of schools, we continue to create workplaces in this ward until every individual working in that ward gets assigned to a workplace, and we repeat this procedure for all wards. for bengaluru, the od matrix is obtained from the regional travel model used for bengaluru. for mumbai, based on the "zone to zone" travel data from [ ] , an origin-destination matrix was extrapolated based on the population of each ward. the above assignments could be improved further in later versions of this simulator. community spaces: community spaces include day care centres, clinics, hospitals, shops, markets, banks, movie halls, marriage halls, malls, eateries, food messes, dining areas and restaurants, public transit entities like bus stops, metro stops, bus terminals, train stations, airports, etc. while we hope to return to model a few of the important ones explicitly at a later time, we proceed along the route taken by [ ] with two modifications. in our current implementation, each individual sees one community that is personalised to the individual's location and age and one transport space personalised to the individual's commute distance. for ease of implementation, the personalisation of the community space is based on ward-level common local communities and a distance-kernel based weighting. the personalisation of the transport space is based on commute distance. details are given in section iv-c. age-stratified interaction: the interactions across these communities could be age-stratified. this may be informed by social networks studies, for e.g., as in [ ] which has been used in a recent compartmentalised seir model [ ] . smaller subnetworks: we create smaller subnetworks in workplaces, schools and communities, and associate certain number people to these smaller networks with the interpretation that people in a smaller subnetwork have high contact rate among them compared to the others. in some more detail, we create "project" networks at each workplace consisting of people in that workplace having closer interaction, a "class" network in each school consisting of students of the same age, a random community network among people in a given ward to model daily random interactions, and a neighbourhood subnetwork among people living in a m× m square . these subnetworks are later used for identifying and testing/quarantining individuals based on a contact tracing protocol. the output of all the above is our synthetic city on which infection spreads. figure provides an indication of how close our synthetic city is to the true city in terms of the indicated statistics. we have used a simplified model of covid- progression, based on descriptions in [ ] and [ ] . this will need updating as we get india specific data. an individual may have one of the following states, see figure : susceptible, exposed, infective (pre-symptomatic or asymptomatic), recovered, symptomatic, hospitalised, critical, or deceased. we assume that initially the entire population is susceptible to the infection. let τ denote the time at which an individual is exposed to the virus, see figure . the incubation period is random with the gamma distribution of shape and scale . ; the mean incubation period is then . days ( . days in [ ] and . in [ ] ). individuals are infectious for an exponentially distributed period of mean duration . of a day. this covers both presymptomatic transmission and possible asymptomatic transmission. we assume that a third of the patients recover, these are the asymptomatic patients; the remaining two-third develop symptoms. estimates of the number of asymptomatic patients vary from . to . . though we have explored other asymptomatic fractions, we restrict attention here to / . symptomatic patients are assumed to be . times more infectious during the symptomatic period than during the pre-symptomatic but infective stage. individuals either recover or move to the hospital after a random duration that is exponentially distributed with a mean of days . the probability that an individual recovers depends on the individual's age . it is also assumed that recovered individuals are no longer infective nor susceptible to a second infection. while hospitalised individuals may continue to be infectious, they are assumed to be sufficiently isolated, and hence do not further contribute to the spread of the infection. further progression of hospitalised individuals to critical care is mainly for assessing the need for hospital beds, intensive care unit (icu) beds, critical care equipments, etc. this will need to be adapted to our local hospital protocol. let us reiterate. once a susceptible individual has been exposed, the trajectory in figure takes over for that individual. further progressions are (in our current implementation) only based on the agent's age. at each time t, an infection rate λ n (t) is computed for each individual n based on the prevailing conditions. in the time duration ∆t following time t, each susceptible individual moves to the exposed state with probability − exp{−λ n (t) · ∆t}, independently of all other events. other transitions are as per the disease progression described earlier. time is then updated to t + ∆t, the conditions are then updated to reflect the new exposures, changes to infectiousness, hospitalisations, recoveries, contact tracing, quarantines, tests, test outcomes, etc., during the period t to t + ∆t. the process outlined at the beginning of this paragraph is repeated until the end of the simulation. ∆t was taken to be hours in our simulator and is configurable. additionally, each individual has two other parameters: a severity variable c n and a relative infectiousness variable ρ n , see [ ] . both bring in heterogeneity to the model. severity c n = if the individual suffers from a severe infection and c n = otherwise; this is sampled at % probability independently of all other events. infectiousness ρ n is a random variable that is gamma distributed with shape . and scale (so the mean is ). the severity variable captures severity-related absenteeism at school/workplace, associated decrease of infection spread at school/workplace, and the increase of infection spread at home. if the individual gets exposed at time τ n , a relative infection-stage-related infectiousness is taken to be κ(t − τ n ) at time t. for the disease progression described in the previous section, this is in the presymptomatic and asymptomatic stages, . in the symptomatic, hospitalised, and critical stages, and in the other stages. to describe the infection spread at transport spaces, let t (n) = if agent n uses public transport and let t (n) = otherwise. let a n,t = if at time t agent n is either (i) compliant and under quarantine, (ii) hospitalised, (iii) critical, or (iv) dead, and let a n,t = if none of the above is true and agent n attends office at time t. we model the effectiveness of masks by reducing the ability of an infectious individual to transmit the infection by %, if a mask is worn (see [ ] - [ ] ); let m n = . if agent n wears a face mask in public transport and m n = otherwise. let β h , β s , β w , β t , β c , β * h , β * s , β * w and β * c denote the transmission coefficients at home, school, workplace, transport, community spaces, neighbourhood network, class network, project network and random community network, respectively. these can be viewed as scaled contact rates with members in the household, school, workplace, community, neighbourhood, class, project and random community, respectively. more precisely, these are the expected number of eventful (infection spreading) contact opportunities in each of these interaction spaces. it accounts for the combined effect of frequency of meetings and the probability of infection spread during each meeting. for a susceptible individual, the rate of transmission is governed by the sum of product of contact rate β and infectiousness in all the interactions spaces. to model infectiousness, we consider three scenarios. interactions without age-stratification: this is the simplest model where interactions within each network is assumed to be homogeneous. a susceptible individual n (who belongs to home h(n), school s(n), workplace w(n), transport space t (n), and community space c(n)) sees the following infection rate at time t: where h c,c (t) = n :c(n )=c f (d n ,c(n ) ) · ζ(a n ) · i n (t)β c r c κ(t − τ n )ρ n ( + c n (ω − )) the expression ( ) can be viewed as the rate at which the susceptible individual n contracts the infection at time t. each of the components on the right-hand side indicates the rate from home, school, workplace, transport space, and community. the additional quantities, over and above what we have already described, are as follows. the parameter α determines how household transmission rate scales with household size, a crowding-at-household factor. it increases the propensity to spread the infection by a factor n −α . we have taken α = . , see [ ] . a common parameter ω indicates how a severely infected person affects a susceptible one, as will be clear from below. (this is to be tuned at a later stage and is set to now). the functions ψ s (·) and ψ w (·) account for absenteeism in case of a severe infection. it can be time-varying and can depend on school or workplace. we take ψ s (t) = . and ψ w (t) = . while infective and after one day since infectiousness. school-goers with severe infection contribute lesser to the infection spread, due to higher absenteeism, than those that go to workplaces; moreover, the absenteeism results in an increased spreading rate at home. the function ζ(a) is the relative travel-related contact rate of an individual aged a. we the function f (·) is a distance kernel that can be matched to the travel patterns in the city. finally, our choice of the infection rate from the community space is a little different from the rate specified in [ ] , in order to enable an efficient implementation. when the distance kernel is f (d) = /( + (d/a) b ) and d a, i.e., the wards are small, then our specification is close to that indicated in [ ] . we take a = . km and b = . , based on a fit on data for bengaluru. as one can see from ( ), we have one community space but with contributions from various wards. this enables inclusion of 'containment zones' and the associated restriction of interaction across such zones, as we shall soon describe. age-stratified interactions: if this is enabled, the home, school, workplace and community interaction rates have an extra factor m h n,n , m s n,n , and m w n,n in the summand which accounts for age-stratified interactions. each of these depends on n and n only through the ages of agents n and n . the resulting contact rate for individual n at time t is then: where h c,c (t) is given in ( ) . computational complexity can be reduced by focusing only on the principal components of m h , m s , and m w . interactions with smaller subnetworks: in this situation, we have additional contact rate parameters, one for each smaller subnetwork: let β * h , β * s , β * w and β * c denote the transmission coefficients at neighbourhood network, class network, project network and random community network respectively. then, an agent n (who belongs to neighbourhood network h (n), class s (n), project w (n) and random community c (n), in addition to home h(n), school s(n), workplace w(n), transport space t (n), and community space c(n)) sees the following infection rate at time t: λ n (t) = n :h(n )=h(n) n α h(n) · i n (t)β h κ(t − τ n )ρ n ( + c n (ω − )) + ζ(a n ) n :h (n )=h (n) n h (n) · ζ(a n )i n (t)β * h κ(t − τ n )ρ n ( + c n (ω − )) (larger neighbourhood interaction) + ζ(a n )f (d n,c(n) ) n :c (n )=c (n) f (d n ,c(n ) ) × n :c (n )=c (n) f (d n ,c(n ) )ζ(a n )i n (t)β * c κ(t − τ n )ρ n ( + c n (ω − )) (close friends' circle interaction) (project network interaction) where h c,c (t) is given in ( ) . the subnetwork interactions are stronger contexts for disease spread. contact tracing targets exactly these subnetworks for additional testing, case isolation or quarantine. two methods of seeding the infection have been implemented. • a small number of individuals can be set to either exposed, presymptomatic/asymptomatic, or symptomatic states, at time t = , to seed the infection. this can be done randomly based either on ward-level probabilities, which could be input to the simulator, or it can be done uniformly at random across all wards in the city. • a seeding file indicates the average number of individuals who should be seeded on each day in the first stage of infectiousness (presymptomatic or asymptomatic). this could be done based on data for patients with a foreign travel history who eventually visited a hospital. a certain multiplication factor then accounts for the asymptomatic and the symptomatic individuals that recover without the need to visit the hospital. the seeding is done at a random time earlier in the time line, based on the disease progression. we calibrate our model by tuning the transmission coefficients at various interaction spaces under the no-intervention scenario in order to match the cumulative fatalities to a target curve. we assume a common upscaling factorβ for the transmission coefficients of smaller subnetworks, i.e., we set β * w =ββ w , β * s =ββ s and β * h = β * c =ββ c . we assume that β = , indicating that the subnetworks account for % of the overall contacts. the following heuristic iterative algorithm inspired by stochastic approximation is then used to identify the best choice of the free parameters. where [exp(m * − m(n))] /a a = min{max{exp(m * − m(n)), a}, /a}, Λ h (n) (resp. Λ w (n), Λ c (n)) is the fraction of infections from home (resp. workplace, community) in the nth where Λ * h = Λ * w = Λ * c = / , and m * is the target slope (the target slope is similarly computed from the cumulative fatalities data in log scale; for example, the india fatalities curve in the range - gives a slope of m * = . ). once the slopes are matched, assuming that the simulator starts on march , we find the delay between the fatalities curve from the simulator and the target data. we then use the resulting contact rates and the above calibration delay to launch our simulations. to avoid any oscillatory behaviour of the calibration algorithm, we also set the scale factor in each of the above update steps to be [exp((m * − m(n))/n)] we do not calibrate β t , the transmission coefficient at transport space. for the calibration step we take this parameter to be zero while tuning the other parameters. a heuristic justification is as follows. bengaluru travel interactions will likely be captured through the local community interactions, and we keep it zero throughout, even in the case studies. for mumbai however, local trains are a key mode of daily transportation with a population of the order of lakh travelling daily using this mode in normal times. however, trains were stopped in mumbai prior to the national lockdown and were running below capacity for at least a week before that. moreover, the initial infections were seeded by travellers that came from abroad. the primary mode of travel for this group is unlikely to be rail transport. so we disabled the transport space while calibrating by setting β t = . subsequently for the trains on/off case study, we used a heuristic calculation of β t ; see [ , section iv]. the above procedures identify the contact-related parameters. other parameters are the distance kernel parameters, the parameter α that accounts for crowding in households, the age-stratified interactions, the distribution parameters for individual infectiousness, the probability of severity, etc. these are set as follows: the simulator has the capability to accommodate interventions and compliance. table viii describes some of the interventions in [ ] , some adapted to suit our demographics, and some new interventions involving the nation-wide -day 'lockdown' in india and various scenarios of 'unlock'. these are fairly straightforward to implement -we modulate an individual's contact rate with an interaction space (both into the interaction space and out of the interaction space) by a suitable factor associated with intervention. for example, one could easily implement and study cyclic exit strategies as done in [ ] . the triggers for cyclic controls could be based on signals such as the number of individuals that are hospitalised, as done in our soft ward containment. yet another one is to quarantine or case isolate based on contact tracing, as we will describe next. our simulator also includes a framework to study the impact of early contact tracing and testing. we assume that contacts of an individual in the smaller networks such as neighbourhood network, project network, class network and random community network can be identified and tested/quarantined. the current contact tracing protocol quarantines certain primary contacts and tests a subset of these (e.g., symptomatic primary contacts). in our implementation, based on our study of icmr's testing protocol, given an index case, all household members, a fraction of the friends circle, a fraction of the inner school/workplace circle, and a fraction of the neighbourhood community are termed as primary contacts of this index case. all of these are quarantined, and a fraction of the symptomatic and another fraction of the asymptomatic among these are tested. those who test positive become new index cases and spawn further contact tracing. the testing fractions are calibrated to match the actual reported cases and the test-positivity rate. we list some limitations of our simulator. • we do not have activity modelling in our simulator. as a consequence, weekly and daily patterns on interactions are not taken into account; for instance, the absence of interaction in workplaces and schools during weekends/public holidays, an increased interaction in public transport during morning and evening peak hours etc. are not taken into account in our model. instead, all these factors are abstracted into a single infection rate for each individual prescribed by ( ), ( ) and ( ). • some of the data that we need in our simulator, such as the household size distribution, workplace size distribution, school size distribution, commuter distance distribution etc., can perhaps be difficult to obtain for some cities. • we have too many free parameters in our model. this can lead to overfitting resulting in high generalisation error. • the framework is computationally intensive. • since the disease spread model has quite a bit of stochasticity (e.g., the incubation time), we need to perform multiple runs of our simulator and take an average of the outputs. we do not have an estimate on the variability of our outputs across multiple runs; such an analysis will be essential to determine the number of runs we need to perform in order for our outputs to be close to the average. generation of a synthetic city is performed via the following steps. ) data gathering and data preparation involves the following. for instantiating households in high-density areas, we sample locations either from a geojson file with boundaries of the high-density areas or from a collection of pre-sampled locations of households in high density areas. common areas where community interactions take place are instantiated at the ward centres, assumed to be the centroids of the polygons. these tasks are accomplished using the following python packages: numpy, random, pandas and shapely. the outputs of this stage are collections of the instantiated individuals, their assigned households, schools, workplaces, transport and community areas. (c) additional processing for generating city files: before generating the city files, additional processing is done on the dataframes which includes computing the distance of the individuals to their respective ward centres. this stage uses the pandas package for processing and generating the city files in the json file format for each instantiated collection namely the individuals, households, workplaces, schools, community centres, and distance between wards. the disease progression part of the simulator is broadly implemented as follows. there are four time steps on a given day. at each time step, we go through each susceptible agent and find out the infection rate given by either ( ) • contact tracing requires us to maintain a list of contacts made by each agent. in our implementation, we assume that each individual has a certain number of contacts that we can trace (which is random, but independent of n). as a result, the space complexity becomes o(n) instead of o(n ). • in the age-stratified interaction as well as od-matrix based distance kernel, we consider dominant terms of the age-based contact rate matrix as well as od-matrix by doing a principal component analysis and by focusing on a few important components. this helps simplify the summations in ( ). these optimisation features appear to be novel features of our simulator. in this work, we built an agent-based simulator to study the impact of various nonpharmaceutical interventions in the context of the ongoing covid- pandemic. we demonstrated the capabilities of our simulator via various case studies for bengaluru and mumbai. some of the key features of our simulator include age-stratified interaction that captures heterogeneity in interaction among people in a given interaction space, the ability to implement various interventions such as soft ward containment, phased opening of workplaces and community spaces, a broad class of contact tracing based testing and case isolation protocols, etc. these features help our simulator to capture the ground reality very well and provide us with realistic predictions. some future directions include bringing in movement of people into and out of the city and studying the impact of various mobility patterns, modelling and studying the impact on public-health oriented decisions on the economy, incorporating activity modelling into our simulator and using the simulator to obtain district-scale or country-scale predictions. we hope that such agent-based simulators find a regular place in every public health official's tool kit. ministry of health and family welfare, government of india covid- india-timeline: an understanding across states and union territories crowdsourced covid -india database containing papers of a mathematical and physical character indsci-sim a state-level epidemiological model for india a minimal and adaptive prediction strategy for critical resource planning in a pandemic spatio-temporal predictive modeling framework for infectious disease spread impact of non-pharmaceutical interventions (npis) to reduce covid mortality and healthcare demand intervention strategies against covid- and their estimated impact on swedish healthcare capacity modeling targeted layered containment of an influenza pandemic in the united states a taxonomy for agent-based models in human infectious disease epidemiology modelling disease outbreaks in realistic urban social networks face mask use and control of respiratory virus transmission in households mask use, hand hygiene, and seasonal influenza-like illness among young adults: a randomized intervention trial respiratory virus shedding in exhaled breath and efficacy of face masks physical distancing, face masks, and eye protection to prevent person-person covid- transmission: a systematic review and meta-analysis consolidated revised guidelines on the measures to be taken by ministries/departments of government of india, state/ ut governments and state / ut authorities for containment of covid- in the country mha order dt. . . on phased re-opening (unlock ) covid- community mobility report epidemiologically and socio-economically optimal policies via bayesian optimization urban poverty and transport : the case of mumbai. the world bank strategies for containing an emerging influenza pandemic in southeast asia projecting social contact matrices in countries using contact surveys and demographic data age-structured impact of social distancing on the covid- epidemic in india estimates of the severity of coronavirus disease : a model-based analysis the effect of control strategies to reduce social mixing on outcomes of the covid- epidemic in wuhan, china: a modelling study european centre for disease prevention and control's covid- website covid- epidemic study ii: phased emergence from the lockdown in mumbai adaptive cyclic exit strategies from lockdown to suppress covid- and allow economic activity key: cord- - q ppl authors: mandal, s.; kumar, m.; sarkar, d. title: lockdown as a pandemic mitigating policy intervention in india date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: q ppl abstract. we use publicly available timeline data on the covid- outbreak for nine indian states to calculate the important quantifier of the outbreak, the sought after rt or the time varying reproduction number of the outbreak. this quantity can be measured in in several ways, e.g. by application of stochastic compartmentalised sir (dcm) model, poissonian likelihood based (ml) model & the exponential growth rate (egr) model. the third one is known as the effective reproduction number of an outbreak. here we use, mostly, the second one. it is known as the instantaneous reproduction number for an outbreak. this number can faithfully tell us the success of lockdown measures inside indian states, as containment policy for the spread of covid- viral disease. this can also, indirectly yield notional value of the generation time inteval in different states. in doing this work we employ, pan india serial interval of the outbreak estimated directly from data from january th to april th, . simultaneously, in conjunction with the serial interval data, our result is derived from incidences data between march th, to june st, , for the said states. we find the lockdown had marked positive effect on the nature of time dependent reproduction number in most of the indian states, barring a couple. the possible reason for such failures have been investigated. global pandemic outbreaks are very common nowadays. india is no exception. the severe acute respiratory syndrome ( ), [ ] avian inunza ( ) , [ ] swine flu ( ) [ ] are to name a few. there were others that did not touch upon india but were recent events, such as mers ( ) [ ] & evd (ebola virus disease) ( , , & most recently in ) [ ] . none of the above, however, touched the global pandemic scale, of what has been attained by novel coronavirus, aka covid- , in a short span of time, starting at the end of past year [ , , ] . the global community responded to this unprecedented situation by various policy interventions. wearing masks & face shields [ , ] in public, social distancing norms [ ] were amongst them. more drastic & perhaps draconian step of lockdown [ ] was taken by governments across the world, as a containment policy measure [ ] . we analyse the eect of lockdown on the propagation of covid- viral disease. the instantaneous version of basic reproduction number [ ] of the infection is plotted against time to gauge the success [ ] (or lack thereof) [ ] of this policy intervention in nine dierent states of india. in the following, it is shown that this pervasive containment policy has borne fruit in most of the considered provinces. time dependent or instantaneous reproduction number [ ] is an accurate projection is an in-situ description of virility or virulence of epidemic diseases. the basic reproduction number [ ] gives us the average number of infectee cases per infector from the previous generation, over a given period of time, in a fully susceptible population. various policy implimentation and containment measures appreciably reduce the number of contacts, in turn reducing, the eective number [ ] of susceptible contacts per potential infector. epidemiologist have devised a time dependent parameter, eective reproduction number to assimilate the eect of policy intervention into the basic reproduction number during an ongoing epidemic. this quantity is dened as follows: consider an individual, who turns infectious on day t. we denote by r e (t) the expected number of secondary cases this infectious individual causes, in future [ ] . the instantaneous reproduction number, on the other hand, compares the number of new infections on day t with the infection pressure (force of infection) [ ] from the days prior to t. it can be interpreted as the average number of secondary cases that each symptomatic individual at time t would infect, if the conditions remained as they were at time t. hence, the stepwise, undulations, crests, troughs & spikes of this estimate is termed as instantaneous or real time measures. there are various ways to calculate this eective instantanous & other time varying reproduction number. they are such to be: . . stochastic dynamic contact model-based method [ ] . a stochastic susceptible-infected-removed (sir) model is considered in this case, in place of a deterministic one. stochastic dynamic model has advantages over the standard deterministic one, in that, it accomodates improved variabilities and allows for better quantication of uncertainies of that number as compared to the standard deterministic model. here, s(t), i(t) & r(t) denote the number of susceptible, infectious and recovered population at time respectively, and that n = s(t) + i(t) + r(t) is the total population. the infectious period of an infected individual is a random variable t ∼ exp (γ) & the reproduction rate is r(t) ≈ βe(t) = β γ , where β & γ are the transmission rate and recovery rate. the mathematical essence of the model can captured by a set of four coupled rst order linear homogenous dierential equations given such to be here, ∼ signies deterministic (average) counterparts. we set s ( ) equals the population of the region, r( ) = , i ( ) is to times the average number of conrmed cases from day to day , and γ the inverse of mean infectious period, obtained from the parametrization of serial interval distribution collected directly from data described in section ( ) . the main diculty with this time varying reproduction number is that it assumes a constant transmissibility, where it may vary & often peak, during the generation time interval and just before the onset of symptoms [ ] . this model also can not accomodate various disease traits like asymptomaticity (non-detection), or human interferences like isolation measures or migration etc. hence we do not look at this method any further here. [ ] . here it is assumed that the total number of secondary infectees that were infected by a single praimary infector follows a poisson distribution. the number of individuals infected on (discrete) date t is usually replaced by the number of daily incidences reported, on the same date t. also, the generation time interval is suitably replaced by the corresponding serial interval interval for all practical purposes. let n t be the number of reported incidences on day t. assuming that the serial interval has a maximum of k days and the number of new cases generated by an infected individual is assumed to follow a poisson distribution with parameter [ ] r. the probability that the serial interval of an individual lies in j days is w j , which can be estimated from the empirical distribution of serial interval or by setting up a discretized gamma prior on it. note only the nonnegative values of serial interval are used here. thus, the likelihood function can be reduced into a thinned poisson distribution as such all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint the instantaneous reproduction number can then be estimated by maximising the likelihood function as follows . exponential growth rate-based (egr) method [ ] . in the early days of the epidemic the number of infected cases rise exponentially. the growth rate (malthusian coecient) r can be estimated by tting a non linear least square tting into the daily incidence curve. the probability density function of serial interval of the outbreak is denoted by f λ (t), then the eective reproduction number is given by the euler lotka (type) equation in case we have a non parametric serial interval distribution then we can dene our eective reproduction number as where λ i are the observed serial intervals. using the publically available data on github [ ] , to create a contact list between infector infectee pairs in the pan indian context, between th january- to th april- . the data is then tted with a log normal / gamma distribution to parametrize the values of mean and standard deviation. from the available data on github [ ] , the daily conrmed case incidences were collected for nine states, for the duration of th march- to st june- . applying the poissonian ml method, the instantaneous r i (t)was plotted for each one of them, as given in gure number two to ten. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint it has been seen from above that, in all the state except gujrat & karnataka, the lockdown as a containment measure has been quite successful. in india the lockdown started from from th march- . after to days of the commencement of the same, seven provinces of india has shown us a signicant downtrend of instantaneous reproduction number. this lag between cause & its eect corresponds to serial time or the generation time interval, that varies from state to state. however, these two states show a opposite trend. after the passage of about one generational time interval, the instantaneous reproduction number peaks sharply. this might correspond to migration [ ] at the beginning of the lockdown. in karnataka, however the value of instantaneous reproduction number uctuates moderately. this is perhaps due to clustering [ ] or inadequate testing policies [ ] , which may be true for both of the states. in what follows next are two province specic case studies. to be doubly sure, that our time dependent reproduction numbers [ ] are calculated correctly over time, we shall t the daily incidence graph of the two provinces which showed contrarian nature in reproduction numbers, during the initiation phase of lockdown. the time dependent reproduction numbers shall be used to t the daily incidences. the result is given in g. ( ) . we show that, the lockdown in india was fairly successful barring a couple of places, due to migration or superspreading etc. we note here that a similar study, with a bigger scope has been reported elsewhere [ ] . but it assumes the parametric serial interval, which is dierent from ours. we have deduced our own serial interval (cf. sec. ) by scraping the pan india raw data and by building our own line list & contact list. hence our result is presumed to be signicantly dierent from theirs and more representative of the actual scenarios [ ] . the eect partial lifting of the lockdown (unlock) is also seen in the results, in terms of increment in r i (t). . acknowledgement sm wishes to thank k. bhattacharya, k. samanta for useful discussions. he also thanks i. mukhopadhyay for useful help with references. the analysis was was performed in r [ ] statistical programming language environment. public health interventions and sars spread avian inuenza virus (h n ): a threat to human health the inuenza a (h n ) pdm outbreak in india middle east respiratory syndrome coronavirus (mers-cov): a review ebola virus disease epidemic in west africa: lessons learned and issues arising from west african countries incubation period of novel coronavirus ( -ncov) infections among travellers from wuhan, china severe acute respiratory syndrome coronavirus : biology and therapeutic options epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (covid- ) during the early outbreak period: a scoping review should we all be wearing face masks? here's why experts are so conicted. newspaper what we know about face shields and coronavirus. newspaper lockdown guidelines: govt's standard operating procedure for social distancing at workplace. newspaper etbfsi: corona impact -modi announces janata curfew -urges citizens to stay at home on sunday. newspaper guidelines for demarcation of containment zones to control covid- . newspaper notes on r toi: how eective has india's lockdown been in controlling covid. newspaper why india's lockdown has been a spectacular failure. newspaper teunis: dierent epidemic curves for severe acute respiratory syndrome reveal similar impacts of control measures how will country-based mitigation measures inuence the course of the covid- epidemic? how generation intervals shape the relationship between growth rates and reproductive numbers force of infection is key to understanding the epidemiology of plasmodium falciparum malaria in papua new guinean children estimation of the time-varying reproduction number of covid- outbreak in china improved inference of time-varying reproduction numbers during infectious disease outbreaks git hub [ ] pti: , people stranded in uttarakhand to return to gujarat in buses. newspaper ballari's jindal steel plant emerges covid- cluster. newspaper even as covid- spikes in rural karnataka, state tests less. newspaper boÃlle: the r package: a toolbox to estimate reproduction numbers for epidemic outbreaks lockdown eect on covid- spreadin india: national data masking state-level trends how data became one of the most powerful tools to fight an epidemic. newspaper r: a language and environment for statistical computing. vienna, austria: r foundation for statistical computing key: cord- -iqnvlnd authors: tiwari, a. title: temporal evolution of covid- in the states of india using siqr model date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: iqnvlnd covid entered during the last week of april in india has caused , deaths with , , number of reported cases. indian government has taken many proactive steps, including strict lockdown of the entire nation for more than days, identification of hotspots, app-based tracking of citizens to track infected. this paper investigated the evolution of covid in five states of india (maharashtra, up, gujrat, tamil nadu, and delhi) from st april to th may . variation of doubling rate and reproduction number (from siqr) with time is used to analyse the performance of the majorly affected indian states. it has been determined that uttar pradesh is one of the best performers among five states with the doubling rate crossing days as of th may. tamil nadu has witnessed the second wave of infections during the second week of may. maharashtra is continuously improving at a steady rate with its doubling rate reaching to . days. also these two states are performing below the national average in terms of infection doubling rate. gujrat and delhi have reported the doubling rate of . days and . days respectively. comparison of these states has also been performed based on time-dependent reproduction number. recovery rate of india has reached to % as the day paper is written coronavirus disease (covid- ) originated from the wuhan city of the hubei province (china) in december has caused global pandemic with more than million positive cases and . million deaths [ ] . most of the countries in the world is affected, and india with the nd largest population in the world and th ranked medical facility in the world [ ] speculated to be one of the severely affected nations of the world [ ] . during the initial stages of covid in india, various mathematical analysis has been done to predict the total number of cases [ ] , peak prediction [ ] as well as on the correlation of the lockdown days on the curve flattening [ ] . in my previous work [ ] , siqr model is used to quantify the spread of the virus in india using reproduction number (ro), infection doubling rate and infected to quarantined ratio. time-dependent transmission parameters like timedependent reproduction number (rt) [ ] has been proven to be more accurate parameters for the analysis of any infectious disease. india witnessed its first positive case on th january , and as of st may, total positive cases has crossed , , with only , deaths [ ] . strict lockdown of the nation for more than days, mobile application based tracing of infected and sealing off hotspot regions (and other measures) seems to be successfully mitigated the intensity at which spread was predicted. contribution of different states of the country to the total reported cases is skewed a lot with states like maharashtra being one of the severely affected state and state-like mizoram with just one confirmed positive case till date. statewise analysis of the growth of cases, instead of the country as a whole, is needed to put forward the precise scenario of covid in india. in this paper, a time-dependent analysis of the five major contributing states of india (maharashtra, up, gujrat, tamil nadu, and delhi) is performed. time-dependent reproduction number using siqr method and the doubling rate of reported cases has been calculated and analysed. recovery rate of the country is also reported to check the variation of the recovered population with time. in this paper, two transmissibility parameters are used to analyse the growth of covid in five major affected states of india. following part of the section defines the concept of the parameter used: this is one of the widely used parameters used to determine the transmissibility of contagious disease over the time duration (t). it is determined using the susceptible infected quarantine recovered (siqr) model used in [ ] . siqr model uses four different rate equations to model the spread of disease defined as follows: in the following equations, denotes the rate of infection, determines the rate at which new cases are detected from the infected population. is the rate at which quarantine are getting removed (recovered or died). is the rate of removal of infectious individuals who are asymptotic (or for any reasons) and didn't get quarantined. reader can refer to [ ] for a better understanding of this model. integrating eq. ( ) and addition of eq. ( ) and eq. ( ) gives us the following two equations: [ ] substitution of eq. ( ) to the eq. ( ) and integration of the resultant over t gives us an equation which is used in the determination of rt : eq. ( ) is fitted with ( ) = [exp( ) − ] using least square fitting method to determine the coefficient ( + ) and used in the siqr model. basic reproduction number (r ) average over time (t) is defined as the following: . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . time-dependent reproduction number (rt) in this paper is determined over every fifth day starting th april for each of the five states. reported positive cases of the states are fitted with eq. ( ) by taking days data for the fitting (fig. ). this is another widely talked and accepted parameter to quantify the spread of any contagious disease in a region. it is defined as the number of days required for a disease to double its infected population in a region. this number for each of the five states is calculated using the data of total number of reported positive cases from st april to th may, . the doubling rate for i th day can be defined as follows: here is the doubling rate at i th day, [q+r](i) is the total number of reported positive cases on i th day, [q+r](i-) is the total number of reported positive cases at day (i-) when cases are half as compared to i th day. recovery rate of any contagious disease is defined as the percentage of recovered cases from the total reported positive cases. recovery rate can be used to compare the quality of health care facility in a particular region or to the immunity of the infected cases. mathematically, this can be defined as the following. here, is the recovery rate on ith day, ∑ [ ] is the total number of recovered individuals in the population on the ith day from day n = and ∑ [ + ] is the total number of reported positive cases on ith day from day n = . time-dependent reproduction number and doubling rate discussed in above subsections . to . is determined for the major affected states of india using data from [ ] . this data is compared with the analysis of the country on whole. point-wise discussion for each of the five states which contributed to more than % of the reported positive cases from the country, is done in the following part of this section. maharashtra (mh) is one of the significantly infected state of the country, and this state contributes % to the total reported cases from india. as of th may, mh has , reported positive cases with , deaths. with the doubling rate of . days on th april, this state is witnessing continuous but slowly mitigating the wave of spread hit during the first week of april (fig. ) . mh performance in terms of doubling rate was continuously below the average of the nation. doubling rate of mh as of th may is . days, lower than other reported four states and equal to of tamil nadu (fig. ). if analysed in terms of rt, mh on th april has rt of . , and on th may it downs to . . even in terms of rt, mh is continuously improving but at a very slow rate, which is lower than the national average rate (fig. ) . . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . gujrat in terms of the doubling rate at the start of the epidemic ( th april) has the doubling rate of . days better than all the other four states included in the study (almost same of delhi). gujrat witnessed the two dip in doubling rate during the first week and third week of april. however, gujrat is improving continuously from the month of may, making gujrat to reach a doubling rate of . days as of th may better than the national average (fig. ) . in terms of rt, gujrat on th april has rt of . and reaching its maximum of . during the second week of april followed by surge during the rest of the month. it has reached to . on th may (fig. ) . delhi is the best performer during initial days, started with a doubling rate of . days followed by dip during the second week of april and the first week of may. this state as of th may has the doubling rate of . days, higher than the national average (fig. ) . in terms of rt, delhi started with . on th april with a slight dip during the second week of april and followed by steady improvement in rt. as of th may rt is . , which is higher than the national average of . (fig. ). this state witnessed many fluctuations in the number of reported positive cases, started with the doubling rate of . days, followed by a very high doubling rate of . during the end of april. tamil nadu witnessed the second wave of infection during the first and second week of may when the doubling rate gets down to . days (very less than the nation's average). as of th may, this state has improved quite significantly, making its doubling rate to reach . days (lower than the country's average (fig. ) . recovery rate of the country as discussed in section . , is defined as the ratio of the total number of recovered population to the total reported positive cases. from recovery rate of % on th april, india has tremendously improved it to reach . % as of th may (fig. ) . this much percentage of recovered positive cases somewhat indicates the flattening of the peak with the active number of cases getting constant. in terms of time-dependent reproduction number, this state has witnessed whooping rt of . during the second week of may, followed by a drastic improvement, making it to reach . (fig. ). uttar pradesh, one of the biggest populated state of the country, has performed unexpectedly well during this epidemic. started with doubling rate of . days one of the lowest (better than mh) is improving continuously with better performance than national's average. as of th may, this state has . days highest in comparison to all other four states (fig. ) . in terms of rt, this state has got a slight increase during the last week of april but has improved quite well, and as of th may rt is . (fig. ) . in this paper, the reproduction number and doubling rate of five major affected states of india are analysed using timedependent reproduction number and doubling rate. time-dependent reproduction number is determined using siqr model. following points conclude the whole state-wise analysisi. uttar pradesh is one of the best performers during this epidemic in comparison to four other analysed states. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint ii. tamil nadu has witnessed major fluctuation in this pandemic with cases rising up again during the second week of may. iii. maharashtra and tamil nadu are performing below the national average in terms of doubling rate. iv. reproduction number of all the states are closed to the national average as of th may . v. recovery of india is increasing continuously making it to % of the total reported positive cases. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint age-structured impact of social distancing on the covid- epidemic in india predictions for the spread of covid- in india and effectiveness of preventive measures modelling and analysis of covid- in india, medrxiv improved inference of time-varying reproduction numbers during infectious disease outbreaks covid india key: cord- -ua qps r authors: golechha, mahaveer title: covid- , india, lockdown and psychosocial challenges: what next? date: - - journal: int j soc psychiatry doi: . / sha: doc_id: cord_uid: ua qps r nan a world pandemic threat covid- mitigation is crucial to the human life and for reducing distortion of livelihood. the covid- pandemic has swept into more than countries with considerable confirmed cases and deaths and has caused public panic and mental health stress (huang & zhao, ) . most of the nations across the world have implemented complete lockdown with stringent social distancing measures for breaking the chain of transmission. the current outbreak of covid- is heavily impacting the global health and mental health. despite all resources employed to counteract the spreading of the virus, additional global strategies are needed to handle the related mental health issues (torales et al., ) . this outbreak is leading to additional health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger and fear globally (torales et al., ) . to protect people and prevent the spread, it is critical that public mental health paradigms and measures are used . on january , india reported first case of covid- and the numbers have risen steadily since then, albeit at an alarming rate in the final days of march. aiming to control community transmission, the world's largest democracy has implemented world's largest nationwide lockdown since march (the lancet, ). the country remains vulnerable towards covid- , given the high population density, socioeconomic fabric and overstretched health-care infrastructure. the total lockdown was the only immediately available, best and ideal solution to the control covid- pandemic in india. the indian government has responded appropriately, adequately and quickly to the covid- pandemic at multiple levels. the lockdown has helped india in buying crucial time: time for extensive contact tracing, time to ramp up testing and most crucially, time to prepare our health system, increasing its health-care infrastructure and preventing it from overwhelming, as it happened in italy, the united states and spain. the lockdown is an effective strategy for containing the spread of infection. however, this is very challenging with added difficulty for larger sections of the society. the social distancing is very difficult for many households in india, especially slum areas; the daily-wage earner has to earn daily money to keep family alive, and people with existing mental health illnesses face severe issues. a long-time lockdown may lead to psychosocial difficulties for vulnerable population and consequently lead to stress, anxiety, frustration, boredom and depression and even suicidal idea and attempts. the lancet psychiatry ( ) also highlighted the mental health needs of vulnerable groups, including those with severe mental illness, learning difficulties and neurodevelopmental disorders, as well as socially excluded groups such as prisoners, the homeless and refugees. nevertheless, the burden of this infection on the global mental health is currently neglected even if it may challenge patients, general population as well as policy makers and health organisations and teams (torales et al., ) . india's health inequalities, flaring economic and social disparities and distinct cultural values had made lockdown a hard measure for the poorer sections of the society. the nationwide lockdown has maximised economic loss and simply debilitated the country's large population of dailywage earners and migrant labourers and become an important mental health problem. the emerging mental health issues related to this global event may evolve into longlasting health problems, resulting in isolation and stigma for vulnerable population in the country. the extended lockdown will lead to economic hardship, famine, psychosocial challenges and law and order issues, which may in turn undermine benefit gauge by lockdown and covid- containment objectives. in indian settings, this may exacerbate health inequalities and reinforce the vicious cycle between poverty and ill health. the social and economic issues due to covid- pandemic will result in mass unemployment, depleted social safety nets, homelessness, increase in gender-based violence, alcoholism, hunger, loan defaults and millions slipping into poverty. this post-covid landscape will definitely leads to an increase in mental health issues such as chronic stress, anxiety, depression, alcohol dependence and self-harm. recent evidences in psychosocial sciences also show that similar pandemics increased the prevalence of symptoms of post-traumatic stress disorder (ptsd), as well as confusion, feeling of loneliness, boredom and anger during and after quarantine (brooks et al., ) . the ministry of health and family welfare, government of india has taken several steps to deal with mental health challenges posed by covid- , which includes development of various guidelines in collaboration with national institute of mental health and neuroscience. the guidelines aimed at enhancing resilience of vulnerable populations against mental health issues. the ministry of health and family welfare has also established helpline for behavioural and psychosocial help. however, a lot needs to be done, including capacity building of frontline health-care worker and a large-scale public engagement campaign to increase help-seeking, creating and spreading awareness through mainstream media and social media giants. the real need is to build community-based capacity to handle local issues long after the acute phase of the epidemic. a small team of peer counsellors work under a local administrator and trained on community mental health issues. it is time to build mental wellbeing and resilience into schools, the community and their families. we need a systemic approach to build the demand for mental wellbeing. the government of india's rashtriya kishor swasthya karyakram (national adolescent health programme) can play a pivotal role in social and behavioural change and enhance adolescent resilience against mental health challenges posed by the pandemic. furthermore, the government should give special attention to systematic psychological health care which is required by health-care staff and patients, and systematic psychological self-care must be given a high priority in coping with the detrimental impacts of covid- and social distancing (matias et al., ) . the nationwide lockdown has proven as a successful strategy for india, and it has also helped in containing the spread of covid- across various states. the lockdown has already achieved the desired effect of flattening the epidemic curve (the lancet, ). therefore, it is right time for india to plan quick gradual, phased and calibrated withdrawal strategy. a well-planned calibrated multiphase exit strategy will be required post lockdown. india can end the lockdown now and additional revenue available from the revival of the economy can be spend on increasing testing, isolation facilities, hospital beds, critical care and comprehensive information, education and communication (iec) on social distancing and mental health and addressing the mental health issues of vulnerable population post lockdown. the country can gain much more through continuation of bans on mass gatherings, school closure, restriction of movement of elderly population and children below the age of years, covering mouths and noses in public, spitting bans, physical distancing to the extent possible in public places and expanded testing. mental health support and followup should be provided even months after the release from isolation for those individuals with prior vulnerable mental health status. meanwhile, india should increase the testing. when we look at the rate which screening is being done, india ranks at the lower end of the spectrum. the country needs 'exponential' ramping up of testing to leverage the benefit provided by nationwide lockdown. the panacea against prolonged lockdown and for reassuming economic activity is large-scale testing. the importance of community involvement, awareness and behaviour change cannot be undermined in the current situation, especially for psychosocial issues due to covid- . risk communication and community engagement is a critical component of the response to covid- (world health organization (who), ). this crisis is not going to be controlled without community participation because ultimately control is based on individual behaviour. the government should take various measures like behavioural change communication, hand washing facilities and improving availability and accessibility of community-based mental health services. community psychological interventions and support might have some effects in reducing ptsd symptoms and depressive and anxiety symptoms in adults during these stressful events. this is an opportunity for india to recognise the importance of strong public health systems and increasing investment in health for making its health system resilient towards future pandemic. the governments need to step up to protect their populations and people in a nonthreatening, non-panicky manner to ensure safety of all individuals. the country should focus more on improving primary care, health-care infrastructure and human resources for health. india's public health-care system is chronically underfunded (at just . % of gdp; chetterje, ), leaving primary care weak. this pandemic could be the much-needed wake-up call to the necessity of long-term changes to india's health system. mahaveer golechha is alumnus of aiims, new delhi; lshtm, uk and london school of economics. mahaveer golechha has developed the concept, gathered various information, developed initial draft and also written the manuscript. the author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article. the psychological impact of quarantine and how to reduce it: rapid review of the evidence gaps in india's preparedness for covid- control. the lancet infectious diseases chinese mental health burden during the covid- pandemic mental health and covid- : change the conversation human needs in covid- isolation the outbreak of covid- coronavirus and its impact on global mental health pandemics, panic and prevention: stages in the life of covid- pandemic the author(s) received no financial support for the research, authorship and/or publication of this article. mahaveer golechha https://orcid.org/ - - - key: cord- -topozldw authors: dimri, v. p.; ganguli, shib s.; srivastava, r. p. title: understanding trend of the covid- fatalities in india date: - - journal: j geol soc india doi: . /s - - - sha: doc_id: cord_uid: topozldw nan the number of covid- cases and related deaths are increasing at an alarming rate in several countries, and some countries have experienced mild spread. globally, covid- has caused an estimated , , cases and , , deaths until now ( / / ). wuhan city in hubei province of china is deemed as its epicenter, where the first covid- case was reported in december . since, then the virus has spread over countries and territories around the world, with varying spread rates and fatalities (fanelli and piazza, ) . the worldwide lockdown and social distancing have played a great role to keep the reproduction number in check, and thus controlling the outbreak (kupferschmidt, ) . so far reported fatality rate of the corona virus pandemic is somewhere between normal flu ( . to . %) to severe acute respiratory syndrome (sars) family of viruses ( to %). in india, so far the fatality rate is about %, which is half of the world average. forecasting the future of pandemics, including covid- , is difficult. the accuracy of an epidemic and pandemic forecasting largely depends on the data availability and uncertainty estimation. despite this fact, still forecasting utilizing mathematical models has become crucial to better understand the present circumstances and plan the future. mathematical models are invaluable tools for analyzing the spread and control of infectious diseases (hethcote, ) . in the present work, we provide a statistical forecasting approach for the covid- cases in india and its potential implications for planning and decision making to contain the same. the standard epidemiological modelling approach usually follows the reproduction number of the diseases, and models it using a well-known system of differential equations known as sir (susceptible -infectious -recovered) model (batista, ) . the differential equations for a generalized sir model can be written as follows: where s(t) = number of susceptible cases at time 't'; i(t) = number of infected persons and r(t)= number of recovered cases at time 't', respectively. β is the contact rate and /γ is the average period of infections. the constant n = s + i + r is the fixed number of populations in a certain region/country. in this case, the births and natural death are not modelled. the initial conditions can be expressed as s( ) = s , i( )= i and r( )=r . now, the parameters β, γ, and the initial values s and i (as obtained from available data) are required to utilize the sir model. the required parameters can be assessed by minimizing the difference between the actual and predicted number of cases. moreover, there are several papers available on the sir model and generalized seir model (please refer to hethcote, ; fanelli and piazza, ; peng et al. ), hence we are not discussing it more here since it is not our main focus. the objective of listing equations and variables within the sir model is to give an idea to a general reader about the various considerations involved in the model. often statistical epidemiological analysis applied in such cases assumes an exponential outbreak, which is to some extent true in a very early stage of the epidemic. the exponential model is based on the fixed reproduction number of the disease. the total number of cases can be obtained by considering the fact that each infected person contaminates the other susceptible one (where n > known as reproduction number): where, t and t represents time in days and incubation period,which relies upon the type of disease; a is coefficient of exponential series. in the case of covid- ,the incubation period ranges somewhere between to days. it is to note that the above equation does not assume any kind of inhibition or intervention. in order to forecast the covid- pandemic behavior in india, we first examined the total number of confirmed cases and the rate of daily increase in the number of cases reported in india ( fig. a and b) . besides, fig. (a and b) depicts the total confirmed deaths and the rate of daily increase in the number of deaths. the data is fetched from the web-page maintained by johns hopkins university (https:// raw.githubusercontent.com/cssegisanddata/covid- /master/ csse_covid_ _data/csse_covid_ _time_series/). this is a dynamic data, and the figures below show data starting from january until may . please note that the number of confirmed cases is dependent on how much testing has been done, hence we choose to further analyze reported number of covid- death cases, which are much more reliable numbers, than the infected cases. we looked at the total death data in india and plotted it on a loglog scale (fig. ) . from equation ( ) it is obvious, if the number of deaths follows exponential increase, then in the log-normal plot they will appear linearly increasing, whereas if they follow power-law increase then they will appear linear in log-log scale (dimri, ; dimri et al. ) . it is obvious from fig. , that deaths until april , follow power-law and the predicted deaths are in good agreement to the actual. however, this relation (data trend) appears to be invalid when the latest death data is analyzed hence, we did not use the powerlaw relation for further analysis. in order to understand and forecast covid- behavior until june , , we attempted a quadratic and exponential fit to the data. as evident from fig. , the total number of deaths after one month from now ( / / ) would reach approximately , if the quadratic trend is followed. otherwise, the death toll can reach as high as about , (± %) in the extreme case, as indicated by the exponential trend. table represents the week wise death values until june, , as forecasted using quadratic simulation. note that these predictions are statistical, and assume no interventions which are in place. results are based on the most feasible scenarios and may vary in actual cases, depending upon the situation. our two approaches, one based on exponential fit to the data, and another based on simulating quadratic time series, gave completely different predictions, however, we expect them to behave like this, because they are fundamentally different. we believe that these two methods represent upper and lower bound scenarios of possible covid- deaths in india, which could be a good suggestion to policy makers and authorities. none of these methods are meant to predict the epidemic and determine the life span of a pandemic in terms of the number of days/ months. the methods presented here are very good indicators to model dynamic data and draw short term fig. . shows a log-log plot of the total number of covid- related deaths in india (blue curve), starting from march until april . a power law curve fit to the data (excluding initial data points to obtain a more robust fit) is shown in orange color. according to power law, two prediction dates marked by red plus sign correspond to and april respectively, and the corresponding death toll was approximately and . inference. for instance, in fig. if the actual number of deaths go below quadratic fit, then we can assume that the outbreak is in the decline phase, however, if the number of deaths increases more than the fit, then we cannot rule out the possibility of further outbreak. results presented in fig. are more realistic and fundamentally more robust, where the effects of constraints such as social distancing and lockdown are baked within the data used to create a simulated time series. in order to forecast the final size of the covid- pandemic in india, a data-driven sir model is employed. the covid- pandemic life cycle (spread) pattern is anticipated to be "bell-shaped", as indicated by fig. (b) . this helps to detect the inflection point and the peak of infections to distinguish acceleration and deacceleration phases. the results suggest that infected cases in india are at the acceleration phase (initiation of its inflection point) and the size of the epidemic will be about , infected cases until june (fig. a) . note that the early segment of the curve is fitted with data, whereas the remaining segment is predicted based on the sir model.this model assumes that it is a rational portrayal of the one-stage epidemic and represents the dynamic process of covid- infections in a population over a specific time.hence, the forecast is as good as data are. the forecasting may vary with new data or altered data (batista, ) . in this note, we have presented the analysis of short-term forecasting of covid- infections in india based on sir, quadratic and exponential approaches. if the situation remains stable and data collection methods do not change much, then the predicted total number of deaths due to the pandemic until june will be about . these two predictions provide us bounds of deaths forecasted for two different scenarios, i.e. usual trend and extreme case. uncertainty prevails in the future, regardless of model and data, which need to be kept in mind while doing or reading any prediction, and forecasting covid- is not an exception. it is commendable that india despite having the largest population density managed to limit the outbreak with its timely intervention in terms of country lockdown. nevertheless, the present analysis would be very helpful to deal with the unwanted future rising trend of the covid- infections in india and develop guidelines or strategies to contain the pandemic. fig. . shows total covid- deaths in india and simulation of covid- deaths with confidence intervals of % (red curve). please note this is not just a curve-fitting exercise (actual reported deaths are represented by blue curve), rather a pure simulation of time series. shows results from sir model: (a) total number of predicted together with observed cases, and (b) number of covid- cases per day in india. the different colour shades represent various epidemy phases, e.g. red=fast growing phase; yellow=transition to steady-state phase, and green=conclusion phase (plateau stage). doi: . doi: . /s - - fractal models in exploration geophysics: applications to hydrocarbon reservoirs fractal behaviour of the earth system analysis and forecast of covid- spreading in china, italy and france ending coronavirus lockdowns will be a dangerous process of trial and error the mathematics of infectious diseases epidemic analysis of covid- in china by dynamical modeling we thank director, csir-ngri for support and permission to publish the work. key: cord- -kvtqpgqq authors: chatterjee, s.; sarkar, a.; karmakar, m.; paul, r. title: studying the progress of covid- outbreak in india using sird model date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: kvtqpgqq we explore a standard epidemiological model, known as the sird model, to study the covid- infection in india, and a few other countries around the world. we use (a) the stable cumulative infection of various countries and (b) the number of infection versus the tests carried out to evaluate the model. the time-dependent infection rate is set in the model to obtain the best fit with the available data. the model is simulated aiming to project the probable features of the infection in india, various indian states, and other countries. india imposed an early lockdown to contain the infection that can be treated by its healthcare system. we find that with the current infection rate and containment measures, the total active infection in india would be maximum at the end of june or beginning of july . with proper containment measures in the infected zones and social distancing, the infection is expected to fall considerably from august. if the containment measures are relaxed before the arrival of the peak infection, more people from the susceptible population will fall sick as the infection is expected to see a three-fold rise at the peak. if the relaxation is given a month after the peak infection, a second peak with a moderate infection will follow. however, a gradual relaxation applied well ahead of peak infection, leads to a two-fold increase in the peak infection. the projection of the model is highly sensitive to the choice of the parameters and the available data. our model provides a semi-quantitative overview of the progression of covid- in india, with model projections reasonably replicating the current progress. however, since the pandemic is an ongoing dynamic phenomenon, the reported results are subjected to regular updates in consonance with the acquired real data. in the post-ww- era, the world probably has not witnessed such catastrophic morbidity and the looming threat of severe economic challenges caused by the worldwide outbreak of the disease covid- caused by severe acute respiratory syndrome coronavirus (sars-cov- ). the detection of the disease in the human host was first reported in wuhan, china on december as a cluster of cases of pneumonia. as the highly contagious disease transmitted rapidly all over the globe, the outbreak was declared as a pandemic by the who on march . tackling the outspread of the disease is found to be very challenging across the world for the following reasons: (a) conventional flu-like symptoms in human carriers and (b) human-to-human transmission via asymptomatic human hosts and (c) the absence of a proper clinical doctrine (e.g. vaccine, drugs, concrete ideas about the immunological response, etc.). extensive testing and imposition of containment measures to maintain social distancing turn out to be the effective remedies to prevent disease transmission at the current stage of the epidemic at several places. to evaluate the impact of these preventive measures on infection spread, recovery, death tolls, and various other associated factors, mathematical models become useful in predicting realistic, quantitative estimates. a preliminary analysis * sspsc @iacs.res.in † sspas @iacs.res.in ‡ sspsc @iacs.res.in § mcsmk @iacs.res.in ¶ raja.paul@iacs.res.in suggests that the classic mean-field susceptible-infected-recovery-death (sird) model by kermack and mckendrick [ , ] , can be used to obtain a quantitative picture of the epidemic [ ] [ ] [ ] [ ] [ ] [ ] . in this article, implementing the sird model, we report the temporal progress of covid- transmission in india, various indian states and compare it with some other countries around the world. a similar model used by fernandez-villaverde et al [ ] provides a detailed overview of the pandemic situation in the usa and many other countries. india implemented a nation-wide lockdown from march , . on the day of the announcement of nation-wide lockdown india had about corona positive cases while the first covid- positive was detected on january , . the socio-economic constraints in the indian context alludes that: (a) 'too-prolonged' lockdown is difficult to sustain; (b) the sole imposition of containment measures without a manifold increase in testing capacity is a futile endeavor; (c) if the implementation of the lockdown measures is lenient, containment of the spread is highly improbable. henceforth, the feasible solution for limiting the spread lies in carefully balancing various key epidemiological factors. that is where the importance of the current model predictions becomes relevant. this study further highlights the effect of lockdown on the disease spread and predictions about the variability in the infection peak upon the severity of the containment measures (and/or the lack of it). the model predicts that, in india, the height of the peak infection decreases with stricter lockdown, but at the cost of 'time' (position of the peak shifts to a later month). thus, with a large susceptible, the infection will stay for a long time if existing infections are not quarantined immediately or no proper medicine/vaccine is employed. the key is to quarantine the infection in small pockets while in lockdown and prevent inter-pocket transmission. the model further underlines that in the highly contagious zones ('red' zones where covid- positive cases continue to grow), if the present lockdown is extended and reinforced with stricter quarantine measures, the new infections will gradually plummet down flattening the covid- curve at a much faster rate. our study also explores the plausibility of universality in the spread of the covid- outbreak amongst different countries [ ] and compares the situation in india with few other countries (e.g. germany, usa, south korea, spain) in the relevant time window (february -april). due to the simplicity of the sird model, we found it difficult to fit the observed patterns of the pandemic using the available data. the real data for analysis in india's context is collected from the repository with an interactive interface hosted at https://www.covid india. org. the data for other countries are taken from the repository with an interactive interface hosted at https: //www.worldometers.info/coronavirus. the purpose of this article is not to make any quantitative prediction that should be used to design policies, but for the research purpose only. model we employ the standard sird model where the population n is divided into sub-population of susceptible (s), infected (i), recovered (r) and dead (d) for all times t. thus, n = s +i +r+d. the following set of mean-field differential equations governs the temporal dynamics of the population of susceptible (s), infected (i), recovered (r), dead (d) and describes a comprehensive picture of the sird epidemic evolution: here, β, γ, δ are the parameters determining the characteristics of infection, recovery and deaths respectively (fig. a) . when a susceptible person interacts with an infectious person, the susceptible become infected at a rate βsi/n . large variability is observed in the rate γ that an infected individual is no longer infectious or equivalently has recovered in this simplified model. literature [ ] [ ] [ ] suggests that, on the average, infectiousness appears to start from - days before the symptoms are visible. the infectiousness increases to its peak before the arrival of the symptoms and remains for about - days after the peak infection. thus an infected individual remains infectious for about days on the average and then recover. in our preliminary analysis, we set the recovery rate γ ∼ / , which however does not give the best fit for all the cases we studied. in essence, the numerical values of the model parameters are obtained from the best fit. initial values (time t = days) of the number of infected, recovered and deaths (i , r , d ), are chosen from real data. the choice for the initial number of susceptible (s ) is quite difficult. in the absence of antibody, the entire population can be susceptible to the covid- pandemic. nevertheless, the geographical, social, and economical characteristics of a region (and various other demographic factors) can substantially influence this number. we used two different approaches to get an estimate of s . first, we study the data for the large countries where the cumulative positive cases have reached closer to a plateau. though, the infected population at the plateau can be determined only when the epidemic is over. dividing this number by the total population of the country gives a fraction that appears to be of the order for − for germany, usa, spain, italy, and − and − for south korea and china respectively. thus an estimate of the susceptible may be obtained by multiplying the population of a country by this fraction. the number of susceptible obtained in this way, however, indicates a lower bound as many individuals with mild or no symptoms go unreported. another possibility to estimate the fraction would be to test the number of positive cases by the number of tests carried out. this number would be an upper bound since there are many regions within a country that remains completely isolated and the populations in such pockets would not be susceptible. the ratio between the number of positive cases and the total number of tests for different countries are given in the following; the fraction is . for the usa, . for south korea (as per data up to may ), . for spain, . for germany (as per data up to may ). conventionally, in epidemiological modeling s ∼ n . in our simulation, we have reasonably varied s within this range to obtain the best fit with real data in a case by case manner (i.e for india and other countries). with the formulation of the model, comes the quantitative estimate of the speed at which the disease spreads across a population. in other words, from the deterministic sird model, the objective is to assess how fast a human carrier would infect people belonging to the population of susceptible? the quantity that determines the transmission speed of the pandemic is the effective reproduction number or replacement number (r e ) [ ] . often the basic reproduction number r , defined as the average number of secondary infections that occur when an infec- tious person (primary or source of infection) is placed into a susceptible population, is used in the epidemiological models. r can be estimated from the very early stage of the infection when the infectious person mixes freely with the susceptible population. estimating r is often challenging due to lack of unbiased data as all secondary infections cannot be determined exactly; especially for covid- , where asymptomatic cases are hardly identified (fig. b) . the effective reproduction number (r e ), which we used in this study, evaluates the mean number of new infections (infected from the susceptible pool) directly transmitted/induced by a typical infected person and can vary over the entire duration of the infection (fig. c) . in the sird model, r e can be represented as β/(γ + δ). from the best fit of the data, we find that γ >> δ, yielding r e ∼ β/γ. if r e > , the disease starts spreading in a population infecting more and more people, but spreading does not occur if r e falls below . it is easy to notice that longer a person remains infectious (i.e. /γ days), can give rise to very large r e even if the number of interactions per day (i.e. β) is small. containment measures in terms of social distancing and lockdown have been implemented world-wide to mitigate the transmission speed of the outbreak. we implemented the effect of lockdown in the model by modifying the infection rate and obtained the best-fit. we chose the following functional form of time-dependent infection rateβ(t) where it gradually decreases after the containment measures are enforced [ , ] . before lockdown, the infection rate is β which is constant. when the lockdown is imposed on day τ (counted from the initial time point t = or day as chosen in the simulation), the time-dependent infection rateβ(t) diminishes with every progressing day which is assume to vary exponentially in the following manner [ ] : here, ζ ∈ [ , ] is the infection parameter (or interaction parameter) and t is the delay in the number of days before the effect of lockdown is visible in the propagation of infection. without lockdown ζ= , referring to rapid infection while ζ = means that infection is contained (e.g no interaction between infected and susceptible population, hence no transmission). ζ ∈ [ , ] reflects the asymptotic mitigation of the infection rateβ(t), when containment measures are imposed. lower the value of ζ, stricter is the containment measures (or the manifestation of the same) [ , ] . here the initially chosen value of β ends with ζβ. essentially, the initial value of β determines the characteristic properties of the disease which depends on the effective interaction of people in a region, social behavior, density of population, etc. the terminal value ζβ reflects the effect of the containment and how the social distancing is being maintained. the functional form ofβ(t) is arbitrary and chosen semi-empirically to obtain the best fit with the available data. the model simulation, data analysis, and plotting are carried out in python. the analysis of the covid- data, using the deterministic compartmental sird model, sheds light on the primary characteristics of the temporal evolution of the pandemic. relevant parameter values chosen for the india and few indian states are listed in table s -s . the best-fit parameters chosen for foreign countries are listed in table s . we carried out the sird model analysis on covid- progression in india's context (and few other countries) all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint with realistic variations in following parameters: rates of infection (β), recovery (γ) and deaths (δ), the initial number of susceptible (s ) and the effective reproduction number (r e ). detailed results are described in the following and illustrated in fig. - , fig. s -s . in a nutshell, we start with the initial susceptible population (s ) varying in the range ∼ - million s , keeping the effective reproduction number r e fixed at ∼ . , and show how the model prediction fits with the indian data without a lockdown, the location of the infection peak and the relative deviation from the real data ( fig. a) . the best fit is obtained by tuning the rates of infection (β), recovery (γ), and deaths (δ) keeping s constrained in the mentioned range. then, we incorporate the effect of containment-measures/lockdown in the functional form of β and show how the effect of the containmentmeasures has altered the location and the height of the infection peak (fig. b ). next, we explore how the variability in the effective reproduction number r e influences the infection peak ( fig. - ). furthermore, we analyze the covid- progression in few indian states e.g kerala, maharashtra, delhi, and west bengal ( fig. - ) and foreign countries e.g south korea, germany, usa, spain ( fig. - ) . lastly, we explore, in brief, what happens to the outspread, if the lockdown is lifted (in other words, containment measures are relaxed) in the indian context ( fig. - ). india without lockdown: what could have happened? the first covid- positive human host was reported in india on th january . the exponential growth of the number of infections, from th january onward, reached a number on th march , the day on which india imposed a nation-wide lockdown (fig. s a) . using the sird model, we first explored what could have happened, if the containment measures had not been undertaken. as mentioned earlier, we chose the factor ∼ − (obtained in case of germany and few other countries by dividing the cumulative population at infection peak by the actual population of the country) and multiplied it the indian population of ∼ to estimate the lower bound of the susceptible population (s ). it turns out that it would be a 'good' estimation to have a 'working' s in the range ∼ . with susceptible population s varied in the range ∼ - million (for fixed r e ∼ . ), the peak of the infection occurs in the first half of may ( fig. a ). as expected, the peak height (infected population at the peak) increases with increasing s . for an initial susceptible pool of s ∼ , the peak reaches a height of . million, whereas the peak jumps to ∼ . million for s ∼ million ( fig. a) . the total death toll is estimated to reach about , - , for s in range ∼ - million, during july -august, ( fig. a) . next, we introduced the effect of containmentmeasures in the infection rateβ(t) (eq. - ). numerical analysis is carried out to investigate whether the pro-all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint gression of the outbreak is mitigated after the lockdown is imposed. straightening of the growth curve: from the real data, it appears that the infection rate begins to reduce, - days after the national lockdown is implemented ( fig. a, inset) . we further observed that the growth curve for the infected population displays a straightening feature during the lockdown time frame. this is expected to be observed if containment measures are initiated; the unhindered exponential growth before the lockdown slows down due to the effect of containment measures during the lockdown. while slowing down and deviating from the exponential trajectory, the infection growth curve (time progression of the infected population size) acquires a distinctive straightening feature until the very recent surge ( fig. a , inset). next, adding the lockdown effects into the picture, we fit the theoretically obtained infection growth curve with the real data. the best fit with the current set of parameters demonstrates that, due to the effect of the present lockdown, the infection peak dwarfs down to about . million from about . million in 'without lockdown' scenario (dashed curve, fig. b and inset). the infection peak is projected to reach a peak at the end of june, tentatively ( fig. b, b , inset). the estimated death toll also reduces substantially compared to the earlier scenario without containment measures. however, the model also shows that the situation can be improved further. the infection growth curve can be dwarfed down further if the lockdown is extended and reinforced stringently in covid- prone zones. in that case, the infection growth curve noticeably flattens with the infection peak reduced further. as mentioned earlier, s is a very crucial parameter in governing the position and the height of the infection peak. in the following, we summarize how the variations in the size of the susceptible population s influence the infection growth curve. keeping r e fixed at ∼ . , we varied the size of the total susceptible population within a range of - million ( fig. a- b ). the model analysis shows that the larger the size of the susceptible population, the higher the infection peak (fig. ) . moreover, for the larger size of the susceptible population, attainment of the infection peak is delayed with the infection peak shifted to a later time zone (fig. b, b , inset). these characteristic features are consistent in both without and with lockdown scenarios. thus, it is evident that the key to containing the outspread lies in keeping s small. this is feasible only when interactions between a demographic region with the recent occurrence of infections and a region with no 'latest' instance of infection are strictly barred. besides the 'global' lockdown (in a nation-wide sense), locally keeping an infected region isolated from other proximal unaffected regions may help to keep s in check. the next question that crops up is what happens to the magnitude of effective reproduction number (r e ) when containment measures are put in place. we discuss in the following, how the effective r e changes with time during the lockdown (fig. ) . effective reproduction number (re) and lockdown: we start with r e in range . ≤ r e ≤ . in the beginning. as the lockdown is implemented, less number of people interact. therefore, the effective infection rate (β (t)) starts decreasing over time. how much the reduction would be forβ(t) in longer time regime, is determined by the factor ζ in eq. . the reducedβ(t) settles at a value ζβ due to the containment effects. thus, if the recovery rate γ is fixed, the r e will diminish and reach a valueβ (t) γ ∼ ζβ γ . the decrease in r e due to the effect of lockdown is evident in fig. where the effective r e all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint reduces to ∼ % of its initial value (before lockdown). the smeared color shades enveloping the dashed lines label the variations in r e within the mentioned range. as expected, the higher the value of r e , the taller the infection peak. this feature is consistent both in presence and absence of lockdown (fig. , , inset) . next, we investigate, whether the value of r e , extracted from the best fit with real data, is unique (of course with marginal variation) or the variation is nonmarginal. what would be the scenario if re is large? instead of fixing r e in the beginning, we varied the rates of infection (β), recovery (γ), and deaths (δ) without any restriction on the resulting value of r e . we aimed to verify whether the best fit of real data with the theoretical curves (infection, recovery, and death) can be obtained for a set of (β, γ, δ), other than the already chosen values in fig. - , with no apparent constraint on the values of r e . we find that, for a fixed size of susceptible population of about . - . million, the real data can still be fitted with the theoretical curves, even if the r e is large (r e ∼ . , fig. ). similar to fig. - , the active infection cases deviate from the theoretical infection curve without lockdown, as the enforced lockdown effectively slows down the progression of infection (fig. , , inset) . note here, that in comparison with fig. - , the location and height of the infection peaks change (both in the cases of without lockdown and with lockdown), as effective r e is increased ∼ -fold (fig. ) . in tandem with the definition of r e , we observe that greater the value of r e , larger the size of the infected population (compare fig. b , r e ∼ . ; and fig. , r e ∼ . ). it is also noteworthy to mention that here the recovery rate γ = . day − correspond to about ∼ days compared to days as discussed earlier. a prolonged infectiousness leads to the rise in the r e and consequently the total number of infected people. from the above observations, we connote that the exactness of r e can be ascertained, when we have more data points in the time evolution of the infected, recovered, and dead population. the current model setup may not be able to precisely pinpoint the exact 'real' r e . how well the individual indian states are doing? in india, the first covid- positive case was reported in kerala on january , , and now almost half of the active covid- positive cases are from maharashtra. in this note, we explore the covid- progression in these states along with delhi and west bengal and compare the features of pandemic progression with each other (fig. - , s b) . after the first case being detected in kerala on january , the second and third cases were reported on feb - . after february , there was no new case detected in kerala till march . the previous three cases were all recovered within february . the 'second-wave' of infections started from march . from march onwards, there was a rapid upsurge of infections. however, about two weeks after the national lockdown is imposed, kerala reached its infection peak. it is evident from fig. a - b that the downfall of the infection is rapid, as the infection curve moved past its peak. if the lockdown was not enforced, the infection was projected to occur around mid-may. but, fig. b alludes that kerala implemented the containment measures so well that the infection peak occurred early at a much lower height (fig. a- b) . the model analysis further projects that due to the effect of lockdown, r e reduces to ∼ % of its initial value during the upsurge of infections before lockdown. the reduced value of r e is << , which means kerala is on the way to become a covid- free state soon if the trend continues. in maharashtra, the first case was detected on march . the total infected population is yet to attain its peak. the projected infection peak would occur around the end of may or early june if the present trend continues and containment measures remain enforced in places (fig. c- d) . similarly, in delhi and west bengal, the infection growth curves are yet to attain their respective peaks (fig. a- d ). the first cases in these states were reported on march and march respectively. the peaks are projected to be reached at the end of june and mid-all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . july for delhi and west bengal respectively, if the enforced lockdown remains deployed and the current trend continues (fig. b, d ). it is important to note that, in states, maharashtra, delhi and west bengal, the estimated r e plummets down to value > . , even after staying months under lockdown. among the indian states we analyzed, kerala turns out to be the only exception where the effective r e reduces to a value << , meaning that further 'out-ofbound' spreading is unlikely to occur there if the current trend is followed. it is evident from fig. a- d and s a that both germany and south korea have moved past the infection peak. the infected population is decreasing day by day in those countries. the best fit with real data is obtained for the initial r e ∼ . and ∼ . for germany and south korea respectively. however, as the containment measures were undertaken in those countries, the effective transmission (or r e ) reduced to ∼ - % from the initial values for the respective countries (fig. b, d ). this observation, suggests that the counter-measures to fight the pandemic (e.g containment measures, social dis-all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint tancing, quarantining, testing, etc.), undertaken in these countries, were reasonably successful in repressing the outspread. moreover, the reduction of r e to - % of its initial values, rescales the r e for the respective countries to a value < . which alludes that new infections are declining and any more 'out-of-bound' infection growth is unlikely to occur if the current trend is followed. we analyzed covid- progression data for two more countries: usa and spain (fig. a- d) . the usa is approaching the infection peak and will reach its peak shortly if the current trend continues (fig. b) . however, contrary to the usa, spain has already passed the infection peak and the infected population is decreasing gradually (fig. d ). spain imposed a nation-wide lock-down on march . model analysis (fitting parameter optimization) suggests that, due to the effect of lockdown, r e for spain reduced to % of its initial value. but in the usa, the reduction in r e is only ∼ % meaning that the implementation of local containments was not that stringent. contrary to the infection curves for germany, south korea, spain (fig. - ) , india is yet to reach the infection peak (the usa is about to reach the peak.). the following remarks briefly summarize where india stands compared to these countries. . the effective containment during the present lockdown in india indicates that the infected population might reach its peak at the end of june (fig. ) whereas ger-all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . many, south korea, and spain have already moved past the peak and daily new infections are decreasing ( fig. - ). . since india has a large population, the infection is expected to stay for a longer duration. germany, south korea, and spain might have the advantage of a smaller population of the susceptible. we allude that the higher the actual population of a country, the higher would be the effective size of the susceptible pool for that country while making the previous statement. the key is to contain the infections in small zones and prevent transmission between infectious and non-infectious zones. . the growth of the infected population in germany, south korea, and spain were greater than that experi-enced in india which gave india an additional advantage of 'buying precious time'. slow growth rate alludes to a smaller peak value at the zenith of the infection. however, as mentioned earlier, the height of the peak is subjected to the effective size of the initial susceptible pool (s ). for better clarity and wider accessibility to general readers, we discuss and summarize the important observations from our study in q&a form in the following: all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint how accurate are the model predictions? the sird model is a drastically simplified approach to thoroughly understand the dynamics of covid . from the available data, it is now clear that a susceptible person goes through a latent period of - days after coming in contact with an infected individual. subsequently, the person remains infectious for several days (∼ days). the infectious individual may or may not develop symptoms. the current model does not incorporate any of these de-tails and hence fitting is imperfect. moreover, data used to fit with the model also vary between different locations leading to uncertain predictions. how sensitive are the model predictions to parameter variations? we investigated the sensitivity of the model to parameter variations, focusing in particular on the parameters all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint to investigate the universality in the covid- outspread across different countries, we looked into iterative time lag maps for the cumulative confirmed infected (c = i+r+d), recovered (r), and dead (d) population [ ] . using the iterative maps, we try to extract the correlation between a population on the day n and day n + . from the recurrence plots (population count on n th day vs population count on (n + ) th day) in fig. s , we ob-all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint serve that the real data for all the cases follow the same power law of the following kind: f (x) = ax b . the factor and exponent a and b are similar for all the countries considered in the plots. this finding indicates that there exists an underlying universality in the outspread of the pandemic across various countries. rapid lifting of the local containment paves the way for inter-mingling between regions with no positive cases (green) and regions with positive cases found lately (red). this, in turn, results in rapid transmission of the disease across zones (all zones becoming red), rendering the purpose of preceding lockdown futile. on the contrary, initially, the partial lifting of local containment only in the green zones bars the import of transmissions from red zones. when a red zone becomes green, the local containment can be lifted from that region. due to the effect of this gradual lifting, the red zones diminish over time, with 'greens' taking over the 'reds'. how effective are the quarantine measures? can quarantining single-handedly contain the transmission? a common perception of flu and other infectious diseases is that an infected individual spreads infection when symptoms appear. in the case of seasonal flu, infection mostly occurs when a person has symptoms [ ] . however, as we understand from the literature survey, an individual with covid- would be contagious before developing symptoms. the incubation period for covid- is days, and maximum infectiousness appears to be - days before the symptoms appear. thus infection spread by an individual is maximum he/she becomes sick [ , ] . due to limitations of the testing procedure diagnosis takes about days after symptoms are visible, i.e., days from the day of infection. clearly, on the average, an infected individual is beyond the peak of maximum infectiousness after this time. thus, a reduced rate of infection demands early diagnosis and isolation of positive patients. this means that a covid- patient needs to be identified in the pre-symptomatic stage as evidence suggests the infectiousness of the patient before developing symptoms which is extremely challenging (effectively, rt-pcr needs to be carried out for every individual who might have come in contact with the patient). the epidemic becomes even more complex due to a majority of the infected individual who develops mild or no symptoms [ , ] . therefore even with isolating/quarantining all the infected covid- would not be eliminated for two reasons: a) normally an individual would be tested after symptoms appear which is when he/she has passed the peak of the contagiousness, b) asymptomatically infected person, in general, are not tested but he/she is also contagious like the symptomatic individual. gradual relaxation of the containment versus extended lockdown? relaxing the containment: we have investigated the effect of relaxing the containment measures at different time points for india ( fig. a- d) . we find if the containment is relaxed before the peak infection is reached at the end of june, the infection would rise rapidly to a great extent (fig. a) . the peak height reduces, if the containment measures are relaxed, when the infection is close to the peak, a time point around the rd week of june (fig. b) . however, if the relaxation occurs a month after the peak infection, a second peak arrives which is lower than the first infection-peak (fig. c) . a third possibility is to gradually relax the containment measures after may . the model shows that in this case the original peak does not shift its position but becomes two-fold higher than before (fig. d) . a gradual relaxation could be carried out in steps: (a) first, identify all the sensitive (red) and safe (green) zones having positive and no cases respectively. smaller the size of such zones, easier they can be managed by the administration, and necessary supplies can be arranged. it is important to seal the boundary of the red zones. (b) test for new cases carrying symptoms and randomly test a few having no symptoms. (c) dissolve the boundary between red and neighboring green zones once the red zone does not report a case for two weeks. this process will increase the size of the green zone where more and more people can communicate and business can restart. successively extending the relaxation from the local neighborhood to the cities, districts, states, the containment measures can be relaxed across the country. nevertheless, social distancing is mandatory even after the containment is officially lifted as there might be many undetected cases that can trigger the spread of the disease again. a schematic diagram in fig. summarizes the above-mentioned steps of relaxation and the consequential aftermaths, pictorially. in a nutshell, 'too-early' lifting of containment measures, all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint long before the infection reached its peak, makes the purpose of lockdown 'null-and-void'. the reduced infection rate β, again starts increasing to its initial value yielding a larger r e for the outspread. our model projects that with containment measures in effect the number of active infection would be about , - , at the peak which is expected to appear sometime after mid-june (fig. ) . note that, due to containment the number of susceptible populations decreases drastically to only several million while the total population of india is about . billion. if the lockdown is suddenly relaxed locally after may , the peak infection would rise sharply to . - . million (fig. a) . note that, this number is estimated without altering the susceptible population which is about − times the actual population observed for many large countries. the remaining population considered to be shielded from the infection due to containment and demographic segregation. in the event of complete mixing of the population of the entire country, the peak infection might see a fold rise which would be challenging for any health care system. thus, social distancing measures must remain unless the infectious population is drastically removed. an important aspect of covid- is the number of patients who do not develop any symptoms (fig. b) . this means they would be infecting healthy people unknowingly. according to the who and indian council of medical research (icmr), as much as % of the infected individual can be asymptomatic. thus all the symptomatic cases reported so far, contributes only about % of the total infection. going by the reported number of cumulative infection , as on may , almost all of which are symptomatic, this would correspond to about , people who also had the virus but did not show any symptoms. together, about , people have actually been infected so far in india carrying symptoms or no symptoms. therefore, the number of people in the country who are still susceptible to the infection is sim . billion. one can realize that, with nearly , active infections, free mixing of the countrywide population after may would cause a huge surge in the total number of infections which is nearly impossible to manage by any health care system. it is noteworthy to mention that the total number of cases reported in all over india as well as in various indian states are negligible compared to the total population of the country and states respectively. besides, the severity of the infection with symptoms is relatively less in india than in the usa and other large european countries. whether it is due to the effect of hot and humid weather of india or other meteorological parameters such as high uv index, future research would be able to evaluate. initial susceptible population . - . × table s . list of parameters chosen for the best fit with real data in indian context. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint mathematical models in epidemiology epidemic modelling: an introduction no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity acknowledgments s.c. * and a.s. were supported by a fellowship from the university grants commission (ugc), india. m.k. was supported by a fellowship from csir, india. s.c. ‡ thanks indian association for the cultivation of science, kolkata for financial support. r.p. thanks iacs for support and grant no. emr/ / of serb, dst, india for the computational facility. key: cord- - hgtvm d authors: sarkar, kankan; khajanchi, subhas; nieto, juan j. title: modeling and forecasting the covid- pandemic in india date: - - journal: chaos solitons fractals doi: . /j.chaos. . sha: doc_id: cord_uid: hgtvm d in india, , , confirmed cases and , confirmed deaths due to covid- were reported as of may , . due to absence of specific vaccine or therapy, non-pharmacological interventions including social distancing, contact tracing are essential to end the worldwide covid- . we propose a mathematical model that predicts the dynamics of covid- in provinces of india and the overall india. a complete scenario is given to demonstrate the estimated pandemic life cycle along with the real data or history to date, which in turn divulges the predicted inflection point and ending phase of sars-cov- . the proposed model monitors the dynamics of six compartments, namely susceptible (s), asymptomatic (a), recovered (r), infected (i), isolated infected (i(q)) and quarantined susceptible (s(q)), collectively expressed sarii(q)s(q). a sensitivity analysis is conducted to determine the robustness of model predictions to parameter values and the sensitive parameters are estimated from the real data on the covid- pandemic in india. our results reveal that achieving a reduction in the contact rate between uninfected and infected individuals by quarantined the susceptible individuals, can effectively reduce the basic reproduction number. our model simulations demonstrate that the elimination of ongoing sars-cov- pandemic is possible by combining the restrictive social distancing and contact tracing. our predictions are based on real data with reasonable assumptions, whereas the accurate course of epidemic heavily depends on how and when quarantine, isolation and precautionary measures are enforced. the ongoing coronavirus, sars-cov- epidemic has been announced a pandemic by the world health organization (who) on march , [ ] , and in the first phase the govt. of india has announced days nationwide lockdown from march , to april , , and in the second phase the lockdown has been extended to may , to prevent stage-iii spreading of the virus or human-to-human transmission [ ] . to mitigate the unavoidable economic downturn. due to absence of any specific pharmaceutical inter- ventions, government of various countries are imposing different strategies to prevent this outbreak and the lockdown is the most common one. as for examples, the measures adopted in this time incorporated social distancing, closing schools, universities, offices, churches, bars, avoid mass gatherings, other social places as well as contact of cases (quarantine, surveillance, contact tracing) [ ] . on march , the govt. of india suspended all the international flights till march , [ ] , and on march , the union govt. also suspended all the domestic flights till march , [ ] to maintain the social distancing among the people. the prime minister of india has announced a hours voluntary public curfew ('janata curfew') on march , as a precautionary measure to combat against covid- . the govt. of india followed it up with lockdowns on march , to prevent the emanating threat in districts across the country including major cities where the covid- infection was endemic [ ] . furthermore, on march , the govt. of india has ordered a nationwide lockdown for days, overwhelming the entire . billion public in india [ ] , and the lockdown has been extended to may , to prevent stage-iii spreading of the virus or human-to-human transmission [ ] . predictive mathematical models play a key role to understand the course of the epidemic and for designing strategies to contain quickly spreading infectious diseases in lack of any specific antivirals or effective vaccine [ , , , ] . in the year , kermack & mckendrick [ ] developed a fundamental epidemic model for human-to-human transmission to describe the dynamics of populations through three mutually exclusive phages of infection, namely susceptible (s), infected (i) and removed (r) classes. mathematical modeling of infectious diseases are now ubiquitous and many of them can precisely depict the dynamic spread of particular epidemics. several mathematical models has been developed to study the transmission dynamics of covid- pandemic. a bats-hosts-reservoir-people network model has been developed by chen et al. [ ] to study the transmission dynamics of novel coronavirus. lin et al. [ ] extended the seir (susceptible-exposed-infectious-removed) compartment model to study the dynamics of covid- incorporating public perception of risk and the number of cumulative cases. khajanchi et al. [ ] studied an extended seir model to study the transmission dynamics of covid- and perform analysis of viral dynamics using mathematical models have helped gain insights into the understanding of viral infections such as tuberculosis, dengue, and zika virus [ , , , , ] . here, we developed a new epidemiological mathematical model for novel coronavirus or sars-cov- epidemic in india that extends the standard seir compartment model, alike to that studied by tang et al. [ ] for covid- . the transmission dynamics of our proposed model for covid- is illustrated in the figure . we develop here a classical seir (susceptible-exposed-infectious-recovered)-type epidemiological model by introducing contact tracing and other interventions such as quarantine, lockdown, social distancing and isolation that can represent the overall dynamics of novel coronavirus or covid- (sars-cov- ). the model, named sarii q s q , monitors the dynamics of six compartments (classes), namely susceptible individuals (s) (uninfected), quarantined susceptible individuals (s q ) (quarantined at home), infectious but not yet symptomatic or asymptomatic infectious individuals (a), infected or infectious with symptoms/clinically ill (i), isolated infected individuals (i q ) (infected or life-threatening or detected) and the recovered compartment (r) (no more infectious). the total size of the individuals is n = s + s q + a + i + i q + r. asymptomatic individuals have been exposed to the virus, but have not yet developed clinical symptoms of the covid- or sars-cov- [ ]. in our model, quarantine describes the separation of coronavirus infected populations from the susceptible individuals before progression of clinical symptoms, whereas the isolation refers to the dissociation of coronavirus infected populations with such clinical symptoms. the rate of change in each compartments at any time t is represented by the following system of nonlinear ordinary differential equations: the model is supplemented by the following non-negative initial values: herein, t ≥ t represents time in days and t indicates the starting date for the system of the coronavirus epidemic. in our model construction, β s represents the probability of transmission per contact between an infective and a susceptible class, and ε s is denoted by the daily contact rate per unit of time. here the parameter β = β s ε s is explicitly associated with the measures like lock-down, social distancing, shaking hand, coughing and sneezing etc., which exactly decrease the number of social contacts. by enforcing con- tact tracing, a proportion ρ s , of individuals exposed to the coronavirus is quarantined. the quarantined classes can either move to the compartment s q or i q , depending on whether they are effectively infected individuals or not, whereas the another proportion − ρ s , consists of populations exposed to the coronavirus who are missed from contact tracing and move to the infectious class i (once infected) or remaining in susceptible class s (if uninfected). then the quarantined classes, if uninfected (or infected), move to the class s q (or i q ) at a rate of ( − β s )ρ s ε s (or β s ρ s ε s ). those who are not quarantined individuals, but asymptomatic infectious individuals, will move to the asymptomatic compartment a at the rate of tined susceptible class due to fever and/or illness-like clinical symptoms. we symbolize ξ a , ξ i and ξ q are the rates of recovery individuals of asymptomatic class, symptomatic or clinically ill patients and isolated individuals, respectively. our model introduces some demographic effects by considering a proportional natural decay rate δ in each of the six individuals, and Λ s represents the constant inflow of susceptible individuals. asymptomatic population develop to infected population at the rate γ a , so the average time spent in the asymptotic class is γa per unit time. in similar fashion, γi represents the mean duration for infected individuals. we ignore the rate of probability of transforming susceptible again after having cured (recovered) from the disease infection. it is to be noted that our sarii q s q model did not take into account many important ingredients that take part a key role in the transmission dynamics of covid- such as the influence of the latency period, the inhomogeneous disease transmission network, the influence of the measures already considered to fight the coronavirus diseases, the features of the individuals (for example, the influence of the stage-structure, individuals who are already medically unfit). some recent mathematical models incorporate asymptomatic such as in ndairou et al. [ ] but others do not include them [ ]. the basic reproduction number, symbolized by r , is 'the expected number of secondary cases produced, in a completely susceptible population, by a typical infective individual' [ , ] . the dimensionless basic reproduction number provides a threshold, which play a crucial role in determining the disease persists or dies out from the individual. in a more general way the basic reproduction number r can be stated as the number of new infections created by a typical infective population at a disease free equilib- rium. r < determines on average an infected population creates less than one new infected population during the course of its infective period, and the infection can die out. in reverse way, r > determines each infected population creates, on average, more than one new infection, and the disease can spread over the population. the basic reproduction number r can be computed by using the concept of next generation matrix [ , ] . in order to do this, we consider the nonnegative matrix f and the non-singular m −matrix v, expressing as the production of new-infection and transition part respectively, for the system ( ), are described by the variational matrix of the model ( ) computed at the infection free state ( the basic reproduction number r = ρ(f v − ), where ρ(f v − ) represents the spectral radius for a next generation matrix f v − . thus, the basic reproduction number of the system ( ) is . ( ) we calibrated our sarii q s q model for covid- to the daily new infected cases and cumulative table . the description of the sarii q s q model are given in table , list of key estimated parameter values are specified in table and estimated initial population size are given in the table . by calibrating the sarii q s q model parameters with real data up to april , we make an attempt to forecast the evolution of the epidemic in india and provinces of india. in the model exploration, we did not consider the demographic effects because of the short epidemic time scale in compare to the demographic time scale, that is, Λ s = δ = . to recognize the most influential parameters with respect to clinically ill infected population, we the prcc results has been shown in the figure for six time points that represents the highest positively correlated parameters are the disease transmission rate β s , contact rate ε s of all the individuals, the probability rate γ a at which the asymptomatic individuals develops clinically symptoms and highly negatively correlated parameters are the quarantined rate ρ s of uninfected individuals, recovery rate ξ a of asymptomatic infected individuals and the recovery rate ξ i of infected individuals, accounts the most uncertainty with respect to the infected individuals. thus, the prcc analysis yields these six parameters β s , ρ s , ε s , γ a , ξ a , and ξ i are the most influential parameters out of parameters. therefore, we estimated these six parameters by using least square method. the most important challenge in any mathematical model based study is to estimate the model parameters and the initial population size. the solution of the sarii q s q model system ( ) depends on both the parameter values and initial population size. the model parameters have been estimated assuming the initial population size and fitting the model simulation with the observed covid- cases. the assumed initial population sizes are presented in the table . we have estimated six parameters, probability of disease transmission (β s ), quarantined rate of susceptible individuals (ρ s ), contact rate of entire individuals ( s ), probability rate at which asymptomatic individuals develop clinical symptoms (γ a ), recovery rate of asymptomatic infected individuals (ξ a ) and rate of recovery for infected individuals (ξ i ) as these parameters are more sensitive in prcc analysis. the parameters are estimated from the observed daily new covid- or sars-cov- viruses. although, we have shown the plot validating model simulation optimize the error in parameter estimation [ ] and errors are listed in the table . first we have applied a five days moving average filter, which is a low pass filter, to smooth the random variation in the observed daily new covid- cases. the observed daily covid- cases are fitted with the model simulation by using least square method, which locally minimizes the sum of the square of errors. the square of sum of the error computed as Σ n i= (c(i) − s(i)) , where c(i) represents the observed daily new covid- cases on i-th day, s(i) is the sarii q s q model simulation on i-th day and n is the sample size of the observed data. it has been observed that different set of parameter values can minimize the sum of the square of errors between the observed daily new covid- cases and the sarii q s q model simulation but we have considered the set of parameter values, which produce realistic r . varying the random values of initially we have validated the model simulation with the observed covid- cases. the sources and duration of the observed data has been presented in table . model simulated from the first date of coronavirus infection and up to april, for whole india and for seventeen states of india. the model simulation fitted with the observed daily new covid- cases and cumulative covid- cases. the parameter values are taken from table and the table and the initial population size from table . to describe how best to minimize individuals impermanence and morbidity due to sars-cov- , it is important to see the relative significance of various ingredients responsible for disease transmission. transmission of sars-cov- is directly related to the basic reproduction number r . we compute the sensitivity indices for r for the parameters of the sarii q s q model. this indices apprise us how important each parameter is to disease transmission. sensitivity analysis is mainly used to describe the robustness of the model predictions to the parameters, as there are generally errors in collection of data and assumed parameter values. sensitivity indices quantify the relative change in a state variable when a parameter alters. the normalized forward sensitivity index for r , with respect to the disease transmission coefficient β s can be defined as follows: which demonstrates that r is a increasing function of β s . this implies that probability of disease transmission has a high influence on covid- control and management. the sensitivity indices of other parameters are given in the table . in the table , some of the indices are positive (and some are negative) which means if the parameter increases then increase the value of r (and if the parameter increases then decrease the value of r ). to control the outbreak of sars-cov- , we must select the most sensitive parameters who have most influence to reduce the diseases. as for example, the transmission rate β s has an impact in reducing the covid- diseases, which can easily be observed from the table . therefore, we draw the contour plots for r in the figure and figure dependence on the rate of disease transmission probability β s and the quarantine rate ρ s . contour plot shows that for the higher values of β s the reproduction number r increases significantly, which means that the sars-cov- disease will persist among the human and spread throughout the community if the public not take the preventive measures. thus, to control r must reduce the disease transmission coefficient β s and increase the period of quarantine rate ρ s . thus, we may conclude that to end the covid- outbreak enhance the quarantine and reduce the probability of disease transmission following contact tracing, social distancing, limit or stop theaters and cultural programme etc. for set of parameter values in the table and estimated parameter values in the table , we plot a bar diagram for the basic reproduction number r in the figure . from the bar-diagram in the figure , it can be observed that the basic reproduction number r for the state maharashtra is too high, which indicates that the substantial outbreak of the covid- in the state maharashtra. will be more accurate. however, this prediction gives us an overview of the pandemic, which will lead to decide future planning. in this study, we fitted sarii q s q model to forecast the pandemic trend over the period after april, by using the observed data from the first day of infection to we cov- and the evolution of epidemic become accessible at an unparalleled pace. howbeit, important questions still remain undetermined and precise answers for forecasting the transmission dynamics of the epidemic simply cannot be acquired at this stage. we emphasize the uncertainty of accessible authentic data, specially concerning to the accurate baseline number of infected individuals, which may guide to the equivocal outcomes and inappropriate predictions by orders of size, as also identified by the other researches [ ] . we hope that our predictions will be handy for govt. and different companies as well as the people towards making resolutions and considering the suitable actions that contain the spreading of the coronavirus to the possible stage. all the data used in this work has been obtained from official sources. all data supporting the findings of this study are in the paper and available from the corresponding author on request. observed data points are displayed in the red dot histogram and the blue curve represents the best fitting curve for the sariiqsq model. the first and third rows represents the daily new cases of coronavirus diseases, whereas the second and fourth rows represents the cumulative confirmed cases of covid- . the estimated parameter values are listed in the table . the initial values used for this parameter values are presented in the table . observed data points are shown in the red dot histogram and the blue curve represents the best fitting curve for the sariiqsq model. the first and third rows represents the daily new cases of coronavirus diseases, whereas the second and fourth rows represents the cumulative confirmed cases of covid- . the estimated parameter values are listed in the table . the initial values used for this parameter values are presented in the table . table : data duration and their sources. the first column list the name of india and its provinces, the second column list the source of data, the third column 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( ) modeling the dynamics of novel coronavirus ( -ncov) with fractional derivative estimating clinical severity of covid- from the transmission dynamics in wuhan, china early dynamics of transmission and control of covid- : a mathematical modelling study the impact of the media awareness and optimal strategy on the prevalence of tuberculosis fatmawati, parameter estimation and fractional derivatives of dengue transmission model a dynamical model of asymptomatic carrier zika virus with optimal control strategies dynamics of tuberculosis transmission with exogenous reinfec- tions and endogenous reactivations modeling and analysis of tuberculosis (tb) in khyber pakhtunkhwa estimation of the transmission risk of the -ncov and its implication for public health interventions modelling strategies for controlling sars outbreaks mathematical modeling of covid- transmission dynamics with a case study of wuhan analysis and forecast of covid- spreading in china, italy and france on the definition and the computation of the basic reproduction ratio r in models for infectious diseases in heterogeneous populations reproduction numbers and subthreshold endemic equilibria for compartmental models of disease transmission a methodology for performing global uncertainty and sensitivity analysis in systems biology avoidable errors in the modelling of out- breaks of emerging pathogens, with special reference to ebola -novel coronavirus ( -ncov): estimating the case fatality ratea word of caution campus quarantine (fengxiao) for curbing emer- gent infectious diseases: lessons from mitigating a/h n in xi'an key: cord- -emh feb authors: chatterjee, saptarshi; sarkar, apurba; chatterjee, swarnajit; karmakar, mintu; paul, raja title: studying the progress of covid- outbreak in india using sird model date: - - journal: indian j phys proc indian assoc cultiv sci ( ) doi: . /s - - - sha: doc_id: cord_uid: emh feb we explore a standard epidemiological model, known as the sird model, to study the covid- infection in india, and a few other countries around the world. we use (a) the stable cumulative infection of various countries and (b) the number of infection versus the tests carried out to evaluate the model. the time-dependent infection rate is set in the model to obtain the best fit with the available data. the model is simulated aiming to project the probable features of the infection in india, various indian states, and other countries. india imposed an early lockdown to contain the infection that can be treated by its healthcare system. we find that with the current infection rate and containment measures, the total active infection in india would be maximum at the end of june or beginning of july . with proper containment measures in the infected zones and social distancing, the infection is expected to fall considerably from august. if the containment measures are relaxed before the arrival of the peak infection, more people from the susceptible population will fall sick as the infection is expected to see a threefold rise at the peak. if the relaxation is given a month after the peak infection, a second peak with a moderate infection will follow. however, a gradual relaxation of the lockdown started well ahead of the peak infection, leads to a nearly twofold increase of the peak infection with no second peak. the model is further extended to incorporate the infection arising from the population showing no symptoms. the preliminary finding suggests that random testing needs to be carried out within the asymptomatic population to contain the spread of the disease. our model provides a semi-quantitative overview of the progression of covid- in india, with model projections reasonably replicating the current progress. the projection of the model is highly sensitive to the choice of the parameters and the available data. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. in the post-ww- era, the world probably has not witnessed such catastrophic morbidity and the looming threat of severe economic challenges caused by the worldwide outbreak of the disease covid- caused by severe acute respiratory syndrome coronavirus (sars-cov- ). the detection of the disease in the human host was first reported in wuhan, china, on december , as a cluster of cases of pneumonia. as the highly contagious disease transmitted rapidly all over the globe, the outbreak was declared as a pandemic by the who on march , . tackling the outspread of the disease is found to be very challenging across the world for the following reasons: (a) conventional flu-like symptoms in human carriers and (b) human-to-human transmission via asymptomatic human hosts and (c) the absence of a proper clinical doctrine (e.g., vaccines, drugs, concrete ideas about the immunological response, etc.). extensive testing and the imposition of containment measures to maintain social distancing turn out to be the effective remedies to prevent disease transmission at the current stage of the epidemic at several places. to evaluate the impact of these preventive measures on infection spread, recovery, death tolls, and various other associated factors, mathematical models become useful in predicting realistic, quantitative estimates. a preliminary analysis suggests that the classic mean-field susceptible-infected-recovery-death (sird) model by kermack and mckendrick [ , ] , can be used to obtain a quantitative picture of the epidemic [ ] [ ] [ ] [ ] [ ] [ ] . in this article, implementing the sird model, we report the temporal progress of covid- transmission in india, various indian states and compare it with some other countries around the world. a similar model used by fernandez-villaverde et al [ ] provides a detailed overview of the pandemic situation in the usa and many other countries. india implemented a nation-wide lockdown from march , . on the day of the announcement of nation-wide lockdown, india had about corona positive cases, while the first covid- positive was detected on january , . the socioeconomic constraints in the indian context alludes that: (a) 'too-prolonged' lockdown is difficult to sustain; (b) the sole imposition of containment measures without a manifold increase in testing capacity is a futile endeavor; (c) if the implementation of the lockdown measures is lenient, containment of the spread is highly improbable. henceforth, the feasible solution for limiting the spread lies in carefully balancing various key epidemiological factors. that is where the importance of the current model predictions becomes relevant. this study further highlights the effect of lockdown on the disease spread and predictions about the variability in the infection peak upon the severity of the containment measures (and/or the lack of it). the model predicts that, in india, the height of the peak infection decreases with stricter lockdown, but at the cost of 'time' (position of the peak shifts to a later month). thus, with a large susceptible, the infection will stay for a long time if existing infections are not quarantined immediately or no proper medicine/vaccine is employed. the key is to quarantine the infection in small pockets while in lockdown and prevent inter-pocket transmission. the model further underlines that in the highly contagious zones ('red' zones where covid- positive cases continue to grow), if the lockdown is extended and enforced with proper quarantine measures, the new infections will gradually plummet down flattening the covid- curve at a much faster rate. our study also explores the plausibility of universality in the spread of the covid- outbreak amongst different countries [ ] and compares the situation in india with few other countries (e.g., germany, south korea, usa, spain) in the relevant time window (february-april). due to the simplicity of the sird model, we found it difficult to fit the observed patterns of the pandemic using the available data. the real data for analysis in india's context is collected from the repository with an interactive interface hosted at https://www.covid india.org. the data for other countries are taken from the repository with an interactive interface hosted at https://www.worldometers.info/coronavirus. the purpose of this article is not to make any quantitative prediction that should be used to design policies, but for the research purpose only. we employ the standard sird model where the population n is divided into sub-population of susceptible (s), infected (i), recovered (r) and dead (d) for all times t. thus, the following set of mean-field differential equations governs the temporal dynamics of the population of susceptible (s), infected (i), recovered (r), dead (d) and describes a comprehensive picture of the sird epidemic evolution: drðtÞ dt ¼ ci ð Þ here, b, c, d are the parameters determining the characteristics of infection, recovery and deaths respectively (fig. a ). note that, in the current scenario i represents the population of symptomatic infection. when a susceptible person interacts with an infectious person, the susceptible become infected at a rate bsi=n. large variability is observed in the rate c that an infected individual is no longer infectious or equivalently has recovered in this simplified model. literature [ ] [ ] [ ] suggests that, on the average, infectiousness appears to start from to days before the symptoms are visible. the infectiousness increases to its peak before the arrival of the symptoms and remains for about - days after the peak infection. thus, an infected individual remains infectious for about days on the average and then recover. in our preliminary analysis, we set the recovery rate c $ = , which however does not give the best fit for all the cases we studied. in essence, the numerical values of the model parameters are obtained from the best fit. initial values (time t ¼ days) of the number of infected, recovered and deaths ði ; r ; d Þ, are chosen from real data. the choice for the initial number of susceptible (s ) is quite difficult. in the absence of antibody, the entire population can be susceptible to the covid- pandemic. nevertheless, the geographical, social, and economic characteristics of a region (and various other demographic factors) can substantially influence this number. we used two different approaches to get an estimate of s . first, we study the data for the large countries where the cumulative positive cases have reached closer to a plateau. though, the infected population at the plateau can be determined only when the epidemic is over. dividing this number by the total population of the country gives a fraction that appears to be of the order for À for germany, usa, spain, italy, and À and À for south korea and china, respectively. thus, an estimate of the susceptible may be obtained by multiplying the population of a country by this fraction. the number of susceptible obtained in this way, however, indicates a lower bound as many individuals with mild or no symptoms go unreported. another possibility to estimate the fraction would be to test the number of positive cases by the number of tests carried out. this number would be an upper bound since there are many regions within a country that remains completely isolated and the populations in such pockets would not be susceptible. the ratio between the number of positive cases and the total number of tests for different countries are given in the following; the fraction is . for the usa, . for south korea (as per data up to may ), . for spain, . for germany (as per data up to may ). conventionally, in epidemiological modeling s $ n. in our simulation, we have reasonably varied s within this range to obtain the best fit with real data in a case by case manner (i.e., for india, few indian states and other countries). with the formulation of the model, comes the quantitative estimate of the speed at which the disease spreads across a population. in other words, from the deterministic sird model, the objective is to assess how fast a human carrier would infect people belonging to the population of susceptible. the quantity that determines the transmission speed of the pandemic is the effective reproduction number or replacement number (r e ) [ ] . often the basic reproduction number r , defined as the average number of secondary infections that occur when an infectious person (primary or source of infection) is placed into a susceptible population, is used in the epidemiological models. r can be estimated from the very early stage of the infection when the infectious person mixes freely with the susceptible population. estimating r is often challenging due to lack of unbiased data as all secondary infections cannot be determined exactly; especially for covid- , where asymptomatic cases are hardly identified (fig. b) . the effective reproduction number (r e ), which we used in this study, evaluates the mean number of new infections (infected from the susceptible pool) directly transmitted/induced by a typical infected person and can vary over the entire duration of the infection (fig. c) . in the sird model, r e can be represented as b=ðc þ dÞ. from the best fit of the data, we find that c [ [ d, yielding r e $ b=c. if r e [ , the disease starts spreading in a population infecting more and more people, but spreading does not occur if r e falls below . it is easy to notice that longer a person remains infectious (i.e. =c days), can give rise to very large r e even if the number of infectious interactions per day (i.e., b) is small. containment measures in terms of social distancing and lockdown have been implemented world-wide to mitigate the transmission speed of the outbreak. we implemented the effect of lockdown in the model by modifying the infection rate and obtained the best-fit. we chose the following functional form of time-dependent infection ratẽ bðtÞ where it gradually decreases after the containment measures are enforced [ , ] . before lockdown, the infection rate is b which is constant. when the lockdown is imposed on day s (counted from the initial time point t ¼ or day as chosen in the simulation), the time-dependent infection ratebðtÞ diminishes with every progressing day which is assumed to vary exponentially in the following manner [ ] : here, f ½ ; is the infection parameter (or interaction parameter) and t is the delay in the number of days before the effect of lockdown is visible in the propagation of infection. without lockdown f ¼ , referring to rapid infection while f ¼ means that infection is contained (e.g., no interaction between infected and susceptible population, hence no transmission). f ½ ; reflects the asymptotic mitigation of the infection ratebðtÞ, when containment measures are imposed. lower the value of f, stricter is the containment measures (or the manifestation of the same) [ , ] . here,bðtÞ has an initial value b which is constant.bðtÞ diminishes over time and reaches a value fb as containment measures continue. essentially, the initial value of b determines the characteristic properties of the disease which depends on the effective interaction of people in a region, social behavior, density of population, etc. the terminal value fb reflects the effect of the containment and how the social distancing is being maintained. in the current model setup,bðtÞ is meant to account for the changes in the behavior of infection spread due to social distancing and containment measures. this is an external parameter that is expected to decay with time to a smaller value fb when physical contact is avoided. taking a cue from the previous studies [ , ] , the functional form ofbðtÞ is constructed to account for the apparent changes on the infection growth due to containment measures and social distancing. t controls the effective speed at which the slow down in the disease transmission occurs due to the enforced containment measures. the model simulation, data analysis, and plotting are carried out in python. the analysis of the covid- data, using the deterministic compartmental sird model, sheds light on the primary characteristics of the temporal evolution of the pandemic. relevant parameter values chosen for the india and few indian states are listed in table s -s . the best-fit parameters chosen for foreign countries are listed in table s . we carried out the sird model analysis on covid- progression in india's context (and few other countries) with realistic variations in following parameters: rates of infection (b), recovery (c) and deaths (d), the initial number of susceptible (s ) and the effective reproduction number (r e ). detailed results are described in the following and illustrated in figs. , , , , , , , and , fig. s -s . in a nutshell, we start with the initial susceptible population (s ) varied within the range $ - million, keeping the effective reproduction number r e fixed at $ . , and show how the model prediction fits with the indian data without a lockdown, the location of the infection peak and the relative deviation from the real data (fig. a) . the best fit is obtained by tuning the rates of infection (b), recovery (c), and deaths (d) keeping s constrained in the mentioned range. then, we incorporate the effect of containmentmeasures/lockdown in the functional form of time-depen-dentbðtÞ and show how the effect of the containmentmeasures has altered the location and the height of the infection peak (fig. b) . next, we explore how the variability in the effective reproduction number r e influences the infection peak (figs. , ) . furthermore, we analyze the covid- progression in few indian states e.g., kerala, maharashtra, delhi, and west bengal (figs the first covid- positive human host was reported in india on january , . the exponential growth of the number of infections, from th january onward, reached a number on march , , the day on which india imposed a nation-wide lockdown (fig. s a ). using the sird model, we first explored what could have happened, if the containment measures had not been undertaken. as mentioned earlier, we chose the factor $ À (obtained in case of germany and few other countries by dividing the cumulative population at infection peak by the actual population of the country) and multiplied it with the indian population of $ to estimate the lower bound of the susceptible population (s ). it turns out that it would be a 'good' estimation to have a 'working' s in the range $ . with susceptible population s varied in the range $ - million (for fixed r e $ : ), the peak of the infection occurs in the first half of may (fig. a) . as expected, the peak height (infected population at the peak) increases with increasing s . for an initial susceptible pool of s $ , the peak reaches a height of . million, whereas the peak jumps to $ . million for s $ million (fig. a) . the total death toll is estimated to reach about , - , for s in range $ - million, during july-august, (fig. a) . next, we introduced the effect of containment-measures in the infection ratebðtÞ (eqs. - ). numerical analysis is carried out to investigate whether the progression of the outbreak is mitigated after the lockdown is imposed. fig. best fit of the infection and death curves with the real data freely varying the effective r e which appears to be $ . in the early stage. the color shades enveloping the curves denote variation in susceptible population within a range of $ . - : Â . the real data considered for fitting are from march , . relevant parameters for the analysis are b ¼ : day À , c ¼ : day À , d ¼ : day À , s ¼ days, t ¼ days, f ¼ : . . effect of containment measures: how well is india doing? from the real data, it appears that the infection rate begins to reduce, - days after the national lockdown is implemented (fig. a, inset) . we further observed that the growth curve for the infected population displays a straightening feature during the lockdown time frame. this is expected to be observed if containment measures are initiated; the unhindered exponential growth before the lockdown slows down due to the effect of containment measures during the lockdown. while slowing down and deviating from the exponential trajectory, the infection growth curve (time progression of the infected population size) acquires a distinctive straightening feature until the very recent surge (fig. a , inset). next, adding the lockdown effects into the picture, we fit the theoretically obtained infection growth curve with the real data. the best fit with the current set of parameters demonstrates that, due to the effect of the present lockdown, the infection peak dwarfs down to about . million from about . million in 'without lockdown' scenario (dashed curve, fig. b and inset). the infection time evolution of the population of infected and dead for maharashtra, (c) if lockdown was not imposed, (d) due to effect of lockdown peak is projected to reach a peak at the end of june, tentatively (fig. b, b , inset). the estimated death toll also reduces substantially compared to the earlier scenario without containment measures. however, the model also shows that the situation can be improved further. the infection growth curve can be dwarfed down further if the lockdown is extended and reinforced stringently in covid- prone zones. in that case, the infection growth curve noticeably flattens with the infection peak reduced further. as mentioned earlier, s is a very crucial parameter in governing the position and the height of the infection peak. in the following, we summarize how the variations in the size of the susceptible population s influence the infection growth curve. keeping r e fixed at $ . , we varied the size of the total susceptible population within a range of - million (fig. a, b) . the model analysis shows that the larger the size of the susceptible population, the higher the infection peak (fig. ) . moreover, for the larger size of the susceptible population, attainment of the infection peak is delayed with the infection peak shifted to a later time zone (fig. b, b, inset) . these characteristic features are consistent in both without and with lockdown scenarios. thus, it is evident that the key to containing the outspread lies in keeping s small. this is feasible only when interactions between a demographic region with the recent occurrence of infections and a region with no 'latest' the next question that crops up is what happens to the magnitude of effective reproduction number (r e ) when containment measures are put in place. we discuss in the following, how the effective r e changes with time during the lockdown (fig. ). we start with r e in range : r e : in the beginning. as the lockdown is implemented, less number of people interact. therefore, the effective infection ratebðtÞ starts decreasing over time. how much the reduction would be forbðtÞ in longer time regime, is determined by the factor f in eq. ( ). the reducedbðtÞ settles at a value fb due to the containment effects. thus, if the recovery rate c is fixed, the r e will diminish and reach a valueb ðtÞ c $ fb c . the decrease in r e due to the effect of lockdown is evident in fig. where the effective r e reduces to $ % of its initial value (before lockdown). the smeared color shades enveloping the dashed lines label the variations in r e within the mentioned range. as expected, the higher the value of r e , the taller the infection peak. this feature is consistent both in presence and absence of lockdown (fig. , inset) . next, we investigate, whether the value of r e , extracted from the best fit with real data, is unique (of course with marginal variation) or the variation is non-marginal. instead of fixing r e in the beginning, we varied the rates of infection (b), recovery (c), and deaths (d) without any restriction on the resulting value of r e . we aimed to verify whether the best fit of real data with the theoretical curves (infection, recovery, and death) can be obtained for a set of (b; c; d), other than the already chosen values in figs. and , with no apparent constraint on the values of r e . we find that, for a fixed size of the susceptible population of about . - . million, the real data can still be fitted with the theoretical curves, even if the r e is large (r e $ : , fig. ). similar to figs. and , the active infection cases deviate from the theoretical infection curve without lockdown, as the enforced lockdown effectively slows down the progression of infection (fig. , inset) . note here, that in comparison with figs. and , the location and height of the infection peaks change (both in the cases of without lockdown and with lockdown), as effective r e is increased $ twofold (fig. ) . consistent with the definition of r e , we observe that greater the value of r e , larger the size of the infected population (compare fig. b , r e $ : ; and fig. , r e $ : ). it is also noteworthy to mention that here the recovery rate c = . day À corresponds to about $ days compared to days as discussed earlier. prolonged infectiousness leads to the rise in the r e and consequently the total number of infected people. from the above observations, we connote that the exactness of r e can be ascertained, when we have more data points in the time evolution of the infected, recovered, and dead population. the current model setup may not be able to precisely pinpoint the exact 'real' r e . in india, the first covid- positive case was reported in indian state kerala on january , , and now almost half of the active covid- positive cases are from another indian state maharashtra. in this note, we explore the covid- progression in these indian states along with delhi and west bengal and compare the features of pandemic progression with each other (figs. , , s b). after the first case being detected in kerala on january , the second and third cases were reported on february - . after february , there was no new case detected in kerala till march . the previous three cases were all recovered within february . the 'second-wave' of infections started from march . from march onwards, there was a rapid upsurge of infections. however, about weeks after the national lockdown is imposed, kerala reached its infection peak. it is evident from fig. a , b that the downfall of the infection is rapid, as the infection curve moved past its peak. if the lockdown was not enforced, the infection was projected to occur around mid-may. but, fig. b alludes that kerala implemented the containment measures so well that the infection peak occurred early at a much lower height (fig. a, b) . the model analysis further projects that due to the effect of lockdown, r e reduces to $ % of its initial value during the upsurge of infections before lockdown. the reduced value of r e is \ , which means kerala is on the way to become a covid- free state soon if the trend continues. in maharashtra, the first case was detected on march . the total infected population is yet to attain its peak. the projected infection peak would occur around the end of may or early june if the present trend continues and containment measures remain enforced in places (fig. c, d) . similarly, in delhi and west bengal, the infection growth curves are yet to attain their respective peaks (fig. a-d) . the first cases in these states were reported on march and march , respectively. the peaks are projected to be reached at the end of june and mid-july for delhi and west bengal respectively, if the enforced lockdown remains deployed and the current trend continues (fig. b, d) . it is important to note that, in indian states, maharashtra, delhi and west bengal, the estimated r e plummets down to value [ : , even after staying months under lockdown. among the indian states we analyzed, kerala turns out to be the only exception where the effective r e reduces to a value \ , meaning that further 'out-of-bound' spreading is unlikely to occur there if the current trend is followed. it is evident from fig. a -d and s a that both germany and south korea have moved past the infection peak. the infected population is decreasing day by day in those countries. the best fit with real data is obtained for the initial r e $ : and $ . for germany and south korea, respectively. however, as the containment measures were undertaken in those countries, the effective transmission (or r e ) reduced to $ - % from the initial values for the respective countries (fig. b, d) . this observation, suggests that the counter-measures to fight the pandemic (e.g., containment measures, social distancing, quarantining, testing, etc.), undertaken in these countries, were reasonably successful in repressing the outspread. moreover, the reduction of r e to - % of its initial values, rescales the r e for the respective countries to a value \ which alludes that new infections are declining and any more 'out-of-bound' infection growth is unlikely to occur if the current trend is followed. we analyzed covid- progression data for two more countries: usa and spain (fig. a-d) . the usa is approaching the infection peak and will reach its peak shortly if the current trend continues (fig. b) . however, contrary to the usa, spain has already passed the infection peak and the infected population is decreasing gradually (fig. d) . spain imposed a nation-wide lockdown on march . model analysis (fitting parameter optimization) suggests that, due to the effect of lockdown, r e for spain reduced to % of its initial value. but in the usa, the reduction in r e is only $ % implying that the implementation of local containment was not that stringent. fig. representative schematic illustrating the aftermath of slowly relaxing (phasing out) of the local containment measures vs rapid lifting of the same. the boxes bordered in black depict the containment zones. rapid lifting of the local containment paves the way for inter-mingling between regions with no positive cases (green) and regions with positive cases found lately (red). this, in turn, results in rapid transmission of the disease across zones (all zones becoming red), rendering the purpose of preceding lockdown futile. on the contrary, initially, the partial lifting of local containment only in the green zones bars the import of transmissions from red zones. when a red zone becomes green, the local containment can be lifted from that region. due to the effect of this gradual lifting, the red zones diminish over time, with 'greens' taking over the 'reds' (color figure online) contrary to the infection curves for germany, south korea, spain (figs. , ) , india is yet to reach the infection peak (the usa is about to reach the peak.). the following remarks briefly summarize where india stands compared to these countries. . the effective containment during the present lockdown in india indicates that the infected population might reach its peak at the end of june (fig. ) whereas germany, south korea, and spain have already moved past the peak and daily new infections are decreasing (figs. , ). . since india has a large population, the infection is expected to stay for a longer duration. germany, south korea, and spain might have the advantage of a smaller population of the susceptible. we allude that the higher the actual population of a country, the higher would be the effective size of the susceptible pool for that country while making the previous statement. the key is to contain the infections in small zones and prevent transmission between infectious and non-infectious zones. . the growth of the infected population in germany, south korea, and spain were greater than that experienced in india which gave india an additional advantage of 'buying precious time'. slow growth rate alludes to a smaller peak value at the zenith of the infection. however, as mentioned earlier, the height of the peak is subjected to the effective size of the initial susceptible pool (s ). for better clarity and wider accessibility to general readers, we discuss and summarize the important observations from our study in q&a format in the following: to investigate the universality in the covid- outspread across different countries, we looked into iterative time lag maps for the cumulative confirmed infected (c = i?r?d), recovered (r), and dead (d) population [ ] . using the iterative maps, we try to extract the correlation between a population on the day n and day n þ . from the recurrence plots (population count on n th day vs population count on ðn þ Þ th day) in fig. s , we observe that the real data for all the cases follow the same power law of the following kind: f ðxÞ ¼ ax b . the factor and exponent a and b are similar for all the countries considered in the plots. this finding indicates that there exists an underlying universality in the outspread of the pandemic across various countries. to check the predictiveness of the model, we compared the projected outcome with the real data accumulated over the last couple of weeks since our initial submission of the manuscript. we plotted the data and the model prediction in fig. s a -s b (similar to figs. b and d respectively) without altering the parameters. one can notice that, so far, the real data is bounded by the model predicted curves. nevertheless, the sird model is a drastically simplified approach to thoroughly understand the dynamics of covid- progression. from the available information, it is now becoming apparent that a susceptible person goes through a latent period of - days after coming in contact with an infected individual. subsequently, the person remains infectious for several days ( $ days). the infectious individual may or may not develop symptoms. the current model does not incorporate any of these details and hence fitting is imperfect. moreover, data used to fit with the model also vary between different locations leading to uncertain predictions. a compartmental model with multiple species may be useful to study the dynamics of the sub-population [ ] . the model used here to analyze the covid- progression is the well-known sird model. this is a standard epidemiological model with three characteristic parameters for infection, recovery, and death. the model estimates the number of infections within a closed (conserved) population of susceptible bearing the risk of contagion. note that this is 'not' a covid- specific model by construction. for years, people have used this model to study several outbreaks all across the globe [ ] . in our study, the word 'covid- ' enters into the picture only through the best fitting of the 'real data', that determines the instantaneous rates. the biological and clinical nitty-gritty of covid- is beyond the scope of the model. the limitations of this current model prescription are given in the following: (a) the mean-field sird equations do not include the spatial variation in the population density. by construction, there is no spatial degree of freedom in the standard sird model. the term bsi in eq. ( ) alludes that all the infected individuals are equally likely to interact with susceptibles and transmit the disease [ ] . however, in a realistic scenario, this is unlikely to occur. in the current indian context, an individual living in a remote himalayan village is far less likely to encounter an infected person compared to an individual living near marine drive, mumbai. (b) the model assumes homogeneous exposure and response to the disease [ ] . there are various key factors like different demographic features, ethnicity, lifestyle, socioeconomic strata of a sub-population that can induce variability in the exposure to the infection. (c) the model assumes that the contagiousness of an infected person remains constant throughout before his/her recovery and a person is capable of transmitting the disease right after s/he became infected which may not be realistic in the present context. (d) naturally, an increase in the number of tests would also increase the number of infections as more and more undetected infections will be detected. the availability of hospital beds, critical care facilities would also influence the recovery rate in reality. the simplistic model cannot account for all these factors. there are also a few ''what if'' paradigms that cannot be assessed via this model unless further compartments and rate parameters are added upon. few ''what if'' scenarios are: (a) what if the sars-cov- immunity is not permanent? [ ] ; (b) what if there is seasonal variation in transmission rates of the disease? [ ] ; (c) what if the vaccine becomes available within a certain period? and many more. in essence, to address each of these aspects, we need to formulate elaborate models brick by brick in a context-dependent manner. the current working handle of the sird model marks the preliminary footstep along that direction. we investigated the sensitivity of the model to parameter variations, focusing in particular on the parameters that change the rates of infection, recovery (b; c) and most importantly the effective reproduction number or replacement number (r e ) within a feasible range to see the effect the model prediction. the lockdown stringency, characterized by the time-dependentbðtÞ, f, was varied to get an estimate of the infected population. corresponding data are shown in each figure by the shaded envelope around the mean curves. the model appears to be sensitive to the variation in the value of f and s when compared with the real data. increasing (decreasing) the value s , f, and r e rapidly increases (decreases) the population of total infection and death mostly around the peak and alters the position of the peak infection. these parameters can be decreased by enforcing local containment and social-distancing measures. the standard sird model does not contain any spatial degree of freedom. the mean-field nature of the current approach excludes the topological dependence of the model predictions. hence, the spatially explicit modeling incorporating infection hotspots and disease transmission from the hotspots to the rest of the places would yield a more realistic reconstruction of the scenario. a compartmentalized sird model simulated on a virtual network of all indian states where the network connectivity manifests the transmission spread from one state to another would be worthwhile. the spatial topology of the underlying network should also include details like the geographical topology of a region, human mobility, connectivity by transport system, health care facilities, etc. the detailed phenomenological reconstruction on a lattice-based model would shed light on the topological dependence of the predictions, robustly. a similar spatially explicit study using the seir model shows how the disease is transmitted from initial foci/local pockets of infections to entire italy [ ] . we plan to adopt a similar approach in the indian context as a worthy future endeavor. we reiterate that the predictions based on the sird model are simple mean-field predictions. given the public interest on this pandemic, we put it as a disclaimer that, including topological effects may quantitatively alter the picture of the covid- progression in indian context up to a reasonable degree. a common perception of flu and other infectious diseases is that an infected individual spreads infection when symptoms appear. in the case of seasonal flu, infection mostly occurs when a person has symptoms [ ] . however, as we understand from the literature survey, an individual with covid- would be contagious before developing symptoms. the incubation period for covid- is $ days, and maximum infectiousness appears to be - days before the symptoms appear. thus infection spread by an individual is maximum before he/she becomes sick [ , ] . due to limitations of the testing procedure, diagnosis takes about days after symptoms are visible, i.e., days from the day of infection. clearly, on the average, an infected individual is beyond the peak of maximum infectiousness after this time. thus, a reduced rate of infection demands early diagnosis and isolation of positive patients. this means that a covid- patient needs to be identified in the pre-symptomatic stage as evidence suggests the infectiousness of the patient before developing symptoms which is extremely challenging (effectively, rt-pcr needs to be carried out for every individual who might have come in contact with the patient). the epidemic becomes even more complex due to a majority of the infected individual who develops mild or no symptoms [ , ] . therefore, even with isolating/ quarantining, all the infected covid- would not be eliminated for two reasons: a) normally an individual would be tested after symptoms appear which is when he/ she has passed the peak of the contagiousness, b) asymptomatically infected person, in general, are not tested but he/she is also contagious like the symptomatic individual. . . . gradual relaxation of the containment versus extended lockdown? we have investigated the possible effect of relaxing the containment measures at three different time points for india ( fig. a-d) . we find that if the containment would have been relaxed in the middle of may, i.e. the before the projected peak infection is reached at the end of june, the infected population would rise rapidly to a great extent (fig. a) . the peak height reduces, if the containment measures are relaxed, when the infection is close to the peak, a time point around the rd week of june (fig. b) . however, if the relaxation occurs a month after the peak infection, a second peak arrives which is lower than the first infection-peak (fig. c) . a third possibility is to gradually relax the containment measures after may . the model shows that in this case the original peak does not shift its position but becomes twofold higher than before (fig. d) . a gradual relaxation could be carried out in steps: (a) first, identify all the sensitive (red) and safe (green) zones having positive and no cases respectively. smaller the size of such zones, easier they can be managed by the administration, and necessary supplies can be arranged. it is important to seal the boundary of the red zones. (b) test for new cases carrying symptoms and randomly test a few having no symptoms. (c) dissolve the boundary between red and neighboring green zones once the red zone does not report a case for weeks. this process will increase the size of the green zone where more and more people can communicate and business can restart. successively extending the relaxation from the local neighborhood to the cities, districts, states, the containment measures can be relaxed across the country. nevertheless, social distancing is mandatory even after the containment is officially lifted as there might be many undetected cases that can trigger the spread of the disease again. a schematic diagram in fig. summarizes the above-mentioned steps of relaxation and the consequential aftermaths, pictorially. in a nutshell, 'too-early' lifting of containment measures, long before the infection reached its peak, makes the purpose of lockdown 'null-and-void'. the reduced infection ratebðtÞ again starts increasing yielding a larger r e promoting the outspread. it is imperative to note that there are certain differences in the concepts and implications of lockdown, containment measures, and social distancing. in the indian context, ideally, lockdown implies that containment measures are enforced in every nook and corner of the country. however, the intervention of containment measures can be applied locally. for example, in principle, the nation-wide lockdown can be lifted, but containment measures can remain in action in places that are identified as infection hotspots. hence, the word 'lockdown' refers to the restrictions (social, economical) applied over a very large region (e.g., a state or the whole country) whereas the 'containment measures' refers to implementing the same disciplines locally as well as universally. social distancing, on the other hand, is rather a personalized affair. people can maintain social distancing even when a lockdown is not in place. in an ideal scenario, if all individuals within a closed community maintain social distancing without 'lockdown', new infections are unlikely to occur. in that note, our model projects that, with containment measures and social distancing in effect, the number of active infection (noncumulative) would be about , - , at the peak which is expected to appear sometime toward the end of june (fig. ) . nevertheless, to reduce the economic impacts, it is essential to relax the strict containment measures applied across the country. through our model, we checked several scenarios for applying the relaxation and estimated the evolution of the infection. if the containment measures were suddenly relaxed after may , the peak infection would have increased sharply to . - . million (fig. a) . it is imperative to mention that, this number is estimated without altering the susceptible population which is about À times the actual population observed for many large countries. the remaining population is considered to be shielded from the infection due to containment and demographic segregation. note that, due to containment (and social distancing), the size of the susceptible population is kept at a value of only several million while the total population of india is about . billion. upon lifting the containment measures, the effective susceptible population should also increase. in this simplistic model, since the attributes are based on a closed population, no additional increment in the number of susceptibles upon the lifting of containment measures is considered. in the event of unrestricted mixing of the population of the whole country, the peak infection might see a fold rise which would be challenging for any health care system to deal with. thus, social distancing measures must remain in place unless the infectious population is contained or drastically reduced. in a nutshell, the four scenarios depicted in fig. a- (fig. a) . but, in reality, in the indian context, we observed that the lockdown was still in place after may . thus, fig. a remains as a ' what could have been' scenario. note that when we say 'lockdown', we assume that both the containment measures and social distancing norms are enforced/followed. now the question is, do any of these plots (fig. a-d) corroborate with the present situation (real data as of may )? in india, th phase of lockdown was enforced (rather extended) from may onward. however, during this phase, various relaxation measures were also given. in that note, the closest theoretical consideration would be the scenario depicted in fig. d . to analyze the situation, we compare two scenarios side by side from a more recent perspective (evolved when the manuscript was under revision): time evolution of infection curves (a) with lockdown (containment measures ? social distancing in place) as depicted in fig. b; (b) containment measures gradually relaxed as depicted in fig. d . in figs. b and d, the real data was up to may . in fig. s a-s b , we re-plotted the real data up to may , with the theoretical curves of figs. b and d. the real data up to may , in both fig. s a -s b, reasonably falls within the range enveloped by the theoretical curves (with marginal deviation). the range of the active infection peak in fig. s a , is about . - . million occurring between the end of june to mid-july whereas in fig. s b , the infection peak is predicted to be in the range of . - . million also occurring at the end of june. thus, from fig. s a -s b combined, we gather that the active infection peak may be above . million and likely to be in a range of . - . million. according to this analysis, the peak is likely to occur during the end of june and mid-july. however, this is merely a model prediction; the dynamics, in reality, depends on a myriad of factors which are beyond the scope of this simple model. although the nation is under lockdown, it is observed that the number of positive cases is still growing at large. a distinct feature of this growth is the local resurgence of infections. as gleaned from various news reports, even after several days with a few new cases, suddenly, there had been jumps in the covid- positive cases in quite a few places. in other words, 'lull' 'green' zones are, all of a sudden, turning into 'red' zones. we discuss a few plausible factors behind the resurgence: (a) cross-country reverse migration: due to the lockdown, a large population of migrant workers reeling at the bottom of the economic barrel got stranded in different places without much subsistence. these people started returning to their homes taking desperate measures. during this migration, humanto-human transmission of covid- might have occurred to a great extent due to a lack of social distancing adding fuel to the 'resurgence' of infection. (b) lack of 'test, trace and contain': interestingly, an important aspect of covid- is the number of patients who do not develop any symptoms (fig. b) . in india, primarily the testing capacity was devoted to the persons showing typical symptoms of covid- . the asymptomatic pool largely remained unnoticed at the initial stages of infection outgrowth which probably contributed to the resurgence of infections. moreover, it is not sufficient to only isolate the positive cases but to trace all those people who came in contact with the individual tested positive and find the source of infection. this is known as 'contact tracing'. if the source of the infection is not traceable, this could indicate an insufficient testing or asymptomatically positive source. extensive use of the app-based modern technology may become useful to trace contacts, however, often at the cost of privacy. in india, where a large portion of the population has no 'digital footprint', contact tracing becomes even harder. south korea flattened the infection curve with extensive testing and other mentioned measures. in india, a similar endeavor of a magnitude proportional to its humongous population seems extremely challenging. with the limited capacity and huge population, randomized testing, at least in the infectious neighborhood, is an immediate solution to detect and isolate the asymptomatic individuals. in both the above-mentioned scenarios, the majority of the infection spreading is likely to be spearheaded by the asymptomatic human hosts who remain undetected due to a lack of randomized testing and come in social contact with others. this means that they would be infecting healthy people unknowingly. according to the who and the indian council of medical research (icmr), as much as % of the infected individual can be asymptomatic. thus, all the symptomatic cases reported so far contribute to only about % of the total infection. going by the reported number of cumulative infections , as on may , almost all of which are symptomatic, this would correspond to about , people who also had the virus but did not show any symptoms. together, about , people have actually been infected so far in india carrying symptoms or no symptoms. therefore, the number of people in the country who are still susceptible to the infection is still in the order of billion. one can realize that, with so many active infections, extensive mixing of the countrywide population soon after the lockdown is over (after may) would cause a huge surge in the total number of infections which is nearly impossible to manage by any health care system. to estimate the asymptomatic population from the model, we rewrite the equations as follows: di a ðtÞ dt ¼ sðbi s þ b i a Þ=n À ða þ m Þi a ; di s ðtÞ dt ¼ ai a À ðm þ dÞi s ; drðtÞ dt ¼ m i a þ mi s ; ddðtÞ dt ¼ di s here, the total infectious population is segregated into two compartments: (a) symptomatic i s and (b) asymptomatic or mildly symptomatic i a population. a susceptible person can be infected upon contact with a symptomatic or asymptomatic individual with rates b; b respectively. the infected individual can remain asymptomatic or mildly symptomatic and transit into a symptomatic state with rate a. the asymptomatic and symptomatic persons can recover at rates m and m respectively. for a symptomatic individual, death occurs with rate d. for simplicity, we assumed no death for asymptomatic population. we find that with an s in range $ - million and r e $ : , new model data (fig. s ) matches with the previously plotted population of symptomatic infection (see fig. ). the asymptomatic infection peak appears to be about fold larger than the symptomatic infection peak. thus the current lockdown can only be relaxed in the presence of extensive testing of symptomatic and asymptomatic population and contact tracing. it is noteworthy to mention that the total number of cases reported in all over india as well as in various indian states are negligible compared to the total population of the country and states respectively. besides, the severity of the infection with symptoms is relatively less in india than in the usa and other large european countries. whether it is due to the effect of hot and humid weather of india or other meteorological parameters such as high uv index, future research would be able to evaluate. the model predicts the infection peak for india at the end of june or the first half of july (fig. ) assuming that the social distancing measures will remain in place. the model shows that as the size of the susceptible population increases, the infection peak shifts to a later date (fig. b, inset) . thus, if the human mobility between regions increases, that would lead to an effective expansion in the number of susceptibles. this increase in susceptible population would not only lead to a surge in infections but also delay the occurrence of the infection peak by a few weeks. lately, we have been observing an uprise in the new covid- positive cases daily. this may be attributed to the transmission of the pathogen via asymptomatic carriers and reverse migration of migrant workers from one province to another within india. whether asymptomatic transmission in tandem with elevated human mobility plays a crucial role in the recent infection surge is a topic of our ongoing work [ ] . our results also exemplify that, the best fit of the real data can be obtained for different r e values with the difference being non-marginal (figs. , ) . this may be a limitation of the current model setup to zero in on the exactness of characteristic r e corresponding to the outspread. as mentioned earlier, a spatially explicit model considering a network of indian provinces connected by human mobility, domestic travel from one place to another, and corresponding disease transmission graphs may lead to deeper understandings of the dynamics of the ongoing pandemic in india. epidemic modelling: an introduction publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations acknowledgements we thank santanu bhattacharya, heiko rieger, soumitra sengupta, jayanta kumar bhattacharjee, deb shankar ray, sankar prasad bhattacharyya, parongama sen for exciting discussions and valuable suggestions. sa.c. and a.s. were supported by a fellowship from the university grants commission (ugc), india. sw.c. thanks indian association for the cultivation of science, kolkata for financial support. m.k. was supported by a fellowship from csir, india. r.p. thanks iacs for support and grant no. emr/ / of serb, dst, india for the computational facility. key: cord- -y ianyqi authors: bamji, mahtab s.; murty, p. v. v. s.; sudhir, parimala diana title: nutritionally sensitive agriculture—an approach to reducing hidden hunger date: - - journal: eur j clin nutr doi: . /s - - -x sha: doc_id: cord_uid: y ianyqi cereal-based diets of the people in developing countries are qualitatively deficient in micronutrients—vitamins and minerals—due to low intake of vegetables, fruits, legumes and foods of animal origin. consumption of nutritious millets has also come down in india. calorie sufficiency may ensure protein sufficiency (though not protein quality), but it does not ensure adequacy of micronutrients. studies in several countries in asia, and india show that with education and advocacy even farmers with small and marginal land holdings can be persuaded to raise homestead vegetables and fruits gardens and increase household vegetables consumption. backyard poultry also has good acceptance and impact on household egg consumption. for best results, the community, especially the mothers have to be educated about the importance of nutrition for health and wellbeing. studies done by the authors in the villages of medak district, of the south indian state of telangana, show remarkable improvement in the knowledge of food, nutrition, hygiene and health of mothers with children under years of age, with education–behavioural change communication. impact of nutrition gardens and backyard poultry with high egg-yielding breeds had positive impact on the household consumption of vegetables and eggs. developing countries like india are facing a double burden of diseases. while pre-transition diseases like infectious diseases and malnutrition persist, there is growing incidence of post-transition non-communicable diseases like obesity, hypertension, diabetes, cardiovascular diseases and cancer. india has become the diabetes capital of the world. nutrition influences both the burdens. malnutrition increases susceptibility to infections and resultant morbidity and mortality. prenatal malnutrition has been shown to affect the growth of the foetus resulting in low birth weight (lbw) babies. intra-uterine malnutrition epigenetically alters body composition with higher fat deposition, which in turn predisposes the individual to adult-onset non-communicable diseases. (barker's hypothesis, foetal origins of adult diseases) [ ] . who has recognised diet as one of the important determinants of health. the eat-lancet commission report has compared the food consumption patterns in india, from different income groups, regions and sectors (rural/urban), with the eat-lancet reference diet and highlighted the deviations [ ] . national sample survey office - data were used for comparison since this is the most recent countrywide data. except for the richest %, of indians, the average daily intake of calorie of indians was below the recommended kcal/capita/day. the consumption of fruits, vegetables legumes, meat, fish and eggs were significantly lower. the share of calories from protein sources was only - %, compared to % in reference diet. though the deficits were higher in the lowest decile of consumption expenditure, even the rich indian households do not consume adequate quantities of vegetables, fruits and noncereal protein foods. these findings are akin to those of the national nutrition monitoring bureau surveys in india, which show that the cereal-based indian diets are deficient in the consumption of micronutrient-rich foods like vegetables, fruits, legumes and animal products [ ] . thanks to schemes such as subsidised sale of rice and wheat to families below the poverty line (bpl), through the public distribution system, the consumption of traditional millets has also come down. millets are rich in fibre, many bcomplex vitamins and minerals. the predominantly cerealbased diets have resulted in rampant qualitative deficiency of micronutrients particularly, vitamins a, b , b , b , folic acid, c and minerals like iron, zinc and calcium. while calorie adequacy may ensure protein adequacy (though not protein quality), it most often fails to quench the hidden hunger. a recent study from the national institute of nutrition, hyderabad, india, shows a high prevalence of vitamin deficiencies, particularly, vitamins a, b , b , b , folic acid and vitamin d, assessed by subclinical status (blood values) and dietary intakes, in an apparently healthy urban adult population [ ] . the overall prevalence of anaemia was %. vitamin deficiencies as judged by blood levels were: vitamin a % (despite much higher dietary deficiency), d %; b %; b %; b %; folate % and active b %. vitamin d deficiency has become a major problem even in tropical countries. the dietary intake of all the vitamins except vitamins b and b were close to or lower than % of indian reference. that of vitamin b was only % and folate %. vitamin c was not examined. the study population had high incidence of overweight and obesity, and high levels of homocysteine-an independent risk factor for cardiovascular diseases for whose metabolism b vitamins like folic acid and b are required. this shows that even the apparently well-fed indians from middleincome group suffer from vitamin deficiencies. mineral status was not examined. the three basic strategies for combating micronutrient deficiencies are: (i) supplementation with micronutrients (the pharmacy-based approach), (ii) food fortification and (iii) dietary diversification-a farm-based approach [ ] . crop biofortification through conventional breeding, marker-assisted molecular breeding, or genetic engineering, is the technological approach to enrich the germ plasm with specific micronutrients [ , ] . this strategy is generally used to combat severe deficiency of one or two nutrients. india has two micronutrient supplementation programmes [ ] . ( ) national nutrition anaemia prophylaxis programme. in this programme, all pregnant and lactating women receive mg of elemental iron and µg of folic acid (ifa tablets daily) for at least days during pregnancy and days in post-partum period. preschool children receive mg of elemental iron plus µg of folic acid daily. due to administrative infirmities and lack of awareness regarding the importance of the programme desired results have not been obtained. education of the community to ensure compliance is very necessary for such programmes to succeed. in , the ministry of health and family welfare, india, launched the national iron plus initiative ( ). ( ) massive dose vitamin a supplementation programme to prevent nutrition blindness. in this programme, first dose of , iu of vitamin a is given to children at months of age along with measles vaccine. this is followed by biannual dose of , iu to children between the ages of and months. blindness due to vitamin a deficiency has become rare all over the world, but subclinical vitamin a deficiency (serum vitamin a < µg/dl) due to dietary deficiency persists. opinion among nutrition scientists in india is divided about the need for the vitamin a supplementation programme. its continuation is however needed at least in areas where signs and symptoms of vitamin a deficiency like night blindness and bitot spots persist. the ultimate effort should be to increase the dietary intake of vitamin a and its plant precursor β carotene. food fortification is done either to restore nutrients lost during processing or to enrich foods with nutrients. food fortification has been defined as 'addition of one or more essential nutrients to a food, whether or not it is normally contained in the food, for the purpose of preventing or correcting a demonstrated deficiency of one or more nutrients in the population or specific population groups' [ , ] . it is a convenient and relatively less expensive strategy with a wide outreach and has been used for nutrients like vitamins a, d and some b-complex vitamins and minerals like iron and zinc. the vehicle to be used for fortification should be a food that is consumed by large segments of population regardless of economic status including poorest of poor, and the bioavailability and stability of the fortified nutrients should be good. one of the successful programmes in india is salt fortified with iodine, which has now become a universal programme. the national institute of nutrition, hyderabad, india, has developed salt double fortified with iodine and iron. its use at present is limited. fat soluble vitamins are often added to oils. wheat flour is often fortified with minerals and b-complex vitamins, and who/fao has provided guidelines for it [ ] . fortifying oil with vitamins a and d is mandatory in many countries, including india. the subject of food-based approach including nutrition sensitive agriculture for better nutrition outcomes has been recently reviewed [ , [ ] [ ] [ ] . this review discusses some of the studies in india and other asian countries on nutritionally sensitive farming to combat micronutrient deficiencies. thanks to the green revolution, india has become selfsufficient in the production of cereals like wheat and rice [ ] . production of millets and pulses has however missed the green revolution, but in recent years this shortcoming is being corrected. india ranks among the top two countries in the world for production of milk (white revolution) and vegetables and fruits (rainbow revolution). even the egg production has gone up markedly. despite this, the dietary intake of these income-elastic foods remains low in all segments of population, particularly among the poor, due to lack of awareness regarding nutritional importance of these foods and high cost. even the farmer who produces them prefers to sell them rather than consume at home, because for resource poor farmers with small or marginal land holdings, income is more important than health and nutrition security. importance of income cannot be denied. behavioural change communication (bcc) is needed to stress the importance of dietary diversification to ensure food and nutrition security. high post-harvest losses add to the problem in developing countries, where facilities for cold storage, and processing are inadequate [ ] . agriculture is generally viewed as a source for income and export-at best to meet calorie and protein requirement. the problem of micronutrient deficiencies (hidden hunger) is not understood. unfortunately, the subject of human nutrition is not in the syllabus of agriculture universities, and hence agriculture extension workers fail to understand the need for leveraging agriculture for nutrition security. the subject of nutrition is also very weakly covered if at all in medical syllabus. one of the earliest studies on homestead vegetables and fruits gardening (term, used to indicate gardens next to the home or in farms) for micronutrient security was aimed at improving the intake of provitamin a, β carotene. it was conducted by the national institute of nutrition, hyderabad, india, in the villages of andhra pradesh, india, and the all india institute of hygiene and public health, calcutta, west bengal, india [ , ] . seeds and saplings of vegetables rich in β carotene (green leafy vegetables (glv), orange and yellow vegetables and fruits) were given to farmers and farmers advised to grow them near their home or in their farms. apart from technical knowhow about growing the plants, food and nutrition education was given. in both the centres there was marked increase in the number of families growing β carotene-rich vegetables and fruits, their consumption and improvement in understanding of the problem of vitamin a deficiency, foods rich in vitamin a and signs (bitot spots, xerophthalmia) and symptoms (night blindness) of vitamin a deficiency. calcutta centre reported reduction in the prevalence of bitot spots but in hyderabad centre the results were equivocal. there was some reduction in the common belief that pregnant women should avoid eating papaya since it causes abortion. hellen keller international has supported an extensive programme of improved homestead gardens and backyard poultry in bangladesh, cambodia, nepal and philippines to increase the production and household availability of micronutrient-dense vegetables and fruits and eggs. nutrition education formed an important part of the strategy [ ] [ ] [ ] [ ] . a significant increase in consumption of vegetables and eggs by mothers and children was recorded, mothers' knowledge of nutrition also improved. bangladesh and philippines observed reduction in the prevalence of anaemia. similar reduction was not seen in cambodia and nepal. families' income also showed some increase through sale of farm produce. ms swaminathan foundation in chennai, india, is currently exploring the food system for nutrition model in few villages of wardha district of vidarbha region of maharashtra, and koraput district of odisha, india [ ] [ ] [ ] . community nutrition gardens were also tested. the components of the model are: ( ) survey to identify the major nutritional problems, ( ) design context-specific suitable agricultural interventions to address the local nutritional problems, ( ) improve small farm productivity and profitability, ( ) undertake nutrition awareness programmes and build a cadre of hunger fighters and ( ) introduce monitoring systems for assessing impact on nutrition outcomes. location specific vegetables and fruits that are rich in mn are introduced in homestead gardens. professor m. s. swamiathan advocates genetic gardens for nutrition security [ ] . recent evaluation of the impact of this strategy on household food consumption showed remarkable increase in the monthly consumption of fruits and vegetables-frequency as well as quantity, as seen from a baseline survey in and end-line survey in of a sample of households in each location [ ] . though the authors mention, health and nutrition education as part of the intervention, no data on its impact are given in the sited paper. urban gardens for food and nutrition related outcomes are yet another promising strategy. it was recently reviewed in [ , ] . for nutrition security there has to be awareness and access at affordable cost to balanced diet and correct feeding practices (food security,) safe drinking water, disease-free environment and health care outreach. this will ensure absorption also. over the past two decades, the authors (msb and pvvsm) have tried to develop strategies for each of these in select villages of medak district in the south indian state of telangana (formerly part of andhra pradesh). (see www.dangoriatrust.org.in.) this narrative will be confined to the experience with homestead gardens and backyard poultry to enrich the household diet with micronutrient-rich foods. three studies have been conducted in different sets of villages of medak district in the south indian state of telangana (formerly andhra pradesh). the population of the selected villages ranged between and . most households had small or marginal landholding, own or leased. water source for farming was ground water-bore wells or rain-fed. though water stressed, paddy and sugarcane were the main crops. in dry season, maize or sorghum were grown. maize was sometimes intercropped with red gram (cajuns cajan). only few families raised vegetables. all the households were bpl and eligible for the indian government's subsidy schemes including subsidised food grains through public distribution system. most families belonged to the hindu backward class category. there were a few muslim households. some villages had tribal settlements called tandas attached to them. all households had proper houses, and access to bore well water. in the past few years, government has sponsored two-pit household latrine construction. so now most households have a latrine and claim to use it when asked. technological intervention was combined with robust, food, nutrition, sanitation and health education to bring about behavioural change [ ] [ ] [ ] . in the first study, march-april to march-april [ ] , villages from four mandals (geographical area) were included. all families interested to raise vegetable and fruit gardens were invited to join. in the subsequent two studies (march-april - , and september to april-may ) covering eight to ten villages (population about , - , ); families with pregnant women and preschool children were specifically targeted. however, a family approach was used, and husbands often came for training in farming and poultry technologies ( [ , ] and proceedings of ivth agricultural science congress, new delhi, india-under publication). seeds of a variety of glv (amaranth-amaranthus gangeticus; ambat chuka-rumex vesicarius; corrriander-coriandrum sativum; fenugreek-trigonella foenum-graecum; 'gogu'-hibiscus, cannabinus; spinach-spinacia oleracea), and other vegetables like broad beans-vicia faba; cluster beans-cyamopsis tetragonoloba; french beans-phaseolus vulgaris; tomatoes-lycopersicon esculentum; ladies finger (okhra)-abelmoschus esculentus and saplings of curry leaves-murraya koenigii; drumstick-moringa oleifera and malabar spinach (bachali)-basella alba were distributed to the target households. glv are very rich in all micronutrients, are easy to grow and need relatively less water. some variety or other can be grown throughout the year. beans are rich in proteins, besides micronutrients. they can fix nitrogen and enrich the soil with nitrogen. fruit plants like guava-psidium cattleyanum; mango-magnifera indica; papaya-carica papaya and lime-citrus aurantifolia were selectively given to families who had assured source of water and performed well. papaya and mangoes are rich in β carotene (provitamin a) and vitamin c and guava in vitamin c. farmers grew vegetables like brinjal (eggplant) and gourds out of choice. few households had one or two trees of plants like papaya, mangoes, guava, drumstick (moringa) and curry leaves prior to intervention. interested women were taught to raise saplings of plants like papaya, drumstick and bachali (basella alba, a creeper). the saplings were purchased from them for distribution. each woman raised - saplings, and earned some money. organic methods of farming like vermicomposting and botanical pesticides-decoction of chilli-garlic paste or neem seed, were also taught to reduce the use of chemical fertilisers and pesticides, mostly the latter. centralised meeting (at the dct campus) and decentralised meetings (hands-on training in the villages) were given. help from subject specialists in agriculture/horticulture was taken as resource persons for conducting the training programmes. cooking demonstrations to teach simple foods for complementary feeding were held by involving the mothers. since the literacy levels in mothers have gone up markedly in recent years, pamphlets with important messages in the local language telugu were distributed. even if the woman was illiterate, there was someone in the family who could read and explain. impact on acceptance of homestead gardens was done by keeping records of land diverted from traditional crops like paddy and sugarcane to vegetables and fruits, approximate quantum and variety grown and utilised-household consumption vs sale. families were specifically explained that the purpose of the project was household consumption of home-grown vegetables, particularly by women and children and not for sale. families were also encouraged to grow pulses and millets. improvement in understanding of food, nutrition, sanitation, child caring practices and health (some common infectious diseases-their cause and management) was assessed through initial and end-line knowledge, attitude and practice (kap) surveys of mothers with - -monthold children using pretested questionnaires. initial survey was done by the project staff and final survey by a local woman with proper training, to avoid investigator bias. household consumption of different foods (weekly frequency, and per capita per day consumption) was assessed by questioning the mothers about food consumed in a typical week when there were no guests and no feasting or fasting [ ] . in india, the integrated child development scheme (icds) facilitates preschool education, infant and child feeding and maintenance of records of birth weight and growth of preschool children. all villages above a population of have one or more icds centres called anganwadis, managed by a trained anganwadi workers. in the last two studies, birth weight and monthly growth records of children under years of age were examined to assess the impact on nutrition. initially less than % of the targeted households grew vegetables or fruits. at the end of the study, % of the households had diverted small bits of land (less than half acre) to growing of vegetables and fruits, despite small and marginal holdings. table gives data on crops grown, in the last quoted study as reported by the mothers in the kap survey. a marked increase in the number of households growing vegetables, pulses, maize and millets and a small reduction in households growing rice was reported. some of these changes in cropping patter may be seasonal effects since the initial survey was done in the month of september and final survey in summer-april-may. comparison of initial and end-line kap surveys showed remarkable improvement in mothers' knowledge (and hopefully practice) of balanced diet, nutrients in foods, causes and signs and symptoms of nutritional deficiencies, food taboos during pregnancy (avoid foods like papaya and banana), infant feeding practice (initiation of breast feeding, and feeding colostrum, age of introduction of complementary feeding), washing hands with soap and water (not just water), right cooking practices (washing vegetables before cutting, not discarding excess water after cooking rice-a common practice) and causes of common infectious diseases like diarrhoea, malaria, tuberculosis, jaundice and their management ( [ , ] and proceedings of ivth agricultural science congress, new delhi, india-under publication). in the first two studies, there was significant increase in the frequency [ , ] as well as daily per capita consumption [ ] of glv. similar significant improvement in the consumption of other vegetables was not seen. the homegrown vegetables replaced what was purchased from the market. however, in the first study where control nonintervention households from the same village were included for comparison [ ] , there was a marked decline in the consumption of vegetables in the control households over time due to sharp increase in market price of vegetables. this suggests that homestead production at least shields against escalating market price. monthly inquiries showed that about - % of home-grown vegetables other than glv were sold in the first study. 'for poor households, economic compulsions outweigh nutritional wisdom' [ ] . this trend decreased in the subsequent studies by reiterating the purpose of the study. in the last mentioned study, remarkable improvement in the consumption of glv as well as other vegetables was observed (proceedings of ivth agricultural science congress, new delhi, india-under publication) ( table ). very little was sold. the results of that study suggest that with sufficient advocacy, education and training, daily requirement of vegetables, particularly glv can be met from homestead gardens despite small and marginal holdings. some incentive like free distribution of seeds and saplings would help. this, however, will not ensure micronutrient security, unless the intake of pulses and animal products also goes up. in that study, some increase in milk consumption was also observed. this may be due to the government scheme of distributing buffaloes at highly subsidised rate. impact on birth weight and growth of children aged - months was assessed through the records maintained by the icds centres. in recent years, almost all deliveries are institutional. the aw worker maintains records of birth weight and monthly growth. scrutiny of these records over the study period was done in the second and third studies ( [ ] , under publication). no effect on mean birth weight was observed. the incidence of lbw was less than % compared to the national average of about %. the incidence of moderate and severe malnutrition (weight/age) showed marked decline from over % to about %. in both the studies, seasonal variation was seen with increase in undernutrition percentage during monsoon. this is a known phenomenon due to greater morbidity during monsoons. egg is one of the most wholesome foods. over the years the consumption of meat has come down in india, but that of eggs has gone up due to marked increase in commercial poultry farms [ , ] . commercial farms have largely benefitted urban areas. backyard poultry is an important option for rural areas, and widely adopted, with nondescript birds with low egg yields- - eggs per year. these birds are well acclimatised, have prominent brooding behaviour and mothering ability. in recent years, improved breeds of byp, which can lay - eggs per year, have been developed [ ] . unlike seeds and saplings, which were given free, poultry birds were sold after immunisation. families bought three birds and one was given free as incentive. proper night shelters had to be built to prevent predation. initially two improved breeds gramapriya developed by the project directorate, icar, hyderabad, and rajasri developed by aicp on poultry breeding, sri venakteshwara veterinary university, hyderabad, were introduced. more recently, older birds of rainbow rooster breed, purchased from indbro research and breeding farm, hyderabad, are being distributed. in all the projects, the frequency per week of egg consumption by the families initially was less than . per capita per week consumption was also less than eggs. subsequent to the introduction of the byp with high eggyielding birds there was significant improvement. thus in the two projects, the weekly frequency of egg consumption increased by % and %, respectively. per capita number of eggs consumed per week increased by % and %, respectively, [ ] [ ] [ ] . to facilitate wider dissemination of the model of nutritionally sensitive and environmentally sustainable farming, and backyard poultry (with high egg-yielding birds), along with bcc in the area of, food, nutrition, sanitation and health developed in the earlier projects, dct has set up a rural hub. this project was initiated in september , with financial support from tata, lock heed martin aero structures ltd., hyderabad, under their corporate social responsibility-csr for a period of year. it was further continued with financial support of dangoria charitable trust. the design is to target five villages with a total population of eight to ten thousand, over a period of months. after a month of planning and initial kap survey of mothers with children under years of age, on aspects of food, nutrition, sanitation and health (as described earlier), four centralised training programmes on topics such as maternal and child health and nutrition; nutrition gardens; backyard poultry and food processing are conducted each month for months. decentralised hands on training are also given. an end-line kap survey is conducted in the sixth month. like in the earlier projects, pregnant women and mothers with children under years of age are the main target. for sustainability the anganwadi workers and accredited social health activists from the villages are involved in the training. planting material for raising gardens is given free to families with a pregnant woman and children under years. high egg-yielding poultry are given to all interested families. families buy at least four to five birds. hitherto two sets of five villages have been covered. impact is assessed from the number of families that have started growing vegetables, acceptance of byp and improvement in mothers' knowledge of food, nutrition, child feeding practices, health etc. as judged from initial and end-line kap, surveys as described in the earlier longer duration studies. all the families (except three families in the initial survey) had own land. the three families also had leased land. but the holdings were marginal- - acres. farming and farm labour (working on each other's' farms) was the main occupation. all the women were literate and % had studied beyond fifth standard. some women had studied up to intermediate. table (second set of five villages) show significant increase in the percentage of households growing vegetables at the end of months. some increase in the number of households having byp was also seen. there was remarkable improvement in the mothers' knowledge of food consumption during pregnancy, reduction in pregnancy associated food taboos, infant and child feeding practices, healthy cooking practices and components of a balanced diet. improvement in knowledge of-nutrients in foods, functions of different nutrients was weak though majority did mention foods rich in vitamin a in the end-line survey. understanding of the cause and management of diseases like diarrhoea (contaminated food and water), malaria (mosquito bite), tuberculosis (through cough) and jaundice (contaminated food and water) showed significant increase. over the years, there has been remarkable increase in women's literacy, antenatal check-ups, institutional deliveries (home deliveries are very rare) and immunisation coverage, in the villages of medak district where the authors work. the path from agriculture to nutrition is generally assumed to go via agriculture income. important as income is; income alone cannot ensure dietary diversification unless the community is educated about the importance a balanced diet, and nutrition, for health and productivity. emphasis of agriculture is generally on providing calories to quench hunger and at best proteins. this tends to be achieved through cereals and some legumes. hidden hunger remains hidden from the vision of not only people but also planners and policy makers. nutritionally sensitive and environmentally sustainable agriculture is a more holistic approach, in a country like india where agriculture is the main occupation of more than % of the households. generally farmers are reluctant to deviate from traditional cropping pattern. yet the studies of the authors and others discussed in this paper show that even small and marginal farmers can be persuaded to diversify into raising homestead gardens of micronutrientdense vegetables and fruits by combining social engineering with technological engineering. some incentive like giving free planting martial helps. since most poor rural women work in fields or go for labour work, they were given money for travel and lunch was served, when they came for the centralised meetings to compensate for the lost wage for the day. as mentioned earlier, homestead gardens may be able to supply vegetables to meet the household requirement, but that alone will not be sufficient to meet the requirement of micronutrients. inclusion of pulses, millets and animal husbandry along with horticulture should be attempted. the authors did advise about growing pulses and millets, and gave seeds of finger millet and iron fortified pearl millet to interested households. small but significant improvement in consumption of millets was seen ( table ). pulse consumption did not show any increase. introduction of poultry did help in increasing egg consumption. in the long duration projects ( years), many families set up vermicompost beds. incentive by way of earth worms was given. only few families used botanical pesticides. the remarkable improvement in the mothers' knowledge of food, nutrition, infant and child feeding practices, sanitation and common communicable diseases, with education, is very gratifying since an informed mother is an empowered mother, and can make a lot of difference to the family's diet, nutrition and health. involving the local health functionaries also helps sustainability. all community-based technological interventions should have robust educational component so that the community understands the importance of the technological intervention. nutrition gardens have recently caught the imagination and attention of many state governments and ngos in india. suri has summarised some of these unpublished initiatives [ ] . this movement needs to gain momentum with a robust information, education and training strategy. the current swatch bharat clean india programme in india will hopefully complement this effort in reducing malnutrition. homestead production of diverse foods to ensure dietary diversity assumes particular significance under the present pandemic of coronavirus, when the mobility of humans and material has become highly restricted. adverse impact on nutrition of not only the traditionally poor people but also low middle income groups slipping into poverty and malnutrition is feared. micronutrients have been shown to stimulate immunity and thus protect against viral diseases [ , ] . to mitigate deficiency, supplementation with immunity stimulating micronutrients has been recommended since a balanced diet cannot be assured [ ] . fetal origins of adult disease comparison of the indian diet with the eat-lancet reference diet diet and nutrition status of rural population, prevalence of hypertension & diabetes among adults and infant & young child feeding practices prevalence of vitamin deficiencies in an apparently healthy urban adult population: assessed by subclinical status and dietary intakes chapter : the challenge of hidden hungermicronutrient deficiencies world health organisation/food and agriculture organisation of un improving nutrition through biofortification: a review of evidence from harvest plus national programmes to improve food security and nutritional status micronutrient fortification of food: technology and quality control food fortification-principles and application combating micronutrient deficiencies: food based approaches. rome: fao and cab international nutrition sensitive agriculture to achieve better nutritional outcomes food based approach to combat micronutrient deficiencies dynamics of food consumption and nutrient security in, india home gardening for combating vitamin a deficiency in rural india food-based strategies to control vitamin a deficiency impact of homestead gardening program on household food security and empowerment of women in bangladesh improving diet quality and micronutrient nutrition food security through homestead vegetable production in the smallholder agricultural improvement project (saip) area homestead food production model contributes to improved household food security and nutrition status of young children and women in poor populations a farming system model to leverage agriculture for nutritional outcomes operationalising the concept of farming system for nutrition, through the promotion of nutrition-sensitive agriculture establishing agriculture-nutrition programme to diversify household food and diets in rural india improving household diet diversity through promotion of nutrition gardens in india the impact of urban gardens on adequate and healthy food: a systematic review diversification from agriculture to nutritionally and environmentally promotive horticulture in a dry-land area impact of enriching the diet of women and children through health and nutrition education, introduction of homestead gardens and backyard poultry in rural india promotion of backyard poultry for augmenting egg consumption in rural households poultry food security and poverty in india: looking beyond the farm gate new delhi: ministry of agriculture nutrition gardens: a sustainable model for food security and diversity. orf issue brief no. . observer research foundation optimal nutritional status for a well-functioning immune system is an important factor to fight against viral infections the role of nutrition in the immune system: should we pay more attention acknowledgements the technical support for the studies conducted by the dangoria charitable trust was provided by n. venkatesh (agriculture and horticulture), p. pentiah (poultry) and k. v. lakshmi conflict of interest the authors declare that they have no conflict of interest. also, the little bit of unpublished recent research reported is original.publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. key: cord- -urh xk r authors: singh, vikas; singh, shweta; biswal, akash title: exceedances and trends of particulate matter (pm . ) in five indian megacities date: - - journal: sci total environ doi: . /j.scitotenv. . sha: doc_id: cord_uid: urh xk r abstract fine particulate matter (pm . ) is the leading environmental risk factor that requires regular monitoring and analysis for effective air quality management. this work presents the variability, trend, and exceedance analysis of pm . measured at us embassy and consulate in five indian megacities (chennai, kolkata, hyderabad, mumbai, and new delhi) for six years ( – ). among all cities, delhi is found to be the most polluted city followed by kolkata, mumbai, hyderabad, and chennai. the trend analysis for six years for five megacities suggests a statistically significant decreasing trend ranging from . to . μg/m ( %– %) per year. distinct diurnal, seasonal, and monthly variations are observed in the five cities due to the different site locations and local meteorology. all cities show the highest and lowest concentrations in the winter and monsoon months respectively except for chennai which observed the lowest levels in april. all the cities consistently show morning peaks (~ : – : h) and the lowest level in late afternoon hours (~ : – : h). we found that the pm . levels in the cities exceed who standards and indian naaqs for % and % of days in a year except for chennai. delhi is found to have more than days of exceedances in a year and experiences an average number of episodes per year when the level exceeds the indian naaqs. the trends in the exceedance with a varying threshold ( – μg/m ) suggest that not only is the annual mean pm . decreasing in delhi but also the number of exceedances is decreasing. this decrease can be attributed to the recent policies and regulations implemented in delhi and other cities for the abatement of air pollution. however, stricter compliance of the national clean air program (ncap) policies can further accelerate the reduction of the pollution levels. air quality in megacities is a major concern for human health where a large portion of the population lives, and the pollution levels often exceed the limit values (kumar et al., ; zheng et al., ) . among all pollutants, pm . (particles less than . micrometers in diameter) poses a greater risk as it can penetrate deep into the human body (xing et al., ) . it has been estimated that exposure to outdoor pm . is the fifth leading risk factor worldwide and the third leading risk factor in india (gbd risk factors collaborators, . globally, exposure to pm . accounts for . million deaths and over million disability-adjusted life-years in (gbd risk factors collaborators, . a growing number of epidemiological evidence of acute and chronic impacts of pm . on human health, besides its role in perturbing weather and climate (fuzzi et al., ) , has led the scientific community to monitor levels of pm widely across urban, suburban and rural regions of different countries in the last decade. however, inter-comparison of these results is not always possible either because of the difference in sampling or monitoring instrument or due to different sampling duration. this requires a sampling network that works on one principle with large spatial coverage. in recent times, united states environment protection agency (us-epa) has come up with pm . monitoring at the u.s. embassy and consulates (usec) in various countries using federal equivalent method (fem) approved instrument beta attenuation monitor (bam-metone ) and is providing hourly measurements of pm . in countries of the world. this usec data has been used for the study of pm . levels in the urban environment for different purposes viz; to study the trend and characteristics of pm . ( chen et al., ; fontes et al., ; sreekanth et al., ; liang et al., ; batterman et al., ; san martini et al., ) , to compare with other data and model evaluation (jiang et al., ; li, figure . open street maps of the km × km area surrounding the embassy/consulates (red circle) to show the geographical location of the five indian megacities (a. chennai, b. kolkata, c. hyderabad, d. mumbai, e. new delhi) . while meteorology plays an important role in controlling the air quality, the local emission sources mainly household and traffic emissions (singh et al., a) the pm . concentrations across all the sites are monitored in real-time using fem bam- , having a standard range of - µg m - , resolution of ± . µg m - and h average lower detection limit less than . µg m - , and the data is processed using a common quality control protocol defined by usepa (ray & vaughn, ) . however, we find that there are still negative values with valid flag and outliers (sudden spikes) present in the data set. therefore, we have further processed a quality control check to remove the outliers. any data point which is more than three local scaled median absolute deviations (mad) from the local median of the data within a running window of hours has been considered as an outlier. as the modern-era retrospective analysis for research and applications, version (merra- ) hourly surface reanalysis meteorological products from january to december has been obtained from nasa's global modeling and assimilation office (gmao). these products are available at a horizontal resolution of . °× . ° (https://gmao.gsfc.nasa.gov/reanalysis/merra- /). details of the merra- products and evaluation has been reported by gelaro et al., ( ) , randles et al., ( ) and . the hourly meteorological data (wind, temperature, precipitation, planetary boundary layer height-pblh) have been extracted from the corresponding grids of the latitude and the longitude of the five megacities (supplementary table the air quality data has been analyzed from to . we have used seasonal trend decomposition procedure based on loess (locally weighted scatterplot smoothing) smoothing (stl) (cleveland et al., ) to estimate the trend in pm . as adopted by bigi and ghermandi ( ) to study the trend in pm . in the po valley, italy. stl is a widely used filtering procedure for decomposing time series into three components: trend, seasonal, and remainder or residual. the decomposition is based on a sequence of smoothing procedures using a locally weighted regression known as loess (cleveland et al. ). the loess smoother is based on fitting a weighted polynomial regression for a given time of observation, where weights decrease with distance from the nearest neighbor. time-series of monthly mean pm . concentration at all five megacities were decomposed in trend, seasonal, and remainder components using stl procedure (cleveland et al., ) . as the pm . data is not normally distributed (supplementary figure ) , time-series data were log-transformed before stl decomposition to attain normally distributed residuals and to control heteroscedasticity. time-series data were back-transformed from logarithmic decomposed data to analyse the trend. a significant slope in the monthly trend component was calculated using generalized least squares (gls) regression (brockwell and davis, ) for each site within a % confidence interval (ci) with a significance level (alpha= . ). gls is used to j o u r n a l p r e -p r o o f journal pre-proof estimate the linear relation between an autocorrelated time series and time to obtain independent residuals and a correct estimate of the variance of the regression coefficients. stl and gls analysis were performed using r software. exceedance analysis has been performed and the number of threshold exceedances has been calculated by keeping the threshold of daily mean pm . equal to µg/m and µg/m as per naaqs (cpcb, ) and who (who, ) standards respectively. the linear trend (singh et al., b) in the annual exceedances in six years has been calculated for each site within % confidence interval (ci) with a significance level (alpha= . ) because of the small sample size (labovitz, ) . we have also calculated the number of pollution episodes and the length of each episode. an episode has been considered when the daily mean pm . has exceeded continuously for three or more days. the variation in the pm . levels for a location is an interplay of emissions, geography, and meteorological conditions (alimissis et al., ; ganguly et al., ; nair et al., ) . previously, the diurnal and seasonal variations have been reported for five cities for the period of fewer than four years - by sreekanth et al. ( ) and for four cities excluding kolkata for four years ( - ) by chen et al. ( ) . however, these studies did not discuss the trend in the pm . . various pollution mitigation schemes along with the public awareness programs (ncap, moefcc, ) have been implemented in india since the availability of the usec data. therefore, we analysed the data for a longer period of six years for all available usec sites in india to study the trend, exceedance and variations in details. the diurnal variation of pm . for chennai, kolkata, hyderabad, mumbai, and new delhi is presented in figure all the cities consistently show morning peaks around (~ : - : hrs). a shift of up to two hours in the morning peak hours is due to the season and the geographical location. for a city, the winter peak appears at a later hour of the day than the summer peak hour because of late sunrise and onset of human activities in winter. among all, the cities located in the eastern side of india (kolkata, chennai, and hyderabad) show a peak around an hour earlier than the cities located further west (delhi and mumbai) because of the early sunrise and human activities in the eastern cities. the cities hyderabad and chennai show a sharp peak during morning traffic hours, whereas the same is not true for new delhi, mumbai, and kolkata. the higher levels of pm . during nighttime leads to a smaller peak during morning traffic peak hours. a similar study carried out by chen et al. ( ) has attributed this to the higher population of mumbai and new delhi. this may not be the sole reason as the population of hyderabad and chennai are also large enough to enhance the nighttime emissions. the traffic sources in the vicinity of the monitoring station ( figure ) along with the local meteorology may be responsible for the sharp peak during the morning hours. the morning peak is attributed to the morning fumigation effect after the sunrise (stull, ; nair et al. ), along with morning traffic and household emissions (tiwari et al., b) trapped within the evolving shallow boundary layer. the diurnal peak of pm . occurs in the morning hours for all the cities except for kolkata where the peak pm . is found at midnight. for kolkata, a similar variation in bc has been reported by talukdar et al. ( ) who have also shown the highest peak for bc during midnight rather than morning traffic peak time. this could be due to the late evening household emissions. moreover, higher wind prevalence in the day time on account of stronger sea breeze during the early morning to afternoon as compared to the other periods of the day (gururaja et al., ) can also explain the lower concentration in the day time as compared to the night in kolkata. we also calculated the ratio of the highest to the lowest monthly mean pm . concentration for a city to know the extent of the variability within a year. as the highest pollution levels are found in winter and lowest in monsoon, it can also be considered as the most polluted to the cleanest ratio. this ratio is found to be high for kolkata ( . ) and delhi ( . ) followed by mumbai ( . ), hyderabad ( . ), and chennai ( . ). this suggests that for kolkata and delhi, the winter months pm . levels can be times higher than the monsoon levels. journal pre-proof here we utilize the usec pm . data to calculate the annual trend with the monthly mean pm . across all five indian cities for six years. monthly mean pm . time series at all five locations were decomposed in trend, seasonal and remainder components using stl procedure and the slope in the trend component was calculated using gls. stl decomposition of the monthly mean pm . along with gls fitted models for the five cities are shown in figure . the equation shown in the figure depicts the gls linear regression slope with % ci and the same has been shown in table . as can be seen from figure , all the cities show a significant decline (negative) trend ranging from . to . µg/m per year. the highest decline trend of . ± . µg/m per year was found for new delhi whereas we have also checked whether the trend in the pm . is affected by trend in the meteorological parameters such as wind speed, pblh, and precipitation during the six years. these meteorological parameters are obtained from merra- reanalysis and have been validated (supplementary table ) against the surface observations at the airports. the trend in the meteorological parameters has been calculated in the same way as it was done for pm . . the calculated trend in wind speed, temperature, pblh, and annual precipitation is shown in supplementary figure . it is found that wind speed, temperature, pblh and precipitation do not exhibit a significant change during the study period. therefore, this analysis confirms that the reduction in pm . is not due the meteorology but due to the reduction in emissions. various pollution mitigation schemes along with the public awareness programs (ncap, moefcc, ), could have led to the reduction of pm . levels in delhi. j o u r n a l p r e -p r o o f air quality standards, guidelines, objectives, targets, and limit values are defined by the local authorities to control air pollution. the levels below the standard or limit value are (bran & srivastava, ) for the year found pm . mass concentration - times higher than indian naaqs and who standards. moreover, remote sensing based study by dey et al. ( ) has shown that % of the indian population is exposed to the levels that exceed the who annual air quality threshold of μg/m . the chemical composition of pm . offers vital information on the contributions of specific sources and help to understand aerosol properties and processes. pm . chemical components have been found to vary considerably among different sites across the globe (snider et al., ) . global population-weighted pm . concentrations were dominated by particulate organic mass, secondary, mineral dust as well as secondary inorganic aerosols such as sulfates, nitrates and ammonium (philip et al., ) . in addition to the observed trend of pm . , it is also important to know the variability and trend in the chemical composition. the relation between pm . exposure and associated health effects is linked with physical and chemical characteristics of the pm . , and therefore requires attention along with its sources for better management of urban air pollution (braziewicz et al., ; srimuruganandan and nagendra, ) . however, the unavailability of long-term chemical composition records restricts the detailed analysis of the possible sources. moreover, one can conduct modelling analysis of pm . composition but it is considerably challenging because of the combination of uncertainties in the magnitude and spatial and temporal allocation of primary pm . emissions and our limited understanding of the chemical production pathways for secondary constituents (mathur et al., , appel et al., were observed to be highest during winter followed by post monsoon>summer>monsoon (jain et al., ; kota et al., , sharma and pant et al., ) , so − was reported to be most abundant during summer followed by monsoon>post monsoon>winter (jain et al., ; pant et al., ) . secondary no − is thermally unstable at higher j o u r n a l p r e -p r o o f journal pre-proof temperatures whereas at low temperatures during winter its formation is favorable (cesari et al., ) . higher photochemical activities during the summer season and high humid conditions during monsoon favors the formation of secondary so − (jain et al., ; goel et al., , pant et al., . while na + is observed highest during monsoon owing to its sea origin (jain et al., ; saxena et al., ) , cl − is also significantly linked with wood combustion, open waste burning, coal combustion and industries (rai et al., ; ali et al., ; pant et al., ) , and therefore is observed highest during winter sharma and mandal, ; jain et al., ; sharma et al., ; ) along with the biomass burning marker ion k + (sudheer et al., ; tiwari et al., a) . organic components of pm . like levoglucosan has been linked with biomass burning in winter (pant et al., ) . pahs, linked with biomass burning and road transport, showed the highest concentration during winter, followed by post monsoon> summer>monsoon (gadi et al., ; singh et al., ) . ec and oc which are emitted from vehicular emissions and biomass burning (ram and sarin, ; sharma et al., ) are reported to be higher during winter than summer (jain et al., ; sharma and mandal ; tiwari et al., ) . elemental contribution analysis showed the higher contribution of road dust and soil (marked with higher si value) during summer whereas for the winter season, the contribution of biomass burning was high (marked with higher k value) saxena et al., ; jain et al., ; pant et al., ) . for kolkata, roughly % of the pm . mass was reported to be constituted of ions (na + , k + , mg + , ca + , nh + , so − , no − , cl − ) and carbonaceous particles (ec, oc) (chatterjee et al., ) . higher concentrations of nh + , so − , and no − were observed during winter than summer, however, the so − oxidation ratio, which is an indicator of secondary so − formation, was found to be highest during summer months. kolkata showed the highest na + during monsoon, whereas higher cl − was observed during dry seasons (chatterjee et al., ) and were linked with biomass and coal burning. ec and oc for kolkata as well showed the highest levels during winter, followed by summer and lowest in monsoon (chatterjee et al., ; talukdar et al., ) . for mumbai, the major chemical constituents observed were ions (na + , k + , ca + , nh + , so − , no − , cl − ) and carbonaceous particles (ec, oc) and some trace and heavy metals. while secondary ions (nh + , so − , and no − ), ec and oc were observed higher either during winter or post-monsoon season owing to inland contribution. non-sea salt sources were of anthropogenic origin (joseph et al., ) . elemental analysis showed a significant contribution of the sea during monsoon, and soil dust j o u r n a l p r e -p r o o f journal pre-proof during the summer season (police et al, ) . for hyderabad, the studied chemical constituents were ec and oc (ali et al., ) . while both ec and oc showed the highest winter concentration than during summer, followed by the monsoon, the concentration variation during winter to summer transition for the two carbonaceous fractions is quite different. ec showed a significant decrease during the transition of winter to summer, the same was not true for oc as secondary organic carbon formation and biomass burning added to the total oc levels during summer. elemental analysis showed the importance of sources like resuspended dust and vehicular emission for the city (gummeneni et al., ) . for chennai, the reported chemical constituents of pm . were ions (na + , k + , ca + , mg + nh + , so − , no − no − , cl − , f − ) and some trace and heavy metals (jose et al., ; srimuruganandam and nagendra, showed higher concentration during monsoon, followed by summer>winter (srimuruganandam and nagendra, ) . marine aerosols showed a significant contribution for the coastal city (jose et al., ) . we also performed the five days backward trajectories analysis using the hybrid single particle lagrangian integrated trajectory (hysplit version ) model (stein et al., ; draxler and rolph, ) major sources of primary pm . in india are emissions from the household, power sector, industries, transport, open burning (crop and waste) and dust (conibear et al., ; guo et al., ; venkataraman et al., ) . although the household emissions are dominant across india (apte and pant, ) , vehicular exhaust and dust resuspension (singh et al., a) remain the dominant local source in indian cities (guttikunda et al., . other urban sources include construction dust, industrial exhaust, and domestic cooking and heating . most of the sources of pm . in urban areas are local, however nonlocal contribution can be significant guo et al., ) . for eg.in delhi, local sources contribute ~ % of total pm . , but the non-local sources contribute over % especially in winter (guo et al., ) . the emissions neighboring rural areas, contribute to the urban pollution in india ravindra et al., a; b) . rural households in india rely on kerosene for light in the absence of electricity, and on wood, j o u r n a l p r e -p r o o f journal pre-proof dung, and other solid fuels for cooking and heating. (chowdhury et al., , ravindra et al., c . use of these fuels emit particles, gaseous pollutants, and volatile organic compounds, and therefore are a significant source of secondary particulate matter in both rural and urban areas (pervez et al., ; rooney et al., ) . in addition to household and traffic emissions, open waste burning is also a significant contributor to the total pm . in indian cities kumari et al., ) . the open waste burning is prevalent during winter and over the urban areas with low socioeconomic status (nagpure et al., ) . other sources that determine the urban pm . levels include industries, thermal power plant, brick production, and use of diesel generator sets, however, the influence of these sources is highly variable . future emissions scenario studies conducted over india predict an increase in pm . (venkataraman et al., ; pommier et al., ) , however studies (chowdhury et al., ; purohit et al., ; venkataraman et al., ; conibear et al., ; bhanarkar et al., ) have shown that significant reduction in pm . is achievable by implementation strict measures to reduce the pm . emissions. it has been shown by chowdhury et al., ( ) that a transition from bad fuel to clean fuel in the household has the potential to significantly reduce the pm . levels at the national level. however, at the urban or city level, where cleaner fuel is used, reduction in vehicular emissions (exhaust and non-exhaust) can bring down the pm . levels as observed during the covid lockdown in indian cities and significantly reduce the traffic exposure (singh et al., b) . we propose that the reduction in pm . levels across the cities is due to the recent measures taken to reduce the ambient pollution levels in india. the major recent initiatives that might have helped in the reduction include the launch of the national air quality index (aqi) for public awareness, the formation of environment pollution (prevention and control) authority, implementation of a graded response action plan (grap) and comprehensive action plan lpg is lower than that of solid fuel (deepthi et al., ) , the implementation of pmuy across india would have reduced pm . levels mainly at the regional level (chowdhury et al., ) . however, people's attitudes towards fuel usage may lessen the expected reduction in emission linked with this switch to cleaner fuel usage as solid fuels are much cheaper and easily available (ravindra et al., c) . although waste management is a major challenge (kumar et al., ) , a major step to improve the door-to-door waste collection and disposal as a part of swachh bharat mission (swachhbharatmission.gov.in; ghosh, ) in urban areas could have resulted in the improvement in air quality. for the reduction of traffic exhaust emissions, the emission standard of the fleet was improved to bs-iv from april and bs-vi was scheduled from april . the old fleet scrappage program was launched, and electric vehicles are being promoted. apart from this, shifting to alternate cleaner fuels like cng, ethanol blending in petrol are some of the steps taken for the cleaner transport sector. moreover, the use of a modern public transport system was promoted in recent years to reduce traffic emissions. while these measures reduce the exhaust emissions, the maximum reduction is expected in road dust resuspension emission by regular road dust cleaning by mechanized vacuum dust cleaners (goyal et al., ; gulia et al., ) . other measures include dust control from the building and road construction activities. the stringent measures to limit the crop residue burning. this study reports a detailed analysis of the variabilities and trends in the pm . concentration measured at the us embassy and consulates in the five megacities (chennai, kolkata, analysis of merra- meteorological parameters suggests no significant change in the annual mean wind speed, temperature, pblh, and precipitation in the past six years. despite that, pm . has been found to exhibit a declining trend. we have also reported the number of threshold exceedances of daily mean pm . as per the who ( µg/m ) and indian naaqs ( µg/m ). in addition, the number of pollution episodes and length of each episode (levels above limit values continuously for three or more days) has been reported. we found that the pm . levels in the cities exceed who standards for more than % of days in a year with a few exceptional years in chennai. j o u r n a l p r e -p r o o f so far, we have not come across any study that has suggested a significant decline trend in air quality in indian cities despite the measures by the local authorities. this is the first study, to the best of our knowledge, that has reported statically significant decreasing trends of pm . in indian megacities. this decrease can be attributed to the recent policies and regulations (ncap, moefcc, ) implemented in delhi and other cities for the abatement of air pollution. the implementation of source sector-specific measures related to vehicular emissions, road dust re-suspension and other fugitive emissions, bio-mass/ municipal solid waste (msw) burning, industrial pollution, construction, and demolition activities, etc. were the major steps towards the mitigation of air pollution. the mitigation measures implemented until june were expected to deliver an overall decline of ambient pm . despite economic growth (purohit et al., ) . while a reduction in pm . is found in delhi, it continues to be the most polluted city among five megacities. with the annual rate of reduction observed here, it may take another two decades for the pollution levels to come within indian naaqs levels. therefore, stricter compliance of the ncap policies can further accelerate the reduction of the pollution levels to reduce the health impacts across all india. the results 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india: influence of meteorology characteristics of absorbing aerosols during winter foggy period over the national capital region of delhi: impact of planetary boundary layer dynamics and solar radiation flux record heavy pm . air pollution over china the association between pm . exposure and daily outpatient visits for allergic rhinitis: evidence from a seriously air-polluted environment three-year, km resolution china pm . simulation: model performance evaluation the ion chemistry and the source of pm . aerosol in beijing who global ambient air quality database (update who air quality guidelines for particulate matter, ozone, nitrogen dioxide and sulfur dioxide, global update the impact of pm . on the human respiratory system comparison of ground-based pm . and pm concentrations in china, india, and the us on the association between outdoor pm . concentration and the seasonality of tuberculosis for beijing and the authors are thankful to the national atmospheric research laboratory (narl) andministry of earth sciences (moes) for providing the necessary support. we acknowledge key: cord- -q egnpaq authors: singh, ashish kumar; agrawal, bharti; sharma, anukriti; sharma, prayas title: covid‐ : assessment of knowledge and awareness in indian society date: - - journal: j public aff doi: . /pa. sha: doc_id: cord_uid: q egnpaq covid‐ , which was initiated regionally at wuhan of china, has become a global pandemic by infecting people of almost all the world. human civilizations are facing threat for their survival and livelihood. no country are getting any substantial relief and solution from this pandemic rather to convince their citizens to make aware and taking precaution by changing their living style. in view of this, this study attempted to assess the awareness, threat, symptoms and its prevention among people of india about the covid‐ . a total of responses from all over india were received. the respondents have adequate awareness for covid‐ outbreak and its preventive measures, out of total, % ( ) answered that the virus spreads from one person to another, % ( ) answered that the disease is caused by a virus. peoples understand the importance of social distancing and other preventive measures prescribed by the government with good attitude for coronavirus. peoples are following trusted sources for corona information, having confidence to defeat disease but showed their concern for corona threat, are aware about the virus, its common symptoms and prevention, govt. testing and medical facilities. principal component analysis was used to identify the latent dimensions regarding people's preventive measures and was found that they are majorly adopting three methods, that is, lockdown, naturopathy and social distancing. this study will help government and peoples to understand and handle this coronavirus pandemic effectively and in prevention of covid‐ , which is crucial for the awareness of society in coming time. covid- , which was initiated regionally at wuhan of china, has become a global pandemic by infecting people of almost all the world. human civilizations are facing threat for their survival and livelihood. no country are getting any substantial relief and solution from this pandemic rather to convince their citizens to make aware and taking precaution by changing their living style. in view of this, this study attempted to assess the awareness, threat, symptoms and its prevention among people of india about the covid- . a total of responses from all over india were received. the respondents have adequate awareness for covid- outbreak and its preventive measures, out of total, % ( ) answered that the virus spreads from one person to another, % ( ) answered that the disease is caused by a virus. peoples understand the importance of social distancing and other preventive measures prescribed by the government with good attitude for coronavirus. peoples are following trusted sources for corona information, having confidence to defeat disease but showed their concern for corona threat, are aware about the virus, its common symptoms and prevention, govt. testing and medical facilities. principal component analysis was used to identify the latent dimensions regarding people's preventive measures and was found that they are majorly adopting three methods, that is, lockdown, naturopathy and social distancing. this study will help government and peoples to understand and handle this coronavirus pandemic effectively and in prevention of covid- , which is crucial for the awareness of society in coming time. covid- started from one city of china in december , but in a short span of time, it covered almost all over the world (who, b) . nearly countries of the whole world are struggling for their civilization and livelihood against the coronavirus pandemic. on january , , china declared first death of their years old citizen due to covid- , who was exposed to the seafood market (who, b) , but now death reached exponentially to , on th may (who, a). on february , , who announced this coronavirus disease as covid- (who, c) and pandemic on march , , after reaching the virus infection to countries across the world. covid- and sars coronavirus are similar and because it is becoming a big threat to human civilization as consequences, online awareness programs were initiated and conducted worldwide by who ( c) . proper strategies and funds were set up by who globally to protect the countries with special focus to poor and weaker health infrastructure developing countries. the aim was to reduce the virus communication in society, dissemination of crucial information, providing proper healthcare and to minimize social and economical loss. who also focused on establishing an easy and effective diagnostic system to prevent infection (who c). to prevent the infection socially, the lockdown was imposed globally, which resulted in the halt of all economic and social activity in society. this led to cease global supply chains badly resulting in the global economy in bad shape (ebrahim, ahmed, gozzer, schlagenhauf, & memish, ) . in india, the central government also imposed a nationwide lockdown for the first time on march , and continued it up to till date, that is, on may , . all transport, manufacturing, hotel industry, educational sector, service industry and so forth were closed immediately, people were left to remain as to where they were at the time of lockdown announcement and during lockdown people started working from home, school and colleges classes are running online, a large number of people shifted on a digital platform (mccloskey et al., covid- (who, c) . on the counterpart, our indian government is also making aware of the people by disseminating information through various reliable sources and providing medical facilities and trying to reduce the losses due to coronavirus. but, in india, we have a very huge dense population without well-established medical facilities, which is a matter of concern sohrabi et al. there is very little research in india covering the above factors, so this study is crucial for planning and adopting the preventive measures by public and government officials during this pandemic. hence, this study will help in future to design necessary strategies in indian society to fight against viruses. our study was cross-sectional, carried out by a convenience, nonprobability sampling technique in india. we adopted this sampling because, due to movement constraints during a lockdown, it was impossible to approach a common man in the population. this technique of convenience sampling, which is a nonprobability sampling technique, allows researchers to select respondents directly from the population as per their convenience. this technique was costeffective and time-saving. researchers choose these samples just because they are easy to fix, approach and train. a semistructured questionnaire was developed in straightforward, understandable english by using google form. the questionnaire was disseminated to known through whatsapp, e-mails and other social media platforms. the participants showed enough interest in giving their responses and forwarded it to their contacts, which resulted in getting responses from all over the country. participants who possess smartphones with internet connectivity have participated in this study, which is very common in modern society. participants above years and comfortable in english filled the response with willingness. total, we received responses, but some were filled incomplete, so we eliminated them. finally, we analyzed responses to draw our results. the respondents' sociodemographic profile was accessed by a questionnaire, which includes gender, age, education, place of residence, domicile, marital status and so forth. the questionnaire used for the survey have a separate section to know how they commute and interact to peoples, what are their trusted source of information, two questions were to evaluate the threat level of virus, one dichotomous question for awareness about health facility, six questions to estimate awareness level of coronavirus in society, questions for accessing symptoms, questions for perception about prevention from coronavirus. the process of data collection was held from april , to april , . factor analysis with principal component analysis was used to describe the unobserved underlying latent variables with observed variables (items) of prevention methods adopted by people for coronavirus. bartlett's test of sphericity was used to check interdependency among the items and kmo (kaiser-meyer-olkin measure of sampling adequacy) was used to inspect the sample sufficiency (kaiser, ) . the criterion of eigenvalue > with factor loading greater than . was used to decide the number of factors (latent variables; kaiser, , sharma, , hair, anderson, tatham, & black, . to check the items' internal consistency (reliability index), cronbach's α (cronbach, ) value was calculated and checked. this study presents the key findings from a total of respondents (table ) this study depicts that the respondents belong to states of our country with maximum representation ( ) from uttar pradesh, followed by madhya pradesh and uttarakhand . when people were asked about how they commute, the overall result precipitate that a majority of the respondents ( %) commute by two wheelers, which are open to threat of getting infections, ( %) use their personal cars, so they can manage hygiene factors, ( %) use bus, which are prone to maximum exposure, ( %) uses college bus. thus, we can say that in society, most of the respondents are having the threat of getting exposed for infection (figure ). on the result of question asking regarding the numbers of people they generally interact and do you walk through crowded place daily?, finding of the study indicates that out of total, ( %) respondents reported that they daily interact with more than on the question about whether respondents are preventing from virus, out of the total participants, ( . %) admit that social distancing is crucial to finish virus from transmission. however, ( . %) admitted washing hands during certain period of time and ( %) felt the need of wearing mask. almost ( %) agreed that they should avoid face to face meeting (table ) . the investigators applied the factor analysis using principal component analysis as extraction method, with varimax rotation to describe the underlying unobserved latent variables of respondent's perception for methods to prevent from covid- . the objective of factor analysis was to know that what are the major ways through which people's were preventing themselves from virus table . the kmo measure was . > . (as recommended value of . ; hair, black, babin, & anderson, ; tabachnick & fidell, ) . in addition to this, bartlett's test of sphericity was significant (χ [ ] = , . , p = . ) ( table ). in addition, the sample size is more than times the number of variables (kaiser, ) , considering n:p ratio to be at least , where n is sample size and p is number of variable to be analyzed. all these above results show that factor analysis is suitable and useful for our data. all the items are standardized to ensure the proper interpretation on a common scale. scree plots and eigen values were used to extract the suitable number of factor solutions. three latent factors were fixed after the analysis of kaiser normalization criteria (pett, lackey, & sullivan, ) and scree plots (baldridge & veiga, ; balser, ; balser & harris, ; cleveland, barnes-farrell, & ratz, ; colella, ; stone & colella, ) . these factors are labeled as latent variables f : follow the lockdown, combination of (avoid travelling by any medium, avoid going to market, avoid morning walk, avoid going to office), f : naturopathy, is a combination of (exercise and yoga, eating ginger, garlic, chilies, drinking warm water, avoid going to cold weather) and f : social distancing is combination of (avoid face to face meeting, wash hand and face regularly, wear mask and sanitize, social distancing) and loadings of all about items were greater than . , explaining . %, . % and . % of the variances, respectively. the total variance explained by three factors is . %. table describes each of the three factors and their factor loading. we also conducted reliability test of the selected factors to test how well they measures what they are intended to measure. how reliable they are to measure latent variable, that is, perception to prevent from virus?, value of cronbach's alpha (α) for above is . (table ) , which is good enough to meet the purpose. this study also has some limitations such as questionnaires filled by people who can understand english and possess smartphones with internet connectivity. these educated population segments are mainly will also get an idea of common man psychology, problems and worries of ordinary people to formulate a better and effective strategy. covid- battle during the toughest sanctions against iran. the lancet how will country-based mitigation measures influence the course of the covid- epidemic? toward a great understanding of the willingness to request an accommodation: can requesters' beliefs disable the americans with disabilities act? factors affecting employee satisfaction with disability accommodation: a field study predictors of workplace accommodations for employees with mobility-related disabilities accommodation in the workplace coworker distributive fairness judgments of the workplace accommodation of employees with disabilities. academy of management review essentials of psychological testing covid- and community mitigation strategies in a pandemic multivariate data analysis with readings multivariate data analysis an index of factorial simplicity the application of electronic computers to factors analysis early transmission dynamics in wuhan, china, of novel corona virus-infected pneumonia mass gathering events and reducing further global spread of covid- : a political and public health dilemma making sense of factor analysis: the use of factor analysis for instrument development in health care research study of knowledge, attitude, anxiety & perceived mental healthcare need in indian population during covid- pandemic correlation between weather and covid - pandemic in india: an empirical investigation applied multivariate techniques world health organization declares global emergency: a review of the novel coronavirus (covid- ). international journal of surgery a model of factors affecting the treatment of disabled individuals in organizations. the academy of management using multivariate statistics coronavirus disease (covid- ) situation report − rolling updates on coronavirus disease (covid- ) coronavirus disease (covid- ) situation report - key: cord- -vuvd mvz authors: km, s.; t, m.; ap, m. r.; k, a. title: trace, quarantine, test, isolate and treat: a kerala model of covid- response date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: vuvd mvz kerala reported the first three cases of coronavirus in india in late january. kerala, one of indias most densely populated states, which makes its success in fighting the covid- all the more commendable. moreover, an estimated % of its million population employed or lives elsewhere, more than million tourists visit each year, and hundreds of students study abroad, including in china. all of this mobility makes the state more vulnerable to contagious outbreaks. what is the strategy behind the success story? this paper compares the situation of covid- pandemic in major states and kerala by the different phase of lockdown, and also highlights keralas fight against the pandemic. we used publicly available data from https://www.covid india.org/ and covid- daily bulletin (jan -may ), directorate of health services, kerala (https://dashboard.kerala.gov.in/). we calculate the phase-wise period prevalence rate (ppr) and the case fatality rate (cfr) of the last phase. compared to other major states, kerala showed better response in preventing pandemic. the equation for the keralas success has been simple, prioritized testing, widespread contact tracing, and promoting social distance. they also imposed uncompromising controls, that were supported by an excellent healthcare system, government accountability, transparency, public trust, civil rights and importantly the decentralized governance and strong grass-root level institutions. the proactive measures taken by kerala such as early detection of cases and extensive social support measures can be a model for india and the world. keywords: covid- , kerala, india, testing, tracing, pandemic. since the first case of covid- reported at the end of january, india has reported more than , covid- infections. more than , people have died due to the virus. as of may, the testing positivity rate in the country was near %, the death rate from the pandemic was around % and the doubling rate of disease -or the amount of time it takes to double the covid- infections was days. % recovery rate of infected patients was reported in this period ( ). same as other countries, there are hotspots and clusters of infection in india. nearly % of the active cases are in five major states -maharashtra, tamil nadu, delhi, gujarat and madhya pradesh, and importantly more than % of the cases in five cities, including mumbai, delhi, chennai and ahmedabad, according to government reports ( ) . india, with a draconian nature of nationwide lockdown appears to be done relatively worse in preventing the number of confirmed cases compared to other countries with less restrictive regimes ( ). nearly more than half of patients who have died of the infection have been aged and above, and many have underlying conditions, hewing to the international data about older people being more vulnerable to the disease ( ). at the same time, nearly, percent of the kerala population are aged over ( ). as per economic review by state planning board, around percent men and percent women are diabetic, percent men and percent women are hypertensive, more than one lakh people are being treated for cancer, . lakh people have chronic pulmonary disease and . lakh have asthma ( ). this paper compares the situation of covid- pandemic in above mentioned major states and kerala by the different phase of lockdown and also highlights kerala's fight against the pandemic. kerala a small state in india, the land that proclaims itself as "god's own country" is a heaven for tourists who make a beeline to the backwaters, palm-fringed sunset beaches, lush hills of the western ghats, and the spice plantations on the mountain slopes. kerala has been known around the globe as a model for preventing the spread of covid- . global media have been pouring praise on the state's success ( , ) . kerala reported the first three cases of coronavirus in india in late january, all three victims being indians who had studied in wuhan. later own kerala received people from italy too with positive cases including a whole family tested positive. the state soon began implementing mandatory quarantines for visitors arriving from abroad and from outside of the state, weeks before the centre instituted similar measures across the country. a detailed guideline to deal with a new coronavirus was issued by the department of health and family welfare of kerala on th january , much earlier than the first case detection in india. importation and transmission-based approach for testing strategy on january th , even before the first case of covid- was reported in the state ( ). the critical situation is that kerala is a small state ( , sq.km), but it homes for million people makes it people per square kilometer, eight most densely state in india. other than people living in closely kerala has lakh migrants, who frequently travel to their native land. in addition to that, international travelling is a part of kerala culture, which is connected to the rest of the world through four airports serve around million passengers annually. finally, kerala has . million migrant laborers from other states. simply population density, affluent non-resident keralites and thriving tourism all raise the risk for an outbreak in kerala. however, the containment strategies adopted by kerala have helped in slowing the spread of infection into the community by the end of may ( ). study also suggests that the head start that kerala had in preventing the spread of the disease in the initial phase may help the state in dealing with the next wave of the disease ( ). kerala opted for a combination of massive testing, quarantine and support of the poor with positive short-term effects ( ). by january itself, the government started promoting using the face masks. on february , the state government declared covid- as state calamity and drafted measures to be followed. by the beginning of march, government introduced more precautionary measures by shutting down the schools and colleges and asking all religious and other groups cancel all gatherings, including marriages, to encourage social distancing ( ). on the nutritional point of view, free meals delivered for school children at their home. the government also instructed internet service providers to improve the bandwidth to encourage work from home ( ). the use of traditional medicines for immune-boosting was encouraged, as kerala is the land of ayurveda. we used publicly available data from https://www.covid india.org/ and covid- daily bulletin (jan -may ), directorate of health services, kerala (https://dashboard.kerala.gov.in/). data compiled in this web portal is based on state bulletins and official handles. the details of the data are available on the website. this portal data matches with the data provided by the ministry of health and family welfare, government of india (https://www.mohfw.gov.in/). for the analysis purpose, the number of covid- cases categorized into phases i.e., pre-lockdown (before th march ), st phase of lockdown ( th march to th april ), nd phase of lockdown ( th april to rd may ,) rd phase of lockdown ( th may to th may ), and th phase of lockdown ( th may to st may ). we calculate the phase-wise period prevalence rate (ppr) and the case fatality rate (cfr) of the last phase. the measures are, = * . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint = * where the total covid- is confirmed cases in the i th lockdown phase; pi is the total population of the state and di is the number of deaths i th lockdown phase. it must be noted that a robust estimate of cfr is possible only at the end of the pandemic. however, the dynamics of fatality and recovery rates across affected countries and states would enhance the knowledge base and provide useful information in the ongoing outbreak of covid- . the pandemic is among the worst to have happened in the history of mankind. the disease a little later started sweeping across all the indian states adding up to a dreadful toll. change in cumulative caseload over time in india ( figure ) shows that the infections increased rapidly since march and there was a sharp rise of cases in may . on the other hand, for a population of over a billion, india has approximately . million hospital beds, thousand icu beds, and thousand ventilators as estimated by a research team ( ). the study reveals that most of the beds and ventilators in india are concentrated in seven states; uttar pradesh ( . %), karnataka ( . %), maharashtra ( . %), tamil nadu ( . %), west bengal ( . %), telangana ( . %) and kerala ( . %). deaths . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . period. the total number of new cases has increased consistently nearly in all states over the lockdown period. however, kerala is the only state experiencing a decline in new cases per day till the third lockdown. then, kerala also experienced a spike in the fourth lockdown in the month of may. results also show that among the most affected states, maharashtra and west bengal stand at the top with higher levels of cfr as against kerala. it is also found that kerala recorded negative percentage change in the new covid- cases between lockdown- . and lockdown- . and between lockdown- . and lockdown- . ( ). the state of kerala, where the epidemic started early in the country, has only less than one percent of case fatality rate. while among other most affected states, fatality rate is . percent in gujarat and percent in west bengal. kerala has been known around the globe as a model for preventing the spread of covid- . global media have been pouring praise on the state's success. the state reported the first case of the country in january. the state moved fast because of that by mid-january it had already put in place a strategy to isolate people who showed symptoms in hospitals, to trace their contacts and put them in-home quarantine. kerala has done remarkably well in controlling the virus transmission, even compared with countries with similar populations ( . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . four months on, kerala is being praised for not just flattening the curve of the deadly infection even as it shoots up in many parts of the country but for having an extremely low mortality rate and high recovery rate. what is the strategy behind the success story? identifying the case from the beginning got special attention; intensive training provided to health workers varies from doctors to asha workers to identify the covid- symptoms. health check-up booths established in all railway stations, state borders and airport the check and guide the people coming from outside. for speedier testing, the government set up a facility at virology institute alappuzha with the help of national institute of virology, pune. soon after more testing labs were launched in different parts of the state. in addition to using the centrally procured real-time polymerase chain reaction (pcr) testing kits, kerala was the first state to acquire rapid test kits from the pune-based mylab. the state used testing optimally, figure shows the number of covid- tests and active cases in a different phase of lockdown in kerala, the number of tests and active cases are showing non-linear trend throughout the period but in phase of lockdown both showing an increasing trend. the number samples tested per day never crossed till the beginning of the may only four times more than tests conducted, the average number of tests per day after active cases were till the end of phase (fig ) . one active case per tests was also reported till may . in phase number, tests increased to more than per day due to the return of the people from different part of the country and the world. the average number of tests increased from in the first two phases to in the last periods of the lockdown. till the end of the lockdown, the average number of tests per day stood below . with the rise of active cases, number of tests per day also increased. tests are conducted optimally with prioritizing the groups to be tested rather than the whole population. this selective approach was taken due to the limiting factors include availability, reagents, pcr equipment, trained staffs, protective gear for each collection and cost (rs , per test). the indian council of medical research (icmr) handed out , rdks to kerala in the beginning; instead of testing the general population, the kerala government identified four priority groups. ) healthcare workers who had served patients with covid- and other . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . patients ( , kits). . government staff with public contact, like police personnel, ashas, anganwadi workers and local government staff ( , kits), and essential service providers ( , kits), e.g., -workers of community kitchens, food and grocery deliverers, and ration shop vendors, etc. ) people quarantined at home ( , kits). ) all senior citizens ( , kits). at the beginning (first phase lockdown) one active case per tests reported (fig ) due to the formidable step was taken by the government. contact tracing was conducted effectively by devolved power and funding to grass root-level bodies, and established a social system that promotes community participation and public cooperation. other than that, . lakh volunteers (age group - ) were raised through government registration and trained with local government bodies and deployed to deliver the food, contact tracing and checking those under in quarantine. people who had returned from infected countries after january were tracked and scanned by the help of local government bodies. by the beginning of the march introduced the mandatory quarantine for days for everyone who enters the state and more helplines were created at local levels including a separate helpline for mental health. high risk people who were in contact with the positive cases were tracked, and kept in quarantine helped in optimal utilization of the covid- treatment kits. for the positive cases reported in kerala in april, close to . lakh people were traced and quarantined. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . figure shows the number of people isolated per one active covid- case in a different phase of lockdown in kerala. dynamic tracing will help the government to utilize the available recourse to fight the pandemic. throughout the time, an average number of people kept in isolation per active case. it varied in a different phase of the lockdown, it was high in the beginning, to avoid the risk of community spread. then it reduced to fewer numbers in first two phases of lockdown due to the uncompromising regulations to prevent the social contact while in third phase isolation per active case got increased due to lower number of active cases in that state (fig ) . in the fourth phase as the number of active cases increased the isolation per active case was also reduced, the compulsory isolation for whoever entering the state in this period reduced the risk social contact and the high number of isolation. government set up isolation wards in all medical colleges, district and general hospitals besides around corona care centers were created in hostels, educational institutions and unoccupied buildings. around lakh room were kept aside to face emergencies. the district kasaragod was the highest number of covid- cases registered in kerala, the government opened medical college hospital in two days with more than beds, well-equipped machinery and staffs. by joining with tata group, the government of kerala is developing a -bed intensive covid- treatment center at the same district. may pre-lockdown phase phase phase phase . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint figure shows the percentage of people in home isolation in different phases of lockdown in kerala. it points that out of ten people were isolated in their own home with necessary support including food, medical check-up and counselling and the government was ready with enough number of isolation beds to accommodate a large number of people. the people who were not able to self-quarantine themselves their own house, the government didn't directly admit them in the hospital facilities; they have been admitted in the isolation facilities created in hostels, educational institutions and unoccupied buildings. those who showed symptoms were admitted to hospital facilities and got tested. figure shows the number of hospitalization related covid- in different phases of lockdown in kerala. this intensive approach (systematic contact tracing and isolating) help the health system from being overburdened by people, in average people hospitalized per-day because of that at its peak, only people (in april-phase ) and people in the fourth phase were admitted. average of people per day hospitalized in all phases, but in the last phase, it got increased to people per day due to the return of the people from outside of the state (fig ) . even at the end of may per day, hospitalization never crossed marks and had less than people admitted to health facilities all the time. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . march , kerala announced complete lockdown before the announcement of national lockdown. the most crucial step was taken on march by announcing an awareness campaign named 'break the chain' to create awareness and promote social distancing. the government was holding a press conference every evening to answer all the queries related to the outbreak and to reduce the spread of rumors. local bodies mandate that everyone hold an umbrella when they go out, and distributed umbrellas produced by kudumbashree to promote involuntary social distancing. in high-risk areas, the police force created an online delivery system of essential food items. innovative products have been developed as part of beating the covid- in the state. a smart bin called 'bin- ' has been launched for the collection and disinfection of used face-mask which is based on internet of things (iot) ( ). kerala became the first state that does away with 'zonal classification of districts on the basis of covid- spread where more police would be deployed to ensure the strict adherence of quarantine and lockdown norms ( ). meanwhile, kudumbashree, a keralan grassroots network of local organization and women's self-help groups, has helped the state's containment strategy by producing masks and hand sanitizer. some , community kitchens were established to . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint feed the indigent and unemployed, and kudumbashree has already served , meals a day. kerala's educated population has behaved responsibly, limiting community transmission, and cooperating with authorities. one of the two major challenges that kerala faced in this period was the security of the migrant workers from other states, just after the announcement of the national lockdown, the state set up nearly camps for migrant laborers, by calling them, 'guest workers'. lakh workers were hosted in these places and urged to wait in place till the special trains will be arranged to take them home. the second challenge was the returning migration from abroad; they were tested before taking the flight and rechecked after landing in kerala. once they reach kerala, they will be taken to government facility for quarantine in respected districts and requested to stay there until the time of quarantine is over. same time government set up isolation wards in all medical colleges, district and general hospitals besides around corona care centers were created in hostels, educational institutions and unoccupied buildings. the state got into the action by january and rolled out measures that reduced the spread of the covid- . the first coronavirus case in india was confirmed in kerala's trissur district on january , . ever since, the state has been fighting the pandemic in an exemplary manner. the steps were simple but proactive. the equation for kerala's success has been simple, prioritized testing, widespread contact tracing, and promoting social distance. besides that two factors fuelled this success, the 'formidable' grass root level primary health care system and the experience it gleaned in the last two years when it handled another deadly virus outbreak ( nipah virus outbreak in kerala). state announces its strategy is trace, quarantine, test, isolate and treat in the beginning only. the state soon began implementing mandatory quarantines for visitors arriving from abroad and from outside of the state, weeks before the centre instituted similar measures across the country. they also imposed uncompromising controls, were supported by an excellent healthcare system, government accountability, transparency, public trust, civil rights and importantly the decentralized governance and strong grass-root level institutions. this much decentralized system has hold out the test of two severe floods and another viral outbreak in past years, ordinarily making good use of the active and voluntary engagement of the public. while the rest of india worries about the rate at which new cases are doubling, that question has become almost irrelevant in kerala, the curve has been flattened for now and transmission limited. currently, how it manages to ease the lockdown safely will depend on a large number of factors. the summer monsoon rains, the floods that will follow, as well as returning migrants will add layers of complexity. but one thing is clear: when the next wave of novel coronavirus hits, which it will, the state will be ready. the "proactive" measures taken by kerala such as . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . early detection of cases and extensive social support measures can be a "model for india and the world" covid- india % covid cases from states, % from cities: govt covid curve hasn't 'relatively flattened'. i compared govt data with other nations. the print [internet who. covid- : vulnerable and high risk groups economic review how india's kerala state "flattened the curve kerala's covid- response puts "so-called first world" to shame: british economist strategy for covid- testing in kerala state reverse quarantine: management of covid- by kerala with its higher number of aged population mass media and publications from six countries covid- : kerala shuts down schools and colleges kerala gives internet boost to help people brave covid- vigil covid- in india : state-wise estimates of current hospital beds, intensive care unit (icu) beds and ventilators spatial mapping and demographic characteristics of the covid- positive cases in india: a situational analysis fighting covid : kerala startup launches mask disposal smart bin & uv lightbased disinfection device covid- timeline: a chronology of kerala's fight against the pandemic key: cord- -dhl ynrc authors: unnikrishnan, ranjit; misra, anoop title: infections and diabetes: risks and mitigation with reference to india date: - - journal: diabetes metab syndr doi: . /j.dsx. . . sha: doc_id: cord_uid: dhl ynrc background and aims: the link between diabetes and increased risk of infectious disease has long been recognized, but has re-entered sharp focus following the covid- pandemic. methods: a literature search was conducted in pubmed for articles in english on diabetes and infection. results: diabetes predisposes to infections through alterations in innate and acquired immune defenses. outcomes of infection are worse in people with uncontrolled diabetes, and infection can worsen hyperglycemia in hitherto well controlled diabetes (bidirectional relationship). diabetes does not increase the risk of infection with covid- per se, but predisposes to severe disease and poor outcomes. covid- has also been linked to deterioration of glycemic control as well as new-onset diabetes. conclusions: clinicians caring for people with diabetes should be aware of the increased risk of infections in this population, as well as the possibility of worsening hyperglycemia. a holistic approach with frequent monitoring of blood glucose levels and appropriate titration of medications, along with close attention to nutritional status, is essential to ensure the best possible outcomes. infectious disease is an important, yet oft-neglected corollary of uncontrolled diabetes mellitus. in the pre-insulin era, most deaths among individuals with type diabetes and many among type diabetes occurred as a result of uncontrolled infection. it is a matter of concern that even today, infections continue to cause significant morbidity and mortality in patients with diabetes, notwithstanding the recent advances in antihyperglycemic and antimicrobial therapeutic options. in this short review, we will review the mechanisms underlying increased susceptibility to infection in diabetes and briefly discuss the clinically relevant infections found in patients with diabetes, with particular reference to the ongoing covid- pandemic. indian situation has been highlighted whenever data are available. we searched pubmed for original and review articles in english published, using the following keywords: diabetes and infection, hyperglycemia covid- , tuberculosis, vaccination, infections, and diabetes in india, from till september, . the relationship between diabetes and infection has been known for long and has been traditionally considered as bidirectional ( fig. ) ( ). uncontrolled diabetes affects almost all components of immunity: . dysregulated innate immunity including defective neutrophil and macrophage function ( ) . abnormal complement function, which may be related in part to defects in neutrophil function and cytokine responses ( ) . defects in t-cell responses ( ) . defective humoral (antibody-mediated) immunity ( ) in addition, the widespread vasculopathy typical of longstanding uncontrolled diabetes interferes with the body's ability to combat infection by limiting the ingress of immune cells as well as antimicrobial factors, and by promoting tissue necrosis and gangrene. certain features of the hyperglycemic milieu contribute to the growth of specific micro-organisms (e.g. ketosis promoting the growth of fungi causing mucormycosis). the infections met with in diabetes patients can be broadly classified into two categories. . infections that are common in the non-diabetic population, that also affect people with diabetes, often with more severe clinical presentation and worse outcomes. . infections that are peculiar to individuals with diabetes and virtually unknown in the normal population. these include respiratory infections, genitourinary tract infections and skin and soft tissue infections (table ). in a series of patients with diabetes and infections attending a tertiary care centre in north india, the most commonly encountered infections were those of the soft tissues ( . %), respiratory tract ( . %) and genitourinary tract ( . %). infection of more than one site was present in . % of patients ( ) . diabetes has been shown to increase the risk of lower, but not upper respiratory tract infections ( ) . tuberculosis (tb) is a common comorbidity of diabetes, particularly in developing countries. india faces a double burden with the highest number of tb patients, and the second highest number of individuals with diabetes, living within its borders. the relationship between tb and diabetes is bidirectional; individuals with diabetes are more likely to contract tb, and individuals with diabetes are more likely to have diabetes compared to the general population ( ) . the greater risk of contracting tb in diabetes, as well as reactivation of latent tb, is postulated to be due to a combination of susceptibility to infection with oxidative stress and j o u r n a l p r e -p r o o f increased tissue inflammation ( ) . a recent systematic review on the co-prevalence of tb and diabetes in low and middle-income countries found that diabetes was found in . to % of individuals diagnosed with tb, and that . to % of individuals with diabetes had tb ( ) . tb in diabetes has certain peculiar characteristics that make diagnosis and management difficult (see box ) ( ). genitourinary infections found in patients with diabetes include urethritis, vaginitis, cystitis, and prostatitis. common causative organisms are gram negative bacteria such as e. coli and klebsiella and fungi such as candida. in indian patients with diabetes and uti, the most common organisms isolated were e. coli ( . %), klebsiella ( . %) and enterococcus ( . %) ( ) . infection with extended spectrum beta-lactamase producing e. coli was found to be more frequent in individuals with diabetes. also, nearly % of individuals with positive urine culture were found to be asymptomatic. however, current guidelines state that asymptomatic bacteriuria need not be treated, even among patients with diabetes ( ) . use of sodium-glucose cotransporter- inhibitors (sglt i) for management of hyperglycemia has been associated with increased risk of genital mycotic infections ( ); cystitis and upper urinary tract infections are less common but can occasionally occur ( ) . skin and soft tissue infections found in patients with diabetes include furuncles, carbuncles, and cellulitis. in india, more than % of all skin and soft tissue infections have been shown to be associated with staphylococci ( ) . infection is also an important component of the diabetic foot syndrome. most cases of diabetic foot infection have been shown to be polymicrobial in nature, with predominance of gram-negative organisms ( , , ) . prevalence of antimicrobial drug resistance was also found to be higher among patients with diabetes, which could be attributed, at least partially, to the production of biofilms by the causative organisms ( ) . the antimicrobial management of these conditions does not differ significantly from that in the population without diabetes. achievement and maintenance of tight glycemic control, most often requiring the use of intensive insulin therapy, is key to improving outcomes. covid- is an acute, predominantly respiratory viral illness caused by the novel severe acute respiratory syndrome coronavirus (sars-cov ). from studies conducted in china, europe, and the u.s., it appears that individuals with diabetes are not at higher risk of infection with sars-cov compared to the general population ( , ) (box ). however, it is clear that they do tend to have worse outcomes, with respect to development of more severe illness and mortality risk, than individuals without diabetes ( ) . while mortality due to covid- has been lower in south asian countries such as india, the sheer number of individuals with diabetes in this region represents a huge population at high risk of adverse outcomes due to this infection ( , ) . as individuals with diabetes tend to be older and to have higher burden of cardiometabolic risk factors such as obesity and hypertension (as well as cardiovascular disease per se), it is likely that their increased risk of adverse outcomes is mediated, to a large extent, through these comorbidities than by diabetes per se ( ) . recently, there have been reports of new-onset diabetes following infection with sars-cov , mainly from the u.s. ( ) , but increasingly from elsewhere in the world as well. new-onset hyperglycemia during covid infection can have multiple causes-weight gain following disordered diet and exercise during lockdown, mental stress, and unwarranted use of dexamethasone for mild to moderate cases of covid ( ) . it is also likely that the novel sars coronavirus has a direct diabetogenic potential by way of its effects on the pancreas. the angiotensin converting enzyme (ace ) receptor, by means of which sars-cov enters target cells, is also present on the pancreatic beta-cell ( ) . infection of the beta cell may lead to acute impairment of insulin secretion or even destruction of the beta cell, as has been reported for human herpesvirus infection in africa ( ). in individuals with pre-existing diabetes, the current covid pandemic and the public health/ governmental responses to it are also likely to impact glycemic control in significant ways. lack of accessibility to testing and care during lockdowns, increased snacking and reduced physical activity are likely to worsen diabetes control, and predispose patients to complications ( ) , although such deterioration has not been found in all studies ( ) . • a high index of suspicion is required for the diagnosis of most of these conditions. treatment involves, in addition to specific antimicrobial agents, early and aggressive surgical intervention wherever indicated. the prognosis for many of these conditions is poor, even with prompt treatment. while the deleterious effects of uncontrolled hyperglycemia on infection have been well characterized, there is less information available on whether controlling hyperglycemia can have beneficial effects on infection prevention and control ( ) . analysis of patients with type and type diabetes enrolled in primary care in england have shown a clear increase in long-term risk of infection with increasing hba c ( ) . in a population-based study from denmark, individuals with hba c of . % and above had j o u r n a l p r e -p r o o f hazards ratio of . for infections requiring hospitalisation, compared to individuals with hba c between . and . % ( ) . b. hyperglycemia and morbidity and mortality due to covid : during the ongoing covid pandemic, attempts have been made to link the severity of disease outcomes in covid- with the levels of background glycemic control, as well as the glucose levels at admission and during the course of hospitalization. higher hba c at hospitalization, indicating poor long-term glycemic control, has been associated with higher risk of inhospital death due to covid, although this has not been replicated in all studies ( ) . patients with higher blood glucose levels at admission tended to have the most florid lesions on chest imaging and were more likely to require icu admission and intubation and to die compared to those who had lower blood glucose levels ( ) . in-hospital hyperglycemia was associated with worse clinical outcomes among patients with covid studied in china and the u.s ( , ) . these findings reinforce the need for ensuring tight glycemic control in patients with diabetes during the current pandemic, and also for the maintenance of euglycemia in patients who are hospitalized for covid- . in this context, it should be remembered that some medications used for the treatment of severe covid (particularly corticosteroids) have the potential to raise blood glucose levels, and that the antidiabetic drug regimen will need to be appropriately titrated in patients receiving these treatments ( ) . even in the absence of these treatments, infection with sars-cov has been associated with extremely high insulin requirements among patients with diabetes, and the development of hyperglycemic crises in some cases ( ) . the presence of diabetes is associated with increased risk of treatment failure, relapse, and death in patients with tb ( ); similar results have been reported from india as well ( ) . the role of tight glycemic control in improving treatment outcomes in tb remains controversial ( ) . a study from china showed that treatment outcomes were worse among those with suboptimal glycemic control ( ) . similarly, mahishale et al ( ) showed that optimal glycemic control resulted in % reduction of sputum non-conversion at months of treatment compared to poor glycemic control. however, nandakumar et al ( ) found no correlation between diabetes control and tb treatment outcomes in their study conducted in malappuram district of kerala. in this context, it is interesting to note that recent studies have shown an association of poorly controlled diabetes with better outcomes in individuals with low body-mass index; this needs confirmation in larger studies ( ) . maintenance of tight glycemic control during the peri-and postoperative period has been found to be associated with a lower incidence of surgical site infections in patients with diabetes ( , ) . even though maintenance of tight glycemic control has been long considered one of the cornerstones of diabetic foot management, there is little evidence by way of randomized controlled trials to suggest that foot ulcer outcomes are improved by this approach ( ) ; such trials are urgently needed, considering the global magnitude of the problem of diabetic foot. in a retrospective study of more than patients with covid- from china, well controlled blood glucose (defined as glycemic variability between . to mmol/l) was associated with significantly lower mortality compared to higher blood glucose variability (> mmol/l) ( ) . the role of diet has often been overlooked while managing infections in patients with diabetes. some general points can be summarized from available studies: a. severe infection is a hypercatabolic state and any diet plan for patients with infection should take this into account, ensuring adequate intake of protein and micronutrients to promote healing. this is particularly relevant in the indian context, where the baseline protein intake is extremely low. particularly in patients with diabetes and tb without hepatic or renal insufficiency, it is recommended that proteins should be the major source of energy ( ) . b. supplementation of micronutrients for months has been shown to reduce the incidence of common infections (respiratory, skin, and urogenital) in patients with diabetes ( ) . a recent review ( ) on the role of micronutrient supplementation in diabetic foot ulcers concluded that while there was some evidence to support the role of vitamins a, c, d and e, and zinc in ulcer healing, the level of evidence was not strong enough to support any recommendations for routine supplementation with these nutrients. in patients with risk of limb ischemia and/or hypoalbuminemia, supplementation with arginine, glutamine and betahydroxy methyl butyrate has been shown to improve foot ulcer healing ( ) . c. supplementation of vitamin d has been shown to improve the proportion of sputum smear and culture conversion in patients with active pulmonary tb (with or without diabetes) ( ). d. similarly, vitamin d deficiency was associated with an increased risk of testing positive for covid- , raising the possibility that supplementation of this vitamin could reduce the risk of covid infection; however, it should be noted that this study was not restricted to individuals with diabetes ( ). recently, consensus guidelines have been published for balanced nutrition in the time of the covid pandemic ( ) . these can be summarized as follows. a. individuals not infected with covid, or those with mild to moderate disease, consume a balanced diet rich in vegetables, fruit, legumes, nuts, and whole grain as well as egg and lean meat wherever applicable. b. intake of probiotic-rich food is encouraged, and hydration should be maintained particularly when febrile. c. saturated fat and processed food should be avoided, as should extreme "fad" diets. d. the diet should provide at least g of protein per kg body weight per day in older persons and should contain adequate amounts of micronutrients such as vitamins a, c, and d, zinc, and selenium. e. in severely ill patients, these nutritional requirements should be met by way of oral supplementation wherever possible, with enteral and parenteral supplementation being reserved for the most severely ill individuals who cannot tolerate oral intake. as individuals with diabetes represent a vulnerable subgroup of the population with respect to susceptibility to infection, preventing these infections by means of vaccination assumes j o u r n a l p r e -p r o o f paramount importance. in addition to all routine immunisations recommended for the general population, the american diabetes association provides additional recommendations for the use of pneumococcal, influenza and hepatitis b vaccines in individuals with diabetes ( ) . attempts have been made to formulate similar recommendations for india also ( , ) ( table ) . in this context, it should also be noted that the nationwide lockdowns imposed in india and other countries to combat the spread of the covid- pandemic have had an adverse impact on the coverage of infection control and immunization programs directed against other communicable disease; these countries should gear up to face a recrudescence of many of these hitherto controlled infections in the near future ( ) . infectious disease continues to take a heavy toll of the population with diabetes even in the present day. the increased susceptibility of the individual with diabetes to infection has recently returned to sharp focus with the advent of the covid- pandemic, reiterating the need for achieving tight control of hyperglycemia and managing comorbidities appropriately j o u r n a l p r e -p r o o f in this population from the time of diagnosis of diabetes. also, there are certain unusual infections that appear to be exclusively found in patients with diabetes; the clinician dealing with patients with diabetes should be ever alert to the possibility of these infections, as prompt diagnosis may mean the difference between life and death in many cases. j o u r n a l p r e -p r o o f magnitude of the problem: • million people with diabetes worldwide ( million in india) • million infections with covid worldwide as of september ( . million in india) • diabetes per se not a risk factor for contracting covid infection • severe disease and adverse outcomes more likely in individuals with diabetes • poor outcomes may be linked to other comorbidities such as older age, obesity and hypertension, more frequent among people with diabetes • poor long-term (pre-infection) diabetes control, admission hyperglycemia and inpatient hyperglycemia linked with poor outcomes • covid infection can worsen diabetes control • new onset diabetes has been reported with covid mention ketoacidosis • some treatments used for covid treatment (e.g. steroids) can exacerbate hyperglycemia • adverse effect of pandemic and consequent lockdowns on routine diabetes care. this is likely to exacerbate diabetes control and also add new patients of diabetes to already high numbers. • patients unable to exercise regularly, access healthy diet and procure medications promptly. this will increase morbidity and even mortality. j o u r n a l p r e -p r o o f infections in patients with diabetes mellitus: a review of pathogenesis common infections in diabetes: pathogenesis, management and relationship to glycaemic control the role of diabetes mellitus in patients with bloodstream infections immune dysfunction in patients with diabetes mellitus (dm) type diabeets and its impact on the immune system pattern of infections in patients with diabetes mellitus--data from a tertiary care medical center in indian subcontinent increased risk of common infections in patients with type and type diabetes mellitus diabetes and tuberculosis: an important relationship coprevalence of type diabetes mellitus and tuberculosis in low-income and middleincome countries: a systematic review diabetes and tuberculosis: an appraisal clinical profile of urinary tract infections in diabetics and non-diabetics clinical practice guideline for the management of asymptomatic bacteriuria: update by the infectious diseases society of america genital infections with sodium glucose cotransporter- inhibitors: occurrence and management in patients with type diabetes mellitus case of acute unilateral emphysematous pyelonephritis and bacteraemia on treatment with canagliflozin epidemiology of diabetic foot infections in a reference tertiary hospital in india bacterial etiology of diabetic foot infections in south india microbiological and clinical characteristics of diabetic foot infections in northern india infections and diabetes prevalence and impact of cardiovascular metabolic diseases on covid- in china prevalence and impact of diabetes among people infected with sars-cov- covid- in people with diabetes: understanding the reasons for worse outcomes covid in south asians/asian indians: heterogeneity of data and implications for pathophysiology and research covid- in people living with diabetes: an international consensus clinical characteristics and risk factors for mortality of covid- patients with diabetes in wuhan, china: a two-center, retrospective study new-onset diabetes in covid- national diabetes obesity and cholesterol foundation (ndoc), and diabetes expert group, india. strict glycemic control is needed in times of covid epidemic in india: a call for action for all physicians novel therapeutic approaches targeting the renin-angiotensin system and associated peptides in hypertension and heart failure ketosis-prone type diabetes mellitus and human herpesvirus infection in sub-saharan africans increase in the risk of type diabetes during lockdown for the covid pandemic in india: a cohort analysis acceptability and utilization of newer technologies and effects on glycemic control in type diabetes: lessons learnt from lockdown diabetes and infection: assessing the association with glycaemic control in population-based studies glycemic control and risk of infections among people with type or type diabetes in a large primary care cohort study impact of glycemic control on risk of infections in patients with type diabetes: a population-based cohort study factors associated with covid- -related hospital death in the linked electronic health records of million adult nhs patients admission hyperglycemia and radiological findings of sars-cov in patients with and without diabetes clinical characteristics of patients with diabetes and covid- in wuhan, china glycemic characteristics and clinical outcomes of covid- patients hospitalized in the united states guidance on the management of diabetic ketoacidosis in the exceptional circumstances of the covid- pandemic the impact of diabetes on tuberculosis treatment outcomes: a systematic review effect of diabetes on treatment outcome of smear-positive pulmonary tuberculosis--a report from south india effect of glycemic control and type of diabetes treatment on unsuccessful tb treatment outcomes among people with tb-diabetes: a systematic review the influence of diabetes, glycemic control, and diabetesrelated comorbidities on pulmonary tuberculosis effect of poor glycemic control in newly diagnosed patients with smear-positive pulmonary tuberculosis and type- diabetes mellitus outcome of tuberculosis treatment in patients with diabetes mellitus treated in the revised national tuberculosis control programme in malappuram district impact of diabetes and low body mass index on tuberculosis treatment outcomes postoperative tight glycemic control significantly reduces postoperative infection rates in patients undergoing surgery: a meta-analysis long-term glycemic control and postoperative infectious complications does improving glycemic control accelerate healing of diabetis foot ulcers? association of blood glucose control and outcomes in patients with covid- and pre-existing type diabetes insights on medical nutrition therapy for type diabetes mellitus: an indian perspective micronutrients decrease incidence of common infections in type diabetic outpatients micronutrients and natural compounds status and their effects on wound healing in the diabetic foot ulcer effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: a prospective randomized controlled trial effects of vitamin d supplementation on the outcomes of patients with pulmonary tuberculosis: a systematic review and meta-analysis association of vitamin d status and other clinical characteristics with covid- test results balanced nutrition is needed in times of covid epidemic in india: a call for action for all nutritionists and physicians comprehensive medical evaluation and assessment of comorbidities: standards of medical care in diabetes suggested use of vaccines in diabetes rssdi-esi clinical practice recommendations for the management of type diabetes mellitus covid- pandemic and challenges for socio-economic issues, healthcare and national health programs in india j o u r n a l p r e -p r o o f • diabetes confers increased risk of common and uncommon infections.• individuals with diabetes have worse outcomes with covid- .• there is a bidirectional link between tuberculosis and diabetes.• good glycemic control improves outcomes in most infections. ☒ the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐the authors declare the following financial interests/personal relationships which may be considered as potential competing interests: key: cord- -t elb w authors: chanda, arnab title: covid- in india: transmission dynamics, epidemiological characteristics, testing, recovery and effect of weather – corrigendum date: - - journal: epidemiology and infection doi: . /s sha: doc_id: cord_uid: t elb w nan it has been brought to our attention that figure b published in 'covid- in india: transmission dynamics, epidemiological characteristics, testing, recovery and effect of weather' showed an incorrect depiction of india's international boundary. the figure has been corrected as follows: covid- in india: transmission dynamics, epidemiological characteristics, testing, recovery and effect of weather key: cord- -hquc v c authors: gupta, rajan; pal, saibal kumar; pandey, gaurav title: a comprehensive analysis of covid- outbreak situation in india date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: hquc v c the outbreak of covid- in different parts of the world is a major concern for all the administrative units of respective countries. india is also facing this very tough task for controlling the virus outbreak and has managed its growth rate through some strict measures. this study presents the current situation of coronavirus spread in india along with the impact of various measures taken for it. with the help of data sources (till th- th april ) from various state units of india and ministry of health and family welfare, government of india, this study presents various trends and patterns. this study answers six different research ques-tions in a comprehensive manner. it has been reported that growth rate of infected cases has been controlled with the help of national lockdown, however some uncontrolled mass level events had negatively impacted the infected cases. with the help of exponential and polyno-mial regression modelling, the predictions of up to cases have been done by the end of april . it has also been seen that there are some prominent clusters and patient nodes in the network of patients which are the major influencers for covid- spread. also, death rate case predictions have been done through multi-class classification models with an accuracy of %. at the end, strategies for continuation for lockdown has been discussed and presented. it appears that only essential services should be open for the citizens of india and the national lockdown should be carried on for next - weeks. this study will be useful for the government of india and various states of india, administrative units of india, frontline health workforce of india, researchers and scientists. this study will also be favorable for the administrative units of other countries to consider various aspects related to the control of covid- outspread in their respective regions. united kingdom. with respect to the recovered patients list, china is at the top of the list followed by spain, germany, italy, iran and the united states of america. india was placed comfortably out the list of infected nations by huge margins, but recent events led to its rise to th position which is a point of concern. the mortality rate is controlled at less than % right now, which is better than the ~ . % mortality rate of world, but the model of spread is slowly moving towards an exponential trend which can lead to massive loss of lives and infrastructure. india is being looked upon by various nations now as a world leader and even who acknowledged that world is looking towards indian strategies to contain the outbreak of this epidemic [ ] . india accounts for almost one-fifth of the world's population and is second leading country in terms of population in the world. india contributes heavily to the world's gdp and is amongst the most prominent developing country in the world with fairly strong economic growth percentages [ ] . india's good camaraderie with majority of the nations in the world and its helpful nature makes it a perfect ally for other countries. therefore, the analysis of covid- outbreak in indian region is closely watched and monitored by the world and there is a need of comprehensive analytical studies based on different strategies taken by indian administrators from time to time. india has been following a nationwide lockdown since -march- , which was a one-day lockdown, followed by a -day lockdown after two days. every activity in india since then has been happening with permission from various administration units and almost all the domestic and international travels have been either banned or monitored closely. india is yet to get into the third phase of covid- outbreak i.e. the community outbreak as seen by various countries around the world, but the cases have been rising continuously. india's lockdown period has been impacted by two major events in the recent days which were related to the mass exodus of laborers and workers from one state to other states (especially from delhi to neighboring states) and conduction of a religious event in delhi which led to spike in the number of cases in various states of india. during this time, the indian prime minister has been trying to connect with indian citizens through innovative strategies and coming up with various engagement activities which are impacting the whole nation. with so much happening in india right now, it becomes imperative that we study the current situation and impact of various such events in india through data analysis methods and come up with different plans for future which can be helpful for the indian administrators and medical professionals. the current study explores various aspects associated with the covid- outbreak in india and the various regions situated in india. the specific research questions (rq) explored in this study are as follows.  rq : how has the situation changed in post-lockdown period in india i.e. what is the outbreak situation after -march- in india as compared to pre-lockdown period?  rq : what are the short terms predictions for the number of infected cases in india for the next - weeks based on current situation?  rq : has the lockdown been followed by the indian citizens after -march- ? has the social distancing worked for indian citizens? what are the mobility changes in the various regions of india?  rq : whether the community outbreak spread started in india with the conduct of a religious event in delhi? how is the outbreak different for citizens related to event and for citizens not related to the event?  rq : which are the prominent clusters which were formed in the last few weeks with respect to covid- outbreak in india? does network analysis provide influential points in the infected patient network?  rq : whether the national lockdown should be opened after th april in india or should it continue? are there any partial regions for which lockdown can be removed? which all essential services should be opened in india after one week under restricted lockdown? the current study is divided into five sections. first section has laid the context of the study. the second section discusses various literature review and analytical techniques followed by the different researchers across the world. the third section presents the methodology and research variables of the study. the fourth section presents the results and findings of the study along with the discussion of the achievement of the various research questions explored in this study. and finally section five concludes this study and present limitations and future directions for this research work. as per different papers available in literature, there are a few studies that focus on the trend analysis and forecasting for indian region. the studies [ ] [ ] on indian region presents long term and short term trend, respectively. these studies use time series data from john hopkins university database and present forecasting using arima model, exponential smoothing methods, seir model and regression model. however network modelling and pattern mining are not attempted in these versions of the studies and that too at the regional level, hence the current study attempts to do that. also, the studies in indian region from the past are more focused on presenting time series analysis based on the overall data for indian region rather than covering other sources of information apart from just considering the number of infected patients, so the need to analyze the patients background and information is required for the authorities to get better insight about the situation. similarly, there are other mathematical models that were developed for analyzing the trends of covid- outbreak in india. a model [ ] for studying the impact of social distancing on age and gender of the patients in india was presented. it compared the country demographics amongst india, italy and china and suggested the most vulnerable age categories and gender groups amongst all the nations. the study also predicted the rise of infected cases in india with different lockdown periods. similarly, a network structure approach was used by one of the study [ ] to see whether any specific node clusters were getting formed. but only travel data nodes were considered by the authors to check which the prominent regions are affecting indian travelers coming back to the india. also, the study presented the sir model to see the rate of spread of the corona virus amongst patients in india. analysis on the testing labs and infrastructure was also presented by earlier authors. work of medical doctors and frontline health workers was also presented by some studies [ ] . it was found that in india, the role of health workers was less stressed as the spread stage of corona virus was still in phase two or the phase of local transmission rather than the community transmission as compared to other nations like italy, spain and usa. however, it was also claimed that indian healthcare infrastructure is not very strong as per the who guidelines and in case of community spread, the indian government may find it difficult to manage the spread. some detailed discussion on the nature of the corona virus was also presented by some studies [ ] [ ] . apart from india, a few models are also available for other countries primarily for china, italy and usa as the number of infected patients was high. studied like [ ] [ ] [ ] [ ] [ ] worked on various mathematical models to determine the spread of the disease, predict the number of infected patients, commenting on the preparedness for each country in tackling covid- spread and finding the patterns of flattening curve in different conditions. a lot of researches are still in preprint stage for the world level and are yet to be peer reviewed. with respect to the research activities conducted in the indian region, the studies are yet to work on the impact of different policies working towards containment of the corona virus. even in the preprint databases, there are fewer evidences available which worked in the indian region with more granularities and came up with analysis that can support the decision making of the various administrators in india to curb the lockdown and work on future strategies. therefore, this study attempts to work on a comprehensive level to analyze the covid- spread in india and impact of various strategies imposed by the government at both state level and central level. to answer the different research questions, specific methodologies have been used which covers up different data set, data sources, modeling techniques and outcome variables. the overall variables covered up in the study are shown in figure . for the first research question, the time series data from the time period of th january till th april has been covered from the indian database of covid- [ ] . this dataset was divided into three parts of th january to th march , th march to nd march and rd march to th april . trend analysis and average number of infected cases were compared at both the national level. on the same dataset, the second research question has been answered using the exponential modelling to predict the short term trends for the next three weeks. the exponential modelling can be done using equation . where, n and n are the total cases at time t and t, respectively, and γ is the growth rate. by definition [ ] , n = n needs the doubling time (α) that is expressed as α = ln( )/γ through ln(n/n ) = ln( ) = γt. if the growth rate evolves with time, depending on the effective prevention strategies, then the doubling time changes with time. thus, the time-dependent growth rate γ(t) causes the time-dependent doubling time α(t), defined as α(t) = t ln ( ) for the third research question, the mobility data set [ ] from google has been considered after nd march to see the patterns in mobility of indian citizens at prominent places in . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint india. also, the number of operational places and events conducted during lockdown data has been analyzed through news reports and channels. based on the news reports, the major events were traced and people getting infected due to such events have been covered from the indian data repository created using crowdsourcing channels [ ] . the patients were categorized as infected from the event as compared to other patients who were not related to the event. the trends and patterns were analyzed after conduction of this event i.e. in the first week of april . the data was also confirmed from various news reports in india. to understand the patterns existing in the patients of covid- in india, their demographic details were studied in detail since th january from the crowdsourced database in india [ ] and rules were generated for the patients with potential probabilities. network analysis [ ] was also conducted on the patients and node centralities [ ] were calculated the patients. based on the patient database and number of infected cases along with the various secondary reports from the news media and consulting firms, the success of engagement activities and lockdown strategies have been analyzed, which answers the research question . the findings of the different types of data analysis conducted on various types of datasets are presented in the current section as follows. the national lockdown for one day was announced on nd march by the central government of india, before which majority of the schools, colleges, markets, cinema halls, etc. were already shut down by respective state governments. merely, two days after this one day curfew, a -day lockdown was announced by the central government banning all the movement and restricting the indians to stay at home. the citizens were allowed to step out only in emergency situations and that too with prior permissions from the local administration. all these instructions were given in the hope of flattening the curve of infected cases and to restrict the exponential growth of the patients in india. is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint there are almost confirmed cases reported in india as on the morning of th april with more than % cases being active. the death rate has been keeping under % at all the stages of the covid- spread. looking at the graph in figure , it is clearly evident that a spike has been reported in india after nd march i.e. the time when lockdown was announced. it clearly shows that indian authorities were quick enough to sense the spread rate in indian region and taking necessary steps of maintaining social distancing by announcing a rigid step of lockdown. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. looking at the growth rate of infected cases on daily basis (blue line) and the trend line of expected growth (red line) in figure , it appears that in early days of infection the growth rate was quite high due to low number of cases. the growth rate has been calculated as the difference in number of cases between two consecutive days divided by the count of infected cases on the previous day of the two days under consideration multiplied by . since, in the early days the count was in single digits, so the growth rate was pretty high. hence ignoring that period, considering the second phase of time period from th march to nd march i.e. exactly before the lockdown, the growth rate has been hovering around % with trend line forecasting it to be maximum around %. however, for the time period after lockdown i.e. from nd march onwards, the growth rate slightly increased, but it remained around a similar mark of %. and the trend line also predicted the growth rate on per day basis to be around maximum of %. therefore, it can be said that the national lockdown has been able to contain the growth of the number of cases of covid- patients. without lockdown, the growth might not have been contained in india and may have gone into the exponential zone too quickly. this gives all the state level and national level administrators and health workers to get prepared for the rising number of cases. exponential modelling has been used to predict short term predictions at national level. first, the growth for doubling days was calculated, i.e. the number of days to double the number of infected cases have been calculated. as seen from figure , the first image shows that prior to the lockdown period average number of days to double the cases was majorly above four, while the average period drop down near to three after lockdown. as per the predictions . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint (trend line in red) the average number of days is constantly decreasing when the number of cases is rising in india. based on the exponential model, the predictions for the next weeks were made for the infected cases in india. considering that doubling rate is going as per the historical evidences, the number of predicted cases in india is shown in table . based on the exponential modelling based growth of the number of covid- cases in india, polynomial regression line was plotted with different degree values. a total of degrees were checked between to and root mean error (rme) was checked for all cases. the lowest rme reported was . for . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint the model with degree . thereafter, the prediction model of polynomial regression of degree was built and used for the prediction values. for training set, data for days was considered starting from -march- to -april- . this was due to the fact that prior to rd march, only cases were reported in indi within days which was impacting the prediction model. for evaluation, data from a short time period of -april- to -april- was used. other train and test sets were also considered and predictions were similar. with these prediction values, it is estimated that the values for infected cases may rise near to , in india which may not be a really good situation in india. the concept of social distancing was suggested by a lot of health experts around the world as it was important that the chain of physical interaction between humans must be broken. the major step in this direction was to announce lockdown at national level. indian government took this suggestion seriously and started with the one-day implementation of lockdown on nd march and then announcing a -day lockdown till th april . it was welcomed by a lot of citizens in india. the same was suggested by google through its mobility report as shown in figure . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint as per the google's method of calculation, every day changes for the number of visits and length of stay at different places were compared the baseline values. the baseline value was considered as the median value for the corresponding day of the week. there were six different categories which were considered important for social distancing and there was a significant drop down seen in five of these categories. graph shows a % decline as compared to the baseline in the visits at retail and recreation places like restaurants, cafes, shopping centers, theme parks, movie theatres, etc.; % decline as compared to the baseline in the visits . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint to the grocery & pharmacy places like markets, food shops, farmer places, drug stores, pharmacies, etc.; % decline as compared to the baseline in the visits to the parks like public beaches, dog parks, marinas, national gardens, public gardens, etc.; % decline as compared to the baseline in the transit stations like bus stations, public transports, metro stations, train stations, etc.; and % decline as compared to the baseline at the workplaces like private and government offices. it was seen that a % increase as compared to the baseline was observed at the residential places which implies that more indians are now staying at their homes. all these numbers cannot be % as a lot of frontline health workers, administrators, pharmacists, grocery store and people involved in other essential services were on duty during the lockdown as well. however, the basic purpose of lockdown to maintain social distancing has been achieved to good potential. citizens are spending more time at their homes as compared to crowded places. so it can be said that indian citizens have been able to follow the lockdown effectively. during the lockdown period, there were two mass events reported in india. one was related to the exodus of the laborers to their respective states in india [ ] and the other was a religious event which happened in new delhi at a mass level [ ] . there are around % citizens living below poverty line and have to depend on the daily wages to feed their families. once the lockdown was announced, the fate of these . billion people was under scanner and that is why even the government of india came up with a package of more than billion usd to help these workers and laborers. all the respective state governments also came up with the different infrastructural setup for providing food and money to the needy citizens. some agencies reported that in providing food security, india and the neighboring nations depending on india may fall short of food [ ] while the others reported loss of millions of job [ ] during the lockdown due to such mass exodus. however, the numbers of infected cases were not impacted much by this mass movement as majority of workers were not carrying any infection with them during their movements from workplaces to their native places. as seen from figure , the average number of days to double the infected cases from corona virus without any cluster event was estimated to be . as per the health ministry, while it is . after delhi's religious event took place [ ] . this event resulted in formation of clusters in the whole country as people who attended this event went to different parts of the country without following any rules of getting quarantine. some of them even came from out of india to attend this event and no rules were followed by them regarding covid- protection. this resulted in a sharp spike in the number of infected cases after st march . as per the figure , at least % of the total infected cases reported on th april were linked to the religious event in delhi [ ] . out of over cases reported, a minimum of cases were suspected to be due to the religious event in delhi. this event took the graph sky high in a week's time with growth slowly moving towards exponential path and india entering into the third phase of community transmission for covid- virus. many regions of india which were totally isolated with the infection of corona virus, also reported their first case in the first - days of the conduction of the event. therefore, it can be said that religious event that happened in delhi has really pushed the bars higher for infected cases from coronavirus in india. it has far more serious consequences than it seems right now and authorities needs to be really alert as people linked to this event have gone back to different parts of the nation. based on the data available from crowdsourced database at covid- -india dot org [ ] , network of the patients and their demographic details was created. the patient id, the countries of travel, and any mass events were considered as the nodes and connection between each patient and his travelling history or event attending history was considered as edge in the network. presenting the visualization of the network consisting of nodes was out of scope for this paper; however degree centrality of important nodes was calculated and is presented in table . degree centrality of the nodes is calculated as the number of connections with that particular node divided by the total number of edges present in the network. the top nodes based on their nodes centralities were religious event in delhi, italy, gulf countries, united kingdom, mumbai, saudi arabia and the first patient. it was found that these were the major hotspots responsible for the rapid spread of coronavirus in india. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint based on the patient database, classification model was developed to check that on the basis of the demographic features, can a patient have the probability to be deceased. other patterns were mined for the rules for covid- patients; however rules were not significant enough for the positive cases as data for negative cases was not available. based on the age group of covid- infected patients, it was found that majority cases are in the age group of - years in india, as shown in figure . the deceased patients are majorly above years of age group and majority people who are infected either travelled back from italy or attended the religious event in delhi. [ ] there was a classification model developed around patients who lost their lives after getting infected from the coronavirus. decision tree classification model [ ] was used to classify that out of the given covid- infected patients, whether a patient will be deceased or not. three features were found to be significant which were the age of the patient, gender of the patient, and the state/region of the patient. although a total of patients have been infected from covid- virus so far, but demographic details of all the patients is not known. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint there were living patients and dead patients modelled on the dataset. out of , only patients had complete demographic details available for the modelling, however for rest of the patients, relevant data imputation techniques [ ] were used and missing values were filled up scientifically. accuracy and precision values were computed based on the confusion matrix generated from decision tree classifier model. the model generated a % accuracy as the data points were too less for the model to be trained and tested. moreover, the three-variable model was not sufficient enough to make an significant relevance out of the model. however, the deaths have found to be more prevalent in the age group of or more years and males were more prominent to getting deceased. also, infants were least impacted by coronavirus in terms of life and death. the state of maharashtra and madhya pradesh were found to be the significant regions for the dead cases. not major inferences can be drawn from the classification model as numbers of cases were low, but as per the records of deceased patients, a hint can be taken by the medical and administrative authorities as in which type of patients need extra critical care. considering the numbers in previous sections, there are five major reasons due to which the national lockdown will be difficult to be abolished. firstly, the growth rate of infected cases is continuously increasing. secondly, the doubling time for number of infected cases in india is declining very fast making it a dynamic spread. thirdly, majority of the indians are following the social distancing fairly well with mobility rates going down for public places in india. this is due to the combined efforts of the administrative authorities, engagement activities by the office of prime minister and citizen's will to stay away from social events. fourthly, the sudden mass events are ruining the efforts of the indian authorities to contain the spread of coronavirus. and lastly, the penetration of the people infected from religious event has been really deep in india currently. there is a lot of tension created in india due to spread of infected people and the numbers are rising with each day. thus, it is very difficult for india to completely ban the national lockdown after th april. in extreme conditions, the state wise rate of infection spread needs to be considered and then decision over lifting the lockdown may be taken. table shows the current number of infected cases in different states of india and the associated growth rates for the last days for each state, respectively [ ] . it can be seen that majority of the states have witnessed more than % of growth rate in last one week, which is worrisome situation for all the state authorities. in fact, the national growth has also been towards % mark which is very in the last seven days. the administrators for the regions with less than infected cases can consider the uplifting of ban on lockdown in their respective regions, however uplifting national lockdown looks difficult. the social distancing must be followed for next few weeks so that curve flattening process can continue for some more time. with respect to transportation services, only intra-state travel may be allowed in states where population density is less and reported cases are less than right now. no inter-state domestic travel should be allowed for the time being as it may result in transferring the covid- carriers from one region to another region. international travel flights must not be activated as the number of cases in majority of the regions of the world is very high. european and us region are already facing most of the turmoil, while other parts of the world are seeing rapid rise in number of infected cases. starting inbound international flights to india may disturb the covid- action plan in india. only essential services should be open for the citizens of india and lockdown should be carried on for next - weeks. this study presented a comprehensive analysis of the covid- outbreak situation in india. the cases are rising very fast and they need aggressive control strategies from the administrative unit of india. there are six different aspects covered up in this study and six research questions have been answered comprehensively. they are related to presenting the growth trends of infected cases in india, predictions for the number of infected cases for next few days, impact of social distancing on the citizens of india, impact of mass events on the number of infected cases in india, network analysis and mining of patterns on the patients suffering from coronavirus, and analyzing the strategies for uplifting lockdown in india. the current study implemented various techniques to present the analysis and the results are in sync with few limited studies available in the literature. this study will be useful for the govern-. cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint ment of india and various states of india, administrative units of india, frontline health workforce of india, researchers and scientists. this study will also be favorable for the administrative units of other countries to consider various aspects related to the control of covid- outspread in their respective regions. coronavirus disease (covid- ) pandemic, who novel coronavirus (covid- ) cases, provided by jhu csse india's swiftness in dealing with covid- will decide the world's future, says who, quartz india india is now the world's th largest economy, world economic forum trend analysis and forecasting of covid- outbreak in india seir and regression model based covid- outbreak predictions in india. medrxiv age-structured impact of social distancing on the covid- epidemic in india network structure of covid- spread and the lacuna in india's testing strategy. available at ssrn covid- : how doctors and healthcare systems are tackling coronavirus worldwide a review of coronavirus disease- (covid- ). the indian journal of pediatrics world health organization declares global emergency: a review of the novel coronavirus (covid- ) early dynamics of transmission and control of covid- : a mathematical modelling study. the lancet infectious diseases the effect of travel restrictions on the spread of the novel coronavirus real-time forecasts of the covid- epidemic in china from critical care utilization for the covid- outbreak in lombardy, italy: early experience and forecast during an emergency response risk assessment of novel coronavirus covid- outbreaks outside india covid- tracker doubling time tells how effective covid- prevention works see how your community is moving around differently due to covid- india covid- tracker centrality and network flow visual analysis of network centralities india: coronavirus lockdown sees exodus from cities, aljazzera news channel coronavirus: search for hundreds of people after delhi prayer meeting, bbc news will coronavirus lockdown cause food shortages in india? bbc news india lost more jobs due to coronavirus lockdown than us did during depression, the print . days doubling time for coronavirus worrisome, deccan chronicle coronavirus: , cases liked to tablighi jamaat event, total crosses , , india today news a new decision-tree classification algorithm for machine learning a comparison of imputation techniques for handling missing data key: cord- -e slzb authors: gola, a.; arya, r. k.; animesh, a.; dugh, r.; khan, z. title: fine-tuned forecasting techniques for covid- prediction in india date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: e slzb estimation of statistical quantities plays a cardinal role in handling of convoluted situations such as covid- pandemic and forecasting the number of affected people and fatalities is a major component for such estimations. past researches have shown that simplistic numerical models fare much better than the complex stochastic and regression-based models when predicting for countries such as india, united states and brazil where there is no indication of a peak anytime soon. in this research work, we present two models which give most accurate results when compared with other forecasting techniques. we performed both short-term and long-term forecasting based on these models and present the results for two discrete durations. in december , some people in wuhan, china were infected by the novel coronavirus, named -ncov and since then, this outbreak has spread to more than countries all over the world. this has led the world health organization (who) to declare it as international public health emergency. governments of the nations affected by this pandemic are running around to formulate provisions and provide resources to handle this epidemic. forecasting the infection rate for a nation can act as a huge asset in planning and formulation of policies for such nations. while no model can accurately forecast the rates of infection and mortality, attempts have been made to consider and analyse the strengths and shortcomings of many studies and models presented regarding the coronavirus. whereas the forecast models used by the health department or government of india were not disclosed, we can definitely continue with existing models in separate publications. each of these models took different approaches and techniques to predict the future rates. there has been a profusion of available mathematical techniques to predict the infection rate for the currently ongoing covid- crisis. in past research [ ] , researchers evaluated the performance of majority of these techniques and concluded with two models which can be used for further purposes of estimating the number of cases affected by the coronavirus as these models gave the best predictions. these two models, exponential curve fitting and least square fitted model, can be used for short-term and long-term forecasting respectively. in this study, we implement these two techniques on an updated dataset taken from the official website of ministry of health and family welfare, government of india [ ] . we estimate the number of affected, death and recovered cases for different durations -one from august to september i.e. for weeks, and the other from august to september i.e. for weeks. we believe this forecast would assist the government and certain other official authorities in preparing and organizing necessary resources to deal with this pandemic. this study is organized into five main sections. the paper starts with the general information about history and information of the disease. section provides the survey of the previously employed forecasting models to predict the confirmed cases in indian context. we present our methodology in section and discuss our findings and results in section . we conclude this research work in section alongside providing scope for future improvements. research on estimation of infection rate of covid- has been quite prolific. majority of these revolve around traditional machine learning methods and neural network-based models. r. sujath et. al [ ] and ajit kumar pasayat et. al [ ] used linear regression models while gaurav pandey et, al [ ] employed polynomial regression technique to predict the coronavirus cases in its early months. r. sujath et. al [ ] also used multi-layer perceptron models alongside their stochastic vector autoregression (var) time-series model. another case of using complex learning models is anuradha tomar et. al [ ] applying a lstm model to forecast the number of cases. in case of small epidemics, meyers [ ] studied the forecasted spread using a model of the susceptible-infected-recuperated (sir). in the simulation covid- diffusion experiments, wu et. al [ ] applied the susceptible-exposed-infectious-recovered (seir) model. anastassopoulou al. [ ] performed a simulation study of situation covid- at the very initial stage of pandemics, a model of susceptibleinfectious-recovered-dead (sird) was used. ghosh et al [ ] used a pandemic model of susceptible infectious susceptible (sis) to forecast spread of the covid- in india. kumar et. al [ ] , in order to analyse the indian scenario, has used the arima time series analysis technique. their predictions were very similar to the later reported actual values. basu [ ] has been researching time-based viral spread in india on his own basis. according to his predictions, in early june, total number of cases in india was estimated to cross , and that prediction was quite . cc-by-nc . international license it is made available under a perpetuity. is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted august , . . accurate. sudip ghosh et. al [ ] used linear square fitted modelling while hemanta kumar baruah et. al [ ] fitted an exponential curve for their predictions. short-term forecasting can be done based on elementary analytical approaches instead of diving into complex architectures like disease modelling or neural networks. previous research [ ] has shown that for shorter durations, simplistic curve fitting models achieve better accuracy than regression and pandemic models. observing the patterns of number cases in countries such as china, spain and italy we can infer that the natural infection rate curve will follow a non-linear path initially till it hits its peak and begins to subside. nations such as india, united states of america and brazil are still in the nonlinear portion of the plot and due to the uncertainty of their peak point, forecasting for such countries can only be done for short durations. recovered deaths observing the pattern for india, we can discern a definite exponential trajectory, which can be exploited by studying the time series data in an inverted fashion and then instituting a numerical model established on the latter part of the data. let p(t) be the total number of affected cases. q(t) be the total number of death cases, and r(t) be the total number of recovered cases at a given time t. to verify out assumption of the curve being exponential, we took the natural logarithm of p(t), q(t) and r(t). the resulting plots shown in fig. are linear for each curve, thus establishing our assumption as legitimate. fitting against exponential functions is exceedingly fragile because tiny variations in the exponent can result in large differences in the result. optimising is done across many orders of magnitude, and errors near the origin are not equally weighted compared to errors higher up the curve. the simplest way to handle this is to convert our exponential data to a linear form using a natural logarithm transformation: considering the equations of curve to be: . cc-by-nc . international license it is made available under a perpetuity. is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted august , . . where a and b are constants. taking natural logarithm of both sides: this allows us to use the linear curve fitting method instead of the slower polynomial fitting method which when employed on large values is prone to result in overflow errors. we would later transform the data back into linear space for analysis. we used the polyfit() function of the numpy module placed in python and got the coefficients' values as: the covariance matrices obtained for each case are shown in fig. . a methodology widely used to perform regression analysis is the least square regression method. this is a statistical technique to determine the best line of fit between an independent and a dependent variable. the 'least-square method' combines measurements in order to extract the parameter estimates that define the curve that best matches the results. using the least square rule, given the set of n (noisy) measurements fi, i∈ , n, which are to be applied to the curve f(a), where 'a' is the vector of the parameter values, we seek to minimize the square of the difference between the measurements and the values of the curve to provide an approximation of the parameters 'a^' according to ( ) when we fit our data to the polynomial function graph, the polynomial curve fit is. the same technique of smallest squares is used to identify a certain degree polynomial which has a minimum overall error: where m is the order of the polynomial is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint we obtain a fit by minimizing an error function -sum of squares of the errors between the predictions y(xn,w) for each data point xn and target value tn. here, polynomial of degree is used for fitting the dataset. observing the non-linear pattern in india's covid- infection rate, we employed curve fitting techniques to predict the number of confirmed, death and recovered cases for both short-term and long-term durations. due to the unpredictable nature of the exponential graph, small modifications in input can lead to abrupt changes in our output. thus, we used exponential curve fitting for short-term forecasting for a duration of weeks starting from august , to september , . polynomial regression modelling is used for long-term forecasting for a duration of weeks starting from august , to september , . results for each case are presented in tables and while their respective plots are demonstrated in figs. and . as per our forecasts, the total number of cases in india would cross , , by august , . by august , it would cross , , , and around september , it should exceed the , , value. is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted august , . is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted august , . building upon the previous research [ ] , current study implemented two numerical models to forecast the number of cases related to covid- in india, namely -exponential curve fitting and least square fitted model. both of the models forecasted an upward of lakhs cases and , deaths for the upcoming months. unless there is a sudden peak in the graph and it begins to subside, we are going to face an enormous challenge to handle this pandemic. to prevent a dearth of required resources, government and official organisations should plan factoring in the forecasted cases. this study can be expanded to establish other mathematical and regression techniques for the forecasting of the covid- cases in future. this would be essential in having a diverse assortment of prediction techniques to consider while developing new policies. is the author/funder, who has granted medrxiv a license to display the preprint in (which was not certified by peer review) preprint the copyright holder for this this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint contact network epidemiology bond percolation applied to infectious disease prediction and control nowcasting and forecasting the potential domestic and international spread of the ncov outbreak originating in wuhan, china: a modelling study data-based analysis, modelling and forecasting of the covid- outbreak covid- in india: state-wise analysis and prediction, medrxiv preprint forecasting covid- impact in india using pandemic waves nonlinear growth models short term forecasts of covid- spread across indian states until short term forecasts of covid- spread across indian states until may, , under the worst-case scenario model based case studies in the uk, the usa and india total coronavirus cases in india, publishing date the current covid- spread pattern in india a machine learning forecasting model for covid- pandemic in india seir and regression model based covid- outbreak predictions in india outbreak trends of coronavirus (covid- ) in india: a prediction prediction for the spread of covid- in india and effectiveness of preventive measures time series analysis and forecast of the covid- pandemic in india using genetic programming predicting the covid- positive cases in india with concern to lockdown by using mathematical and machine learning based models review of forecasting models for coronavirus (covid- ) pandemic in india during country-wise lockdown \nearly perfect forecasting of the total covid- cases in india: a numerical approach situation assessment and prediction of corona virus in india key: cord- -wdh jiry authors: ishtiaq, farah title: a call to introduce structured zika surveillance in india date: - - journal: trends parasitol doi: . /j.pt. . . sha: doc_id: cord_uid: wdh jiry india has the climatic conditions conducive to year-round transmission of zika virus, and a structured disease surveillance program should be implemented to prevent an outbreak. such a program should (i) start screening before an outbreak arises; (ii) collect baseline data to assess future disease risk and monitor potential birth defects; and (iii) provide new insights into the ecology of the disease and inform public health policy following the one health concept. antileishmanial immunity to be able to explore the therapeutic potential. another potential target would be the transcription factor hif- a, the master regulator to the response to hypoxia. hif- a alters myeloid cell functions during l. donovani infection, leading to inhibition of t cell responses. it is also required by leishmania to survive inside macrophages. in the case of hif- a, the therapeutic window is very small, since this transcription factor is involved in many vital functions that are unrelated to the immune response. similarly to b cells, we first need to dissect specific pathways of activation and downstream effects of hif- a to better exploit the therapeutic potential of this target. what is the current status of visceral leishmaniasis? which pressing steps should be taken to reduce it? leishmaniasis is on the who list of neglected tropical diseases, despite the fact that the disease is spread over countries and, in the case of visceral leishmaniasis (vl), is still taking a human toll. over a billion people living in endemic areas are at risk of infection worldwide. there are about one million estimated cases of cutaneous leishmaniasis each year, and of visceral leishmaniasis. some % of the vl cases occur in india, bangladesh, sudan, south sudan, brazil, and ethiopia. leishmaniasis mainly affects poor people in tropical and subtropical regions of the world, and is also associated with factors that are independent of genetics, such as malnutrition, poor housing, and population migration. hence, an effective vaccine would be an ideal solution for controlling disease and limiting transmission, especially for species that can be transmitted from humans to humans, such as l. donovani. unfortunately, to date there is no vaccine available on the market. another important point is the constant emergence of drug resistance and consequently the urgent need to develop new drugs. better epidemiological data are also required to thoroughly understand various reservoirs of infection, and gather information on vectors and leishmania strains and species affecting a determinate region in correlation with disease outcome and severity. finally, we certainly need more information on disease transmission and the role of asymptomatic carriers in parasite transmission. the who aims to reduce the overall burden of these diseases by . in your opinion, are we on track to achieve those goals? why? a reduction in the overall burden could definitely be feasible for some countries. unfortunately, as i mentioned before, leishmaniasis is a disease that is associated with poverty, malnutrition, poor housing, and population displacement. the increasing incidence of conflicts and political and economic instability in certain regions of the world has actually worsened the disease burden in those areas in the past decade. a vaccine would be a cost-effective and a long-term solution to limit the overall spread of the disease in endemic countries. unfortunately, i think that we are still far away from having one. leishmanization (subcutaneous immunization with live parasites) has actually conferred a good degree of protection against cutaneous leishmaniasis. however, this method has never been officially approved because of the possibility that large scars may remain after immunization in certain individuals. moreover, the efficacy of leishmanization against visceral strains has not yet been proven in humans. for the moment, control of infection relies on the systemic treatment of patients and on reservoir and vector control. this method will definitely reduce disease burden in the short term, but only until the emergence of drug-resistant strains. a long-term solution is warranted. farah ishtiaq , * india has the climatic conditions conducive to year-round transmission of zika virus, and a structured disease surveillance program should be implemented to prevent an outbreak. such a program should (i) start screening before an outbreak arises; (ii) collect baseline data to assess future disease risk and monitor potential birth defects; and (iii) provide new insights into the ecology of the disease and inform public health policy following the one health concept. the recent outbreak of zika in south america brought zika under the spotlight and led the world health organization (who) to declare it an international public health emergency in , with an immediate need to prepare for, and respond to, any future epidemic. the who has since declared the end of the public health emergency i , but zika, a mosquito-borne flavivirus, remains a cause of global concern, particularly in resource-limited countries in africa and the asia-pacific region. in these countries, the presence of competent mosquito vectors and suitable climatic conditions could support local transmission of the virus. in india, four cases of zika have now been reported in the media. in november and february , three cases of zika were confirmed from a densely populated area (bapunagar) in the city of ahmedabad in western gujarat state, india ii . whilst the three patients (two pregnant women and an elderly man) showed no complications, and had not travelled outside the country, the government confirmed these cases only several months later iii . more recently, in july , a fourth case, reported from tamil nadu state, was confirmed in a man iv . these are not the first cases of zika virus reported from india; a study conducted in detected the neutralizing antibodies of zika virus in one-sixth of blood sera samples, suggesting exposure to the virus [ ] . as i discuss below, india has the ideal ecological conditions to support transmission and to host a zika outbreak; however, no measures were taken to combat future outbreaks and there is as yet no structured disease surveillance program. zika is thought to be primarily transmitted by aedes mosquitoes v at elevations < m above sea level [ ] , but the scientific literature is dichotomous on whether culex mosquitoes can transmit the virus. in india, aedes aegypti is the only mosquito species that is screened for zika, albeit at a low frequency (> aedes mosquito samples screened until september vi . recently, a controversial report originating from china [ ] , and a second report from brazil [ ] , suggested that culex quinquefasciatus could also potentially transmit the virus. cu. quinquefasciatus is widely distributed and prevalent in india and should be screened for zika virus to increase the likelihood of predicting any potential outbreak. furthermore, vector control is key to prevention and control of mosquito-borne infections and, in india, wolbachia-based vector control strategies for aedes mosquitoes are currently being proposed and prioritized for zika [ ] . a recent study [ ] further emphasises the zika transmission potential of aedes mosquitoes, but also highlights sexual transmission via travellers returning from zika virus-affected areas. the role of human movement has clearly been central to disease transmission following a string of recent outbreaks, including ebola, h n influenza, and severe acute respiratory syndrome (sars). the same study [ ] reported that global human mobility places large populations at risk of mosquito-borne zika virus infection. in india, an estimated . billion people ( air travellers arriving per year from outside the country) are susceptible to zika virus exposure at the time of peak seasonal risk, which coincides with dengue outbreak in the rainy season (august). even though these predictions are based on very conservative estimates [ ] , such modelling efforts may offer useful insights to time-sensitive public health decisionmaking in india. in africa and south east asia, many other host species may support zika virus infection; forest-dwelling birds [ ] , horses, goats, cattle, ducks, and bats [ ] have been reported based on serology, but were not verified by viral isolation. the question of whether birds transfer the virus over long distances remains unanswered. in india, infectious disease ecology with respect to wildlife is completely neglected and, consequently, the potential for the zika virus as spillover infection from other animals to humans has never been considered. furthermore, assessing future zoonotic disease risk requires baseline datainformation about where infectious diseases are distributed geographically, taxonomically (with respect to animal reservoirs), and in relation to human populations. this is illustrated in figure ; the key ecological drivers of zika virus and seasonality in india, where warm temperatures prolong the mosquito seasonhigh mosquito density, densely populated areas, and a continuous flow of airline travellersare likely to facilitate virus transmission by increasing humanmosquito-human contact. the indian zika cases have been reported outside the monsoon season and august, which is modelled as month of peak exposure to zika virus [ ] . in addition, the presence of wild animals, such as rhesus macaques and other animals within human habitation, blurs the boundaries between reservoir hosts and spillover infections, further complicating the prediction of zoonotic disease events in india. of the four cases of zika reported in the media, none has been published in a scientific journal. a confirmed case of zika virus disease requires laboratory confirmation of infection by either the presence of zika virus rna or of antigen in serum or other samples (e.g., saliva, tissues, urine, whole blood); or alternatively the detection of igm antibodies against zika virus. the four cases of zika reported in the media in india seem to have been caused by the asian strain of the virus, the same strain that caused the zika outbreak in brazil vii . however, without a confirmed record, it is difficult for the international scientific community to understand the extent of the disease or even to acknowledge the indian government's reluctance to report these cases. furthermore, flavivirus genetic data are key to understanding the parasite's movement and can be used to infer whether a given strain is the result of locally acquired transmission or importation based on relatedness to locally isolated strains (e.g., [ , ] ). without these data we cannot learn (i) if there has been an outbreak of zika virus at the reported sites in india, and (ii) why the extent of outbreak was not as amplified as in south america or french polynesia. the ecological modelling study [ ] predicts august as the time of peak seasonal risk for transmission of zika in india; however, three of the four reported zika cases in india appeared between november and february in areas with relatively poor access to health services. this discrepancy could be due to an extended mosquito transmission season or delayed appearance of symptoms. malone et al. [ ] reported that up to % of cases of adult human infection with zika virus remain asymptomatic, and it is reasonable to assume that the total number of cases in india is likely to be underreported as they can easily be confused with chikungunya and dengue [ ] . the sporadic and small number of zika cases from india probably suggests either apparent immunity to the virus or a lower number of susceptible hosts to maintain transmission between humans and mosquitoes. a similar trend is now being observed in the americas where transmission persists at low but steady levels with no symptoms [ ] . however, the virus may persist in acute or chronic stages in humans or as zoonotic infection in reservoir hosts, which can be a source for future outbreaks. the concept of disease ecology, or the idea that host-pathogen interactions can be studied within the context of their environment, which is central to understanding the epidemiology and to preventing future outbreaks, has remained neglected in india. in fact, india is an ideal place to explore the coevolutionary dynamics of this host-parasite system because of several factors: (i) the high volume of human movements [ ] , (ii) the apparent immunity to zika from circulating strains of the virus [ ] , and (iii) the possibility of transmission in less immunocompetent hosts, such as pregnant women and the elderly viii , and (iv) adults with a prior history of malaria or dengue infections, which may help facilitate transmission and pathogenesis of zika, potentially resulting in a positive feedback loop [ ] . if there is a positive feedback loop, it may result in a malaria or dengue outbreak and/or the spread of strains of zika adapted to hosts with prior infections. whilst there is no influence of pre-existing immunity to dengue in the kinetics of zika infection in macaques [ ] , this work does not rule out a possible role of preimmunity in the immunologic enhancement in zikaassociated neurological and congenital abnormalities. these factors place india in a privileged place to better understand zika evolution in the asian context and whether reported microcephaly cases are zika-linked or not. but to achieve this, there is an urgent need to collect data on microcephaly and other birth defects ix . finally, to reduce the risk of a zika outbreak in the future, india needs a structured disease surveillance program that will go beyond sample screening postoutbreak; the program should include widespread serosurveillance for underlying population immunity, predictive sampling to collect baseline data to assess future disease risk, and should follow the 'one health' approach with the collaboration of public health officials, clinicians, social scientists, and local government. such work, together with enhanced health care infrastructure aimed at improved diagnostics and maternal care, could provide novel insights into the ecology of the disease and protect women of childbearing age from the potential devastating fetal complications. from zika virus-affected areas provide ample opportunity for virus transmission in densely populated areas. in india, three out of four cases occurred outside of the period of peak seasonal risk (august) predicted in [ ] , and none of the patients had travelled outside the country. (b) human habitation is interspersed with wildlife and livestock, blurring the boundaries between reservoir and incidental hosts for zika virus. (c) susceptible or immunologically challenged hosts act as amplifiers in low to moderate transmission. ii www.who.int/csr/don/ -may- -zika-ind/en/ iii www.business-standard.com/article/ economy-policy/why-was-public-kept-indark-for- -months-after-first-zika-case-in-india- _ .html iv www.thehindu.com/sci-tech/health/there-seemsto-be-low-level-transmission-of-zika-virus-in-india/ article .ece v www.who.int/mediacentre/factsheets/zika/en/ vi www.icmr.nic.in/zika/zika% update% -% th% september% .pdf vii https://scroll.in/pulse/ /india-is-expandingzika-surveillance-but-there-was-an-element-of-luckin-finding-the-tamil-nadu-case viii www.who.int/csr/don/ -may- -zika-ind/en/ ix www.thehindu.com/todays-paper/tp-national/ govt-finally-goes-ahead-to-test-microcephalyzika-link/article .ece proliferation of malaria parasites in a host requires mechanisms to spread between red blood cells (rbcs). we discuss here the implications for biology and antimalarial drug development of companion studies that establish the requirement of two plasmodium spp. proteases of the plasmepsin family in parasite egress from, and invasion into, rbcs. protozoan parasites of the plasmodium spp. cause malaria through cyclic waves of replication within the rbcs of infected individuals, followed by infection of new host cells resulting in large numbers of parasites within circulation. the mechanisms that guide malaria parasites through egress from infected host cells, and invasion into uninfected rbcs, are a subject of intense interest, not least because this critical step in proliferation has been little explored for the development of new drugs for the treatment of malaria and combatting the emergence of drug resistance. plasmodium spp. employ intracellular proteases to break down the surrounding vacuolar and rbc membranes to initiate egress into the bloodstream [ ] . two recent papers identify essential roles in egress and invasion for two previously uncharacterized members of the plasmepsin (pm) family of aspartic proteases, pmix and pmx [ , ] . the studies further demonstrate the potential for pmix and pmx as drug targets to block malaria infections in vivo. plasmodium spp. express multiple plasmepsin protease genes during the blood stage that regulate distinct functions through the cell cycle, including hemoglobin digestion and the export of parasite proteins for remodeling of the host cell (e. g. [ , ] ). pmix and pmx, two homologs of a subclass of the plasmepsin family [ ] , are specifically expressed during the schizont stage of development late in the asexual cell cycle, and had not been previously characterized. in parallel, nasamu et al. [ ] and pino et al. [ ] studied the biological functions and potential drug susceptibility of these proteases in plasmodium parasites. the researchers employed a combination of reverse genetics and chemical biology to discover novel, essential functions for these plasmepsin genes in egress and rbc invasion. the two studies use either conditional knockdown [ ] or conditional knockout [ ] in plasmodium falciparum to show that pmix is specifically required for rbc invasion. pmix is enriched at rhoptries [ , ] , organelles released into the rbc during host cell attachment to initiate formation of a parasitophorous vacuole (pv). pmix is required for efficient proteolytic processing of rhoptry factors in vivo [ , ] , with biochemical evidence in vitro for direct activity toward rhoptry-specific substrates [ ] . based on morphology, proteolytic processing by pmix appears to mediate biogenesis of functional rhoptry organelles [ ] . nasamu et al. employed conditional knockdown in p. falciparum to identify an essential function for pmx in rbc egress, with evidence for function also in invasion [ ] . pmx is targeted to exonemes [ ] , among the earliest parasite organelles discharged during egress, and is required in vivo for proteolytic maturation of the serine protease neutralizing antibodies against certain viruses in the sera of residents of india elevation as a proxy for mosquitoborne zika virus transmission in the americas culex pipiens quinquefasciatus: a potential vector to transmit zika virus zika virus replication in the mosquito culex quinquefasciatus in brazil potential for zika virus introduction and transmission in resource-limited countries in africa and the asia-pacific region: a modelling study arbovirus survey in wild birds in uganda a survey for arboviral antibodies in sera of humans and animals in lombok, republic of indonesia genomic epidemiology reveals multiple introductions of zika virus into the united states zika virus: medical countermeasure development challenges zika virus infection and associated neurologic disorders in brazil the missing pieces: lack of zika data from africa complicates search for answers enhancement of zika virus pathogenesis by pre-existing antiflavivirus immunity impact of prior flavivirus immunity on zika virus infection in rhesus macaques spotlight targeting plasmodium proteases to block malaria parasite escape and entry aditya s. paul and manoj t. duraisingh resources i www.who.int/mediacentre/news/statements/ / zika-fifth-ec/en/ key: cord- -xzcml nv authors: uvais, nalakath a; rasmina, vaniyadathil title: physician deaths in india during covid- pandemic date: - - journal: occup med (lond) doi: . /occmed/kqaa sha: doc_id: cord_uid: xzcml nv nan dear sir, we read the report 'physician deaths from corona virus (covid- ) disease' by ing et al., with great concern [ ] . the authors conducted a google search and found reports of physician deaths due to covid- . the average age of death was . years, % were males, and a significant number of them worked as general practitioners and emergency room doctors [ ] . however, the report did not cover physician deaths in india, the second most populous country and a covid- hotspot. india lost its first doctor to covid- on april [ ] . a recent study showed that there were covid- -related physician deaths in india. around % of deaths were below the age of years, % were below the age of years and % were below the age of years [ ] . the average age of death was years (range: - years), which is lower than ing et al. report, but consistent with the much higher proportion of younger people in india. consistent with ing et al., % of the doctors were males and around half worked as general practitioners. around % of deaths were in surgical specialties [ ] . as india currently has the highest number of covid- cases per day, there is an urgent need to protect doctors and other front-line workers through education and training and adequate provision of appropriate personal protective equipment. physician deaths from corona virus (covid- ) disease impact: india loses first frontline warrior as -year-old doctor dies due to covid- in indore a hundred lives lost: doctor deaths in india during the times of covid- key: cord- -kc t y o authors: ray, soumi; roy, mitu title: susceptibility and sustainability of india against covid : a multivariate approach date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: kc t y o purpose: we are currently in the middle of a global crisis. covid pandemic has suddenly threatened the existence of human life. till date, as no medicine or vaccine is discovered, the best way to fight against this pandemic is prevention. the impact of different environmental, social, economic and health parameters is unknown and under research. it is important to identify the factors which can weaken the virus, and the nations which are more vulnerable to this virus. materials and methods: data of weather, vaccination trends, life expectancy, lung disease, number of infected people in the pre-lockdown and post-lockdown period of highly infected nations are collected. these are extracted from authentic online resources and published reports. analysis is done to find the possible impact of each parameter on covid . results: covid has no linear correlation with any of the selected parameters, though few parameters have depicted non-linear relationship in the graphs. further investigations have shown better result for some parameters. a combination of the parameters results in a better correlation with infection rate. conclusions: though depending on the study outcome, the impact of covid in india can be predicted, the required lockdown period cannot be calculated due to data limitation. the entire world has almost stopped theoretically in the month of march . this is one of the most unexpected and unbelievable situation in world's history. a virus, starting its journey from wuhan city of china in december , has now reached almost all major cities and has created colonies very rapidly. as per world health organization (who), the first case of covid was identified on th december [ ] . initially the disease was misunderstood as some variation of influenza. scientists, researchers and doctors, after doing continuous analysis, then came up with information about this novel corona virus. though the drug is not yet in the market, the structural details of the virus are now known to us [ ] . because of its similarities with the behavior of severe acute respiratory syndrome (sars) corona virus, this virus was named as severe acute respiratory syndrome coronavirus (sars-cov- ) and the disease was identified as coronavirus disease (covid ) by who [ ] . seasonal diseases which have higher mortality rate usually belong to sars category. observing the high infection rate, on th march , who declared covid as pandemic [ ] . in , asian countries were badly affected by sars epidemic which originated in china. the worldwide death toll was , having a ratio of : of registered cases [ ] . in , asian flu virus claimed around thousand lives in india [ ] . one of the severest global pandemic in the history of recent past was flu. this flu was first reported in a spanish newspaper, and it infiltrated india through bombay port. the disease was contagious. it claimed million lives worldwide [ ] . it is claimed that one third of the population was infected. different articles claimed china as the origin of the flu [ ] [ ] [ ] . but death in china itself was very few, whereas india lost almost one fifth of its population [ ] . the estimated death toll was million [ ] . the flu was so deadly, that it brought the population down for first time as well as the last time, till date in the history of india. but the virus disappeared almost suddenly after few months. it is assumed that like any other pathogen, this virus also rapidly mutated to a lesser lethal strain and then finally died out [ ] . covid has many similarities with these flu and sars. all are viral and contagious infections, epidemic in nature, turning into pandemic within few weeks, transmitted through droplets and very easily transmissible from human to human. it is also suspected that coronavirus can be transmitted through air and it can survive in environment without any decrease in its efficiency for a long time and thus the chance of infection increases [ ] . if coronavirus is transmissible and airborne, this is an alarming situation for india. normally during season change, indians suffer from different common ailments like cold and cough, nasal congestion, conjunctivitis etc. many of these diseases are infectious and transmissible. a large part of the population suffers from one or more of these issues commonly. along with those common epidemics, covid has to be taken care of. due to nor'westers during march/april the chances of fast spreading of covid is also high. many people are already infected, among which all are not having significant symptoms and hence not identified. finding ways to stop community transmission, case identification at initial stage and controlling the death rate is an emergency. even the cure will not be easy to save the world if the infection is not prevented. faster and easier worldwide transportation system has turned into a curse in case of viral epidemics. due to international travels, almost all the countries in the world have got infected by this transmissible virus within a very short duration simultaneously. covid has affected countries and territories around the world as of th april . from the information of the impact of pandemic in india, we have tried to understand the underlying facts. a large population who lived near and below poverty line got affected by the pandemic [ ] . apparently, it seems that, the sanitation had a significant relation with the disease infection, spread and severity. but the high mortality rate in case of covid even in developed countries raises a question on this easy assumption. light from a different angle may have some answer to it. people from lower economic segment not only failed to maintain sanitation but also suffered from improper diet. lack of consumption of proper and healthy food weakened their immunity. before , no vaccine other than for smallpox was available. no vaccine or antibacterial was invented to prevent the pandemic diseases. it is not very difficult to assume that the practice of vaccination among the poor people in india was also low. so, hygiene was not solely responsible for the devastating death toll of . immunity also played a bigger role in it. in this article, we have tried to give some insight from available worldwide information, in order to understand the nature of this new coronavirus infection which is causing covid . we have tried to inspect its dependencies on other known parameters. a measure of the possible effects of different parameters on the outbreak and infection growth has also been estimated in order to understand the risk in india. the scientists, from different parts of world, already have done researches and have published valuable information. all the important outcomes have been considered and examined before concluding our findings. a common drawback is associated with most of the reported works. they have discussed impact of single dimensions like temperature, vaccination or life cycle of virus. this has restricted the scope of understanding of the virus's overall activities and limited the chance of prediction and prevention. we have tried to overcome this limitation by replacing univariate analysis with multivariate approach. this article has considered different possible aspects to get a robust outcome. to keep the result as unbiased as possible, we have collected data of multiple cities and countries all over the world having different geographical locations and climatic conditions. we have conducted analysis of several relevant factors to look into the situation from all possible corners. possible dependency of the number of total infection and death has been examined against the environmental conditions taking different weather parameters as independent variables. for this purpose, data of cities all over the world has been considered. these cities are significantly affected by sars-cov . we have collected the covid related data from who site and other data from particular websites for each individual type of parameter to minimize the biases. the duration considered to check dependency of weather parameters is from st to th march, as because by st of march, a large number of countries got significantly infected. the days have been limited to th , as by rd week of march majority of the countries applied social distancing and isolation. data beyond that time may have significant impact of isolation. isolation includes noise in the measure of infection and death, as it puts restriction in virus transmission due to lower availability of hosts. the weather information of all those locations have been collected from a single website [ ] to keep it uniform even if the information includes any noise or bias. we also have taken a measure of the population to compare the infection rate. human to human infection depends on the population for transmission. other than these affecting parameters, another checking has been done on the impact due to the lockdown. how the duration of lockdown has been affecting the number of new infection, have also been examined to understand its importance. we have considered life expectancy also to inspect its impact on the number of infected cases and deaths. the life expectancy includes the impact of different parameters like average living standard, socioeconomic situation, health service qualities, natural calamities etc. a comparison with life expectancy refers to be have a relation with all those hidden parameters though the insights of each are not accessible. the data is collected from united nations development program reports [ ] . as proposed in a paper [ ] , vaccination may have great impact on death. in this article, the data of bacillus calmette-guérin (bcg) vaccination has been compared with present death rate of different countries. this observation has a significant impact in our final outcome. this data is collected from who and review articles [ ] [ ] [ ] . the additional factors included in this study are the impact of lung cancer (lc), chronic obstructive pulmonary disease (copd) and lower respiratory infect (lri). these diseases have shown an impact on death rate in many countries which are badly affected by coronavirus. the required data are retried from online resources [ ] . . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . the total number of cases per million and total death per million are very much correlated as per our examination (ρ= . , p= . e- ) as of th april . because of the good correlation, any of these two parameters can be used for prediction analysis and the outcome will remain comparable. in this article we have used either of these parameters to understand the impact of all other parameters on covid and the results are compared later. we have divided our test result into different parts. in the first part we have discussed the impact of different weather parameters on the number of infected cases. we have not considered active cases because the number is ever changing with continuous addition of new cases, elimination of recovery numbers and deaths. initially the number of infected cases increased rapidly due to lack of awareness, availability of more hosts, free movement of hosts etc. and then gradually decreased for enforcement of quarantine, growing awareness like washing our hands regularly, social distancing etc. these qualitative parameters are not traceable but have significant impact on the number of new cases. different cities, selected in this article, have different geographical locations with widely varying atmospheric condition. if any of the considered weather parameters have a significant effect on infection transmission, then that will impact the transmission equally, irrespective of the location. the list of the cities with parameters details is given in the appendix. we have taken data per million to nullify the population bias. as the virus can be transmitted from human to human and can travel a small distance through droplets with airflow, higher population increases the availability of new hosts and hence the rate of infection. our target is to inspect the significance of that impact. this study is very important for india as its population is very high. the correlation between number of registered infected cases per million and the different weather parameters like temperature measures, humidity, dew points and precipitation have been found. we have used pearson's correlation to check the dependency of identified case numbers with the other parameters. we have used linear regression correlation to understand the linearity in the relationship, its statistical significance and to make a prediction. the results are presented in tabular form in table . . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . the p-value in each case is high enough to support null hypothesis and reject any considerable correlation. but we decided to inspect further. each parameter is examined separately to find any possible impact of covid deaths. this method offers exciting information about lowest temperature and highest temperature. we have considered death of . % of population as the threshold. above this rate is considered as a matter of concern. as per central intelligence agency, present population of india is , , , [ ] . the . % of this population is about , , which is a few thousand more than present death count all over world and not an ignorable count. the countries which experienced higher death rate (as well as death) had the minimum temperature below °c as shown in figure . the y-axes are changed to logarithmic scale to enhance the datapoint visibility. the linear trend lines are also shown in the figures for visual depiction of our understanding, that is with increase in minimum temperature the death rate and total death (hence infection rate) decreases. on contrary, for highest temperature of a place, a range of the temperatures has shown higher risk of death due to covid . the countries with high death rate had highest day temperature in between to degree centigrade as per figure . we have given a try to understand the effect of lockdown. how this lockdown is impacting the community transmission is an important study. the entire world is depending on this policy in absence of vaccines. a detailed study of this factor will help us to predict the required lockdown duration for india. we have taken the number of new registered cases of different countries at the starting of lockdown and then after completion of each week till th april . we have considered the total change per week to reduce the noise of a temporary change in rate. a sudden change in the number for one or two days without any consistency does not portray any significant change of the overall situation of a country. the result is presented as graph in figure . only norway and italy have entered into the th week of lockdown and both countries have shown a drop in new cases after th week. but the steadiness is which is yet to be known, and it is highly required to conclude in a positive note. italy has completed days of th week on th april . the new cases registered in this duration are , which is a little lower rate than the rate per day of th week of lockdown. austria and australia have shown notable reduction after weeks of lockdown. after th day of the th week, the average per day new cases is still very low in austria. australia has just completed day of next week as on th april. though per day rate is lower than last week but it is higher for new cases registered in each of the last days. though no conclusion can be drawn about prevention of infection through lockdown, a prospective evidence of slowdown in the rate of spread of covid pandemic is available. for a decisive interpretation the impact of lockdown needs to be observed for few more weeks. cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . https://doi.org/ . / . . . doi: medrxiv preprint life expectancy has no direct impact on infection growth and death due to that. but life expectancy is connected with different facts as discussed in introduction. along with those, depression, low average education and unemployment also have an impact on the life span of a community. to have a measure of all such hidden factors, we have checked the relation between life expectancy and death rate. here we have taken death per million to compare the change in it with respect to life expectancy. the graph is shown in figure . the surprising observation is that, the high death rate is mostly associated with high life expectancy. inspection of causation is required to understand the actual impact of this finding. this is beyond the scope of our present study and can be considered during advance analysis. not all the affected countries are equally prone to covid as per the report of who. though our preceding analyses have failed to find any strong relationship between the discussed parameters and this pandemic, the presence of some factors influencing the rate of spread of this infection and death rate is obvious. a literature [ ] showed some hope in its study of relation between covid and bacillus calmette-guérin (bgc) vaccination. we have repeated that study to find the relation with present scenario. the work was reported in the middle of march when many countries were not as affected as of today. the scenario in usa has changed dramatically in the last weeks; india also has shown significant increase in the number of infected cases in the last days. hence, the repetition of the analysis is necessary before concluding any decision. our study has shown that vaccination has good impact in most of the cases but there are many exceptions too. the comparison is presented in the figure . france, iran, ireland, portugal and sweden have significant death toll even after having good history of vaccination. on the contrary, australia and canada have quite low death rate without vaccination program. hence the hypothesis of any direct relation between bcg vaccination and covid has been rejected. a further, in depth analysis including more details of vaccination program, coverage of the population, specially in the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . below poverty level population, is required to find the exact relation. a low level dependency of death rate on bcg vaccination is visible in the graph which is supported by statistical analysis of correlation resulting in ρ = . and p-value = . . covid is a severe acute respiratory syndrome (sars) disease. it attacks human lungs, creates trouble in breathing and gradually becomes deadly to claim lives. to understand its relation with other lungs disease, a study has been conducted. top diseases of each country are examined to see the burden of other lung diseases. after preliminary scrutiny, we decided to consider lung cancer (lc), chronic obstructive pulmonary disease (copd) and lower respiratory infect (lri). data cleaning and preprocessing was done before analysis. the rank of these diseases which are among the top and primarily responsible for death in a country has been considered for further analysis. if a disease is not listed in a country's top diseases, a numerical value has been considered. the correlation and p-value of these diseases with death rate are ρ = . , p-value = . . the p-value depicts a higher tendency towards null hypothesis though the correlation is average. the relation lc alone is better with death rate. with a ρ = . , p-value = . lc demands a command over death rate due to covid . this finding does not offer any way of prevention of the pandemic but gives an idea about the risk of a country. none of the above discussed parameters has significant effect covid except lungs cancer. though few have shown impact in increase in number of cases (or deaths) in some cities, nothing convincing has been found. it seems like the disease gets transmitted with almost equal potential in different atmosphere. impact of lockdown is also not considerably good to get any definite suggestion. hence the question remains unsolved. how india is going to response to this pandemic? negative minimum temperature, a specific range of maximum temperature, lack of bcg vaccination and tendency of other lungs diseases have shown some positive impact in increasing the number of covid cases and death. we have combined all these four parameters to see their combined effect on death rate. before statistical analysis, we have done preprocessing of each parameter to create four distinguished features. the temperature data are analogous in nature having no significant impact in case of a minute change. using the already acquired knowledge from the previous analysis, we have classified the temperature into two different classes. in case of minimum temperature, values equal to or below °c are considered as one class which has strong negative impact on death and hence represented by . rest of the temperature values which have less impact or no impact on death are considered as . similarly, maximum temperatures between to °c are converted to and rest are to . disease scores are divided into classes - to , to and . score greater than , represents disease rank within top . for these ranks a disease is represented by . scores from to means the disease is ranked between to and rank below is presented by . when a disease is not listed in top diseases of the corresponding country, it has been represented by . this data preprocessing steps are important for better insight. vaccination is represented by number of the years the program is continued in a country since as mentioned before. after creating a clean dataset with these four features, statistical analysis was done to check if any useful correlation is present. this analysis offers a prominent correlation, ρ = . with high acceptance, p = . . the features are plotted in figure along with increasing death rate. in the figure, singapore, australia and france have shown exception in vaccination impact. the probable reason can be the temperature. both singapore and australia are hot countries. australia is not prone to any lungs disease and singapore has low tendency of lc. on the other hand, france has low temperature and high impact of lc in country's death rate. hence, a significant impact of these parameters can be assumed, and this needs further research for definite conclusion. in april, temperature remains significantly high in india (non-hill zones). in most of the areas, specially in the cities which are reporting high rate of cases and death, the lowest temperature remains higher than °c and maximum temperature goes well above °c. india also have different vaccination program for years and bcg vaccination is done for almost % of the population. the negative factor is that the lung diseases are very common in india. copd (rank ), lri (rank ) and tuberculosis (rank ) are major causes of death here, though lc is not that common like other countries which are badly affected by covid pandemic. this information and data dependent statistical analysis is not self-sufficient to understand the nature of coronavirus. along with this geographic, demographic and meteorological analysis, information from other branches of science like virology, biotechnology must be considered. an important finding about such pandemic is their sudden disappearance after few months. it happened every time in the world's history. not considering the expected life of sars-cov with respect to environmental conditions and continuous mutation will be impractical. the faster the virus will selflimit itself, the earlier the rate of infection will go down. india has imposed quarantine through locked down for days starting from rd of march . in last days the number of cases as well as death has increased significantly. the lockdown do restrict the community transmission but the rate is increasing may be because of detection of already infected cases. fast identification of old cases is required to access the effect of isolation on infection transmission rate. the mortality and morbidity ratio may be affected by the immune system of a population and will vary with different life style factors starting from food habits, common diseases, vaccination programs etc. in the high altitude areas (mainly the himalayan region) with low temperature throughout the year, the risk is higher as per our analysis. february, march are not tourism season of these himalayan region of india because of chilling cold, road blockage due to snowfall and for academic session ending with examinations. probably due to little tourist flow, these regions are still not reporting cases of covid . once the severity of pandemic will fall and the country will start resuming its normal life, the free movement of tourists can be a threat for those hilly areas and it could ignite a reappearance of the disease in cities too through the returned tourists. a proper protection plan and . cc-by-nc-nd . international license it is made available under a author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the (which was not peer-reviewed) the copyright holder for this preprint . restricted movement for reasonably longer time after the pandemic is required to keep the citizens safe. to summarize the risk of india with more accuracy, we have to consider the socioeconomic condition too. a good vaccination program, history of having seasonal endemics ensures better immunity against similar diseases. sars-cov- is a new virus and hence the old antibodies cannot completely prevent it. but whether any antibody has any significant impact on its growth or not is under research. cyclicity is ubiquitous for acute infectious diseases [ ] . each disease is unique on its own. the sars diseases occupy the span of two months, march and april, of indian epidemic calendar. the reason is that the seasonal variation has significant impact on transmission of infectious diseases. this is known as seasonal forcing. if the vaccine of tuberculosis is resistive for covid , then the already present antibodies in the blood will reduce the severity of the disease and death rate in india. the epidemiological characteristics of an outbreak of novel coronavirus diseases (covid- ) in china features, evaluation and treatment coronavirus (covid- ). in: statpearls [internet covid- )-and-the-virus-that-causes-it] . who director-general's opening remarks at the media briefing on covid- - sars (severe acute respiratory syndrome the pandemic of influenza in india did the - influenza pandemic originate in china? population and development review what happened in china during the influenza pandemic? flu pandemic that killed million originated in china, historians say flu experts warn of need for pandemic plans mortality from the influenza pandemic of - : the case of india aerosol and surface stability of sars-cov- as compared with sars-cov- estimation of potential global pandemic influenza mortality on the basis of vital registry data from the - pandemic: a quantitative analysis correlation between universal bcg vaccination policy and reduced morbidity and mortality for covid- : an epidemiological study connecting bcg vaccination and covid- : additional data global, regional, and national burden of tuberculosis, - : results from the global burden of diseases, injuries, and risk factors soper he: the interpretation of periodicity in disease prevalence the first author, soumi ray, ph.d. in image analysis from the indian institute of technology roorkee, has done the data analysis, explored useful insights, prepared the manuscript and concluded the work. the second author, mitu roy, b.tech in computer science from haldia institute of technology, conceived the content and retrieved the data to help the first author. none. both the authors declare to have no conflict of interest. none. key: cord- -vxeq afx authors: lodha, rakesh; kabra, s. k. title: covid- pandemic: the way forward date: - - journal: indian j pediatr doi: . /s - - - sha: doc_id: cord_uid: vxeq afx nan in less than mo, more than million confirmed cases and , deaths have been reported across the world due to the covid- pandemic [ ] . this is much more severe than the pandemic influenza that hit the world in . high case fatality is being reported in high risk groups even from countries known to have the best healthcare facilities. it has overwhelmed the healthcare systems and resulted in severe crisis for hospital beds, particularly intensive care facilities (ventilators). there has been a shortage of essential consumables such as personal protective equipment (ppe), predisposing healthcare personnel to developing covid- [ ] . in the absence of definitive treatment (pharmacotherapy) and vaccines, the most effective measure is to prevent infection, particularly in those at high risk of severe disease/ adverse outcome. as covid- infection is spread by droplets, social distancing, practicing adequate hand hygiene, and wearing face mask/ respirator have been considered to be most effective measures [ ] . to achieve better control, a large number of countries/ regions remained under lockdown for variable period; in addition, countries used different testing strategies for controlling the spread. because of unprecedented case fatalities in certain groups including healthcare personnel (hcp) even in industrialised countries, there is a panic amongst general population as well as hcp. as this is a new infection without effective vaccine or pharmacotherapy, there is uncertainty about the course of the pandemic. world has not faced such a pandemic in the recent past, therefore, there are no ready to use tools to handle these emerging problems. a major positive highlight of the present crisis is proactive role played by the medical journals in helping clinicians/ scientists sharing experiences/ research/ perspectives/ opinions to help colleagues to gain confidence and manage their patients efficiently. because of information technology, we are learning from healthcare professionals across the world to help us plan most suitable methods to deal with these challenges. at the same time, there is some concern about the quality of evidence being published and used to guide management and policy. we are passing through an unprecedented crisis, but we need to move forward. first and foremost is to accept the fact that covid- infection is quite unlike the other viral respiratory infections and in absence of effective drugs and vaccine, it is going to stay with us in the near future. however, we need to understand that more than % of patients recover (> % without need for hospitalization, around % with supportive care in hospital). intensive care may be required by approximately % of the cases (about - % of those hospitalized). the overall case fatality among the hospitalized patients (including those needing intensive care) varies from to % and is largely restricted to high risk groups (old age, diabetes, immunosuppression, etc) [ , ] . experience till now suggests that covid- in children and adolescents is less common and less severe than older age group [ ] . but a potential of spread to household members as well as healthcare workers cannot be ignored. with time, atypical presentations are now being reported in children as well [ ] . it is expected that even if covid- infection rate decreases over next few weeks/months, risk of infection will persist and second surge later this year cannot be ruled out. it is also equally important to understand that due to panic of covid- , we cannot afford to neglect non-covid illnesses, particularly in countries such as india which have a high burden of various diseases-both communicable and noncommunicable. there are certain challenges in opening up the services to non-covid illnesses. the major issues include: how to maintain social distancing to prevent infections in crowded hospitals and how to protect hcps. public hospitals (secondary and tertiary care), in countries like india are very crowded and it is a big challenge to maintain social distancing. overcrowded hospitals with inadequate infrastructure predispose to cross-infection in all, including high risk groups. this may have a potential risk of increasing the infection in the community. to decrease overcrowding in hospitals, it is important to resume routine services in phases. in the beginning, we may start consulting patients by appointments only. we should use this opportunity to develop a system of giving appointments in secondary and tertiary care hospitals. majority of people in our country have mobiles and can be encouraged to seek appointments at secondary and tertiary care hospitals. staggered appointments may reduce crowding at a time in opds; this can be facilitated by information technology platforms. this will also reduce inconvenience to the patients. before calling patients to the hospitals, a tele-consultation could be used as a filter. only those who need physical examination may be called to the outpatient department (opd). patients who need consultation along with some investigations, may be asked to get these investigations before coming to the hospital. this may reduce number of visits to the hospital. management of chronic illnesses can be supported by video-/tele-conferencing. given the high burden of infectious illnesses in countries such as india, there is a need for access to health facilities for these patients also. we will continue to face the annual upsurges in vector borne diseases (dengue, malaria), typhoid fever, diarrheal illnesses, other respiratory illnesses; we need to prepare the health systems to provide care to those affected by these acute illnesses. tele-medicine has been in use for quite some time but it was underutilized. recently, the medical council of india has approved it and has provided guidelines [ ] . clinicians need to learn the art of tele-medicine and using various electronic media and documenting consultations to avoid legal issues in future. as of now, there is no proper or structured referral mechanism for healthcare system in india. the government is implementing "ayushman bharat" program for poor families and moving towards universal health coverage [ ] . this is a time that we move towards achieving universal health coverage for whole country by developing robust and easily accessible healthcare infrastructure. this may help in developing a proper referral system and will reduce unnecessary travel and crowd in tertiary care hospital and improve the efficiencies of the facilities. most of the public health programs-childhood immunization, revised national tuberculosis control program (rntcp), vector borne diseases control programs, among others also have been adversely affected by the current situation. the public health system will have to ensure a rapid catch-up to prevent any significant set-back in the progress made so far. the current crisis has also highlighted the excessive dependence of the country on other countries for supply of consumables, ppe, and medical devices and equipment such as mechanical ventilators. while india is a major player in the world for generic medicines, most of the raw material is sourced from other countries, mainly china. the policy makers should take a serious view of this and implement policies for attaining self-sufficiency in this vital area. simultaneously, there have to be efforts for having highest quality products manufactured in india and also strict punitive action against those indulging in manufacture/ sale of sub-standard or fake goods. protection of hcp from infections requires strict adherence to standard precautions with emphasis on respiratory protection. to achieve this, there has to be adequate supply of good quality ppe as well as a rationale use. during the initial period of the pandemic, there was a great concern, almost a panic like state in hcps. therefore, all efforts should be made to provide highest levels of ppes. over a period of time, hcps will develop confidence and acceptance of covid- as another infectious disease which can be faced using proper precautions and appropriate safety gears. initially, hospital administration has to work hard to make the appropriate ppes available to resume the non-covid healthcare services also. use of n masks along with face shields may become a norm with all patient contacts. providing optimal ppe to hcps will also help prevent shortage of the staff in this critical period, by avoiding unprotected exposures to covid patients and subsequent quarantine. additionally, ensuring physical distancing of patients/ attendants and measures to prevent droplet infection will be a big challenge. clinicians and administrators need to work together to assess the number of patients that can be managed in opd depending on available manpower, physical space, etc. depending on the number of children with influenza like illness, a separate acute respiratory infection treatment unit (atu) can be started. the current strategy is to manage covid patients in a separate hospital/ separate part of a hospital. as the numbers of covid cases increase in the population, we are likely to face situations where patients without any respiratory symptoms will also test positive for covid. there may be logistic issues in testing every patient; over a period of time, we will have to assume possibility of infection in every individual; in the same way we should practice standard precautions, and use appropriate ppe. testing of patients prior to elective surgery is also likely to become a norm-for a couple of reasons: safety of hcps and potential for higher complications in infected patients. at present, most of the healthcare facilities are trying to handle covid related issues. the educational activities in medical schools are also suffering. usual teaching activities have been suspended due to fear of transmission of infection and there is uncertainty about resumption of teaching/training of medical students and specialists. routine admissions, elective procedures and surgeries have declined. evaluation of students have been deferred for few weeks. there are challenges about resuming or continuing teaching and training of medical specialties. many institutions have resumed educational activities using available technology [ ] . online teaching is one of the strong tools; this may be the way forward. all institutions need to develop facilities for online teaching. for training, case discussions can be conducted by tele-conferencing and that is going to replace some classroom/bedside teaching in future. practical training and imparting clinical skills will remain a challenge in the coming days. training by using simulation techniques followed by training in small groups may be a useful alternative [ ] . this will need trained teachers and simulation facilities to be developed. clinical rounds are the cornerstone of learning clinical medicine and acquiring art of bedside clinical skills. examination/observation by experienced consultants is considered to be an important tool in identification of clinical problem and progress of sick children. this is likely to change with the current situation. use of tele−/video conference with actual visuals of the patient by using technology may help in utilizing experience of specialists. these technologies are available but not universally. we need to develop these facilities in all the teaching institutions. in current training and teaching of medical specialists, exit exam is an integral part. the exit exam consists of assessing knowledge and skills of a student by theory and practical examinations. theoretical knowledge is assessed by written paper and viva-voce. theory papers can be conducted with some social distancing. viva voce can also be conducted by using electronic media. conventionally, practical clinical examinations are conducted by formal clinical case work-ups and then by assessing student's ability to take proper history, skill of physical examination and then the analytical skill by discussing various clinical possibilities. there will be challenges in conducting clinical case examinations, and also getting examiners from outside of the city because of travel restrictions. now with changed scenario, there may be some challenges in keeping social distancing or wearing ppes by each examinee. use of simulation and electronic/multimedia for assessment of students may be the solution. in india, the academic schedule is variable across the country; start of new session and exit examination dates are variable. there is a need to harmonize the dates for entrance test, academic calendars, and exit examinations to ensure equal opportunity to all the students across india who plan to take entrance test for various courses. opportunity to improve healthcare in india covid- pandemic has given us an opportunity to identify our limitations in healthcare and improve it by innovation. in india, almost % of outpatient care and % of inpatient care is provided by private sector [ ] . however, due to various restrictions and concerns, the main responsibility to deal with the pandemic situation falls upon the already overburdened public health system. this is the time to strengthen our public health systems to provide healthcare to all without financially challenging the population. world has faced a disastrous situation. many countries have very well developed disaster management plans. establishing departments of disaster management in medical colleges may help in adequately dealing with healthcare disasters/ outbreaks as well producing human resources for future to handle similar situations. it may be a virtual department under leadership of a senior person and members from various specialities that play important roles in management. world health organization. coronavirus disease (covid- ) situation reports opinion to address a potential personal protective equipment shortage in the global community during the covid- outbreak a review of coronavirus disease- (covid- ) pathophysiology of covid : why children fare better than adults? multisystem inflammatory syndrome with features of atypical kawasaki disease during covid- pandemic telemedicine practice guidelines enabling registered medical practitioners to provide healthcare using telemedicine health & wellness centers to strengthen primary health care in india: concept, progress and ways forward student's perception of online learning during covid pandemic professionalism and ethics: a standardized patient observed standardized clinical examination to assess acgme pediatric professionalism milestones publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations conflict of interest none. key: cord- -pnid dmq authors: kumar, manish; patel, arbind kumar; shah, anil v.; raval, janvi; rajpara, neha; joshi, madhvi; joshi, chaitanya g. title: first proof of the capability of wastewater surveillance for covid- in india through detection of genetic material of sars-cov- date: - - journal: sci total environ doi: . /j.scitotenv. . sha: doc_id: cord_uid: pnid dmq abstract we made the first ever successful effort in india to detect the genetic material of sars-cov- viruses to understand the capability and application of wastewater-based epidemiology (wbe) surveillance in india. sampling was carried out on and may at the old pirana waste water treatment plant (wwtp) at ahmedabad, gujarat that receives effluent from civil hospital treating covid- patients. all three, i.e. orf ab, n and s genes of sars-cov- , were found in the influent with no genes detected in effluent collected on and may . increase in sars-cov- genetic loading in the wastewater between and may samples concurred with corresponding increase in the number of active covid- patients in the city. the number of gene copies was comparable to that reported in untreated wastewaters of australia, china and turkey and lower than that of the usa, france and spain. however, temporal changes in sars-cov- rna concentrations need to be substantiated further from the perspectives of daily and short-term changes of sars-cov- in wastewater through long-term monitoring. the study results sars-cov- will assist concerned authorities and policymakers to formulate and/or upgrade covid- surveillance to have a more explicit picture of the pandemic curve. while infectivity of sars-cov- through the excreted viral genetic material in the aquatic environment is still being debated, the presence and detection of genes in wastewater systems makes a strong case for the environmental surveillance of the covid- pandemic. the current ongoing global coronavirus disease pandemic, caused by the infection of severe acute respiratory syndrome coronavirus (sars-cov- ), has spread to countries and territories, with . million of the confirmed cases and more than , deaths worldwide, as of june , (who, ) . the active replication of infectious sars-cov- particles in enterocytes of human intestine due to expression of ace receptor causes shedding of virus in the faeces (lamers et al. ; qi et al., ) . the clinically reported symptoms in covid- patients mainly include cough, difficulty in breathing, fever and diarrhoea (gao et al., ; kumar et al., a) . however, during a previous study of covid- patients, sars-cov- rna was detected in faeces more frequently than gastrointestinal symptoms ( %) such as diarrhoea (cheung et al., ) . these results suggest a large number of asymptomatic individuals along with symptomatic patients, discharge the virus which ultimately reaches sewage treatment plants (haramoto et al., ) . the virus can be shed in faeces for several days, even after the patient stops exhibiting respiratory symptoms . zheng et al., ( ) , reported detection of sars-j o u r n a l p r e -p r o o f disease outbreak in a certain catchment by monitoring viral load in the wastewater, as it contains excrement from both symptomatic and asymptomatic individuals (xagoraraki and o'brien, ; choi et al. ; yang et al., ) . wbe was an effective tool during past outbreak of other enteric viruses, such as poliovirus, hepatitis a and norovirus (hellmér et al., ; asghar et al., ; kitajima et al., , kumar et. al., a , it can be used as an early warning tool for the disease outbreak in a community and used to inform the efficacy of the current public health interventions . wbe data can help estimate actual infected population due to the virus, as it also covers asymptomatic and presymptomatic the patients, which may be underestimated by clinical surveillance (bivinis et. al., ; tang et al., ; wölfel et al., a; , kumar et al., a . detection of, sars-cov- rna in wastewater has been reported in australia, china, france, israel, italy, japan, netherlands, spain and the us (ahmed et al., a,b; bar-or et al., ; haramoto et al., ; la rosa et al., ; medema et al., ; nemudryi et al., ; randazzo et al., ; rimoldi et al., ; wurtzer et al., , kumar et al., c . according to some of these studies, after the number of confirmed cases reached to - per million population, sars-cov- rna was detected in wastewater (ahmed et al., a; bar-or et al., ; medema et al., ; nemudryi et al., ; wurtzer et al., , kumar et al., d . to date of submission of this work, there is no study reporting detection of sars-cov- in wastewater in india. as of june , , the number of confirmed cases in india was per million population. the first case of covid- in india was reported on january , and the number of confirmed cases has reached more than , as of june , (ministry of health and family welfare, india). the state of gujarat has reported > , confirmed cases of covid- , as of june , j o u r n a l p r e -p r o o f , with > , confirmed cases in ahmedabad city (ministry of health and family welfare, india). to further understand the capability and potential application of wbe surveillance, we made the first successful detection of genetic material of the sars-cov- virus in india. we also analysed the temporal variation in genetic material loadings in the same wastewater treatment plant during a lockdown period in india. finally, we evaluated the effect of traditional treatment systems on sars-cov- genetic material and aim to assist concerned authorities and policymakers to formulate and/or upgrade covid- surveillance to include an explicit picture of the pandemic curve. wastewater samples were collected on and may, from the old pirana waste water treatment plant (wwtp) at ahmedabad, gujarat which is the largest wastewater treatment plant in asia with a capacity of > m /day. the wwtp is equipped with an upflow anaerobic sludge blanket (uasb) as an advanced process to treat the wastewater. this wwtp is designed to produce treated water with ph, biological oxygen demand (bod), total suspended solids (tss), and chemical oxygen demand of - . , < mg.l - , < mg.l - and < mg.l - respectively. the sampling location for this study was selected based on the fact that pirana wwtp receives the sewage waste of a government civil hospital treating covid- patient. to ensure accuracy and precision, duplicated analyses of the samples were also performed for a raw wastewater, in which the reproducibility was fairly high (average c t difference of . ). several blanks were prepared and run to check the cross-contamination, and sensitivity of the protocol, extraction and instrumentation. all analyses were conducted at the indian council of medical research (icmr), new delhi, an approved facility of the gujarat biotechnology research centre (gbrc). viral rnas were isolated from sewage samples using following steps: precipitation of viral particles; viral rna isolation and quality checking. the sewage samples ( ml) were centrifuged at ×g (model: sorvall st r ,thermo scientific) for min followed by filtration of supernatant using . micron filters (mixed cellulose esters syringe filter, himedia). each sewage filtrate was then concentrated using the poly ethylene glycol (peg) methods. for this method, peg ( g/l) and nacl ( . g/l) were mixed with ml filtrate and this was incubated overnight at °c and rpm (model: incu-shaker tm lr, benchmark). the following day the mixture was centrifuged at ×g (model: kubota , kubota corporation) for mins. after centrifugation, the supernatant was discarded and the pellet resuspended in µl rnase-free water. this was further used as a sample for rna isolation. rna isolation was carried out using a commercially available kit (nucleospin ® rna virus, macherey-nagel gmbh & co. kg, germany). concentrated viral particles ( µl) were mixed with µl ms phage, µl proteinase k ( mg/ml) solution and µl of rav buffer containing carrier rna. here, ms phage was taken as a molecular process inhibition control (mpc; haramoto et al ) for evaluating the efficiency of nucleic acid extraction and pcr inhibition. it is to be noted that ms may naturally occur in wastewater, it is therefore there is possibility that recovered ms may consist both the spiked and background viral content. further steps were carried out as instructed in the product manual (macherey-nagel gmbh & co. kg). final elution was carried out with µl of elution buffer (provided by kit). rna concentrations were determined using a qubit fluorometer (invitrogen). j o u r n a l p r e -p r o o f rnas were analysed for the detection of orf ab, n gene and s gene of sars-cov- and ms (internal process control) by rt-pcr using taqpath tm covid- rt-pcr kit (applied biosystems). amplification was performed in a μl reaction mixture containing μl extracted nucleic acids of each samples. positive control ( μl) (taqpath™ covid- control) and purified negative control ( μl) were used in case of positive and negative control respectively. nuclease free water was used as no template control in this study. further procedures were carried out as described in product manual. rt-pcr experiment consisted of ung incubation at °c for min, reverse transcription at °c for min and activation at °c for min, followed by cycles, each involving denaturation at °c for s followed by annealing/extention at °c for s. the reactions were performed in applied biosystems™ fast real time pcr system (applied biosystem), and interpreted as instructed in the manual. although there is no direct correlation of the c t value to copy numbers as the kit used for the detection is qualitative assay yet we put an effort to calculate number of gene copies present in a unit volume of the sample. for this the well-established principle of . c t change corresponds to -fold change has been used. more precisely, copies of sars-cov- genes were taken as positive control with c t of average for all the three genes i.e. orf ab, n and s, which were then extrapolated to compare it with sample c t values and derive approximate copies of genes in the wastewater sample. the amount of rna used as template was multiplied with the enrichment factor to derive an estimated copy numbers for each wastewater sample. table shows the number of active cases for the city i.e. ahmedabad and india, obtained by deducting recovered cases from total confirmed cases since march, . consistency between abundance of sars-cov- genetic materials and number of confirmed cases was observed in the previous reports in australia, france, italy, spain and japan further, referring to the limitations of the present study owing to lockdown scenario, we recommend that although based mpc analysis, the efficiency of rna extraction and rt-pcr is considered high for all the wastewater samples collected for this study, the efficiency of peg method could have been better established. further, based on indigenous f-phage analysis hata et al., ( ) reported a high efficiency of peg method in japanese wastewater, yet an evaluation of sample concentration efficiency, using the whole process control (wpc) together with mpc is recommended (haramoto et al ) . we recommend longer monitoring with several replicated analyses to evaluate the correlation as well as uncertainties involving rt-pcr (stuart et al ) and then replace the semi-quantitative method employed in this study with precise copy calculations using suitable methods. nevertheless, the bottom line is that the patterns of obtained c t values suggest successful detection of sars-cov- rna from the wastewater samples, their increasing abundance together with an increase of covid- confirmed cases, and their reduction by uasb treatment and aeration pond. in summary, results demonstrated the capability of wastewater-based epidemiology in indian settings and strongly advocates that despite the lack of quality sewer infrastructure or other wastewater collection issues, wbe can be applicable and thus we strongly implementing environmental surveillance of the cvoid- pandemic in india, starting with major cities. while the world is providing high resolution proofs of the wbe concept, india needed indigenous proof of concept and its applicability. in this context, we achieved two major outcomes: i) for the first time in india and top efforts in the world, we isolated sars-cov- genetic material and detected it during a lockdown period owing to good coordination among the government organizations; ii) temporal variation in ct value demonstrated the capability of wbe surveillance in india; and iii) for the third time in the world treated water was analysed for the presence and confirmation of sars-cov- genetic material. the results were of good resolution and provided significant indication of temporal variation in covid- patient loadings. however, owing to limited samples analysed in this preliminary study, even though the case numbers align with increased rna concentrations in wastewater, the temporal changes in sars-cov- rna concentrations needs to be further investigated from the several perspectives of daily, short-term and long-term changes. our results demonstrated that a conventional treatment plant is capable of removing genetic materials j o u r n a l p r e -p r o o f of sars-cov- , however there may not be the complete elimination. in a country like india where sewer systems are not complete and only a part of the waste is received at wwtps, it is essential to study each treatment stage to determine the effectiveness of treatment. this will help reduce the commonly perceived fear of the commons pertaining to the effectiveness of treatment plants as well as transmission through wastewater. the authors declare no competing financial interest. j o u r n a l p r e -p r o o f zhang, w., du, r.h., li, b., zheng, x.s., yang, x. lou, hu, b., wang, y.y., xiao, g.f., yan, b., shi, z.l., zhou, p., a . molecular and serological investigation of -ncov infected patients: implication of multiple shedding routes. emerg. microbes infect. 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as naming all of them involved or helped during analyses or sampling or protocol development would be difficult. special key: cord- -ymurfkbs authors: bhattacharya, sudip; hossain, md mahbub; singh, amarjeet title: addressing the shortage of personal protective equipment during the covid- pandemic in india-a public health perspective date: - - journal: aims public health doi: . /publichealth. sha: doc_id: cord_uid: ymurfkbs nan such resources in the state or national level can be useful so that equipment are not being used can be mobilized with other institutions experiencing scarcity. such approaches may foster collaborative efforts against covid- ensuring efficient use of resources at the systems level. nonetheless, it is only possible to address covid- if we can flatten the epidemic curve by classical intervention measures like lockdown and social distancing processes, which may give lead time to many health care systems to arrange further management of the outbreak. but during exponential phase of pandemic as rapid increase in covid- patients it is very challenging to provide adequate ppes to the health workers of any country. to solve this problem, i.e., to optimize the use of face masks during the pandemic, the centers for disease control and prevention (cdc) identifies levels of operational status: conventional, contingency, and crisis [ ]. during normal times, face masks are used in conventional ways to protect hcws from splashes and sprays. when health care systems become stressed and enter the contingency mode, cdc recommends conserving resources by selectively cancelling nonemergency procedures, cancelling outpatient encounters which might require face masks/ppes. when face masks are unavailable, the cdc recommends use of face shields without masks, taking clinicians at high risk for covid- complications out of clinical service, staffing services with convalescent hcws presumably immune to sars-cov- (severe acute respiratory syndrome coronavirus ), and use of homemade/handmade masks, perhaps from bandanas or scarves if necessary [ ] . many communities in the india and globally are rapidly entering ppe crisis mode. recently news are circulating about the unconventional solutions for ppe at local hospitals, such as plastic garbage bags for gowns and plastic water bottle cut outs for eye protection [ ] . shortage of sanitizer can be solved by using handmade sanitizer having % concentration of alcohol, this type of ideas/news/decisions are facing many continued criticism from medical fraternity as they are perceiving as mockery/knee jerk response. plans for resupply through the repurposing of existing industrial capacity are welcome but seem unlikely to solve the shortage quickly enough as supply chains become affected in the pandemic [ ]. the task force to combat covid- was created to solve precisely this problem, but its inventory is not transparent and news reports suggest its supplies are being distributed unevenly or are insufficient to meet demand [ ] . hcws need supplies and solutions for these shortages now, and for that reason, the journal of american medical association (jama) issued a call for ideas for how to address the impending ppe shortage [ ]. there were many proposals (table ) . . sterilization of used ppe with agents ranging from ethylene oxide, uv or gamma irradiation, ozone, and alcohol was identified as common proposal. there were also novel proposals such as mask-fiber impregnation with copper or sodium chloride, these ideas are not unscientific they were field tested after prior viral epidemics to determine the feasibility of sterilizing ppe [ ] . although scientists acknowledged that the uncertainty about the effects of these sterilizing agents on the structural integrity of ppe, and there is some evidence the fibers in masks and respirators that filter viral particles can degrade and lose their efficacy with ppe reprocessing [ ] . some of the other idea was to reduce patient contact so most of the private clinics remains closed and most of the clinicians doing teleconsultations. alter staffing is also considered as important step, health department of india gave directives to the medical colleges that the all health care workers will work on a rotation basis for minimizing the contact risk [ ] . home delivery of online groceries are another option. in india, a company named "big-bazaar" is already providing online groceries to the peoples who are confined in their homes due to lockdown [ ]. however, such technology-based services are contingent on the availability and accessibility of those services in different countries. in india and other low and middle-income countries, innovative technological interventions should be devised and deployed to ensure timely and efficient distribution of goods and services. such socioeconomic approaches may not only reduce the risks of covid- transmission but also ensure daily necessities of the citizens are met adequately. other measures are like appointing the healthy staffs to the service area and the staffs who have medical conditions are exempted from service delivery. other than that, using government services like relaxing importing rules, use of police forces, converting railway coaches as isolations are also important and innovative steps. legislative steps like mandatory social distancing, curfew, can help the crisis period by flattening the epidemic curve [ ] . these are the short-term conventional solutions. here we propose few more which is out of the box thinking like-production of sanitizer at mass scale by the alcohol industry during covid- crisis period, in india is happening right now [ ] . similarly, in india, the textile industry and hardware industry is producing bulk masks, gowns, caps, protective shields etc instead of producing clothes [ ] . moreover, the automobile industry can make ventilators instead of producing vehicles at this critical period. in india, the mahindra group came out with a prototype ventilator and soon they will start producing [ ] . besides this, global evidence on managing the shortage of ppe can be useful to inform future strategies. for example, taiwan experienced a critical shortage at the beginning of the covid- crisis. implemented this issue was mitigated by several strategies including rapid production and distribution of ppe to prioritized centres resulting in a declined shortage of ppe. these strategies used a -tier personal protective equipment (ppe) stockpiling framework that could maintain a minimum stockpile for the surge demand of ppe in the early stage of a pandemic [ ] . some of these strategies include export prohibition, rationing, and increase production through either mandates or voluntary productions [ ] . we believe many lessons can be learnt from countries like these. these countries provide real-time examples that can be copied by others with similar healthcare systems. such local and global innovations should be evaluated and adopted ensuring patient compliance during covid- to improve health outcomes. in our opinion smart questions need smart answers, in the era of emerging and re-emerging disease outbreaks like covid- , besides the conventional approach we must think differently and implement the success stories of similar countries in india. while health systems in most of the countries are struggling to fight covid- , the operational challenges including safety of the health workforce and prevention of transmission is much higher in resource-constrained contexts. it is essential to prioritize these health issues and adopt best practices to ensure the availability, accessibility, and utility of ppe and other resources in an efficient way. multilevel policy interventions with user-level quality assurance may help in mitigating those issues. perhaps, more importantly, we have to extend our support to each other, act together for our survival, without blaming each other. world health organization ( ) coronavirus disease (covid- ) line rajasthan govt directs private liquor companies to manufacture hand sanitizers the economic times ( ) coronavirus impact on textile industries: indian textile and apparel industry to be affected due to coronavirus attack in china: cmai. available from mahindra's ventilator for coronavirus patients to cost less than rs , ; designed in hours stockpile model of personal protective equipment in taiwan its response to the crisis shows that swift action and widespread healthcare can prevent an outbreak all authors declare no conflicts of interest in this paper. ( ) key: cord- -fsbp fky authors: broor, shobha; dawood, fatimah s.; pandey, bharti g.; saha, siddhartha; gupta, vivek; krishnan, anand; rai, sanjay; singh, pratibha; erdman, dean; lal, renu b. title: rates of respiratory virus-associated hospitalization in children aged < years in rural northern india date: - - journal: j infect doi: . /j.jinf. . . sha: doc_id: cord_uid: fsbp fky objectives: though respiratory viruses are thought to cause substantial morbidity globally in children aged < years, the incidence of severe respiratory virus infections in children is unknown in india where % of the world's children live. methods: during august –july , prospective population-based surveillance was conducted for hospitalizations of children aged < years in a rural community in haryana state. clinical data and respiratory specimens were collected. swabs were tested by rt-pcr for influenza and parainfluenza viruses, respiratory syncytial virus (rsv), human metapneumovirus, coronaviruses, and adenovirus. average annual hospitalization incidence was calculated using census data and adjusted for hospitalizations reported to occur at non-study hospitals according to a comunity healthcare utilization survey. results: of hospitalized children, respiratory viruses were detected among ( %), of whom ( %) had fever or respiratory symptoms. rsv accounted for the highest virus-associated hospitalization incidence ( . / , , % ci . – . ) and % of hospitalizations. there were . / , ( % ci . – . ) influenza-associated hospitalizations ( % of hospitalizations). rsv and influenza virus detection peaked in winter (november–february) and rainy seasons (july), respectively. conclusion: respiratory viruses were associated with a substantial proportion of hospitalizations among young children in a rural indian community. public health research and prevention in india should consider targeting rsv and influenza in young children. rates of respiratory virus-associated hospitalization in children aged < years in rural northern india introduction acute respiratory infections are recognized as an important cause of mortality, hospitalization, and healthcare utilization in young children globally. e respiratory virus infections are increasingly recognized as major contributors to the burden of severe acute respiratory illness in many countries due to expanding global surveillance and the advent of improved molecular diagnostic testing for respiratory viruses. e in studies of respiratory virus detection among children hospitalized with respiratory illness from different parts of the world, rsv and influenza are frequently associated with a substantial proportion of hospitalizations. e these findings are of public health importance because effective and safe influenza vaccines are available but not widely used in many countries, and development of respiratory syncytial virus (rsv) vaccines continues to be an area of intense study although no licensed rsv vaccine is available. , , understanding the incidence of respiratory virus-associated severe illness and the timing of respiratory virus circulation is critical to inform research priorities and policy decisions about introduction of available respiratory virus vaccines for children. india is the second most populous country in the world with % of the world's population of children aged < years, and almost a third of global pneumonia cases among children aged < years are thought to occur in india. public health policies that effectively address causes of severe respiratory illness among children in india would have a substantial impact on global child morbidity and mortality. however, the burden of respiratory virus-associated severe illness among young children in india is unknown. in addition, the few studies that evaluated respiratory viral etiologies of severe illness among children in india were conducted before the advent of newer and more sensitive diagnostic tests, including tests to detect more recently discovered viruses. e using data from population-based surveillance of approximately children for hospitalizations for acute medical illness in rural northern india and concomitant testing for respiratory viruses by real-time reverse transcription polymerase chain reaction (rrt-pcr), we estimate the incidence of respiratory virus-associated hospitalizations among children aged < years. we also describe the timing of virus circulation and clinical presentation of children hospitalized with predominant viruses. the comprehensive rural health services project (crhsp), ballabgarh study site includes a square kilometer area in haryana state, about km south of new delhi. the climate is temperate with a defined colder winter season during novemberemarch and rainy season during julyeseptember. as part of the crhsp, a health and demographic surveillance system (hdss) was maintained under which all residents of the crhsp study site were enrolled in a computerized database with unique identification numbers. the hdss tracked major events such as births, deaths, marriages and migrations. during the study period, the crhsp study site included a population of approximately , persons including approximately children aged < years in villages. the main providers of inpatient care to the crhsp population are a government-funded secondary level facility with beds that provides outpatient and inpatient care and serves e % of the crhsp population, two other government-funded secondary level facilities, and a large number of private health facilities (ranging in size from to beds) that provide inpatient and outpatient health services. health facilities are largely situated outside crhsp villages within a range of e km and largely accessible by two/three wheelers. most facilities have the resources to care for patients requiring supplemental oxygen but transfer patients requiring mechanical ventilation and intensive level to tertiary care facilities outside the district. hospitalized patients were enrolled from the three secondary level facilities and private facilities in ballabgarh and faridabad towns where patients from the crhsp area were likely to seek inpatient care corroborated by health utilization survey. patients were eligible for enrollment if they were residents of the crhsp area and were being hospitalized overnight with any acute medical illness, excluding hospitalizations for the following conditions assumed to be unlikely to be related to respiratory infection: trauma, diarrhea without fever, elective surgery, accidental poisonings, elective blood transfusions, or orthopedic or ophthalmologic conditions. during august ejuly , patients were prospectively enrolled in the study as previously described. data on demographic characteristics, medical history, and clinical symptoms were obtained by interview of patients' caregivers. data on clinical signs were abstracted from the medical record using a standardized data collection form. respiratory specimen samples were collected by study doctors from enrolled patients within h of admission using polyester swabs. during augustedecember , study investigators visited all houses in the villages of the crhsp area to conduct a healthcare utilization survey using a standardized questionnaire that was field testing in previous years; % of households in the area completed the survey. the survey asked whether any member of the household had been admitted to a hospital for an overnight stay during the preceding year (using a reference period of august , ejuly , . for each reported hospitalization, the survey asked about the location and reason for hospitalization, and field workers attempted to validate reports with any available documentation related to the hospitalization. combined throat and nasal swabs were collected from each participant (nasal swabs alone in infants). the swabs were transported in viral transport media on ice to the all india institute of medical sciences (aiims) laboratory within h. samples were then divided into aliquots for respiratory virus detection by rrt-pcr. testing for influenza viruses and influenza virus subtyping was conducted at aiims using us centers for disease control and prevention (cdc) protocols and after laboratory staff received cdc-sponsored training and the laboratory underwent quality control assessment by cdc. testing for non-influenza respiratory viruses was also conducted at aiims using highly sensitive rrt-pcr assays for respiratory syncytial virus (rsv), human metapneumovirus (hmpv), human parainfluenza viruses e (piv e ), adenovirus, and human coronavirus e using cdc protocols e ; protocol are available from cdc upon request. baseline characteristics, clinical symptoms and signs, and length of hospitalization were compared between children with and without respiratory virus detection using bivariate analysis. frequencies of clinical symptoms and signs and median length of hospitalization were also calculated for children with rsv and influenza, the most commonly detected viruses. tachypnea was defined based on integrated management of childhood illness criteria for fast breathing as breaths per minute in children aged < months, in children aged e months, and in children aged e years. hypoxia was defined as an oxygen saturation of < % by pulse oximetry at admission. chisquared test or fisher's exact test was used to calculate pvalues for categorical variables and the wilcoxon test was used to compare continuous variables (sas, version . , sas institute inc., cary, nc). since all children hospitalized with acute medical illness were enrolled, the proportion of respiratory virus detections among children with and without fever or key respiratory signs or symptoms was evaluated. fever was defined as either measured temperature > . celsius at admission or parental report of fever because antipyretic use was common in the study community. key respiratory symptoms or signs were defined as parental report of cough or fast breathing or physician exam findings of tachypnea, crepitations, wheezing, nasal flaring, chest indrawing, grunting, or stridor. inclusion of nasal discharge did not change the proportion of children meeting criteria for key respiratory symptoms or signs. all children, regardless of symptoms or signs, were included in all subsequent analyses. using data from the healthcare utilization survey, the proportion of hospitalizations among children in the study community that occurred at study facilities was calculated as reported hospitalizations at study facilities divided by total reported hospitalizations; % confidence limits were calculated using the wald method. average annual cumulative incidences of hospitalizations associated with detection of each respiratory virus were calculated for children aged < year, e years, and < years. incidences were also calculated for children aged < months for rsv and influenza since maternal immunization with rsv and among the children with respiratory virus-associated illness, history of fever ( %) and cough ( %) were the most commonly reported symptoms. parental report of cough, nasal discharge or congestion, and fast breathing and exam findings of hypoxia, crepitations, wheezing, and increased work of breathing were more common in children with respiratory virus-associated hospitalizations than those without (table ) ; the median length of hospitalization was similar in both groups ( vs. days, p z . ). none of the children died. a larger proportion of children with rsv detection compared to children with other respiratory viruses had a reported history of fast breathing ( % vs. %, p z . ) and exam findings of increased work of breathing ( % vs. %, p < . ), crepitations ( % vs. %, p < . ), and wheezing ( % vs. %, p < . ). of children aged < years residing in crhsp area, ( %) were included in the health utilization survey, and % ( % ci e %) of all acute medical hospitalizations reported on the health utilization survey occurred at study facilities ( respiratory viruses were detected almost year-round among children hospitalized with acute medical illnesses (fig. ) . rsv detection occurred from november through may with a longer period of detection during e than during (fig. ) . in contrast, influenza virus detection peaked during the rainy season in juneejuly when influenza accounted for e % of monthly acute medical illness hospitalizations. detection of other respiratory viruses occurred sporadically throughout the year. based on surveillance of approximately children, this study is the first prospective, population-based study to measure the incidence of respiratory virus-associated hospitalizations among children aged < years in rural india. we found that respiratory virus infections were associated with % of acute medical illness hospitalizations among children aged < years, and one in five children hospitalized for acute medical illness had rsv infection. consistent with prior studies, we also found that virus-associated hospitalization rates were highest among children aged < year. rsv was the predominant virus identified among children aged < year. among children aged e years, incidence rates of rsv and influenza viruses were similar. rsv and influenza viruses circulated with clearly defined but different seasonality and were infrequently detected among children without fever or respiratory symptoms or signs, similar to prior studies. , , the incidence of rsv-associated hospitalizations in our study community was substantial, with an incidence of per , child-years among children aged < years and per , child-years among children aged < year. many studies have reported rsv as the most common respiratory virus resulting in hospitalization in young children, but relatively few have estimated the incidence of rsvassociated hospitalizations. rsv-associated hospitalization rates per , children ranged from to among children aged < year in studies from rural thailand, indonesia, the united kingdom, and the united states; e among children aged < years in hong kong and the united states; and and among children aged < years without and with hiv infection in south africa. our estimates are similar to those of prior studies from the united states, europe and asia. given the high incidence of rsv-associated hospitalization in our study, availability of an effective and accessible rsv vaccine for young children in india would profoundly impact hospitalization rates in this age group. because the incidence of rsv-associated hospitalization is highest in infants aged < months in whom maternal antibody interference with immune responses may make vaccination challenging, rsv vaccination . ( e . ) . ( e . ) a adjusted to account for hospitalizations that occurred at non-study facilities based on data from healthcare utilization survey. b children with co-detection of more than respiratory virus were included in the incidence estimate of each respiratory virus detected. c among infants aged < months, the adjusted incidence of hospitalization for rsv was . hospitalizations/ , ( % ci . e . ). d among infants aged < months, the adjusted incidence of hospitalization for influenza was . hospitalizations/ , ( % ci . e . ). of pregnant women has been suggested as another potential vaccination strategy. e though licensed rsv vaccines are not currently available, candidate vaccines are under development , and data on rsv disease burden will be important for policy decisions about rsv vaccine introduction if a licensed vaccine becomes available. although we found that influenza viruses were associated with a lower incidence of hospitalization than rsv among children aged < years, influenza-associated hospitalizations accounted for % of all acute medical hospitalizations and up to % of monthly hospitalizations during peak circulation. a similar population-based study conducted in western india during the same time period as ours found similar influenza-associated hospitalization rates among children aged < year and higher rates among children aged e years. the contribution of influenza to severe respiratory illness among children in india deserves attention because influenza vaccines are not currently recommended and are not widely available in india. both traditional inactivated influenza vaccines e and live attenuated influenza vaccines e have been shown to be effective against influenza in children in high-income countries. additional studies are needed to further develop the evidence base for policy makers in india to decide whether to support influenza vaccination recommendations for children. these studies should include data on the incidence of severe influenza in other regions of india, the effectiveness of influenza vaccine among indian children, and the costs of influenza in india. a study of influenza vaccine effectiveness among children aged < years in rural india is underway. the timing of respiratory virus circulation varies globally. rsv and influenza viruses circulate during the colder winter months in some but not all temperate countries. however, influenza viruses circulate year-round in some tropical countries and both rsv and influenza virus circulation seems to coincide with increased rainfall in some places. , india is a large and geographically diverse country with temperate, sub-tropical and tropical climates. in our study, conducted in a temperate area, we found that rsv and influenza circulated during clearly defined but different periods. studies from western india suggest that influenza virus circulation is less defined there, with peaks during the rainy season but perennial influenza virus circulation. , additional studies of influenza virus seasonality in other regions of india are needed to determine optimal timing for influenza vaccination and other prevention measures. the advent of highly sensitive pcr assays for respiratory viruses allows easier detection of a wider array of viruses but also presents the challenge of interpreting positive test results. prior studies have shown that some respiratory viruses are frequently detected by pcr among children without fever or respiratory symptoms. , , respiratory virus detection in these children may reflect acute infection with atypical symptoms or prolonged shedding of virus from a prior infection highlighting the utility of a control group of children without acute illness to aid interpretation of test results. our study did not have a control group, but the large majority of children with respiratory virus detection had fever or respiratory findings that support the clinical diagnosis of respiratory infection. our estimates of rsv and influenza-associated hospitalization incidence are supported by prior studies of hospitalized children in which detection of these viruses was rare from control groups comprised of hospitalized children without fever or respiratory symptoms or non-hospitalized children. though adenoviruses, coronaviruses, human metapneumovirus, and parainfluenza viruses have all been previously implicated in the pathogenesis of severe illness, our hospitalization incidence estimates for these viruses should be interpreted with more caution as detection of these viruses has varied among control groups in other studies. , , several points should be considered when interpreting our findings. first, our study was conducted at primary and secondary level health facilities without capacity to provide mechanical ventilation and intensive care for critically ill children. thus, we may have missed hospitalizations of children with more severe illness who were directly admitted to tertiary care hospitals outside the study area. our study community may also have been too small to evaluate the frequency of rare but severe outcomes such as death. second, although we attempted to collect the discharge diagnosis of all enrolled children, these data were largely absent from the medical record and therefore could not be used to aid interpretation of respiratory virus testing results. third, we included testing results for only a select group of respiratory viruses previously identified as being associated with a large proportion of respiratory illnesses in children. therefore, our results reflect the burden of respiratory virus-associated hospitalizations caused by this select group of viruses. we did not include test results for rhinoviruses because interpretation of rhinovirus detection in the absence of a control group is difficult, although rhinovirus was the most commonly detected virus in children with respiratory illness in some prior studies. additionally, we did not conduct testing for coronaviruses other than coronavirus e, and may have underestimated the incidence of coronavirus-associated hospitalization in the study community. lastly, respiratory virus circulation and incidence is known to vary by year. our study was conducted over a two year period and we present average annual cumulative incidences of virus-associated hospitalization. additional studies of respiratory virusassociated disease burden during additional years will be useful for comparison with our findings. the findings and conclusions in this report are those of the authors and do not necessarily represent the views of the centers for disease control and prevention. this study was supported in part by cooperative agreements u ip from the centers for disease control and prevention, atlanta, us. the authors do not have any relevant conflicts of interest to declare. global, regional, and national causes of child mortality: an updated systematic analysis for with time trends since global and 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alaska burden of seasonal and pandemic influenza-associated hospitalization during and after a(h n )pdm pandemic in a rural community in india vaccine effectiveness against laboratoryconfirmed influenza in children to months of age during the e and e influenza seasons vaccine effectiveness against medically attended, laboratory-confirmed influenza among children aged to months influenza vaccine effectiveness among children to months of age during influenza seasons: a case-cohort study prevention of otitis media in children with live attenuated influenza vaccine given intranasally efficacy and safety of and doses of live attenuated influenza vaccine in vaccine-naive children efficacy and safety of a live attenuated, cold-adapted influenza vaccine, trivalent against cultureconfirmed influenza in young children in asia. pediatric infectious disease safety, efficacy, and effectiveness of coldadapted influenza vaccine-trivalent against communityacquired, culture-confirmed influenza in young children attending day care design and initiation of a study to assess the direct and indirect effects of influenza vaccine given to children in rural india seasonality, timing, and climate drivers of influenza activity worldwide epidemiology and seasonality of respiratory tract virus infections in the tropics. paediatric respiratory reviews the authors wish to acknowledge the division of viral diseases, centers for disease control and prevention for providing assay kits used for laboratory testing in this study. key: cord- - hbegx authors: harris, jody; depenbusch, lutz; pal, arshad ahmad; nair, ramakrishnan madhavan; ramasamy, srinivasan title: food system disruption: initial livelihood and dietary effects of covid- on vegetable producers in india date: - - journal: food secur doi: . /s - - - sha: doc_id: cord_uid: hbegx disruption to food systems and impacts on livelihoods and diets have been brought into sharp focus by the covid- pandemic. we aimed to investigate effects of this multi-layered shock on production, sales, prices, incomes and diets for vegetable farmers in india as both producers and consumers of nutrient-dense foods. we undertook a rapid telephone survey with farmers in states, in one of the first studies to document the early impacts of the pandemic and policy responses on farming households. we find that a majority of farmers report negative impacts on production, sales, prices and incomes. over % of farms reported some decline in sales, and over % of farms reported devastating declines (sold almost nothing). price reductions were reported by over % of farmers, and reductions by more than half for % of farmers. similarly, farm income reportedly dropped for % of farms, and by more than half for %. of surveyed households, % reported disruptions to their diets. a majority of farm households reported reduced ability to access the most nutrient-dense foods. around % of households reported ability to protect their staple food consumption, and the largest falls in consumption were in fruit and animal source foods other than dairy, in around half of households. reported vegetable consumption fell in almost % of households, but vegetables were also the only food group where consumption increased for some, in around % of households. our data suggest higher vulnerability of female farmers in terms of both livelihoods and diet, and differential effects on smaller and larger farms, meaning different farms may require different types of support in order to continue to function. farms reported diverse coping strategies to maintain sales, though often with negative implications for reported incomes. the ability to consume one’s own produce may be somewhat protective of diets when other routes to food access fail. the impacts of covid- and subsequent policy responses on both livelihoods and diets in horticultural households risk rolling back the impressive economic and nutrition gains india has seen over the past decade. food systems, and particularly those making available the most nutrient-dense foods, must be considered in ongoing and future government responses. disruption to food systems has been brought into sharp focus by the covid- pandemic, but such disruptions are a persistent feature of these complex systems, so it is important that we learn from the current crisis to be better prepared for the next one. this paper uses novel empirical data to understand disruptions to production, livelihoods and diets in agricultural households in india, to draw lessons from covid- and particularly its effects on nutrient-dense perishable food items for making food systems more resilient. the objective is to gain a better understanding of how food system disruption affects the various roles of vegetables in food systems, and we draw on food systems theory and frameworks, and research on food system effects of previous shocks, to frame our study in the indian context. food systems have been defined as "all the elements [...] and activities that relate to the production, processing, distribution, preparation and consumption of food, and the output of these activities" (hlpe ) . key outputs are the diets that people can access through the food system; the livelihoods of those involved across the food system; and the environmental effects of the food system. these complex and spontaneous systems are shaped by a range of drivers, from the biophysical and technological to the political and socio-cultural (hlpe ) . when there are disruptions to these drivers, there is potential disruption to food systems. importantly, different foods are likely to be affected differently by food system shocks. four months into the covid- pandemic, the un food and agriculture organisation (fao ) stresses that global stocks of staple food crops such as rice and wheat are adequate and looks set for a good harvest, depending on how long the pandemic and restrictions last. perishable foods howeversuch as dairy, meat, fruit and vegetablescannot be easily transported and stored and are more vulnerable to food system disruption. restrictions to movementwhether of people, trucks or shipshave significant potential to disrupt production and trade in vegetables and their inputs, and their perishability means this may result in vastly increased food waste at a time when production is uncertain. it is precisely these perishable foods that are the most nutritious (having the most nutrients per calorie) (beal et al. ) so concerns about food system disruptions also play out in concerns over reductions in diet quality. some of these hypothesised impacts from food systems theory have been studied in previous shocks, and signal some areas of the food system that will be important to understand in the current crisis. in terms of production, a study using a system dynamics model suggested that a severe pandemic with > % reduction in labour availability can create widespread food shortages even in developed nations (huff et al. ) . this prediction was in fact witnessed during the ebola epidemic in west africa that began in , where movement and labour were severely curtained and production volume of staple crops was reduced by % (huber et al. ). in contexts where shocks lead to food gluts or shortages, a second key area is effects on food prices. often the most nutritious foods increase most: in indonesia a drought and financial shock in - led to a % increase in the price of leafy greens alongside smaller rises in other food prices, for instance (block et al. ) . a % rise in staple food prices during the food price crisis led to a % increase in total food expenditure across low-and middle-income countries, putting pressure on household food baskets (darnton-hill and cogill ) . healthy diets based on diverse plant foods are already too expensive for over . billion people in the world (hirvonen et al. ) , and shocks such as covid- that reduce incomes or increase prices will only exacerbate this situation. reductions in diet quality (even while maintaining sufficient calories) has been seen in other significant food system shocks, with households tending to protect staple food consumption over the consumption of more expensive but more nutrient-dense foods (darnton-hill and cogill ). in the indonesia example, consumption of eggs fell by over half, and of green leafy vegetables by up to % (block et al. ) , severely limiting diet quality. different populations are also affected differently: while covid- does not distinguish between rich and poor, the diets of the most marginalized in society will be most affected and the least able to adapt. the coping strategies employed by farming households during shocks (such as borrowing and relying on social networks) are likely to have broader welfare implications in the longer term that need to be captured and understood (galiano and vera-hernández ) . overall, the type of shock matters: a biophysical shock affects food production and availability, and thereafter perhaps prices (béné et al. ). an economic shock affects farmers' ability to procure inputs and labour, but also consumers' ability to afford food and therefore demand (block et al. ) . a health shock experienced directly by a household leads to changes in health expenditures and reductions in labour, either in the short term or longer term depending on the type of pandemic (hiv being chronic, ebola being acute, for instance) (harris ; gillespie ) . the covid- pandemic (an acute health shock) and its associated social and policy responses (broader production and economic shocks) are exceptional in that they potentially affect multiple food system drivers at the same time; affect the food system from inputs and production to trade and marketing to price and affordability to consumer demand; and affect almost every scale, from local to global. in this crisis, it is important to understand how farmers experience the shock of covid- as both producers and consumers of food. the produce of vegetable farmers in particular is likely to be among the most disrupted, as outlined above. our hypothesis based on previous research is that production might be disrupted and sales might fall for these farmers, impacting livelihoods; reduced incomes are likely to lead to less diverse and healthy diets in these households; and these impacts will be different for different types of farmers across socio-economic groups. we therefore aimed to understand impacts on the livelihoods and diets of vegetable farmers in india through the multi-layered shock of covid- . india reported its first case of covid- on january th , and early response measures related to the limiting of international travel and health system preparedness. it was only with increasing cases in late march that individual states ordered lockdowns, and on march th a full national lockdown was ordered, extended several times and still in place at the time of writing, though with relaxations applied according to the severity of covid- in different zones. the lockdown coincided with peak harvest (rabi) season for certain fruits and vegetables in many parts of india (fao ), and agricultural work was largely allowed to continue, with agricultural operations remaining out of the purview of the covid- lockdown restrictions (padhee and pingali ) except in active containment zone areas. public and private transport restrictions however limited the domestic movement of seasonal workers and agricultural inputs, especially crop protection products, and significant negative impact was realized in terms of accessing markets for sales. sudden closure of outlets left vegetable producers with reduced customer base, with street food vendors, restaurants and supermarkets mandated to close, though small food shops and open-air markets were allowed to open with time restrictions (gain ). the current study was undertaken with farmers engaged in existing, forthcoming, and recently concluded projects with the world vegetable center (worldveg) in four indian states (table ) . data were collected between may th- th , six weeks into the national lockdown and in the early stages of various government relief packages. in jharkhand, about % of the vegetable produce was procured by the project itself during the lockdown; about % of the farmers we interviewed in jharkhand were part of this initiative, and the johar project was explicitly working with women farmers. in andhra pradesh, about % of the tomatoes produced were supplied to a processing factory through the project and its partners; about % of the farmers we interviewed in andhra pradesh were part of this initiative. the study used a phone-based survey method to elicit information about how vegetable farmers in four indian states were affected by the lockdown measures imposed to contain covid- . phone-based interviews were necessary because it was not possible to visit farmers in person. worldveg staff identified farmers from their projects with whom they worked directly and for whom they had phone numbers, and purposively selected farmers to call until they reached their sample size quota of farmers. as only one single staff member was available in the projects in andhra pradesh and karnataka, their quota was raised to . the quota followed a rule-ofthumb as we did not have information available for the appropriate power calculations. responses were recorded by the staff members in real time using a customized smartphone application which reported and aggregated the data. informed consent was sought and recorded before each interview. the study was virtually risk free for participants and the study plan was therefore exempted from ethical review by the institutional biosafety and research ethics committee of worldveg before implementation. we aimed to limit the interviews to min and therefore included only questions in the survey. these covered questions on production and wastage (vegetables produced, changes in production, reasons, and mitigation strategies); questions on prices, sales, and farm income (changes in each, reasons, and mitigation strategies); and questions on diets (changes in consumption of different food groups, reasons, and mitigation strategies). change in diets was asked as a binary question ('has your household diet changed as a result of covid- ') and we also looked at changes in the balance of the individual food groups consumed. importantly, each of the questions relied on farmers' perceptions of change since covid- ; we did not define a timescale but rather let the respondents attribute change to covid- as they viewed it. change within each of the quantitative questions was captured as a likert scale (for instance: increased a lot (more than doubled)|increased a little (less than doubled)|no change| decreased a little (not to half)|decreased a lot (less than half)) sometimes presented with a percentage range (for instance: sold nothing at all (> %)|lost most of sales ( %- %)|lost half of sales ( %- %)|lost some sales ( %- %)|lost little to no sales (< %)|increased sales). qualitative questions (such as reasons and coping strategies) were asked without pre-defined responses, with enumerators instructed to probe for multiple answers and select the most appropriate responses from a multiple-choice list. we also collected some basic farm and household data in order to compare farms and households on proxies for key socio-economic issues (gender of the farmer, as a proxy for gender differences; and farm size, as a proxy for income/economic status). of the initial sample of farmers contacted for this study, rejected the interview, had not produced vegetables, and provided incomplete information, therefore the analytical sample had observations for farmers. descriptive analyses were undertaken for each topic, with particular sections also analysed by gender and farm size (larger or smaller than ha (ha)) to understand heterogeneous effects. ordered logit models were used to estimate the influence of farm and household characteristics on selected outcomes. we use ordered logit regressions to analyse associations between the intensity of self-reported changes in vegetable livelihoods (quantity sold, prices, income) and diets (change in consumption per food group) due to covid- and major household characteristics (farm size, gender of the farmer, and the number of produced vegetables). the dependent variables are on to -point likert scales. where necessary we invert the order of the variables, so that higher values always reflect a worse situation of the household. to control for differences between the projects and their context, we add a set of state dummies to the list of independent variables. across our survey a quarter of farmers were women (table ). this was driven by the project in jharkhand where half of the respondents were women, while in all other states very few farmers were women ( - %). jharkhand also had much smaller farm sizes (average . ha) compared to the . to ha farms in the other three states. in disaggregated analyses (not shown here) female farmers had slightly smaller farms on average than their male counterparts. overall, % of farmers reported disruptions to production; % to sales; and % to diets. farmers produced a diverse range of vegetables. the median number of vegetables produced was , the mean , and % of households produced five or more types of vegetable. this varied by state, with farmers in andhra pradesh mainly producing tomatoes, but farmers in other states producing - vegetables on average. figure shows the main vegetables produced by each farmer (self-reported), to which questions on production, sales and prices related. the 'other' vegetable category included several cucurbit species, beans, radish, beetroot and cauliflower, each of which was produced by less than % of farmers and combined into one collective category for visualization. of all types and locations of farms with interruptions to their production, most reported that prices were too low to continue with production ( %) or that they could not find buyers ( %). of problems associated with production, most cited lack of transport ( %), many cited lack of inputs ( %), lack of harvest labour ( %), and some cited lack of storage ( %). again this varied by state, though transport was cited in every state. women farmers were less likely to suffer from lack of labour (but had smaller farms on average) but were more likely to see prices as too low. large farms were more likely to lack labour and storage, and smaller farms had difficulty accessing inputs, in particular. farmers who experienced reduction in sales due to covid- sold their produce through multiple marketing channels, from selling directly to consumers through fresh markets, to selling through collectors/middlemen (table ) . only two farmers sold directly to institutions, and another two to exporters or supermarkets. more female farmers sold directly to consumers and did not have supply contracts, and more male farmers sold through collectors and had a higher diversity of sales channels. the average number of marketing channels among smaller farms (< ha) was . less than among larger farms. a vast majority of farmers saw declines in vegetable sales, prices and farm incomes (fig. ) . over % of farms saw some decline in sales, and over % of farms saw devastating losses of sales (sold almost nothing), slightly higher among female farmers, and double among small farms compared to large (data not shown here). prices reduced for over % of farmers, and by more than half for % of farmers. similarly, farm income dropped by for % of farms, and by more than half for %. we estimated an ordered logit model to assess the association of farm size, gender of the farmer, and the number of produced vegetables with covid- related shocks (table ). the results show that a higher diversity of produced vegetables is significantly associated with a better development of sales but worse changes in prices and income. women experienced a stronger disruption to the price of their vegetables. farm size was not significantly associated with any of the variables. of surveyed households, % reported disruptions to their diets. a majority of farm households reported ability to protect their staple food consumption, meaning their food security in terms of calories (fig. ) , though % of households did report a fall in ability to procure staple foods. the largest falls in consumption were in fruit and animal source foods other than dairy, in around half of households. pulse, dairy and vegetable consumption fell in - % of households. vegetables were the only food group where consumption reportedly increased in a significant proportion of households, with around % reporting an increase. the major reason for increases in vegetable intakes was eating the farm's own production, while reasons reported for reductions in vegetable consumption were mostly due to reduced physical availability and affordability. women farmers were significantly more likely than men to report a stronger reduction in consumption of vegetables, fruits, and dairy, controlling for other factors (p < . in separate ordered logit regressions), and were much less likely to be able to afford vegetables than men ( % of women versus % of men specifically quoting price changes; % of women versus % of men quoting changes in general affordability; data not shown here). we asked about coping strategies used by farm households to mitigate the impacts of covid- on sales, income and diets. in terms of farm income (table ) , the most common strategies have been to find new markets (including selling door-todoor), reduce prices, and eat the farm's own production. all of these are practiced more by female than male farmers. women were only half as likely as men to apply no coping strategy for production. to deal with reduction in sales, most were leaving harvest in the field, feeding vegetables to livestock, and sharing vegetables with others. smaller farms were generally less likely to reduce their production or destroy the harvest (plant less, leave vegetables in the field, compost vegetables, or feed to livestock). to mitigate the effects on farm incomes, most are finding new markets and reducing prices, with female farmers reducing prices more than men, and small farms more than large farms. in total % of farmers plan to produce less, fig. major vegetables produced in the study areas during the survey in terms of dietary coping strategies, the most common were reducing household expenses and eating more own- note: the number of supply channels is tested for equality of means (t-test), all others comparison test for equality of proportions (z-test), sample are all households that have been unable to sell some of their vegetables due to covid- , n = * p < . , ** p < . , *** p < . produced food (table ). other households relied on financial coping strategies, such as buying cheaper food, and borrowing money. most coping strategies were used more by households in which the farmer is female, particularly the financial strategies; and these households were almost twice as likely to have received food aid or other formal support. this study has shown food system effects of covid- reported by farmers on production, livelihoods, food environments and diets in households involved in vegetable production in four indian states. our data is limited by its convenience sample and moderate sample sizes across different states, limiting the generalizability of the findings. as with all surveys, the findings rely on the accuracy of the data portrayed by the respondents, and we asked specifically about the perceptions of farmers on changes since covid- rather than use independently verifiable data. our focus on vegetable farmers was deliberate, because we wanted to understand the impacts on a sector providing nutritious foods, but of course our findings cannot necessarily be generalized to farmers of other crops, or to households relying on other livelihoods. nonetheless, this is one of the first studies to document the early impacts of the pandemic and policy responses on farming households, and provides an important snapshot of impacts on a sector that provides both decent livelihoods and healthy diets in india. while we did not investigate the direct effects of sickness in farming households, the subsequent lockdown policy was perceived by farmers to have affected production (through lack of labour, storage and inputs); sales (through drops in demand and lack of transport); prices and income (with reductions due to lack of demand); and diets (in terms of ability to access the most nutrient-dense foods). these core findings largely mirror the findings of previous research on food system disruptions (jaacks et al. ) . a survey of vegetable value chains in ethiopia similarly found increased farm losses alongside shortage of inputs and labour; reduced producer prices for vegetables, though retail prices so far unchanged; and both vegetable trade and consumption reduced (tamru et al. ) . these studies therefore concur broadly with what we saw in india. a study on retail prices in india found that these had increased and then stabilised in india on a national level, but that this varied by the particular type of vegetable (pingali and mittra ) , an issue we were not able to address in this study. indian newspapers have similarly reported issues with finding harvest labour, transport to market, reduced demand by buyers and retailers, and increased retail prices for vegetables in different states (pothan et al. ) . we look forward to further covid- food system studies to compare our results further. in addition to the core findings, sub-analyses of our data suggest that female farmers reported higher vulnerability in terms of both livelihood and diet. women farmers claim to use more mitigation strategies to first secure their income, and then to secure their diet. the reasons women cite for changes in vegetable consumption show that they perceived themselves to be particularly affected by changes in food prices and affordability. so, the mitigation strategies available to them are not sufficient to protect their livelihoods and diets from income and price shocks. our findings suggest that farming households in general find it hard to mitigate the worst of these shocks in the short term, accepting lower prices to maintain sales, but still with interruptions to the flow of vegetables to consumers, thereby affecting diets more broadly in the country. producing a variety of different vegetables appears to mitigate impact on sales (perhaps through diverse sales routes) but not on incomes (as prices are hit). the ability to consume one's own produce is somewhat protective of diets when other routes to food access fail: due to the inability to sell their own produce, many households consumed more of their own vegetables and a proportion increased their consumption note: test for equality of proportions of the two group applying each strategy (z-test), respondents were able to quote more than one coping mechanism, * p < . , ** p < . , *** p < . note: test for equality of proportions of the two group applying each strategy (z-test), respondents were able to quote more than one coping mechanism * p < . , ** p < . , *** p < . above previous levels. this route to dietary resilience is particular to the sample (horticultural households) but it does suggest that producing vegetables provides some resilience to dietary shocks for some households. so far, the major responses of the indian government to ensure livelihoods of farmers have been making loans more available and providing tax relief and direct farmer payments. in our work, smaller and larger farms see differences in the impacts of covid- , and therefore implement different coping strategies and require different types of support from the government in order to continue to function. government response to ensure food security has been to double allocations under the public distribution system (pds) and provide cash payments to out-of-work labourers (but not self-employed farmers). female farmers in particular report accessing food aid according to our data, but it should be noted that the pds system provides grain and pulses but not vegetables or other nutrient-dense foods that are seen to be badly hit in our data. understanding farmers' real-time coping strategies and limitations through studies such as this might help policy-makers to prepare strategies that take into account the lived experiences of farming households. the challenge is to carefully weigh the remaining direct epidemiological risks of the virus against the livelihood and dietary hazard to both consumers and farmers. the impacts of covid- and subsequent policy responses on both livelihoods and diets in horticultural households risk rolling back impressive economic and nutrition gains india has seen over the past decade. india's right to food legislation commits the government to action in this area, and suggests that food systems, and particularly those making available the most nutrient-dense foods, must be considered in ongoing and future government responses. impact of climate-related shocks and stresses on nutrition and food security in selected areas of rural bangladesh macro shocks and micro outcomes: child nutrition during indonesia's crisis maternal and young child nutrition adversely affected by external shocks such as increasing global food prices health shocks, household consumption, and child nutrition poverty, food insecurity, hiv vulnerability and the impacts of aids in sub-saharan africa gender implications of poor nutrition and health in agricultural households affordability of the eat-lancet reference diet: a global analysis. the lancet global health food systems. a report by the high level panel of experts on food security and nutrition of the committee on world food security food security and nutrition: building a global narrative towards . a report by the high level panel of experts on food security and nutrition of the committee on world food security the economic and social burden of the ebola outbreak in west africa how resilient is the united states' food system to pandemics impact of the covid- pandemic on agriculture and food security in india. presentation broadcast from the harvard t.h. chan department of global health and population lessons from a pandemic to repurpose india's agricultural policy how did covid- impact india's food prices? tata-cornell institute for agriculture and nutrition blog local food systems and covid- : a glimpse on india's responses. rome: fao available from impacts of the covid- crisis on vegetable value chains in ethiopia. ifpri covid blog acknowledgments the willingness of vegetable farmers to contribute to this study at short notice is greatly acknowledged. we also acknowledge the support of ms. funding information no specific funding was used in the research reported here. all authors and field officers used their time funded under world vegetable center budgets to undertake this work. conflict of interest the authors declare no conflict of interest in the preparation of this paper.open access this article is licensed under a creative commons attribution . international license, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the creative commons licence, and indicate if changes were made. the images or other third party material in this article are included in the article's creative commons licence, unless indicated otherwise in a credit line to the material. if material is not included in the article's creative commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. to view a copy of this licence, visit http://creativecommons.org/licenses/by/ . /. jody harris is lead specialist in food systems at the world vegetable center, bringing a food systems and policy focus to work on healthy diets, and undertaking research to further understand the role of vegetables in complex food and social systems. she is an applied researcher with a particular interest in the policy and social drivers of healthy diets and nutrition. her phd in development policy is from soas, university of london. she has p r e v i o u s l y w o r k e d a t t h e international food policy research institute (ifpri) and the institute of development studies (ids) as well as several universities and international ngos, conducting research and designing programmes in various contexts in asia and africa, particularly vietnam and zambia.lutz depenbusch joined the world vegetable center in november to work in its impact evaluation team. his research focuses on the effectiveness, efficiency, and distributional effects of the center's research and development projects. currently he works on projects related to home gardens, farm mechanization, plant breeding, plant protection, and scaling techniques. he has implemented research projects in bangladesh, cambodia, india, kenya, and myanmar. lutz obtained his phd in economics as part of the global food research training program at the university of goettingen, germany.arshad ahmad pal is a scientist in post-harvest technology at the world vegetable center in india, specialising in horticulture, postharvest management of fruits and vegetables, postharvest physiology and technology, value chains and project management. he plans and manages research and development for different projects within the region, providing technical and administrative leadership to the national project team. his phd in horticulture science is from charan singh university, india, and he has previously worked for the central institute of temperate horticulture (icar) in india.ramakrishnan madhavan nair was appointed regional director for the world vegetable center south and central asia in march . he also leads the worldveg global legume breedi n g p r o g r a m a n d t h e i n t e r n a t i o n a l m u n g b e a n improvement network (imin). ram has over years of experience in managing and leading national and international projects, and his extensive academic publication record includes peerreviewed journal articles, conference papers and, book chapters. he received his phd with a specialization in plant breeding from kerala agricultural university, india. in , he won the sardi breakthrough innovation award and in , ram and his team won the worldveg science of excellence award for their work on mungbean. key: cord- -vo imub authors: khanna, divya; khargekar, naveen chandrahas; khanna, ajay kumar title: implementation of early detection services for cancer in india during covid- pandemic date: - - journal: cancer control doi: . / sha: doc_id: cord_uid: vo imub early detection of cancer greatly increases the chances of better survival. the emergence of covid- pandemic has disrupted several essential health services globally and early detection of cancer services is one of them. the routine cancer screenings have plummeted in many developed countries since the crisis. india has highest estimated lip and oral cavity cancer cases worldwide ( , , . %) and the secondhighest number of breast ( , , . %) and cervix uteri ( , , . %) cancers in asian sub-continent. not only india has high burden of cancer, but the majority ( - %) of patients have advanced disease at the time of diagnosis. hence is it imperative that early detection services should be kept functional at out-patient settings so that at least the patients coming to hospitals with early signs and symptoms can be diagnosed as early as possible. strategies need to be adopted to continue early detection services and ensure safety of patients and health care workers from covid- transmission. early detection of cancer greatly increases the chances of successful treatment and better survival. recognizing possible warning signs of cancer and taking prompt action leads to early diagnosis. while improving early diagnosis generally improves outcomes, not all cancer types benefit equally. common cancers, that can be diagnosed at early stages from signs and symptoms and for which early treatment is known to improve the outcomes are generally going to benefit most from the early diagnosis. examples include breast, cervical, colorectal and oral cancers. , the emergence of the disease covid- has resulted in an unprecedented global health crisis. on th january , the world health organization declared it as a public health emergency of international concern. the pandemic has spread exponentially and unpredictably across the world devastating economy and global health care services. by th july , the numbers of global covid- confirmed cases and deaths have exceeded , , and , respectively. countries have adopted many preventive strategies like social distancing, lockdowns, and quarantine of suspected cases intending to minimize community spread of the disease. covid- pandemic has disrupted several essential health services globally and early detection of cancer services is one of them. the routine cancer screenings have plummeted been in many developed countries since the crisis. as per global cancer observatory (globocan) , india alone has contributed to , , ( . %) of total cancer cases of the asian continent ( , , cases) with more than one-third being oral, breast and cervical cancer cases. india has the highest estimated lip and oral cavity cancer cases worldwide ( , , . %) and the second-highest number of the breast ( , , . %) and cervix uteri ( , , . %) cancers in asian sub-continent. not only india has a high burden of cancer, but the majority ( - %) of patients have advanced disease (stage - ) at the time of diagnosis. rural areas of india ( % of the total population) have an even worse situation, where patients and families have to travel long distances to reach a tertiary care oncology center. delayed detection of cases leads to poor survival rates. -years relative survival rate for oral cavity, breast and cervical cancer from indian cancer registries cases is as low as . %, . %, . % respectively. the indian government had launched an operational framework for the country's first national cancer screening program in under the national programme for prevention and all paƟnets/persons will be screened for the following: paƟents details such as contact number and address will be stored in electronic medical record for future follow-up. if the report comes posƟve then paƟent will be called for cancer screening aŌer the covid- management and aŌer quaranƟne as per the local administraƟon protocol if the report is negaƟve then paƟent is immediatly called for cancer screening . no to all paƟent will be directed to cancer screening opd . both paƟent and health care worker will be using appropriate ppe during screening. control of cancer, diabetes, cardiovascular diseases and stroke (npcdcs). as per the guidelines, there will be mandatory screening for oral, breast, and cervical cancer in people over the age of in districts of india before the program expands to other areas. , on th may , due to the covid- pandemic impact, the government of india has currently suspended the door-todoor screening of people above years of age as part of the national program based on the risk associated oral cavity examination. however, emergency cases requiring a biopsy will be addressed as per the protocol. these are temporary guidelines and subject to revision depending on change in the overall situation. thereby, the early detection of cancer services will primarily be restricted now to out-patient settings in primary, secondary and tertiary care centers. to ensure that patients can identify early signs and symptoms of common cancers there is a dire need of health education campaigns for self-examination by patients for early signs and symptoms of cancers such as white patch (leukoplakia) / red patch (erythroplakia)/ nonhealing ulcer in mouth and difficulty in opening of the mouth, lumps in the breast/nipple discharge from the breast, postmenopausal/inter-menstrual/ sexual contact bleeding pervagina or excess foul-smelling discharge per vagina. tobacco quitline services in india and other health portals and social platforms can be utilized for spreading the information which may enable the patient to visit hospitals timely when they detect any signs/symptoms through self-examination. even before covid- pandemic, population-based screening was confined to very few geographical regions in india due to various limitations. majority of patients were diagnosed when they visit hospital out-patient settings with early signs and symptoms. if, early detection of cancer at outpatient settings of hospital will also be halted during current pandemic, then the already poor graph of late detection and survival of cancer patients will likely to worsen further. hence is it imperative that early detection services should be kept functional at out-patient settings so that at least the patients coming to hospitals with early signs and symptoms can be diagnosed as early as possible. following strategies can be adopted when continuing early detection services at out-patient settings: . social distancing and limiting only attendant per patient inside the hospital . arrange a simple screening algorithm or questionnaire for early detection of potentially covid- infectious persons. . travel advisory posters can be displayed to facilitate the screening process by prompting patients to be proactive by self-reporting travel history . usage of adequate personal protective equipment (ppe) by both health care workers and patients during their visit. . strictly adhering to hospital infectious control policies and standard operating procedure for infection prevention and containment. . considering web-based/ telemedicine for outpatients if resources are available. this will minimize bidirectional exposure to coronavirus infection of both the patient and the healthcare team. . prevention of long-distance travel of patients for early detections services especially for rural-based patients by capacity building of health-care manpower and resources that can perform early detection of cancer at peripheral rural health centers. to facilitate the early detection of cancer services in a hospital there needs to be the establishment of the following: . screening camps outside the hospital for the screening of suspected covid- patients as per the flowchart (figure ), . creating a fever clinic where all suspected patients and health care workers can be assessed, . creating isolation wards and covid- diagnostic set up in the hospital wherever possible, . if covid- diagnostic and management facility is not available in the hospital then ensuring safe and prompt referral of all suspected patients and health care staff to covid- management hospitals, . the information of the patients such as their contact number and place of residence can be collected and stored in their electronic medical record. in this way a database of patients who are eligible for cancer screening can be maintained and through audio/video communication can be called for screening depending on their covid- status and their signs and symptoms. the database can be linked with on-going cancer registry programs of defined geographical population. the author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. cancer control: early detection. who guide for effective programmes. world health organization guide to cancer early diagnosis. world health organization detail/ - - -statement-on-the-second-meeting-ofthe-international-health-regulations-( )-emergency-commit tee-regarding-the-outbreak-of virus disease (covid- ) situation report- epic health research network. delayed cancer screenings international agency for research on cancer, world health organization. globocan -estimated cancer incidence, mortality and prevalence worldwide cancer research in india: challenges & opportunities cancer survival in africa, asia, the caribbean and central america india launches plan for national cancer screening programme government of india. national programme for prevention and control of cancer, diabetes, cardiovascular diseases and stroke (npcdcs) lockdown poses new challenges for cancer care in india population-based cancer screening programmes in low-income and middle-income countries: regional consultation of the international cancer screening network in india cancer management in india during covid- key: cord- -ssdzd t authors: atal, shubham; fatima, zeenat; balakrishnan, sadasivam title: approval of itolizumab for covid- : a premature decision or need of the hour? date: - - journal: biodrugs doi: . /s - - - sha: doc_id: cord_uid: ssdzd t itolizumab is a first-in-class anti-cd monoclonal antibody that was initially developed for various cancers and was later developed and approved in india for treatment of moderate to severe chronic plaque psoriasis in . this drug is now being re-purposed for covid- . the potential utility of itolizumab in covid- , based on its unique mechanism of action in ameliorating cytokine release syndrome (crs), was proposed first in cuba with approval of a single-arm clinical trial and expanded access use. subsequently, a phase ii, open-label, randomized, placebo-controlled trial has been conducted in covid- patients in india after receiving regulatory permission. based on the results, the indian drug regulatory agency recently approved itolizumab in july for ‘restricted emergency use’ for the treatment of crs in moderate to severe acute respiratory distress syndrome (ards) due to covid- . this has drawn sharp criticism within the scientific community, with the approval being granted on the basis of a relatively small phase ii trial, without conduct of a conventional phase iii trial, and lacking availability of the claimed supportive real-world evidence in the public domain to date. in a global scenario where finding a successful treatment for covid- is of utmost priority, a biologic agent has been re-purposed and approved with a successfully completed rct, in a country where cases and mortality due to covid- are growing exponentially. however, instead of welcoming the approval with open arms, many doubts are being raised. this is an issue that needs to be considered and dealt with sensitively, as well as scientifically. amidst the ongoing struggle to find a successful treatment for covid- , itolizumab became the first novel biologic therapy to be approved in the world for covid- -for patients with moderate to severe complications. the indian drug regulatory agency (central drug standard control organisation, cdsco) recently approved itolizumab for 'restricted emergency use' for treatment of cytokine release syndrome (crs) in moderate to severe acute respiratory distress syndrome (ards) due to covid- , followed by a similar approval in cuba [ , ] . 'restricted emergency use' requires fulfilment of certain requirements for use including written informed consent of patients, explaining risks and benefits of the drug and putting a risk management plan in place to manage any adverse effects. the drug can be given only in hospitals and medical institutions, and is not meant for sale at retail pharmacies [ ] . itolizumab is a first-in-class monoclonal antibody, first developed for auto-immune diseases in india, where it received approval for treatment of patients with active moderate to severe chronic plaque psoriasis in [ ] . it has been approved for the same indication in cuba as well, but not in other countries yet [ ] . the potential utility of itolizumab in covid- , based on its mechanism of action, led to expanded access use and conduct of a trial in cuba, retrospectively registered with the cuban regulatory agency (center for the state control of medicines, equipment and medical devices, cecmed) in may . this trial recruited patients with critical and severe illness, and moderately ill patients with very high risk of developing severe symptoms [ ] . encouraged by the initial promising results with the first few patients seen in this index trial, regulatory permission was received to repurpose the drug for covid- in india. the drug was studied in an open-label, randomized, controlled, phase ii trial at four hospitals in india to assess the safety and efficacy of itolizumab in preventing crs in moderate to severe ards due to covid- [ ] . on the basis of the results of this phase ii trial, itolizumab was granted approval for 'restricted emergency use' for this indication in covid- patients in july [ ] . the data obtained from the cuban single-arm trial, in conjunction with the indian data, also led to the drug's approval for the same indication in covid- in cuba later in the same month; data on the results submitted to the cuban authority are not available [ ] . on one hand, this is welcome news as a potentially life-saving treatment is now available for an important subset of covid- patients-those having crs-mediated ards. but, on the other hand, the relative paucity of evidence available makes it necessary to carefully evaluate the scientific validity of this approval. further questions arise as the drug has not been included in the clinical management protocol recommended by the national task force on covid- in india, despite getting approval from the country's regulator, because of insufficient evidence. the innovator company, biocon ltd, claims to have supportive real-world data on nearly patients that they intend to provide to the authorities concerned [ ] . itolizumab is a humanized anti-cd monoclonal antibody (mab), specifically targeting the srcr- (scavenger receptor cysteine-rich like domain ) of cd . it has a molecular weight of kda and contains two heavy chains and two light chains linked with a disulfide bond [ ] [ ] [ ] . the parent antibody of itolizumab is ior t , a murine mab, which has shown therapeutic efficacy in psoriasis and rheumatoid arthritis. itolizumab, being a humanized mab, is less immunogenic and has a better safety profile with the same therapeutic efficacy as ior t [ , ] . itolizumab is a mab directed against cd , a surface glycoprotein found on mature t cells, immature b cells, the b a subset of b lymphocytes, and certain regions of the brain. it plays a pivotal role in cell proliferation, adhesion, differentiation, and survival. its extracellular region is composed of three srcr domains. cd is a co-stimulatory molecule, and its stimulation is responsible for t h activation, and differentiation of t cells, which promotes a proinflammatory response. thus, by inhibiting cd , itolizumab downregulates the synthesis of proinflammatory cytokines and adhesion molecules that eventually leads to reduced interferon-γ (ifnγ), interleukin (il)- , and tumor necrosis factor-α (tnfα) levels, along with reduced t-cell infiltration at the inflammatory sites [ ] . interestingly, these anti-inflammatory effects are not achieved by inhibiting ligand binding and causing t-cell depletion, but by inhibiting new receptor formation, stimulating loss of existing receptors or by blockade and internalization or downregulation of receptors. in vitro experiments have shown that itolizumab does not cause t-cell depletion but inhibits t-cell proliferation induced in the presence of alcam (activated leukocyte cell adhesion molecule or cd ) and excess il- , and downregulates the phosphorylation of intracellular proteins implicated in the cd -mediated activation pathways [ ] . so, it inhibits the downstream inflammatory cascade by a unique mechanism of action. safety data for itolizumab has been derived mainly from the two multicenter clinical trials of patients with chronic plaque psoriasis, and from a study of patients with rheumatoid arthritis [ , , ] . no treatment-related severe adverse effects (aes) were noted in these trials. the various aes observed with itolizumab were infusion-related reactions (such as nausea, rash, urticaria, flushing, cough, wheezing, dyspnea, dizziness, and headache), pyrexia due to infections, pruritus, antidrug antibody formation, and transient decrease in mean lymphocyte count. infusion reactions, the most common adverse event, have been reported in - % of patients. the frequency and severity of infusion reactions were noted to decrease with subsequent infusions. other frequent adverse events (> %) are diarrhea, pyrexia, upper respiratory infections, and pruritus [ , ] . itolizumab is not recommended for patients with active infection or a history of recurring infections, latent tb infection, children, patients with hepatic and renal impairment, or pregnant and lactating women [ , ] . as summarized in our article, crs is a phenomenon implicated in severe covid- disease where there is an uncontrolled release of inflammatory cytokines including various interleukins, tnfα, ifnγ, and other mediators [ ] . this severe systemic acute inflammatory response can cause damage to multiple organs including acute lung injury and ards, which is being reported as one of the serious complications in covid- patients [ , ] . higher levels of these cytokines and mediators have been observed in the plasma of covid- patients requiring intensive care [ ] . a . -fold higher mean il- concentration has been shown in patients with complicated covid- compared with noncomplicated disease [ ] . amelioration of crs is an important strategy to reduce the severity of pulmonary and systemic complications in such covid- patients, which can reduce the need for intensive care and mechanical ventilation. based on the strategy of reducing the pulmonary hyperinflammation through modulating the crs, several randomized controlled trials (rcts) of il- inhibitors such as tocilizumab and sarilumab are exploring their potential in patients with serious covid- across the globe [ ] . the mechanism of action of itolizumab is different from that of other selective immunomodulatory approaches (e.g., il inhibitors) being tried for treatment of crs associated with covid- , as it selectively targets the cd -alcam pathway and decreases the activation, proliferation as well as differentiation of t cells into pathogenic effector t cells. production of pro-inflammatory cytokines like il- , tnfα, and infγ is decreased along with t-cell infiltration, but the regulatory function of treg cells is preserved [ ] [ ] [ ] [ ] [ ] [ ] . it may perhaps be a better immunomodulatory approach for combating crs-induced ards in covid- with its ability to stop the production of pro-inflammatory cytokines rather than just inhibiting these cytokines as the other agents do. a phase ii, multi-centric, open-label, two-arm, randomized, pivotal clinical trial was conducted in patients in india [ ] . the trial included adults aged > years of either sex with a confirmed virological diagnosis of sars-cov- infection with reverse transcription polymerase chain reaction (rt-pcr) assay who were hospitalized due to clinical worsening of covid- infection with an oxygen saturation at rest in ambient air ≤ %. patients had moderate to severe ards, as defined by a ratio of arterial oxygen partial pressure and fractional inspired oxygen (pao /fio ) of < , or > % deterioration from the immediate previous value. in case of a delay in rt-pcr results, biomarker data-either baseline serum ferritin level ≥ ng/ml or il- levels > times the upper limit of normal (uln)-was required for inclusion of the patient into the study. patients with known severe allergic reactions to mabs; known history of hepatitis b, hepatitis c, or hiv; active tuberculosis (tb) infection or having a history of inadequately treated or latent tb; absolute neutrophil count (anc) < /mm , platelet count < , /mm , and absolute lymphocyte count (alc) < /mm ; those on immunosuppressant drugs in the past months; and those who had participated in other clinical drug trials using anti-il- therapy were excluded [ ] . itolizumab was administered at a loading dose of . mg/ kg, chosen as it is the approved dose in patients with chronic plaque psoriasis and has been administered as an intravenous (iv) infusion in several phase ii and iii clinical trials, without any evidence of dose-limiting toxicities. an additional dose of . mg/kg was administered after week in some patients, if required, based on the physician's discretion; up to four weekly doses were allowed in the study [ ] . with a : randomization, patients were randomized to receive itolizumab plus supportive care, while patients received supportive care alone in the control arm. the primary outcome was comparison of the -month mortality rate between the two arms. the secondary outcomes were plasma levels of biomarkers, lymphocyte count, c-reactive protein (crp), pao /fio , radiological response, duration of hospitalization, and remission of respiratory symptoms [ , ] . all patients receiving itolizumab recovered fully and were discharged from hospital, whereas three out of ten patients ( %) in the control arm died. there was also significant improvement in key efficacy parameters of lung function such as pao and spo (oxygen saturation) without increasing oxygen flow in the itolizumab arm. all patients on itolizumab were weaned off oxygen by day , and none needed ventilator support, unlike the control arm. key secondary endpoints of the clinical markers of inflammation such as il- , tnfα, serum ferritin, d-dimer, lactate dehydrogenase (ldh), and crp showed clinically significant suppression after itolizumab dosing and correlated well with clinical and radiological improvement in symptoms and chest x-ray images, respectively. itolizumab was well tolerated overall and found to be safe, with the infusion reactions manageable with slowing the infusion rate [ ] . these results are in line with the findings of the cuban study, a single-arm, non-controlled clinical trial, where covid- patients were treated with itolizumab [ , ] . it has been claimed that % of severely ill patients were discharged from the intensive care unit (icu) after days of treatment, while moderately ill patients showed a reduction in the rate of disease progression. however, no further details about this trial are available. two studies on preprint servers are available presently; both are from the same cuban trial (rpcec ). one study shows that a single dose of itolizumab decreased the serum il- levels after h of administration in moderate to critically ill elderly covid- patients [ ] . in another study, the authors concluded that in moderately ill elderly covid- patients, itolizumab treatment was associated with a significantly reduced risk of admission to icu and a times lower risk of death [ ] . the approval of itolizumab for restricted emergency use to treat covid- patients with the complication of moderate to severe ards comes at a time when cases and hospitalizations are increasing alarmingly; the mortality has exceeded thousand in india [ ] . this approval presumably comes with the intention of providing a viable life-saving treatment option for a specific subset of covid- patients. itolizumab is not a new investigational drug, having been approved since for psoriasis. the drug is being repurposed and positioned as a relatively more affordable option for treating crs in covid- patients compared with other immunomodulatory drugs like tocilizumab, which are also being used off-label. tocilizumab is still under investigation in various countries including india, at the stage of phase iii trials [ , ] . there is not enough evidence yet from completed studies that these drugs reduce mortality in covid- patients. under these circumstances, the recent approval of itolizumab on the basis of a phase ii trial has understandably drawn sharp scrutiny from experts. questions have been raised, mainly regarding the small sample size of the trial, exemption of a larger phase iii trial, lack of published data regarding off-label use for covid- , and substantial claims being made through media without peer review or scientific publication [ ] . these arguments have been defended by the company mainly on the basis of the desperate need for treatment to prevent mortality due to complications such as ards in seriously ill covid- patients amidst the burgeoning pandemic, and that their trial successfully fulfilled all scientific and regulatory requirements [ ] . inconsistencies and potential fallacies have been observed by the scientific community pertaining to the study design used and withdrawal of two patients who experienced adverse events on initiation who were not considered randomized and were excluded from the trial analysis; one of these patients later died [ ] . does this breach the principle of intention-to-treat analysis? moreover, there is confusion whether all patients were actually randomized as it was reportedly stated that the first five participants were given itolizumab sequentially. this was done as per recommendations of the trial's drug and safety monitoring board. it also purportedly led to refusal by the subject expert committee (sec) of cdsco to give the emergency approval to itolizumab at an earlier stage in late may [ , ] . from the data made available to date, the baseline spo and values of inflammatory markers like crp, d-dimer, ferritin, and ldh are not known; instead, a difference in proportion of improvement or mean change from baseline has been provided [ ] . while all patients were on oxygen at baseline, a higher proportion of patients ( %) were on non-invasive ventilation (niv) in the control arm at baseline compared with the treatment arm ( %), three of whom eventually went on to have the adverse outcome of death [ ] . there is no doubt that finding a successful treatment for covid- that can save lives in this pandemic, which has taken close to . million lives worldwide to date, is of utmost priority [ ] . in this scenario, a biologic agent has been re-purposed, successfully completed a rct, and received approval for restricted emergency use in a country where cases and mortality due to covid- are growing exponentially. so, instead of welcoming the approval with open arms, why are so many doubts being raised? this is an issue that needs to be considered and dealt with sensitively, as well as scientifically. the trial that led to itolizumab approval in india was an open-label, multicenter rct, but the total sample size, being a phase ii study, was only patients, of whom only patients actually received the drug [ ] . although the primary endpoint (i.e., mortality at month) was significantly in favor of itolizumab, it cannot be claimed with certainty that this result would reflect real-world effectiveness. it is unclear whether a design such as simon's two-stage design, which can lead to greater confidence in the significance of results obtained even from a smaller size phase ii trial, was followed for this trial or not [ ] . however, it is to be noted that this type of study design is suitable for a single-arm study. while the sample size may have been sufficient for the primary outcome parameters, the trial is likely to be underpowered for many secondary efficacy parameters; the 'statistically significant' advantage of itolizumab for these parameters does not hold credence. it is also not known what constituted the best standard of care at the sites in the trial or whether steroids were part of the treatment regimens for these patients. this is important in light of the established effectiveness of steroids in patients with moderate to severe covid- pneumonia [ ] . the results are certainly encouraging, and are claimed to have been obtained through fulfilment of the due regulatory requirements, leading the indian drug regulator to approve the drug for emergency use. the need to conduct a phase iii clinical trial has also been waived, allowing the innovator to carry out post-marketing surveillance (phase iv) [ ] . this adds further to the scrutiny and raises more questions. typically, phase ii trials are designed to evaluate the drug's efficacy in people with the disease being studied along with determining the common short-term adverse effects and risks associated with the drug. they also test different dose regimens of the study molecule to derive the optimal dosage for disease. a phase iii trial is a large, multi-center trial considered crucial to proving the efficacy of a drug in a sufficient number of patients compared with placebo or standard of treatment; it provides evidence of clinical and statistical significance of any treatment effects obtained [ ] . these questions have perhaps compelled the regulator to instruct the innovator company to revise its proposed phase iv protocol to keep safety as the primary objective, and increase the sample size as well as geographic distribution of study sites [ ] . furthermore, media claims of mortality reduction in covid- have been made while the results have not yet been peer reviewed and scrutinized within the scientific community. whether the study was methodologically robust cannot be determined unless the study protocol or the results in their entirety are available. now there are reports questioning the scientific validity of this phase ii trial and pointing out inadequacies in its design [ ] . the cuban regulatory study is non-randomized and single arm (non-controlled); data available for that study is even more scant [ ] . it was proclaimed earlier that the real-world data for 'off-label' use of the drug on compassionate grounds will be published; all patients being cured of covid- [ ] . the latest statement claims availability of real-world evidence on patients [ ] . it is being argued that any such real-world data for itolizumab is less likely to include cases that recovered without the use of itolizumab, and it may include only those patients who were successfully treated with the drug, which will not reflect the true results [ ] . the lack of confidence in the drug, or rather in the evidence available to date, has been echoed in the exclusion of the drug from the latest clinical management protocol released by the national task force for covid - in india, and a statement made by the chief of the apex body of medical research in the country [ ] . however, in cuba it has been included in the covid- management protocol since april, before the grant of approval [ ] . itolizumab, which is manufactured in india, is relatively cheaper than other lifesaving options in severe covid- , such as tocilizumab or remdesivir, and its randomized trial is being touted as 'robust'. however, these justifications have seemingly not been accepted by the scientific community. the approved itolizumab formulation of mg/ ml costs inr (~ us$ ) per vial. the average cost of therapy at a dose of . mg/kg, comprising four vials, is estimated to be ~ inr , (~ usd ), which is less than the treatment cost with tocilizumab, which varies between inr , and inr , (~ usd - ) per vial [ ] . however, this cost is still high, as only a small proportion of patients in india can access or rather afford this cost for complete treatment where the average per capita monthly income is inr , (~ usd ) [ ] . the data and protocols from the drug trials in india and cuba should be published at the earliest in their entirety; this may assuage many of the doubts and concerns regarding the strength of evidence. even with the restricted use approval, a phase iii trial of the drug should have been directed in india, as for tocilizumab, which is currently undergoing a large phase iii trial in the country despite more real-world and randomized data being available for this drug. however, the emergency due to this pandemic has to be considered; the approval given is not completethe restricted use necessitates fulfilment of important prerequisites of use. the phase ii data and the claimed realworld evidence does come entirely from the respective countries of approval, which gives some confidence for the use of the drug. at this point in time, a guarded approach is needed regarding both use and evaluation of itolizumab as a drug for treatment of covid- . perhaps publication of the trial data from the indian and cuban studies with support from the real-world off-label use data may provide satisfactory answers to some, if not all, of the crucial questions raised. even so, more evidence would undoubtedly be warranted in terms of both randomized and real-world studies to be really convinced of the efficacy and safety of this drug for its purported use in covid- . for now, itolizumab does give physicians a therapeutic option to potentially save lives in an important subset of covid- patients. dcgi gives nod for restricted emergency use to itolizumab for moderate to severe covid- patients ?o=rn&id= &seo=cuba-autho rizes -the-use-of-itoli zumab -in-cases -of-covid - emergency use authorization itolizumab-a humanized anti-cd monoclonal antibody with a better side effects profile for the treatment of psoriasis itolizumab provides sustained remission in plaque psoriasis: a -year follow-up experience an anti-cd monoclonal antibody (itolizumab) reduces circulating il- in severe covid- elderly patients a multi-centre, open label, two arm randomized, pivotal phase trial to study the efficacy and safety of itolizumab in covid- complications biocon to give more data on itolizumab after use in covid- treatment rejected immunological and histological evaluation of clinical samples from psoriasis patients treated with anti-cd itolizumab a clinical exploratory study with itolizumab, an anti-cd monoclonal antibody, in patients with rheumatoid arthritis alzumab (itolizumab) solution for iv infusion rationale for targeting cd as a treatment for autoimmune diseases safety, efficacy and pharmacokinetics of t h, a humanized anti-cd monoclonal antibody, in moderate to severe chronic plaque psoriasis-results from a randomized phase ii trial efficacy and safety of itolizumab, a novel anti-cd monoclonal antibody, in patients with moderate to severe chronic plaque psoriasis: results of a double-blind, randomized, placebo-controlled, phase-iii study itolizumab, an anti-cd monoclonal antibody, as a potential treatment for covid- complications il- inhibitors in the treatment of serious covid- : a promising therapy? pharm med role of the innate cytokine storm induced by the influenza a virus covid- acute respiratory distress syndrome (ards): clinical features and differences from typical pre-covid- ards clinical features of patients infected with novel coronavirus in wuhan interleukin- in covid- : a systematic review and meta-analysis. medrxiv biocon presented insights into clinical study that enabled dcgi approval of itolizumab for covid- an anti-cd monoclonal antibody (itolizumab) reduces circulating il- in severe covid- elderly patients preprint (version ) available at research square use of a humanized anti-cd monoclonal antibody (itolizumab) in elderly patients with moderate ministry of health and family welfare government of india ctri. a study on treatment of covid- patients with study drug along with standard of care biocon's breakthrough drug itolizumab receives dcgi nod for its use in moderate to severe covid- patients the worrying ways in which biocon's itolizumab trial was deeply flawed sec meeting to examine covid- related proposal under accelerated approval process made in its th meeting held on . . at cdsco, hq new delhi optimal two-stage designs for phase ii clinical trials effect of dexamethasone on days alive and ventilator-free in patients with moderate or severe acute respiratory distress syndrome and covid- : the codex randomized clinical trial key phase clinical trial waived for biocon drug the drug development process the hindu business line, . covid- : biocon to amend phase- trial protocol for psoriasis drug itolizumab itolizumab: why real-world data can't substitute randomised controlled trials treatment of sars cov- pneumonia with the anti-cd monoclonal antibody itolizumab biocon to give more data on itolizumab after use in covid- treatment rejected icmr says biocon's drug trial not good enough to prove mortality reduction how effective are the drugs approved to treat covid- patients in india? https ://scien ce.thewi re.in/healt h/cdsco -remde sivir -favip iravi r-dexam ethas one-tocil izuma b-itoli zumab india's per-capita income rises . % to rs , a month in fy authors' contributions all the authors have substantially contributed to the conception, and drafting the work and revising it critically for important intellectual content and final approval of the version to be published. key: cord- - sz authors: singh, vikas; singh, shweta; biswal, akash; kesarkar, amit p.; mor, suman; ravindra, khaiwal title: diurnal and temporal changes in air pollution during covid- strict lockdown over different regions of india date: - - journal: environmental pollution doi: . /j.envpol. . sha: doc_id: cord_uid: sz abstract lockdown measures to contain covid- pandemic has resulted in a considerable change in air pollution worldwide. we estimate the temporal and diurnal changes of the six criteria air pollutants, including particulate matter (pm . and pm ) and gaseous pollutants (no , o , co, and so ) during lockdown ( th march – rd mha, ) across regions of india using the observations from real-time monitoring sites of central pollution control board (cpcb). significant reduction in pm . , pm , no , and co has been found in all the regions during the lockdown. so showed mixed behavior, with a slight increase at some sites but a comparatively significant decrease at other locations. o also showed a mixed variation with a mild increase in igp and a decrease in the south. the absolute decrease in pm . , pm , and no was observed during peak morning traffic hours ( - hrs) and late evening ( - hrs), but the percentage reduction is almost constant throughout the day. a significant decrease in day-time o has been found over indo gangetic plain (igp) and central india, whereas night-time o has increased over igp due to less o loss. the most significant reduction (∼ - %) was found in pm . and pm . the highest decrease in pm was found for the north-west and igp followed by south and central regions. a considerable reduction (∼ - %) in no was found except for a few sites in the central region. a similar pattern was observed for co having a ∼ - % reduction. the reduction observed for pm . , pm , no , and enhancement in o was proportional to the population density. delhi’s air quality has improved with a significant reduction in primary pollutants, however, an increase in o was observed. the changes reported during the lockdown are combined effect of changes in the emissions, meteorology, and atmospheric chemistry that requires detailed investigations. in the meteorology. although navinya et al. ( ) have used the data for six weeks and however their study was limited to sites. they reported the changes in diurnal variation supplementary table s . the changes in pollutants level during the covid- lockdown across india can partially or the overall decrease in the concentration of the six criteria air pollutants is shown in figure table . day-time. night-time enhancement in o of ~ - % or even higher in the igp and north- west regions due to the reduction in the removal of o at night (brown et al., ) . moreover, heterogeneous chemistry near the surface involving aerosols can also be responsible for the direct loss of o (jacob, ) . o was found to have mixed variation but a considerable decrease in the south region. the pdf analysis also suggests a reduction in pm . , pm , no and co concentrations, the amount of reduction observed for pm . , pm , no was found to reduce with respect to population suggesting a larger decline in populated areas. however, the change in o is found to increase with the population. air quality in the megacity delhi improved significantly during the lockdown. the levels of no , pm , and pm . reduce significantly (~ - %), whereas a moderate decrease was observed for co and so . the o in delhi follows a site-specific trend but shows a mean increase of ~ % due to increased photolysis production because of the reduction in particulate matter over delhi. to mitigate air pollution in india, it was planned to implement source and sector-specific akash biswal: visualization, investigation, writing, reviewing and editing amit kesarkar: discussion, reviewing and editing ravindra khaiwal: investigation, discussion, reviewing suman mor: discussion, reviewing and editing air quality status during malaysia movement control order (mco) due to does lockdown reduce air pollution? evidence from cities in northern china correlation between environmental pollution indicators and covid- pandemic: a brief study in californian context objective evaluation 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quality in megacities of india: present benefits, future challenges and way forward. aerosol and air quality research covid- 's impact on the atmospheric environment in the southeast asia region. science of the total environment emission factors and global warming potential of various solid biomass fuel-cook stove combinations ozone monitoring instrument observations of interannual increases in so emissions from indian coal-fired power plants during effect of lockdown amid covid- pandemic on air quality of the megacity delhi, india. science of the total environment seasonal characteristics of so , no , and co emissions in and around the indo-gangetic plain covid- pandemic persuaded lockdown effects on environment over stone quarrying and crushing areas. science of the total environment air quality across a european hotspot: spatial gradients, seasonality, diurnal cycles and trends in the veneto region impact of lockdown measures to combat covid- on air quality over western europe. science of the total environment - / -dm-i (a), government of india covid- pandemic and environmental pollution: a blessing in disguise covid- pandemic: impacts on the air quality during the partial lockdown in são paulo state, brazil. science of the total environment examining effects of the air pollution in india: bridging the gap between science and policy emissions of air pollutants from primary crop residue burning in india and their mitigation strategies for cleaner emissions real-time monitoring of air pollutants in seven cities of north india during crop residue burning and their relationship with meteorology and transboundary movement of air air pollution trend in chandigarh city situated in indo-gangetic plains: understanding seasonality and impact of mitigation strategies analysis of diurnal and seasonal behavior of surface ozone and its precursors (nox) at a semi-arid rural site in southern india regional biomass burning trends in india: analysis of satellite fire data the impact of covid- as a necessary evil on air pollution in india during the lockdown exploring the relationship between surface pm . and meteorology in northern atmospheric chemistry and physics lockdown in india dramatically reduced air pollution indices in lucknow and new noaa's hysplit atmospheric transport and dispersion modeling system drivers for spatial, temporal and long-term trends in atmospheric ammonia and ammonium in the uk. atmospheric chemistry and changes in air quality during the lockdown in barcelona (spain) one month into the sars-cov- epidemic emissions from open biomass burning in india: integrating the inventory approach with high-resolution moderate resolution imaging modis) active-fire and land cover data severe air pollution events not avoided by reduced anthropogenic activities during covid- outbreak. resources, conservation and recycling changes in air quality related to the control of coronavirus in china: implications for traffic and industrial emissions who global ambient air quality database (update india m population, version . university of southampton key: cord- - mxd zxf authors: singh, brijesh p.; singh, gunjan title: modeling tempo of covid‐ pandemic in india and significance of lockdown date: - - journal: j public aff doi: . /pa. sha: doc_id: cord_uid: mxd zxf a very special type of pneumonic disease that generated the covid‐ pandemic was first identified in wuhan, china in december and is spreading all over the world. the ongoing outbreak presents a challenge for data scientists to model covid‐ , when the epidemiological characteristics of the covid‐ are yet to be fully explained. the uncertainty around the covid‐ with no vaccine and effective medicine available until today create additional pressure on the epidemiologists and policy makers. in such a crucial situation, it is very important to predict infected cases to support prevention of the disease and aid in the preparation of healthcare service. in this paper, we have tried to understand the spreading capability of covid‐ in india taking into account of the lockdown period. the numbers of confirmed cases are increased in india and states in the past few weeks. a differential equation based simple model has been used to understand the pattern of covid‐ in india and some states. our findings suggest that the physical distancing and lockdown strategies implemented in india are successfully reducing the spread and that the tempo of pandemic growth has slowed in recent days. a very special type of pneumonic disease that generated the covid- pandemic was first identified in wuhan, china in december and is spreading all over the world. the ongoing outbreak presents a challenge for data scientists to model covid- , when the epidemiological characteristics of the covid- are yet to be fully explained. the uncertainty around the covid- with no vaccine and effective medicine available until today create additional pressure on the epidemiologists and policy makers. in such a crucial situation, it is very important to predict infected cases to support prevention of the disease and aid in the preparation of healthcare service. in this paper, we have tried to understand the spreading capability of covid- in india taking into account of the lockdown period. the numbers of confirmed cases are increased in india and states in the past few weeks. a differential equation based simple model has been used to understand the pattern of covid- in india and some states. our findings suggest that the physical distancing and lockdown strategies implemented in india are successfully reducing the spread and that the tempo of pandemic growth has slowed in recent days. the novel corona virus (covid- ) started from wuhan, china and thus, initially known as the wuhan virus, expanded its circle in south korea, japan, italy, iran, usa, france, spain and finally spreading in india. it is named as novel because it is never seen before mutation of animal corona virus but certain source of this pandemic is still unidentified. it is said that the virus might be connected with a wet market (with seafood and live animals) from wuhan that was not complying with health and safety rules and regulations. the pandemic have been recorded over countries, territories, and areas with about , , confirmed cased and , deaths (who). the covid- is very similar in symptomatology to other viral respiratory infections. as it is novel virus, the specific modes of transmission are not clearly known. originally it is emerged from animal source then spread all over the world from person to person. initially, there has been speculation about the virus spreading while the infected person is not showing any symptoms, but that has not been scientifically confirmed. on march , , who changed the status of the covid- emergency from public health international emergency to a pandemic? nonetheless, the fatality rate of the current pandemic is on the rise (between - %); relatively lower than the previous sars-cov ( / ) and mers-cov ( ) outbreaks (malik et al., ) . thus, covid- has presented an unprecedented challenge before the entire world. symptoms of covid- are reported as cough, acute onset of fever and difficulty in breathing. out of all the cases that have been confirmed, up to % have been deemed to be severe. cases vary from mild forms to severe ones that can lead to serious medical conditions or even death. it is believed that symptoms may appear in - days, as the incubation period for the novel corona virus has not yet been confirmed. however, in india days minimum quarantine period is declared by government for suspected cases. since it is a new type of virus, there is a lot of research being carried out across the world to understand the nature of the virus, origins of its spreads to humans, the structure of it, possible cure / vaccine to treat covid- . india also became a part of these research efforts after the first two confirmed cases were reported here on january , . then in india screening of traveler at airport migrant was started, immediate chinese visas was canceled, and who was found affected from covid- kept in quarantine centers (ministry of home affaires government of india, advisory). in continuation, we take a look at few of the interesting and important research being carried out in india with respect to covid- . icmr, india claims that sari patients with no record of international travel or contact with infected persons tested positive for covid- . hence it is important to optimize testing by developing strategies to identify potential cases that have a higher chance of being infected. since the availability of the resources like testing kits, labs, health personnel etc. is limited in india as for as concerned the population, the most practical approach is to test symptomatic patients presenting to hospitals, hotspots and aggressive testing to identify and contain local chains of transmission. in absence of a definite treatment modality like vaccine, physical distancing has been accepted globally as the most efficient strategy for reducing the severity of disease and gaining control over it (ferguson et al., ; singh & adhikari, ) . also in india it is reported that the country is well short of the who's recommendations of minimum threshold of . skilled health professionals per , population (anand & fan, ) . therefore, on march there are already various measures such as social distancing, lockdown masking and washing hand regularly has been implemented to prevent the spread of covid- , but in absence of particular medicine and vaccine it is very important to predict how the infection is likely to develop among the population that support prevention of the disease and aid in the preparation of healthcare service. this will also be helpful in estimating the health care requirements and sanction a measured allocation of resources. it is well known fact that covid- has spread differently in different countries, any planning for increasing a fresh response has to be adaptable and situation-specific. data obtained on covid- outbreak have been studied by various researchers using different mathematical models (chang, harding, zachreson, cliff, & prokopenko, ; rao srinivasa arni, krantz steven, thomas, & ramesh, ) . many other studies (anastassopoulou, russo, tsakris, & siettos, ; corman et al., ; gamero, tamayo, & martinez-roman, ; huang et al., ; hui et al., ; rothe et al., ; singh, ) on this recent epidemic have been reported so many meaningful modeling results based on the different principles of mathematics. most of pandemics follow an exponential curve during the initial spread and eventually flatten out (junling, dushoff, bolker, & earn, ) . sir model is one of the best suited models for projecting the spread of infectious diseases like covid- where a person once recovered is not likely to become susceptible to the infection again (kermack & mckendrick, ) . susceptible-infectious-recovered (sir) compartment model (herbert, ) is used to include considerations for susceptible, infectious, and recovered or deceased individuals. these models have shown a significant predictive ability for the growth of covid- in india on a day-to-day basis so far. a recent study has shown that social distancing can reduce cases by up to % (mandal et al., ) . further, time series models have been employed for predicting the incidence of covid- disease. as compared to other prediction models, for instance support vector machine (svm) and wavelet neural network (wnn), arima model is more capable in the prediction of natural adversities (zhang, yang, cui, & chen, ) . a time dependent sir models have been defined to observe the undetectable infected persons with covid- (chen, lu, chang, & liu, ) . a stochastic mathematical model (chatterjee, kaushik, arun, & subramanian, ) of the covid- epidemic has been studied in india. the logistic growth regression model is used for the estimation of the final size and its peak time of the corona virus epidemic in many countries of the world and found similar result obtained by sir model (batista, ) . it is well known that the effects of social distancing become visible only after a few days from the lockdown. this is because the symptoms of the covid- normally take some time to come out after getting infected from the covid- . the peak infection is reached at the end of june with in excess of million infective in india and the total number infected is estimated to be million (singh & adhikari, ) . other estimates indicates that, with hard lockdown and continued social distancing, the peak total infections in india will be million and the number of infective by september is likely to be over , million (schueller et al., ) . due to the recent development of this pandemic, we are interested in addressing the following important issues about covid- : . what is the expected time to stop new corona cases? . what is the expected maximum number of corona cases? . the significance of lockdown. in this paper, instead of developing a mathematical model for the pattern of spread of covid- , an attempt has been made to resolve these above issues in india. let us define a function called tempo of disease that is the first differences in natural logarithms of the cumulative corona positive cases on a day, which is as: where p t and p t − are the number of cumulative corona positive cases for period t and t− , respectively. when p t and p t − are equal then r t will become zero. if this value of r t that is, zero will continue a week then we can assume no new corona cases will appear further. in the initial face of the disease spread the tempo of disease increases but after sometime when some preventive majors is being taken then it decreases. since r t is a function of time then the first differential is defined as. where r t denotes the tempo that is the first differences in natural logarithms of the cumulative corona positive cases on a day, r t is the desired level of tempo that is, zero in this study, t denotes the time and k is a constant of proportionality. equation is an example of an ordinary differential equation that can be solved by the method of separating variables. the equation can be written as. integrating equation , we get. where c is an arbitrary constant. taking the antilogarithms of both sides of equation we have. r t = e kt + c ) e kt e c ) r t = ae kt ð Þ where a = e c . this equation is the general solution of equation . if k is less than zero, equation tells us how the corona positive cases will decreases over the time until it reaches zero. value of a and k is estimated by least square estimation procedure using the data sets. the paper used series of daily cases from the website covid india.org (coronavirus outbreak in india, n.d.) . in this study the day wise cumulative number of corona positive cases from april , -june , has been used to know when the tempo of disease will become zero and what will be the size at that time. also an attempt has been done to understand the significance of lockdown kerala and telangana. large variation observed in the percent confirmed cases among total testing cases, from . in bihar to . in maharashtra. in punjab the recovery rate is very low however in karnataka the percent confirmed among total test is very low means either the disease prevalence is low or the quality of testing kit is not good. in gujarat and delhi it is . and . % respectively. these percentages are very low because the testing are done in the hotspots only if the population of hotspot only is considered that these percentages might be more. government suggested and implemented social distancing and lockdown to control the spread of covid- in the society. in table an attempt has been made to show the summary statistics of tempo table which reveal that lockdown is significantly affects the spread of covid- . figure show that tempo of disease r t is declining toward zero with time, more rapidly in kerala and telangana than other states. whereas, in rest of the states it is declining slowly toward r t = . covid- has been declared as pandemic by who and is currently become a major global threat. prediction of a disease may help us to understand the factors affecting it and the steps that we can take to control it. the government of india has taken preventive measures such as complete lockdown in the very early stage of disease, physical distancing and case isolation. the most important issue is that many healthcare professionals are visiting each and every household in the hotspot area across the country to trace and isolate infected persons to curtail the spread of disease. in order to support the prevention of the disease and aid to the healthcare professionals, an attempt has been made to develop a simple model for the prediction of confirmed covid- cases and to utilize that model for forecasting future covid- cases in india. as per the model forecast, the confirmed cases are expected to gradually decrease in the coming weeks. it is also likely that the efforts such as lockdown and physical distancing affect this prediction start to decline. on the basis of considered data, one can predict that the final size of corona virus pandemic in india will be around million by the end of september. the exponential model used in this study is a data driven model. thus, its forecasts are as reliable and can capture the dynamics of the pandemic. due to real time change in data daily, the predictions will accordingly change. hence, the results from this paper should be used only for qualitative understanding. brijesh p. singh https://orcid.org/ - - - the health workforce in india. geneva: who. human resources for health observer. series no. data-based analysis, modelling and forecasting of the covid- outbreak estimation of the final size of the second phase of the coronavirus covid epidemic by the logistic model modelling transmission and control of the covid- pandemic in australia healthcare impact of covid- epidemic in india: a stochastic mathematical model a time-dependent sir model for covid- with undetectable infected persons detection of novel coronavirus ( -ncov) by realtime rt-pcr impact of non-pharmaceutical interventions (npis) to reduce covid- mortality and healthcare demand. imperial college covid- response team forecast of the evolution of the contagious disease caused by novel corona virus ( -ncov) in china the mathematics of infectious diseases clinical features of patients infected with novel coronavirus in wuhan the continuing -ncov epidemic threat of novel coronaviruses to global health-the latest novel coronavirus outbreak in wuhan estimating initial epidemic growth rates contributions to the mathematical theory of epidemics-i emerging coronavirus disease (covid- ), a pandemic public health emergency with animal linkages: current status update prudent public health intervention strategies to control the coronavirus disease transmission in india: a mathematical model-based approach model-based retrospective estimates for covid- or coronavirus in india: continued efforts required to contain the virus spread transmission of -ncov infection from an asymptomatic contact in germany covid- in india: potential impact of the lockdown and other longer term policies modeling and forecasting novel corona cases in india using truncated information: a mathematical approach age-structured impact of social distancing on the covid- epidemic in india comparison of the ability of arima, wnn and svm models for drought forecasting in the sanjiang plain key: cord- -rhhx gcg authors: vasantha raju, n. title: indian publications on sars-cov- : a bibliometric study of who covid- database date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: rhhx gcg nowadays, the whole world is under threat of coronavirus disease (covid- ). the ongoing covid- pandemic has resulted in many fatalities and forced scientific communities to foster their research and development (r & d) activities. as a result, there is an enormous growth of scholarly literature on the subject. in order to combat this novel coronavirus, the open access to scientific literature is essential. on this line, many reputed academic institutions and publication firms have made their literature on covid- accessible to all. by maintaining the database of updated information on global literature on coronavirus disease, the world health organization (who) is playing a pivotal role. the present study analyzed indian publications on sars-cov- accessible through who covid- database. the research data was restricted for the period of / / to / / . the analysis was carried out in light of the objectives of the study. the study found the considerable and constant growth of indian publications on covid- from mid-april. it is interesting to note that the prolific authors belong to either aiims or icmr institutes. majority of the covid- articles were found to be collaborative publications. the study noticed that no research publications on covid- have appeared from north eastern region. regarding the research output on covid- , the performance of largest states like uttar pradesh, madhya pradesh and bihar was found to be poor. delhi state contributed highest publications on covid- . the all india institute of medical sciences (aiims), new delhi was the most productive institution in terms of publications. it is also important to note that the central government undertakings like aiims and icmr, new delhi and its affiliated institutions shared largest proportion of publications on covid- . the indian journal of medical research has emerged as the productive journal contributing highest number of the publications. the highest contribution in covid- research takes the form of journal articles. in terms of research area, the majority of the publications were related to epidemiology. the study reported covid, coronavirus, india, pandemic, sars etc. as the frequently occurred keywords in the covid- publications. the highly cited publications were of evidenced based studies. it is observed that the studies pertaining to virology, diagnosis and treatment, clinical features etc. have received highest citations than general studies on epidemiology or pandemic coronavirus or novel coronavirus which is taxonomically termed as sars-cov- and named by world health organization (who) as covid- which emerged from wuhan city, hubei province of china by the end of has caused unprecedented panic across the world. the rapid transmission of this virus from human to human made the world health organization (who) to declare this as the public health emergency of international concern and called it as global pandemic (song & karako, ) . as on may , , globally covid- cases have been reported and caused deaths. highest human casualty reported from usa with deaths (world health organization situation report, ). the bibliometric studies which helps in quantifying the research publication pattern in a particular domain have also been done to assess the research productivity of scientific literature on covid- . bibliometric studies help in identifying the emerging area of research, provide evidence of impact of research through citations, helps in identifying right scholarly literature to consult for study and also for carrying research forward, and also helpful policy makers to strategize the potential research areas and funding. there were few bibliometric studies on covid- publications pattern worldwide (dehghanbanadaki et al, ; hossain, ; nasab, & rahim, ) . there is hardly any studies on country specific. in this regard here in an attempt has been made to look into the indian contributions to covid- research publications. the study used world health organization ( for current study the researcher used the following keywords to retrieve data on indian publication from who covid- database. who has made its covid- database searchable freely and data can be exported to .csv and ris format. the search terms used for retrieving the data were "covid- " and "india". the "title, abstract and subject" option available on the database website was used to retrieve the documents. the search results retrieved results for the search term. the database was search on th may . the data was exported from .csv format to excel sheet for further refinement of data and analysis. after thoroughly reviewing the data, it was found that there were few repeatable titles and titles not associated with indian author or authors and articles other than english language were excluded from the study. only articles written in english were included in the study. in all articles were considered for the final analysis. the study analyzed the date-wise indian publication pattern on covid- , most profile authors, institutions with highest publications, states with highest publication based corresponding authors state affiliation, top journals in which indians have published their publications frequently and document type and research area, author keywords tree map analysis and highly cited covid- documents of indian authors. for retrieving the citation data for identifying the top cited documents, google scholar citation database was used. in order to determine the research focus or area of indian publications on covid- , the author used the similar subject categories of earlier study done by lou, et al ( ) the study used descriptive statistics to analyze and visualized the data. the data analysis and result of the study is presented here in this section. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . figure- indicates the datea-wise daily publication pattern of indians on covid- . all the publications that have been included in the study were curated from march , to may , in who database. as it can be seen from table- cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . the state-wise publication profile was created by using corresponding author state affiliation. is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . this geographic heat map is generated by using freely available excel template developed by www.indzara.com . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint the bubble chart (figure- ) shows that government medical and research institutions importance in times of health crisis. it is worth mentioning that, the national institute of virology, pune has recently developed igg elisa test kit for coronavirus for speeding the antibody test, which is a first of its kind in india (prasad, ) . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint the indians have published their publications on novel coronavirus or covid- in journals. ( . %) were commentary/opinion/perspective/viewpoints kind of documents, ( . %) were reviews, . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . ( . %) were of guidelines/protocol/report related publications, another same number of documents were news items, ( . %) were editorials and ( . %) were short communications. if one were to see the document type, all kinds of documents ranging from articles to short communications were published. in terms of research area, of the publications of them were related to epidemiology, which accounts for . % of the total publications, ( . %) were related to diagnosis & treatment, ( . %) publications were on virology and ( . %) publications were of laboratory examinations related studies the hierarchical tree map (figure- ) indicates the frequency of author assigned keywords to the documents that they have published on covid- . keywords are helpful in identifying key domains of research and its growth. the keywords of corpus contained words with . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint unique words, same have been used to identify the frequency of keywords on covid- . it is found that "covid" ( times), "coronavirus" ( times), "india" ( times), "pandemic" ( times), "sars" ( times), "cov", "health", "management", "syndrome" found times each. other keywords frequently appeared in the document can be seen in figure- . eighty nine articles have received citations in all with an average citations of . per documents. table- table, followed by the article "full-genome sequences of the first two sars-cov-. cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . chloroquine and hydroxychloroquine in the treatment of covid- with or without diabetes: a systematic search and a narrative review with a special reference to india and other developing countries. the results of the study reflect the current indian scholarly publications on covid- or sars- published more number of articles than any other journals, it accounts for almost % of total . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint publications. icmr and its other associated institutions have published largely on this journal on covid- . indian research is largely done in the area of epidemiology and its impact on diabetes, cardio patients, environmental impact and pandemic outbreak, less studies on clinical prognosis, pharmaceutical interventions, and laboratory based studies or virology related studies on sars-cov- . the highly cited publications were of evidenced based studies, for instance "chloroquine and hydroxychloroquine in the treatment of covid- with or without diabetes: a systematic search and a narrative review with a special reference to india and other developing countries" or "prudent public health intervention strategies to control the coronavirus disease transmission in india: a mathematical model-based approach" which have been cited by times and other studies as well. as this pandemic is no way to go early, the research is shifting from basic to experimental studies across the globe (nasab & rahim, ) , if we see the top highly cited documents in india also gradually studies are shifting more towards evidence based medical research for finding drugs or vaccine at the earliest for this highly infectious disease. this bibliometric study though provides a bird-eye-view of the publications pattern of indians on covid- , one must be bit cautious in generalizing the results of this study. who covid- database curated only expert-referred scientific articles and literature available through litcovid database of national library of medicine (nlm). it has not included the articles available through preprint servers or central subject repositories such as medrxiv and biorxiv or arxiv e-print server o ssrn repository. it is suggested to take up a similar study using dimension.ai or semantic scholar's cord- dataset which includes articles deposited in preprint servers on covid- to see the different publications pattern of indian publications on novel coronavirus or covid- in a much larger scale. the dynamic nature of inclusion of literature to the who database on a daily basis is also be considered while generalizing this study. swarup india journal of medical research of covid : first suicidal case in india! goyal full-genome sequences of the first two sars-cov- viruses from india a bibliometric analysis of covid- research activity: a call for increased output bibliometric analysis of global scientific research on coronavirus (covid- ) current status of global research on novel coronavirus disease (covid- ): a bibliometric analysis and knowledge mapping (ssrn scholarly paper no. id ) coronavirus disease : a bibliometric analysis and review covid- india dashboard bibliometric analysis of global scientific research on sarscov- (covid- ) coronavirus | national institute of virology develops elisa test to detect antibodies. the hindu covid- : real-time dissemination of scientific information to fight a public health emergency of international concern who coronavirus disease (covid- key: cord- - mfnxkaw authors: bhargava, anurag; shewade, hemant deepak title: the potential impact of the covid- response related lockdown on tb incidence and mortality in india date: - - journal: indian j tuberc doi: . /j.ijtb. . . sha: doc_id: cord_uid: mfnxkaw india has the highest burden of incident tuberculosis (tb) cases and deaths globally. tb is strongly associated with poverty and this risk is largely mediated by undernutrition in india. covid- response related lockdown has resulted in an economic crisis which may double levels of poverty, has exacerbated food insecurity, and disrupted tb services. these developments may have serious implications for tb progression and transmission in india. the nutritional status of a population is a strong determinant of the tb incidence, and undernutrition in adults alone accounts for - % of tb incidence in india. a systematic review has shown that a % increase in tb incidence can occur per one unit decrease in body mass index (bmi), across the bmi range of . - kg/m . we believe that one unit decrease in bmi (corresponding to a - kg weight loss) may result in the poor in india as a result of the lockdown and its aftermath. this may result in an increase in estimated (uncertainty interval) incident tb by ( , ) cases. a % reduction in tb case detection between end march and may , may result in an estimated (uncertainty interval) additional ( , ) tb deaths [ . % increase ( . , . )] in . disadvantaged social groups, those living in states with higher levels of poverty, undernutrition, and migrant workers are at particular risk. we suggest enhanced rations including pulses through the public distribution system, direct cash transfers to the poor pending restoration of livelihoods. tb services should be resumed immediately with enhanced efforts at case detection including active case finding. to prevent deaths among tb detected within the national tb programme, systemic identification, referral and management of severe disease at notification should be considered. india has the highest burden of incident tuberculosis (tb) cases and deaths globally. tb is strongly associated with poverty and this risk is largely mediated by undernutrition in india. covid- response related lockdown has resulted in an economic crisis which may double levels of poverty, has exacerbated food insecurity, and disrupted tb services. these developments may have serious implications for tb progression and transmission in india. the nutritional status of a population is a strong determinant of the tb incidence, and undernutrition in adults alone accounts for - % of tb incidence in india. a systematic review has shown that a % increase in tb incidence can occur per one unit decrease in body mass index (bmi), across the bmi range of . - kg/m . we believe that one unit globally, india has the highest numbers of poor people according to the world bank. using a monthly per capita expenditure cut-off, the government of india estimated in - that % live below the poverty line. in india poverty is closely associated with childhood and adult undernutrition. according to the results of the national family health survey- (nfhs- ), % of adult women and % of adult men have undernutrition defined as a body mass index (bmi) less than . kg/m . the prevalence of undernutrition is higher in rural india, especially in the states of jharkhand, bihar, madhya pradesh, odisha and uttar pradesh, in women, in those belonging to scheduled tribes and scheduled castes, and in the poor. while . % of women in the highest wealth index were underweight, in the lowest wealth index, . % had a low bmi, with a similar differential in the men. according to the world health organization leafy vegetables, fruits is below recommended intakes. a particular concern is protein intake which is predominantly derived from cereals, and cereal proteins are of poorer in a systematic review of six large cohort studies, it was seen that bmi and tb incidence had a consistent and inverse exponential relationship and that low bmi was causally related to tb incidence. in the most recent cohort study which examined the effect of bmi and tb incidence, low bmi (< . kg/m ) was associated with an adjusted hazard incident and prevalent tb. in a cohort study a protein intake less than % was strongly associated with tb incidence. low levels of serum albumin and serum transferrin (both markers of protein nutritional status) were strongly associated with an increased risk of tb. in a case-control study in zambia, the effect of household socioeconomic position on tb prevalence was largely mediated by protein intake (adjusted odds ratio . ). in this high hiv prevalence setting, the population attributable fraction for tb was higher for protein deficiency in diet ( %) when compared to hiv ( %). in india ( - ), as the poorest % of the population also consume less protein, , therefore, low protein consumption may be a risk factor for development of tb. the potential impact of weight loss in the poor households on tb incidence can be estimated using the results of a systematic review of cohort studies linking bmi to tb incidence. the average slope gave a reduction of tb incidence of . % [ % ci: . , . ] for an increase of bmi by one kg/m for bmis in the range of . - kg/ as well as the converse increase in tb incidence by . % for one unit decrease of bmi. therefore, a reduction in bmi at population level due to reduction in consumption among the poorest sections of the society is also conversely expected to be associated with a . % increase in tb incidence in the poorest sections. the under-detection was more than % in andaman & nicobar, uttar pradesh and bihar; and less than % in odisha, goa, arunachal pradesh, mizoram and sikkim. there was no effect of lockdown on tb under-detection in lakshadweep ( %) and ladakh ( % over-detection). (see table and globally, it has been predicted that an average % decrease in tb case detection over a period of three months of lockdown will lead to an additional ( % increase) deaths in . this is assuming an absence of a rebound in case detection above values prior to the lockdown. we applied the same model to india using estimates. considering the observed % reduction in detection over an eight week period, there will be an estimated due to the covid- related lockdown, the potential increase in incidence and mortality due to tb has the potential to wipe out the gains made in the last few years. to address the issue of excess mortality due to lockdown related under-detection, and bmi is based on six studies, all from high-income countries we have also not provided a combined increase in tb incidence and mortality due to lockdown induced impoverishment and under-detection. despite this, the numbers estimated and presented are significant enough for the programme to act. we have assumed similar under-detection among tb patients living with and without hiv. the present situation is dynamic and evolving there are many other factors that can modify the final impact. among these, the response of the public health system, the social protection provided by different state governments to the poor and the responsiveness of the economy to the stimulus offered will shape the future of the tb epidemic. the author(s) received no specific funding for this work. world health organization (who) revised national tuberculosis control programme (rntcp) national strategic plan for tb elimination - the global burden of latent tuberculosis infection: a re- estimation using mathematical modelling . bhargava a. undernutrition, nutritionally acquired immunodeficiency, and tuberculosis control tuberculosis control in india: refocus on nutrition half of the world's poor live in just countries accessed may , . . ministry of statistics and programme implementation; 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government of india lakh crore relief package under pradhan mantri garib kalyan yojana for the poor to help them fight the battle against corona virus national institute of nutrition. dietary guidelines for indians national sample survey office; ministry of statistics and programme implementation; government of india. nutritional intake in india prevalence of undernutrition, its determinants, and seasonal variation among tribal preschool children of odisha state, india. asia-pacific j public heal the impact of the economic crisis and the us embargo on health in cuba towards elimination of tuberculosis in a low income country: the experience of cuba increased incidence of tuberculosis in zimbabwe, in association with food insecurity, and economic collapse: an ecological analysis. plos one predicted impact of the covid- pandemic on global tuberculosis deaths in stop tb partnership in collaboration with imperial college;avenir health hopkins university and usaid. the potential impact of the covid- response on tuberculosis in high-burden countries: a modelling analysis clinical profiles of early and tuberculosis-related mortality in south korea between and : a cross-sectional study early death by tuberculosis as the underlying cause in a state of southern brazil: profile, comorbidities and associated vulnerabilities government of india. ministry of finance: finance minister announces government reforms and enablers across seven sectors under aatma tuberculosis deaths are predictable and preventable: comprehensive assessment and clinical care is the key maharashtra manipur meghalaya mizoram nagaland odisha puducherry punjab rajasthan sikkim tamil nadu telangana tripura uttar pradesh uttarakhand west bengal total ** *notification data extracted on june from the nikshay website ; **when compared with previous year ( march to may ), the national under-detection was %• covid- response related national lockdown in india may double levels of poverty, has exacerbated food insecurity, and disrupted tb services.• worsening of undernutrition among the poor may result in an additional estimated incident tb cases • tb under-detection during lockdown could result in an additional estimated tb deaths in • we recommend enhanced rations including pulses and direct cash transfers for the poor.• we recommend ramped up active case finding and early detection of severe disease. key: cord- -bsmni sh authors: dhungana, nimesh title: human dignity and cross-border migrants in the era of the covid- pandemic date: - - journal: world dev doi: . /j.worlddev. . sha: doc_id: cord_uid: bsmni sh the coronavirus (covid- ) outbreak, and the resultant lock-downs and cross-border travel restrictions have reinvigorated public debates about the vulnerability of the global migrants, together with the responsibility of the states to ensure a dignified treatment of migrants. situating within the debates on capability-based development and human dignity and drawing on emerging evidence from nepal, this opinion piece seeks to explore how returnee nepali labour migrants from india are subject to dignity violation within the government's response to the covid- . the paper tentatively concludes that the nepali government's decision to seal its border with india, and its subsequent interventions to curtail the flow of outbreak, have undermined the human dignity of nepali migrants. in so doing, the paper raises a normative question as to whether, to what extent and for how long, poor and marginalised populations such as labour migrants should be expected to endure suffering and dignity violation in the interests of protecting the health of the population at large. the role of contextual politics in shaping the response to the intersecting nature of cross-border and public health crisis is highlighted. attention is also drawn to the potential of political response against dignity violation, in exposing the ineptitude of the state to safeguard the well-being of its returnee migrants. the coronavirus outbreak, and the resultant lockdowns and cross-border travel restrictions have reinvigorated public debates about the vulnerability of the global poor and the deprivation they face. "if coronavirus doesn't kill me, hunger will" is a quotation from an informal worker in india that, in part, expresses the acute struggle for survival facing informal workers and migrants across the global south (dhillon, ) . emerging literature has shown internal migrants enduring deteriorating economic and health conditions, with limited access to preventive health services, and lack of social protection provisions in areas of basic income, food and housing (pulla, ; sen, rajan & banerjee, ; sengupta & jha, ) . concerns are also being raised over how tighter border restrictions and growing state surveillance are making cross-border migrants further susceptible to health and socio-economic marginalisation (daniels, ; hargreaves, kumar, mckee, jones & veizis, ; kluge, jakab, bartovic, d'anna & severoni, ; mcauliffe & bauloz, ) . informed by these urgent concerns, the present article seeks to explore how nepali labour migrants returning from india are subject to dignity violation in the wake of the covid- pandemic; and whether political response is emerging against such dignity violation, and if so, in what form. given the fast-evolving context of pandemic response in nepal, together with limited scholarly evidence surrounding the topic, the paper is based primarily on a targeted review of selected journal articles and media articles from nepal, along with petitions and reports from rights groups based in nepal, focused on the first two months of the border closure ( march - may). while human dignity is a hotly contested topic, within the contemporary global governance discourse, the notion is closely linked to the liberal idea of human rights. the un declaration of human rights, for instance, states "all human beings are born free and equal in dignity and rights", asserting the interdependence between the two concepts in the interest of promoting global equality and justice (united nations, ) . subsequent international guidelines and conventions have sought to reinforce the link between human dignity, human rights and state responsibility (un general assembly, ) . in recent years, as part of the shift towards rights-based humanitarianism, human dignity has also gained prominence in the humanitarian sector (slim, ) . within the field of development studies, the concept of human dignity may be located in the debates on human development and capability-based development. according to martha nussbaum, human dignity combines elements of "internal capability", in the form of "bodily health", and "external capability", in the form of "having control over one's environment" (nussbaum, , pp. - ) . broadly speaking, human dignity is concerned with one's selfworth as a human being (intrinsic dimension), together with the duty of the state to ensure concrete provision for the protection and promotion of human well-being (external dimension). despite these normative and policy claims, another line of scholarship has argued that poor and marginalised communities routinely face assaults on their human dignity, owing to unequal power relations, lack of social safety provisions, coupled with discriminatory laws and policies, and bureaucratic indifference (farmer, ; gupta, ; harrell-bond, ; yamin, ) . by putting a critical spotlight on what they see as the irresponsibility, ineptitude and power abuse prevalent within some state institutions, these scholars have called for a shift from normative and philosophical discussions on human dignity to what kaufmann, kuch, neuhaeuser & webster ( ) terms a "negative approach to human dignity", with a focus on how certain social groups are subject to "humiliation, degradation or dehumanization" (p. ). on march , faced with the growing risk of community-level transmission of the virus from the nepali migrants re-entering the country from india (basnet, koirala, pandey & koirala, ) , the nepali government decided to seal its open border with india, which has historically been a subject of bi-lateral political dispute (shrestha, ) . the decision triggered a major border crisis, involving an influx of returnee nepali migrants, who faced growing threat of virus, loss of livelihoods, as well as police surveillance in the indian cities (sengupta & jha, ) . many were stranded at various indo-nepal border checkpoints (shah, shah & shah, ) , forcing some to take life-threatening measures such as crossing a river that flows between indo-nepal border (badu, ) . in the face of growing public and media criticism of the failure to attend to the plight of the stranded migrants, an agreement was apparently reached between the indian and nepali to set up quarantine centres along the border, and provide the migrants with basic food and shelter (giri, ) . however, more than eight weeks into the border closure, it appeared neither government has managed to ensure that the quarantine facilities meet basic standards of health, hygiene and security. some media reports have quoted quarantined migrants as saying "this is a jail, not a quarantine facility" (paudel, a) , underlining the nature of neglect prevalent within the government-run quarantine facilities. these facilities, according to emerging media reports, appear far from consistent with the world health organization standards, which call for "respect and dignity" to be maintained in the management of quarantine facilities (world health organization, ). experts have warned of growing cases of anxiety and depression among quarantined migrants (shah et al., ) , with at least one incident of a returnee migrant committing suicide inside a quarantine facility (dhakal, ) . concerns are also raised that the overcrowded quarantine services, instead of curtailing the spread of the outbreak, are seemingly exposing the migrants and wider community to an increased risk of infection (basnet et al., ) . of concern is also how the central government's response to the pandemic has tended to blame and scapegoat returnee migrants. for instance, the prime minister of nepal, k.p oli, has repeatedly termed the "unchecked nepali migrants", because of their tendency to defy government-run health screening and quarantine facilities, as responsible for the increased cases of covid- (nepal pm: unchecked migrants from india contributing to rise in covid- cases, ) . at the local level, there have been cases of government authorities deploying questionable measures of contact tracing and health surveillance such as 'red marking' houses of the returnee migrants, in a bid to ensure closer monitoring of and compliance with the government-imposed -day quarantine (red mark painted on foreign returnees houses in jhapa, ) . although these measures may be justifiable from an urgent public health perspective to reduce the risk of community-level transmission, they have risked stigmatising and discriminating returnee migrants. the above accounts do not mean that nepali migrants have passively accepted how they are being treated. in some places, stranded migrants have been reported to have protested the government's decision to seal the border without guaranteeing the safe return of the migrants (badu, ) . there are reports of migrants fleeing quarantine facilities, as a show of discontent about the ways such facilities are managed (paudel, a) . investigative journalists and civil society activists, in turn, have sought to capture and publicise the insecurity and neglect experienced by stranded migrants. one media account quotes a migrant as asking, "why do i have a citizenship card if my government won't make arrangements for me? only for voting? i feel as if i am not a nepalese citizen", thereby asserting their political right to return home and calling on the state to fulfil its responsibilities towards its citizens (paudel, b) . civil society groups have expedited their efforts to monitor violations of the rights and dignity of migrants (advocacy forum nepal, ; nepali times, ) . such efforts are expressed in the language of rights, freedom and dignity of migrants, as enshrined in the national constitution and international conventions (nepali times. ( ) , most notably the constitution of nepal, which guarantees the right to live with dignity, and the international covenant on civil and political rights, ( ) , which specifically condemns any state's intervention that "threatens the life or well-being of the community" in the name of emergency management (un general assembly, ) . the crisis and growing societal pressure have also reactivated certain state institutions. in response to the petition filed by legal activists, on april , the supreme court of nepal demanded that the government uphold the rights of the migrants to return to the country, while also ensuring adequate testing and treatment provision, together with food and shelter for stranded migrants (advocacy forum nepal, ; pradhan, ) . similarly, the national human rights commission, after launching a high-level human rights monitoring initiative to oversee the situation of migrants, has appealed to the government that returnee migrants be provided with adequate health check-ups, food and shelter, and are ensured "dignified repatriation to their homes" (national human rights commission of nepal, ; p. ). whether or how these mix of protests, pressure groups and petitions have succeeded in changing the conduct of the government is a question that merits further investigation. but they represent noteworthy political initiatives sparked by the covid- pandemic, geared at holding the state accountable to its citizens in the midst of a major crisis. the paper tentatively concludes that the nepali government's decision to seal its open border with india, and its subsequent interventions to curtail the flow of outbreak have undermined the human dignity of nepali migrants, defined as a combination of internal capability and external capability (nussbaum, ) . it also raises a major normative question as to whether, to what extent and for how long, poor and marginalised populations such as returnee migrants should be expected to endure dignity violation in the interests of protecting the health of the population at large. that cross-border migrants, notably refugees and asylum seekers, often experience bodily hardship, humiliation and even death as part of the detention and deportation practices in the receiving or destination states is increasingly documented (debono, ; squire, ) . according to squire ( ) , the ill-treatment of refugees represents "a crisis of modern humanism", characterised by normalisation and tolerance of injustice against those who are deprived of basic social and economic security (p. ). nepal's case is reminiscent of these long-standing and emergent cases of injustice facing marginalised migrants. at the same time, it also departs from existing cases, in the sense that it is returnee citizens, neither asylum seekers nor 'stateless' refugees, with constitutional and legal rights, whose dignity is being undermined in response to a pandemic. according to crisis scholars ansell, boin & keller ( ) , the governance of cross-national crisis demands "extreme adaptation and unprecedented cooperation" across wide-ranging administrative and political systems (p. ). in the present case, timely cooperation between both the 'home state' (i.e. nepal) and 'destination state' (i.e. india) seemed central to ensure effective governance of the pandemic. forging a bi-lateral cooperation, however, is not independent of the wider politics between the two countries. for example, at the time of writing this paper, the two countries are locked in a serious border dispute, with the nepali side accusing india of encroaching on its territory, which the indian side has denied (nayak, ) . not only does such political tension stand to interfere with the effective governance of crossborder migration, it also throws into doubt the prospect of timely and effective bilateral cooperation in responding to the pandemic. further attention into these larger political dynamics is necessary in preparing for and responding to a public health crisis of cross-national nature. finally, the intersecting crisis of covid- and cross-border migration in nepal has renewed political discourse and demands surrounding the rights and dignity of poor migrants. indeed, research on the socio-political dimensions of disasters has long pinned hopes on disasters as a catalyst for renewed political activism for accountability and justice (curato, ; pelling & dill, ) . the point is not to overly idealise the transformative potential of the political actions sparked by the covid- crisis in nepal. but they represent noteworthy politics, in their ability to have laid bare the chronic ineptitude of the state to safeguard the everyday security and human dignity of returnee migrants. legal intervention to strengthen criminal justice system during covid- in nepal managing transboundary crises: identifying the building blocks of an effective response system nepalis are swimming across the mahakali to get home covid- containment efforts of a 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humanitarian ethics: a guide to the morality of aid in war and disaster governing migration through death in europe and the us: identification, burial and the crisis of modern humanism international covenant on civil and political rights universal declaration of human rights key considerations for repatriation and quarantine of travellers in relation to the outbreak of novel coronavirus -ncov power, suffering, and the struggle for dignity: human rights frameworks for health and why they matter key: cord- -nv kfp z authors: ghosh, kapil; sengupta, nairita; manna, dipanwita; de, sunil kumar title: inter-state transmission potential and vulnerability of covid- in india date: - - journal: nan doi: . /j.pdisas. . sha: doc_id: cord_uid: nv kfp z abstract since the first case of covid- traced in india on th january , the total no. of confirmed cases is amplified. to assess the inter-state diversity in spreading potentiality of covid- , the exposure, readiness and resilience capability have been studied. on the basis of the extracted data, the outbreak scenario, growth rate, testing amenities have been analysed. the study reflects that there is an enormous disparity in growth rate and total covid- cases. the major outbreak clusters associated with major cities of india. covid- cases are very swiftly amplifying with exponential growth in every four to seven days in main affected states during first phase of lockdown. the result shows the vibrant disproportion in the aspect of, hospital bed ratio, coronavirus case-hospital bed ratio, provision of isolation and ventilators, test ratio, distribution of testing laboratories and accessibility of test centres all over india. the study indicates the sharp inequality in transmission potentiality and resilience capacity of different states. every state and union territory are not well-prepared to contain the spreading of covid- . the strict protective measures and uniform resilience system must be implemented in every corner of india to battle against the menace of covid- . a new respiratory tract infectious disease covid- caused by coronavirus - has emerged out of the city of wuhan, china [ ] in december , which has already spread worldwide with its deadly effect. suddenly, it has been transformed into an extraordinary catastrophe towards the world's geopolitical scenario, economic structure and health system [ ] . the magnitude of its aftermath is extraordinary [ ] . reuters has released a statement of un secretary-general, where he has warned that the world will encounter the most challenging emergency situation since world war ii with covid . on th january, , world health organization (who) announced this health disaster as public health emergency of international concern (pheic) and ultimately on th march, , who has considered this disease as a pandemic. this emergency situation has an extensive worst impact on the national economy, social and psychological issues as well as on the international affairs of every affected territories [ ] . who has coined a new term 'infodemic' [ ] and information circulated through social media would traumatize people in several times [ ] . the prime and initial factor of covid- must be identified as a challenge on the basis of humanitarian ground [ ] . who in this context, the fact is noteworthy that every state of india is not equally well-equipped with adequate medical infrastructure to provide necessary health care facilities to the covid- patients. proper medical amenities are highly inaccessible especially to the citizens residing in the remote areas of different states across the country. the inequal service of health sector in various states promote to flourish the rate of contagion countrywide. the low testing rate, deficiency and miserable condition of quarantine centres, rejection of hospitals for admitting patients, scarcity of ventilation systemsare the regular hazardous phenomena of india surging the country's gross no. of positive covid- cases. the fact is evident that the present alarming situation of india is a definite outcome of sharp interstate disparity in the aspect of necessary remedial readiness and resilience capability to combat against covid- . existing gaps in healthcare infractures and socioeconomic vulnerabilities may lead to sharp jump in outbreak of the virus [ ] therefore, the assessment of interstate discrepancy in corona virus outbreak rate and medical accommodations are explicitly imperative to detect the disparity of transmission capability of the states all over india. this study is very crucial not only to focusing the current situation but to also gaining comprehensive idea about the near future scenario and make necessary preparedness to cope with the situation. this paper aims to highlight the interstate variations in transmission potential of covid- and to assess the exposure, preparedness and resilience capacity in different states in india. . materials and methods the present study is based on secondary data sources. state and district wise data regarding the confirmed case of covid- and test records from th january to st may, have been collected from publicly available portal of covid india.org. the data is validated by a group of volunteers. census of india's report has been used to obtain the state wise population of . covid- test centres locational information has been gathered from the indian council of medical research (icmr) official bulletin ( april, ). national health profile - report has been used to obtain the state wise hospital bed, per capita health expenditure, poverty ratio and aged population (above years). slum household information has been gathered from census of india ( ) slum house section. several newspaper reports have also been used to interpret the problem in different states and union territories in india. state wise available hospital beds (government hospitals only) and projected population data are used to calculate the availability of hospital bed ratio in different states. to identify states wise potential for hospital shortages, the covid confirmed cases and hospital bed ratio has also been calculated. confirmed cases per persons in different states have been identified on the basis of projected population ( ) and total confirm cases as of st may, . finally, the ratio of confirmed cases (case per persons) and hospital bed (bed per persons) are identified. a scatter diagra m is prepared to show the relationship between slum population and total positive case. the first covid - case in india was identified at thrissur, kerala on th january, and the ministry of india has confirmed that % casualty have been recorded among the age group of above years whereas % death is reported within the age group of - years. according to who, the older population is explicitly identified as vulnerable group to the menace of coronavirus infection. the availability of beds for elderly population in india is . per old population. to understand the actual scenario of coronavirus and to know whether the current interventions are adequate or falling short, appropriate data of various administrative unit all over the country in temporal basis is required. test ratio per thousand people in india is very low ( . ) in respect to italy the study reflects another striking fact of unequal distribution of testing centres all over the country. in india, . % area is falling under km. buffer zone of different testing centres and this km buffer area may be considered as maximum limit of accessibility without considering the geographical factors of regional accessibility (figure ) . the map shows that the extension of testing related service is maximum in the southern part of the country. moreover, the western coastal region and the portion of north, north-west india are well-covered with the services of testing labs. but on the other side, the parts of the eastern, central, extreme northern india are mostly uncovered in this context which increase the magnitude of vulnerability of the people residing in these particular regions. major findings form the above discussions can be summarized in following table- • in india, recovery rate of covid- patients is increasing and during first phase it was . % and in last phase it reaches to about % with great inter-state variation. • major outbreak clusters are located in western and northern india and they are associated with major cities. j o u r n a l p r e -p r o o f since the first covid- case reported on th january, , spreading pace is not uniform throughout the county. presently in india, the intensity of severity and casualty are increasing daily in a steady rate and yet to reach at the peak. community-dependent disaster managing system and preparation [ ] is significant to diminish the resultant fatalities and damages [ ] . although, the present study identifies the outbreak hotspot at district, scaling up of hotspot area identification to village or municipality (local administrative unit) may help to better monitoring system. most emphasis should be given to enhance the testing activities of the suspected people and enforce them to stay isolated. a strategy of community quarantine could be helpful to prevent the people being exposed to the virus [ ] . the accurate and updated information of every districts across the country must be circulated to prevent the spreading of coronavirus contagion and to build resilience against this disease. so, the development of proportionate resilience system in every part of india is a mostly crucial issue, which can support to achieve speedy and sustainable retrieval from the menace of covid- . covid- control in china during mass population movements at new year. the lancet review and analysis of current responses to covid- in indonesia: period of launch of global humanitarian response plan for covid- infodemic" and emerging issues through a data lens: the case of china how to fight an infodemic technology and citizen behaviour in pandemic: lessons from covid- in east asia coronavirus covid- : facts and insights building resilience against biological hazards and pandemics: covid- and its implications for the sendai framework systematic approach is needed to contain covid- globally projecting the transmission dynamics of sars-cov- through the post pandemic period transmission potential and severity of covid- in south korea monitoring transmissibility and mortality of covid- in europe world economic forum, how fast is coronavirus spreading? the round table politics and the covid- pandemic: the turkish response covid- , risk, fear and fall-out prevention is better than the cure: risk management of covid- nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study predictions and role of interventions for covid- outbreak in india covid- , is india's health infrastructure equipped to handle an epidemic? community quarantine strategy against coronavirus disease in anhui: an evaluation based on trauma center patients technical advisory group for infectious h. covid : what is next for public health? community-based disaster preparedness and climate adaptation: local capacity building in the philippines major organisations' website accessed census of india coronavirus pandemic: daily updated research and data key: cord- -t d b authors: séguin, béatrice; hardy, billie-jo; singer, peter a.; daar, abdallah s. title: genomic medicine and developing countries: creating a room of their own date: journal: nat rev genet doi: . /nrg sha: doc_id: cord_uid: t d b the notion that developing countries must wait for the developed world to make advances in science and technology that they later import at great cost is being challenged. we have previously argued that developing countries can harness human genetic variation to benefit their populations and economies. based on our empirical studies of large-scale population genotyping projects in mexico, india and thailand, we describe how these resources are being adopted to improve public health and create knowledge-based economies. a significant additional benefit is building the capacity for scientific research and internalizing advances in technology, whatever their source. in collins et al. described the future of genomics research as a house and the human genome project as its foundation. the question this raises is who will live in that house? will it be only those lucky few in the industrialized economies, or will all people be able to find a room, no matter where they come from? the use of genomic information to develop therapeutics is growing in industrialized countries . in the developing world, however, advances in genomics are perceived to be out of reach; critics question why countries would invest in genomic research when they face other more pressing health needs such as poverty, infectious diseases and the lack of basic infrastructure. in addition, the high cost that is associated with genomic research and the inadequacy of existing regulatory and intellectual property regimes are seen as significant obstacles . we too have argued that developing countries are the ones that can least afford to waste their limited health resources on ineffective diagnostics and therapies , . until now, the more immediate health applications resulting from investing in genomic sciences, in developing countries and globally, have been attained through the sequencing of genomes of microorganisms and viruses such as the severe acute respiratory syndrome (sars) coronavirus and the influenza virus [ ] [ ] [ ] [ ] [ ] . but infectious diseases are not the only major cause of morbidity and mortality in developing countries; the rates of non-communicable disease are also increasing . currently, one-third of all deaths in the world are caused by cardiovascular diseases. of these, nearly % occur in developing nations. by the year , the number of new cancer cases will increase by a staggering % in developing countries as opposed to only % in developed countries . wanting to assess the resources that the developing countries already possess to improve public health we chose to focus our case studies on large-scale genotyping initiatives in human populations, which stand to address both infectious diseases (host response) as well as chronic diseases through a better understanding of the correlations between genotype and phenotype. investing in this field, identifying niche areas within it and within areas of local interest, and building life sciences-based capacity around such knowledge in developing countries might not only contribute to improving local health but also potentially stimulate economic development. at the very least, such approaches will help understand disease susceptibility and drug responses in the local population . there is increasing realization that science and technology are vital to human development, and that the life sciences are particularly relevant to developing countries. to break the cycle of dependence, emerging economies , and other developing countries are beginning to build infrastructures for local innovation and capture the value of their scientific research. the concept of genomic sovereignty that we describe in this article is linked to the wish of the three countries described here -mexico, india and thailand -to capture the value of their investments in these large-scale genotyping projects. a crucial outcome of investments in these projects and related life-science technologies is the acceleration of the capacity to build scientific research and the ability to internalize new technologies, whether spawned locally or imported. despite the perception that the benefits of genomics are unattainable outside the industrialized world, large-scale genotyping efforts exploring human genomic variation have been initiated in several emerging markets. here, we discuss the results of a cross-comparison of three case studies of genotyping initiatives taking place in mexico, india and thailand. using previously described methods (box ), we conducted in-depth interviews to develop case studies of the mexican national genomic medicine institute (inmegen) (box ) , the indian genome variation database consortium (igvdb consortium) (box ) and two smaller initiatives in thailand, the thailand snp discovery project, and the pharmacogenomics project at the thailand centre for excellence in life sciences (tcels) (box ) . we explored the motivations for undertaking these largescale genotyping initiatives, the adoption of genomic medicine in each country, the mechanisms that the three countries are envisioning or implementing to develop genomic medicine appropriate to their own circumstances, and the potential ethical, legal, social and cultural issues that have arisen or might arise as a result. here, we define genomic medicine as health applications derived from genomic approaches and research, manifested, amongst others, in both boutique personalized medicine and population or sub-population level pharmacogenomics and theragnostics , . until now there has been little data based on empirical studies that describe how the emerging knowledge of human genomic variation can be practically applied to improving health in the developing world. our findings provide a snapshot that will be of interest to other emerging and developing economies that are interested in the evolution of genomic studies, particularly their intersection with public health and as potential sources of economic activity. in this respect, the findings are relevant to the private sector in both industrialized and developing countries, and to those international organizations that are interested in how science and technology can be used to achieve and accelerate health security and human development in general. our cross-comparison analysis of the above cases has generated a roadmap that will help readers better understand the ways in which these three countries are harnessing human genomic variation studies. the roadmap is made up of several common themes that emerged from the data. it represents the key factors contributing to the establishment and potential future success of the initiatives we studied. these include political will, institutional leadership, local health benefits, genomic sovereignty and the aspiration to create knowledge-based economies. political will. in all three countries, government leadership, political support and/or government legislation were crucial to the establishment of the genotyping projects discussed here. in thailand, tcels, which oversees the thai pharmacogenomics project, was established by royal decree of the king of thailand in june . similarly, in mexico, inmegen was the first department of the mexican national institute of health (m-nih) to be legislated with the support of all political parties in congress, thus providing a strong message that genomic medicine is a priority for the mexican people. subsequently, inmegen received an initial investment of us$ million from the mexican government. in , the ministry of health in india pledged $ million towards research in medical genomics . more recently, the indian government's national biotechnology development strategy and the thai government's national biotechnology policy framework identified genomic medicine as an investment opportunity. accordingly, the igvdb consortium received public funding for its genotyping initiative through the federal government's council for scientific and industrial research. undoubtedly, political will was instrumental to the initial development stages of these initiatives -it enabled them to access the necessary public funding. nevertheless, given that genomic medicine and these initiatives are still in their infancy, objective criteria by which to measure their success have yet to be agreed upon. importantly, in developed countries, critics suggest that the promise of the human genome project was overhyped and that it has failed to deliver on its potential . in this context, the definition of success will probably pose a challenge as the initiatives in mexico, thailand and india are seeking continued political support, and healthy scepticism is called for. with this narrow understanding of the potential of genomics, the criticism is indeed valid, and we did encounter sceptic voices; for example, some key informants worried that inmegen is superfluous and expensive to maintain. however, if we consider genomics more widely, especially including its capacity to improve public health, the picture is different. for example, we are much better able to track sars now that we have its genomic sequence than when the disease surfaced just a few years ago. nevertheless, the genotyping initiatives discussed here qualitative case study methods were used for this research , . the case studies of the following genotyping initiatives were selected for three reasons: first, to our knowledge, these initiatives were the most advanced with respect to planning or implementation; second, the countries the initiatives were housed in give a good regional representation; and third, access to key informants was facilitated by existing contacts with individuals involved in these initiatives. we collected data between june and january . we performed in-depth, face-toface (or by teleconference call), semi-structured interviews with key informants representing scientists and managers from the mexican national institute of genomic medicine (inmegen), the indian genome variation database (igvdb) consortium, the thai snp initiative, the national center for genetic engineering and biotechnology in thailand (biotec), the thai centre of excellence for life sciences (tcels) as well as key informants from diverse backgrounds such as the media, non-governmental organizations, regulatory agencies, ministries of health, and experts in the area of genomics, pharmacogenetics and/or ethics from developed and developing countries. we also collected data from documents such as publicly available materials that were relevant to the study questions. interviews lasted approximately one hour and were audio-taped and transcribed. data were analysed in several phases. theme categories were identified by analysing the interview transcripts by generative or open coding (analysis of words repetitions, key terms and key words). the next phase of data analysis consisted of axial coding of the data to build connections within and between theme categories. in the final phase, core concepts were identified using selective coding. we ensured authenticity of the study by having other members of our research group cross-validate the coding , . the study was approved by the committee on use of human subjects of the university of toronto, canada. each interviewee provided written consent. the mexican national institute of genomic medicine (inmegen) is one of twelve national institutes of health in mexico. created in , it aims to develop a national platform in genomic medicine that is focused on national health problems and is based on the genomic structure of mexican populations. it received an initial investment of us$ million from the mexican government. most of mexico's population is considered mestizo resulting from a dynamic admixture of over ethnic groups, spaniards and, to a lesser extent, africans, within the last years. inmegen has genotyped over , mestizos from different regions of mexico, analysing , to , snps. this information is triggering a series of disease-related genomic studies in mexico that will be used to improve health care for the mexican population, and is likely to be useful to other latin american countries with similar population profiles. inmegen's first step focused on generating the mexican hapmap in order to facilitate the next phase of research, which will concentrate on relating genomic information of the mexican population to significant causes of morbidity and mortality in mexico, including macular degeneration, diabetes mellitus, hypertension and obesity, cancer, infectious diseases and cardiovascular diseases. will need to anticipate scepticism and, as such, establish strategic plans outlining criteria that can be used to measure success. our key informants pointed to inmegen's and tcels's leadership in establishing communication strategies to engage the public on matters of genomics. for instance, in an effort to engage the young mexican public on issues of genomic medicine, inmegen has developed a comic book series entitled 'la medicina genómica, el genoma humano' describing the human genome, potential applications, and ethical, legal and social issues that arise out of human genomics. in addition, the institute promoted understanding of the mexican hapmap project through radio appearances and publications for the general public. similarly, tcels, in conjunction with local scientists, is preparing a book on 'pharmacogenomics for layman' to be released in june . each of these initiatives is publicly funded, hence their dependence upon public support. investing in public engagement programmes will help raise the level of understanding of the public, possibly increasing the likelihood of public support. however, in mexico and thailand, some key informants told us that local critics consider some of the genomics public engagement activities as propaganda. although public understanding will ensure public demand of genomic products and services, and encourage physicians to implement genomic medicine in their practice, genomics institutes will have to strike a balance between public relation activities and proper public engagement activities to avoid hype. despite this concern, increased public understanding of genomics can ensure that the public have realistic expectations as to the benefits associated with genomic medicine as well as the length of time it will take to reap these benefits. institutional leadership in all three countries has also led to international collaborations. for example, inmegen is engaged in several strategic collaborations in industrialized countries, including nestlé international headquarters, genóma spain, the pharmacogenetics for every nation initiative (pgeni), the translational genomics research institute (tgen), john hopkins university, the broad institute and the public population project in genomics (p g). these collaborations enable inmegen to participate in research and policy decisions on the international level that are frequently led by industrialized countries, indicating that investment in genomic medicine is providing inmegen with the opportunity to participate in the global economy. likewise, some of the same researchers leading the genotyping initiatives in india and thailand are collaborators on the human genome organisation (hugo) pan-asian snp consortium -an international genotyping project that focuses on anthropology and human migration (box ) . the consortium has required scientific groups from different geopolitical environments and varying levels of scientific infrastructure to work together towards a common goal. according to key informants, several crucial factors contributed to its success, including leadership, equal partnerships, good intentions, stewardship and consensus. as a result, the hugo pan-asian snp consortium has generated goodwill between the member countries, which in turn might act as a foundation for future pan-asian collaborative studies with a focus upon health as opposed to anthropology. these north-south and south-south collaborations are valuable as they leverage the infrastructure available in host countries for the benefit of less well-developed countries; enabling them to participate as equal contributors to genomics and increasing the likelihood that they will reap benefits from it. our previous work has shown that political will and institutional leadership are necessary to promote a successful biotechnology sector in developing countries . these case studies provide evidence of how developing countries are leveraging these two characteristics in order to coordinate the necessary policy and public requirements for the establishment of genotyping initiatives and the eventual adoption of genomic medicine. investing in genotyping projects can provide these countries with the necessary tools to better understand drug response, disease mechanisms and disease susceptibility in their own populations . however, translation of evidence-based population allelic frequencies into targeted health interventions for local populations is seen as a challenge globally , . in mexico, these challenges are being addressed and the integration of inmegen within the mexican ministry of health facilitates more effective translation of genomic findings into public health applications. specifically, key informants thought the results of inmegen's studies could inform local health decision making -for example, by focusing health promotion campaigns at mexican sub-populations that might be at higher risk of certain chronic diseases. the - inmegen work plan is supportive of this model for public health genomics, as it reports that genomic medicine has the potential to reduce mexican health-care costs related to diabetes management by % between and (ref. ). we found this feature of inmegen to be unique in the developing world. according to one key informant, largescale genotyping projects, and the capacity building that is associated with them, have already accelerated the ability of the country to deal with public health problems in india. the tools of genomic analysis have, for example, been used to genotype polio and japanese encephalitis viruses, and have enabled public health officials and researchers to identify the evolution and spread of different strains. thus, public health officials are able to track and manage infectious disease outbreaks more effectively. initiated in , the indian genome variation database (igvdb) consortium is a collaborative network between the institute of genomics and integrative biology (igib), the centre for cellular and molecular biology (ccmb), the indian institute of chemical biology (iicb), the central drug research institute (cdri), the industrial toxicological research centre (itrc) and the institute of microbial technology (imtech). the aim of the consortium is to construct a public dna-variation database with , samples from unrelated indian sub-populations that are selected on the basis of their geographical locality and linguistic categories. this aim will further research on disease predisposition, adverse drug reactions and population migration, with the ultimate goal of improving both local and global health. linguistic categories include tibeto-burman, dravidian, indo-european, and austro-asiatic from northern, southern, eastern, western, central and northeastern india. thus far for phase , analysis has been carried out on, and validation is ongoing for, both reported and novel snps located within disease genes that are thought to be prevalent in both the indian and the global population. although the igvdb consortium is providing their data to be used by the academic community, research conducted by the igvdb consortium that results in discoveries and/or potential commercialization opportunities will be protected by intellectual property and will need to be licensed through them. other downstream applications are likely to emerge from basic research being conducted in india. for example, researchers at the igvdb consortium have recently demonstrated an association between a haplotype at the adrb locus (encoding a beta- -adrenergic receptor) and the response to salbutamol in asthma patients in the indian population , . others have found a possible link between tardive dyskinesia and specific polymorphisms located within the catechol-o-methyltransferase (comt) genes . data from these studies could lead to improved diagnostics for treatment of patients in india. in contrast to inmegen, the igvdb consortium, the tcels pharmacogenomics project and the thai snp discovery project are not incorporated within their respective health ministries. consequently, although key informants emphasized that these initiatives would be used to better understand the biological determinants of disease, to address local prevalent health concerns, and to reduce health-care costs through improved use of therapeutics and reduced adverse drug reactions, it is not yet clear how quickly this knowledge will be adopted into public health interventions. this will pose a particular challenge in the context of thailand's health system, which offers universal health coverage. the government will have to decide where genomic medicine ranks in terms of resource allocation. achieving local health benefits through genomic medicine is a lofty challenge but one that many key informants described as a key motivator and maintained is achievable in the long term. if health applications are developed from these initiatives, widescale adoption of genomic medicine and delivery of products and services will vary depending on each country's local health care and delivery systems. for instance, unlike mexico and india, thailand has implemented universal health care that could serve as a driver for the adoption of genomic medicine as it could, in turn, promote public health savings. one application that two thai key informants cited as amenable to public health interventions is the screening of patients with human immunodeficiency virus (hiv) for susceptibility to nevirapine-induced skin rash; nevirapine is an antiretroviral treatment that we were told is commonly used in thailand. nevertheless, there were a number of concerns raised by interviewees regarding the capacity within rural communities of developing countries to take up these technologies; concerns ranged from aspects regarding public and physician understanding to the ability to deliver the services. these concerns further raise issues of who in developing countries will benefit from these new technologies and they will need to be addressed through appropriate governance methods in order to ensure equitable delivery and access. genomic sovereignty. in , the united nations educational, scientific and cultural organization (unesco) declared the human genome 'the heritage of humanity' in the records of the th session of the general conference (volume ; resolutions). but critics suggested that this stance could result in 'bio-colonialism' or 'genetic piracy' of human samples in developing countries that do not have the resources to carry out the research themselves . several key informants in mexico maintained that the unique patterns of variation that might exist in subpopulations have implications for the development of genomic diagnostics and genomic medicine, and as such are the equivalent of sovereign resources. similarly, in india, there is a history of lobbying to protect the indian genome from foreign exploitation as a response to the export of human samples by foreign researchers who often failed to acknowledge indian collaborators or participants [ ] [ ] [ ] . consistent with the idea that unique patterns of genomic variation are sovereign resources and should be protected from foreign prospectors, mexico has recently enacted an amendment to mexico's general health law that aims to protect the national genomic sovereignty of mexicans . in india, although there is no specific legislation concerning genomic sovereignty, the country has made an effort to prevent the wholesale export of human biological material without prior arrangements through the government in their guidelines for exchange of human biological material for biomedical research purposes, last revised in november . by contrast, in thailand, the concept of genomic sovereignty did not appear as explicitly in our key informant interviews, although there was recognition of the need to protect thai dna samples through clear regulation or legislation. it was noted that, although there are institutional guidelines within universities and hospitals, there is no central national legislation on the export of human dna samples. however, other thai researchers expressed concerns that guidelines and/or legislation pertaining to genomic sovereignty might impede international collaborations and partnerships. the ability to implement genomic sovereignty legislation and to protect their resources from foreign exploitation seems to be key for each country to ensure that they can leverage the genomic variation data to encourage local innovation and participate as equal partners in the global knowledge-based economy. the thai snp discovery project is a collaboration between mahidol university's faculty of medicine, ramathibodi hospital and oracle co. ltd (thailand), the national center for genetic engineering and biotechnology (biotec, thailand) and centre national de genotypage (cng, france) , . a snp database will contain allele frequency and linkage disequilibrium (ld) block patterns for all genes identified in the human genome and their regulatory regions in thai and other populations (french, japanese and african). the database will also contain other information, such as genomic sequences, genomic structure, primer sequences and functional genomic information. the information from this database will be used to identify disease-associated genes, for the candidate gene approach, for systematic genome screening and for pharmacogenomic research. it will also form the thai contribution to the human genome organisation (hugo) pan-asian snp consortium. the thailand centre of excellence in life sciences (tcels) pharmacogenomics project has performed snp genotyping of genes involved in drug response. for example, it has collected , samples for five pharmacogenomics projects: the human immunodeficiency virus (hiv) pharmacogenomics project (nevirapine-induced skin rash, see main text); drug allergy to allopurinol and carbamazepine; pharmacogenomics in childhood acute lymphoblastic leukaemia; pharmacogenomics in oncology chemotherapy (using fluorouracil); and pharmacogenomics in thalassaemia. in addition, tcels is collaborating with the riken institute in japan, which has collected , samples of patients with post-traumatic stress disorder in the attempt to understand any genomic contributions to this syndrome. other disease areas that will be investigated by the tcels pharmacogenomics project include diabetes, cardiovascular diseases, rheumatoid arthritis, hiv/aids, lupus, childhood leukaemia and dihydropyrimidine dehydrogenase (dpd) deficiency. knowledge-based economy. key informants in our study indicated that stimulating the economy through innovation is a desired outcome. this seemed to be particularly relevant for key informants at inmegen, who stressed this outcome as a major motivator to the creation of a genomic medicine platform; they saw investment in genomic medicine as a potential entry point for mexico into the global knowledge-based economy. although intellectual property protection does not guarantee the development of a commercial product, many still suggest that, in health biotechnology, intellectual property protection remains a vital factor towards the establishment of a private sector and the commercialization of products in developing countries , , . an early example from is shantha biotechnics private, a spin-out company from the osmania university in hyderabad, india, that leveraged its patented innovative manufacturing process in the pichia pastoris expression system to produce a recombinant hepatitis b vaccine . as a result, they were subsequently able to drive down the cost of the hepatitis b vaccine within india . although this example is specific to health biotechnology, the model is also applicable to genomic medicine. given the criticisms of the inadequacy of intellectual property protection systems in developing countries, we decided to focus on how each of these initiatives chose to approach this challenge. mechanisms for intellectual property protection exist in mexico, india and thailand. in mexico and thailand, inmegen and tcels are actively engaging in specific intellectual property and commercialization activities, which will hopefully offset the general opinion that these countries have traditionally weak patenting cultures, especially among academic and hospital researchers. however, establishing such intellectual property protection systems seems to involve different strategies. we found that inmegen, some members of the igvdb consortium, and the tcels pharmacogenomics project were developing and exploring models to facilitate the translation of early stage research to commercialized products. inmegen has a comprehensive plan for intellectual property protection: it has entered into a collaborative relationship with the mexican institute of intellectual property (impi) to share expertise. currently, impi and inmegen are in negotiations for a $ million grant, which would enable them to maintain an in-house intellectual property office through which inmegen could provide mexican researchers with the infrastructure and expertise needed to acquire patents on their research. inmegen also intends to use the impi grant to kick-start an in-house business incubator -a key factor in technological innovation , which will offer support and consulting services in business planning, commercialization, marketing, operations and information technology. key informants at inmegen argued that because the institute is integrated within the m-nih system, having intellectual property over its discoveries will also help to integrate the generated knowledge into the public health system. similarly, in thailand, the tcels pharmacogenomics project -by virtue of its association with tcels -has the ability to use the available in-house lawyers to manage its own intellectual property needs. tcels also works closely with the department of intellectual property at the ministry of commerce. for example, tcels assists in filing for intellectual property protection, coordinating researchers and external organizations, analysing the maturing of innovations, finding potential investors and licensing opportunities, and negotiating royalties and terms of agreement. although the genotyping projects, at least in mexico and thailand, seem to aspire to foster the development of commercial products through intellectual property protection, we are not aware of any concrete products or services in the short-term pipeline. furthermore, such products or services are unlikely to be developed soon, considering the complexity of these research initiatives. we therefore searched for evidence of current small-to-medium enterprises that have, or are actively developing, human genomic medicine products and services. we did not find any specific firms in mexico, although both thailand (two start-up companies offering personal genotyping and wellness services were identified) and india (avesthagen has announced it is initiating a large-scale genotyping project of the parsi genome) show evidence of burgeoning local private-sector involvement in human genomic variation studies and genomic medicine. despite the existence of a few companies, it is too early in their development to provide a detailed analysis of their capabilities, business models and economic benefit. however, key informants from the private sector did tell us that interfacing with public research centres is often a challenge. creating and maintaining bridges between the public and commercial sector is thought by some to be necessary for knowledge translation and commercialization. despite the existing scepticism around the adoption of genomic medicine in emerging markets and developing countries, the above examples are indicative of an effort to increase the likelihood that the knowledge they generate will provide them with a competitive edge in a knowledge-based economy. concluding remarks if the human genome project is the foundation of a house representing the future of genomics, mexico, india and thailand are already claiming and building their rooms in that house. they are not the only glossary admixture the pattern of genetic variation that results when a population is derived from founders that originated from more than one ancestral population. a dna segment that contains markers that are in significant linkage disequilibrium with each other, which implies that there is low recombination activity within the block. linkage disequilibrium (ld) . a measure of genetic associations between alleles at different loci, which indicates whether allelic or marker associations on the same chromosome are more common than expected. the union of a therapy with a diagnostic that can determine the presence of a series of predictive biomarkers, including genomic, metabolomic and proteomic markers. theragnostics will enable clinicians and physicians to limit the number of adverse drug reactions and refine treatments for their patients. this international collaboration between china, india, indonesia, japan, korea, malaysia, nepal, the philippines, singapore, thailand and taiwan aims to study the genetic diversity in asian populations. the results from the study will be made available to the public. although this initiative is not focused on health applications, its goal is to uncover the breadth of genetic diversity and the extent of genetic similarity in asia. the human genome organization (hugo) is an international organization of scientists originally involved in the human genome project. hugo pacific, which is sponsoring the pan-asian snp initiative, is a chapter of hugo and is based at the university of tokyo, japan. the study began in the middle of and was completed in late (ref. ). ones; china's beijing genomics institute is preparing to sequence the entire genome of one hundred chinese individuals , and south africa's africa genome education institute is devoted to educating the public about the structure and function of genomes, and plans to study the genetic basis of diseases relevant to the south african population. brazil, which has long been considered a leader in genomic sciences in the developing world, has invested in cancer genomics (see genomics advances in brazil at the world health organization web site) and the sequencing of parasite and plant genomes . specifically, in , the organization of nucleotide sequencing and analysis (onsa), in sao paulo, brazil, completed the first published sequence of the xylella fastidiosa bacterium, a plant pathogen responsible for disease in economically important crops such as citrus . this effort was in large part responsible for establishing the subsequent capacity in genomic sciences in brazil and it has brought moderate economic benefits . alellyx, for instance, is a biotechnology company that spun out of the onsa network and focuses on crops that are of economic importance to brazil. alellyx also holds, amongst others, the us patent on the whole genome and gene sequences for disease diagnostics of x. fastidiosa, which they are currently using to develop disease resistance and pesticide research . in addition to our case studies, these examples indicate that emerging economies are beginning to establish footholds in genomic sciences. the findings we report here suggest that a clear motive for the genotyping and associated life-sciences initiatives is to improve health and capture the value of research to help create knowledge economies. we found that political will and institutional leadership were crucial in developing a vision and a plan, and in the implementation of large-scale population genotyping initiatives in mexico, india and thailand. in contrast to many developed countries, we found these three countries to be more focused on practical applications of genomics rather than solely on advanced basic research. another difference between these three developing countries and other developed countries is the extent to which industry (for example, glaxosmithkline) drives genomics research and development in developed countries. also, inmegen in mexico is unique in the extent of its integration with public health needs, partly owing to its relationship from its inception to the mexican ministry of health. the large-scale human genotyping projects described in this article are not unlike the early sequencing efforts in brazil -they are helping to build scientific capacity, which is in line with the increased focus on innovation in science and technology as the engines of economic growth in developing countries. they are setting the scene for local discovery, development, commercialization and delivery of affordable health products. they might allow these countries to be more competitive in the global economy and perhaps, in niche areas, to leap-frog ahead of some advanced economies. us national human genome research institute. a vision for the future of genomics research putting pharmacogenetics into practice the power of pills: social, ethical and legal issues in drug development, marketing and pricing pharmacogenomics in admixed populations the ethical, legal and social implications of pharmacogenomics in developing countries: report of an international group of experts a universal microarray for detection a universal microarray for detection of sars coronavirus the genome sequence of the sarsassociated coronavirus reverse transcriptase pcr diagnostic assay for the coronavirus associated with severe acute respiratory syndrome realities and enigmas of human viral influenza: pathogenesis, epidemiology and control characterization of a novel coronavirus associated with severe acute respiratory syndrome grand challenges in chronic noncommunicable diseases the double burden of communicable and non-communicable diseases in developing countries pharmacogenetics and geographical ancestry: implications for drug development and global health india's health biotech sector at a crossroads chinese health biotech and the billion-patient market accelerating health product innovation in sub-saharan africa mapping translational research in personalized therapeutics: from molecular markers to health policy shifting emphasis from pharmacogenomics to theragnostics india invests heavily in genomics research science communication in transition: genomics hype, public engagement, education and commercialization pressures conclusions: promoting biotechnology innovation in developing countries translating pharmacogenomics: challenges on the road to the clinic what is next in 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tag collection for tropical crop sugarcane the genome sequence of the plant pathogen xylella fastidiosa. the xylella fastidiosa consortium of the organization for nucleotide sequencing and analysis brazilian genomics and bioinformatics: instituting new innovation pathways in a global context basics of qualitative research: techniques and procedures for developing grounded theory similarity of the allele frequency and linkage disequilibrium pattern of single nucleotide polymorphisms in drug-related gene loci between thai and northern east asian populations: implications for tagging snp selection in thais evaluation of resequencing on number of tag snps of atherosclerosis-related genes in thai population india's guidelines for exchange of human biological material for all links are active in the online pdf we gratefully acknowledge n. jadeha, m. maliakkal and s. essajee for their contributions to this project. thank you to j. clark for her comments on the manuscript. the authors declare competing financial interests; see web version for details. key: cord- -ew n i z authors: nambiar, devaki; sankar, hari; negi, jyotsna; nair, arun; sadanandan, rajeev title: field-testing of primary health-care indicators, india date: - - journal: bull world health organ doi: . /blt. . sha: doc_id: cord_uid: ew n i z objective: to develop a primary health-care monitoring framework and health outcome indicator list, and field-test and triangulate indicators designed to assess health reforms in kerala, india, – . methods: we used a modified delphi technique to develop a -item indicator list to monitor primary health care. we used a multistage cluster random sampling technique to select one district from each of four district clusters, and then select both a family and a primary health centre from each of the four districts. we field-tested and triangulated the indicators using facility data and a population-based household survey. findings: our data revealed similarities between facility and survey data for some indicators (e.g. low birth weight and pre-check services), but differences for others (e.g. acute diarrhoeal diseases in children younger than years and blood pressure screening). we made four critical observations: (i) data are available at the facility level but in varying formats; (ii) established global indicators may not always be useful in local monitoring; (iii) operational definitions must be refined; and (iv) triangulation and feedback from the field is vital. conclusion: we observe that, while data can be used to develop indices of progress, interpretation of these indicators requires great care. in the attainment of universal health coverage, we consider that our observations of the utility of certain health indicators will provide valuable insights for practitioners and supervisors in the development of a primary health-care monitoring mechanism. under the thirteenth general programme of work and the triple billion targets, the world health organization (who) aims to increase the number of people benefitting from universal health coverage (uhc) by one billion between and . central to this effort is the expansion and improvement of primary health-care services. , progress in achieving uhc can be analysed using the who and world bank's uhc monitoring framework, , but this requires adaptation to local contexts to ensure health reforms keep pace with targets. health programmes in india, as well as the national health policy and flagship ayushman bharat scheme, are being evaluated in relation to the aims of uhc; various efforts are currently underway at both a national and state level, notably in haryana and tamil nadu. according to national sample survey estimates from - , morbidity levels in the southern state of kerala are reportedly four times the national average with disparities by sex and place of residence. although the state has made gains in maternal and child health, it must sustain these gains while addressing the substantial and growing burden of hypertension, diabetes and cancer; vaccine-preventable diseases; , and emerging viral infections such as nipah virus and severe acute respiratory syndrome coronavirus (sars-cov- ). [ ] [ ] [ ] kerala has been subject to unregulated privatization and cost escalation, resulting in persistent inequalities in service access and health attainment between population subgroups. in , the government of kerala announced aardram, a programme of transformation of existing primary health centres to family health centres; with increased staffing, these family health centres provide access to a greater number of services over longer opening hours compared with the original primary health centres. apart from the who's monitoring framework, many countries have done uhc and primary health centre monitoring exercises , alongside independent exercises such as the primary health care performance initiative. however, most of these frameworks are intended for global comparison or decision-making at national levels. the argument for tracking health reforms is clear, but such a monitoring process must be specific to kerala and local decision-making, while also complying with national and global reporting requirements. periodic household surveys offer population-level data, but are not frequent enough to inform ongoing implementation decisions. routinely collected and disaggregated health system data are vital, but are often marred by quality issues as well as technological and operational constraints. we began a -year implementation research study assessing equity in uhc reforms in january . in our first two phases we aimed to develop a conceptual framework and a health outcome indicator shortlist, followed by validation of these indicators using data from both health facilities and a population-based household survey. we report on the fieldtesting and triangulation components of this implementation research project, which took place during and . we reflect on early lessons from the field-testing and triangulation and, drawing broadly from ostrom's institutional analysis and development framework, we emphasize how monitoring can support learning health systems. , we also discuss how the monitoring of uhc progress requires a flexible approach that is tailored to the local political economy. [ ] [ ] [ ] objective to develop a primary health-care monitoring framework and health outcome indicator list, and field-test and triangulate indicators designed to assess health reforms in kerala, india, - . methods we used a modified delphi technique to develop a -item indicator list to monitor primary health care. we used a multistage cluster random sampling technique to select one district from each of four district clusters, and then select both a family and a primary health centre from each of the four districts. we field-tested and triangulated the indicators using facility data and a population-based household survey. findings our data revealed similarities between facility and survey data for some indicators (e.g. low birth weight and pre-check services), but differences for others (e.g. acute diarrhoeal diseases in children younger than years and blood pressure screening). we made four critical observations: (i) data are available at the facility level but in varying formats; (ii) established global indicators may not always be useful in local monitoring; (iii) operational definitions must be refined; and (iv) triangulation and feedback from the field is vital. conclusion we observe that, while data can be used to develop indices of progress, interpretation of these indicators requires great care. in the attainment of universal health coverage, we consider that our observations of the utility of certain health indicators will provide valuable insights for practitioners and supervisors in the development of a primary health-care monitoring mechanism. research field-testing of health-care indicators, india devaki nambiar et al. we began with a policy scoping exercise for the state of kerala in . we then created an -indicator longlist from existing primary health-care monitoring inventories, , [ ] [ ] [ ] [ ] and undertook an extensive data source and mapping exercise, adapting a process previously conducted in the region. we applied a modified delphi process in two rounds, consulting key health system stakeholders of the state (frontline health workers, primary care doctors, public health experts and policymakers), and obtained a shortlist of indicators (available in the data repository). we then field-tested and triangulated some of the indicators using facility-based data (phases and ) and a population-based household survey (phase ). in phase (december ) we selected three family health centres in coastal, hilly and tribal districts (trivandrum, idukki and wayanad, respectively) of the state. we communicated the definitions and logic of the indicators to facility staff, and studied their data-recording methods to synergize our processes with theirs. from these initial steps, we prepared a structured data collection template (available in the data repository) that we provided to the three family health centres. based on inputs from phase and a second round of consultations with state-level programme officers, we refined the indicator list. in phase (june-october ), we used a multistage random cluster sampling technique to generate data related to the indicators at the population and facility level. we applied principal component analysis using stata version (statacorp, college station, united states of america) to data from the latest national family health survey ( - ) to categorize districts into one of four clusters according to health burden and systems performance. using an opensource list randomizer from random. org, we randomly selected one district from each of the four clusters, and then randomly selected both a primary and a family health centre from each of the four selected districts. the people served by these eight health facilities were the population of interest in our study. we held on-site meetings with the staff of the eight health facilities and provided them with excel-based templates (microsoft corporation, redmond, united states of america) to input data for the financial year march -april (data repository). data were sourced from manual registers maintained at facilities. in addition to off-site coordination, we also provided data-entry on-site support to the health staff, visiting each facility at least four times between may and december . we compiled data from the facilities to obtain annual estimates for all health outcome indicators using excel. our sample size estimation was based on the proportion of men and women eligible for blood pressure screening under the national primary care noncommunicable disease programme, that is, those aged years or older. we estimated a sample size using routine data reported by the noncommunicable disease division of the kerala health and family welfare department ( - ), aiming at a precision of % at a % confidence interval (ci), with a conservative design effect of (i.e. a doubling of the sample). health facility catchment areas were grouped by wards, also referred to as primary sampling units. eligible households within a primary sampling unit had at least one member aged years or older. individual written informed consent was sought from each participant before administration of the survey. we employed and trained staff to collect data using hand-held electronic tablets with a bilingual (english and malayalam) survey application. the survey, conducted during june-october , included questions on sociodemographic parameters, health outcome indicators (e.g. noncommunicable disease risk behaviours and screening; awareness of components of aardram and family health centre reform) and financial risk protection (e.g. out-ofpocket expenditure). national family health survey (round iv) state level weights were applied during analysis. we compared data on selected indicators using stata and excel. since our focus was on how indicators were being understood and reported across facilities, we did not expect indicators to directly correspond between facilities and households, but only to approximate each other. all components of the study were approved by the institutional ethics committee of the george institute for global health (project numbers / and / ). we obtained data from health facilities in total (seven family health centres and four primary health centres) during phases and . during phase , we acquired facility data on indicators from eight health facilities (four family, four primary) jointly serving a population of ( table ). the household survey was undertaken in the catchment areas of these facilities, and we acquired data from a representative sample of individuals in households (table ) . we observed both variations between and uniformity in the indicators from health facilities and the household survey (table ). in studying these patterns, we made four key observations (box ). first, the method of reporting our indicators varied between facilities, even although all raw data required to calculate selected indicators were present in manual registers. in the case of indicators related to national programmes (e.g. reproductive, child health and tuberculosis-related indicators), data were uploaded directly to national digital portals without any analysis at the facility level; officers responsible for data compilation and analysis exist only at the district level. feedback from facility staff included requests for adequate training on new or revised reporting systems, and clarification of their role. this situation may improve with the complete digitization of health records under kerala's e-health programme. our second observation is that there exist two problems with the globally recommended indicators: (i) manual routine data reporting at the facility level may be inadequate to construct the global indicator precisely; and (ii) globally relevant data may not be considered relevant to the periodicity (monthly) or level (facility) of review. from the facility-level data, the cover- field-testing of health-care indicators, india devaki nambiar et al. age of antenatal care reported by family health centres was . % ( / ); in household surveys, full coverage of antenatal care was observed for . % ( / ) of eligible women (table ) . here, antenatal care refers to women aged - years having a live birth in the past year and receiving four or more antenatal check-ups, at least one tetanus toxoid injection, and iron and folic acid tablets or syrup for at least days as numerator. the coverage rate is calculated from a denominator of the total number of women aged - years who had a live birth in the past year, which requires retrospective verification of antenatal coverage. however, in some facilities, the antenatal care coverage indicator was calculated using the previous year's number of deliveries plus % as the denominator, and the number of pregnant women who had received antenatal care as the numerator. it was therefore not always clear that the data from any particular individual were included in both the numerator and denominator and, with a target as the denominator, coverage could surpass %. practitioners noted the disconnect between monthly target-based reporting and annual retrospective measurement. our third observation is that definitions and reporting that reflect actual health-provision patterns require to be standardized; otherwise, discrepancies will be observed between data sets. for example, the indicator for acute diarrhoeal diseases among children younger than years was . % ( / ) according to facility records; however, a prevalence of more than times this percentage ( . %; / ; % ci: . - . ) was reported in the household survey (table ) . several chronic care indicators, newly introduced as part of the introduction of family health centres, also showed discrepancies. for instance, the percentage of people screened for blood pressure and blood glucose was . % ( / ; % ci: . - . ) and . % ( / ; % our fourth observation is that such triangulation exercises, as well as obtaining feedback from health workers, programme managers and administrators, are vital for accurate assessment of uhc coverage. a major problem reported by staff and officials is that health facility data are usually just a tally of patient visits, which is simple to produce, as opposed to the actual number of (potentially repeat) patients receiving care or services. state officials have been encouraging a move towards electronic health records to generate more precise indicators, but adoption and integration of these will only be possible when the technology itself is better aligned to facility-level process flows, requiring user inputs, investment and time. other issues raised include: the need for appropriate staff (including temporary contractual staff) training in programme guidelines and reporting requirements; the need for clarity in definitions of treatment (e.g. chronic disease patients may be advised to modify lifestyle factors, which would be missed if treatment monitoring included only those prescribed medication); and the availability of free or subsidised tests relevant to disease control that are reflected in monitoring indicators, particularly for chronic care (e.g. glycated haemoglobin tests for diabetes care ) at the primary health centre level. as already observed in india and other low-and middle-income countries, our results indicate that any approach to improving or monitoring the quality of health-care must be adaptable to local methods of data production and reporting, while ensuring that emerging concerns of local staff are considered. although validity checks are a staple of epidemiological and public health research, such triangulation processes in health systems are infrequent. the every newborn-birth study was a triangulation of maternal and newborn healthcare data in low-and middle-income countries, and some smaller-scale primary-care indicator triangulation exercises have been undertaken by india's national health systems resource centre. , while there exists a variety of approaches to monitoring primary health-care reforms, we consider the most appropriate to be the generation (and modification, if necessary) of indicators from routine data, and their triangulation with household survey data. increasingly, routine data are being digitized to improve accessibility and interpretation, as is the case in kerala. useful considerations when introducing digital health interventions in low-and middle-income countries are intrinsic programme characteristics, human factors, technical factors, the health-care ecosystem and the broader extrinsic ecosystem. our observations demonstrate the continuous and complex interplay between these characteristics; the real value of selected indicators may also be determined by how staff understand and interpret them. our study had several limitations. our indicator selection using the delphi method could have undergone additional rounds, but we considered it more important to get the monitoring process underway and reduce the burden on health workers. some facility-based information could not be acquired due to the additional health department burden of flood relief and nipah outbreak management in the state. our household survey sample was the population aged years and older, resulting in undersampling for other indicators being fieldtested (e.g. newborn low birth weight). an increase in sample size could allow a more precise estimation of all indicators. finally, the reference periods for the facility data and the household survey did not directly overlap; a timed sampling should be undertaken in the future to improve the precision of triangulation. observing the utility of indicators in practice is a key first step in the move towards uhc, requiring investment and commitment. using indicators, standards and other forms of technology, which are easy to adopt, can be problematic because we amplify certain aspects of the world while reducing others. our examination of family health centre reforms cautions that, while data can be used to develop indices of progress, interpretation of these indicators requires great care precisely because of the way they are related to powerful decisions around what constitutes success or failure, who will receive recognition or admonition and, ultimately, the legacy of aardram reforms. we anticipate that our observations will contribute to healthcare reforms in low-and middle-income countries, such as the use of field triangulation to enhance the accountability and relevance of global health metrics. if such activities are carried out in constructive partnerships with state stakeholders and do not introduce unfeasible costs to the system, they may contribute to a sustained and reflexive monitoring process along the path to uhc. ■ observation : data are available at the facility level, but in varying formats and platforms meant for different purposes; digitization may improve this situation. observation : established global indicators may not be useful or interpreted as intended in a local context, and may need to be adapted. observation : operational definitions, thresholds for interpretation and processes of routine data collection must be refined for older indicators and developed for newly introduced indicators. observation : triangulation and feedback from the field level, with qualitative input from local actors, remains vital, particularly for chronic diseases. field-testing of health-care indicators, india devaki nambiar et al. Цель Разработать систему мониторинга первичной медикосанитарной помощи и перечень показателей конечных результатов в отношении здоровья, а также провести тестирование на местах и всесторонне рассмотреть показатели, предназначенные для оценки реформ здравоохранения в штате Керала, Индия, в - гг. Методы Авторы использовали модифицированный «дельфийский» метод для разработки перечня показателей, состоящего из пунктов, с помощью которого осуществлялся мониторинг первичной медико-санитарной помощи. Авторы использовали метод многоступенчатой кластерной случайной выборки, чтобы отобрать один район в каждом из четырех районных кластеров, а затем таким же образом выбирали семью и центр первичной медико-санитарной помощи в каждом из четырех районов. Авторы испытали на местах и всесторонне оценили показатели с использованием данных учреждений и анкетирования домохозяйств на уровне популяции. Результаты Полученные данные выявили сходство между данными учреждений и данными анкетирования по одним показателям (например, низкая масса тела при рождении и услуги предварительной проверки), но различия по другим показателям (например, острые диарейные болезни у детей младше лет и скрининг артериального давления). Авторы составили четыре важных замечания: (i) данные доступны на уровне учреждения, но в различных форматах; (ii) определенные глобальные показатели не всегда могут использоваться для местного мониторинга; (iii) практические определения требуют уточнения; (iv) всестороннее рассмотрение и обратная связь с мест критически важны. Вывод Наблюдения говорят о том, что, хотя данные можно использовать для разработки индексов прогресса, интерпретация этих показателей требует большой осторожности. В достижении всеобщего охвата услугами здравоохранения авторы считают, что их наблюдения о полезности определенных показателей здоровья дадут ценную информацию для практикующих врачей и руководителей при разработке механизма мониторинга первичной медико-санитарной помощи. objetivo elaborar un marco de supervisión de la atención primaria de salud y una lista de indicadores sobre los resultados en la salud, así como realizar ensayos de campo y triangular los indicadores previstos para evaluar las reformas sanitarias en kerala, india, - . métodos se aplicó un método delphi modificado para elaborar una lista de indicadores que incluye elementos para supervisar la atención primaria de salud. además, se empleó una técnica de muestreo aleatorio por conglomerados de etapas múltiples para seleccionar un distrito de cada uno de los cuatro conglomerados de distritos y, a continuación, se seleccionó una familia y un centro de atención primaria de cada uno de los cuatro distritos. se realizaron ensayos de campo y se triangularon los indicadores mediante el uso de datos de los centros y una encuesta domiciliaria basada en la población. resultados los datos obtenidos revelaron similitudes entre los datos de los centros y los de las encuestas para algunos indicadores (por ejemplo, el peso bajo al nacer y los servicios de control previo), así como diferencias para otros (por ejemplo, las enfermedades diarreicas agudas en niños menores de años y la evaluación de la presión arterial). se formularon cuatro observaciones críticas: i) los datos están disponibles a nivel de los establecimientos, pero en distintos formatos; ii) los indicadores globales establecidos no siempre son útiles para realizar una vigilancia local; iii) las definiciones operativas se deben perfeccionar; y iv) la triangulación y las observaciones en el terreno son vitales. conclusión se observa que, si bien los datos se pueden usar para elaborar índices de progreso, la interpretación de estos indicadores requiere gran atención. se cree que las observaciones obtenidas sobre la utilidad de ciertos indicadores de salud permitirán a los profesionales y a los supervisores comprender mejor el desarrollo de un mecanismo de vigilancia de la atención primaria de salud para lograr la cobertura sanitaria universal. geneva: world health organization the astana declaration: the future of primary health care? lancet geneva: world health organization tracking universal health coverage: global monitoring report. geneva: world health organization primary health care on the road to universal health coverage monitoring and evaluating progress towards universal health coverage in india new delhi: government of india, ministry of health and family welfare ayushman bharat -national health protection mission new delhi: niti aayog, national institution for transforming india, government of india a composite indicator to measure universal health care coverage in india: way forward for post- health system performance monitoring framework. health policy plan universal health coverage-pilot in tamil nadu: has it delivered what was expected? chennai: national health mission -tamil nadu field-testing of health-care indicators key indicators of social consumption in india: health | national sample survey th round health inequalities in south asia at the launch of sustainable development goals: exclusions in health in kerala, india need political interventions india state-level disease burden initiative diabetes collaborators. the increasing burden of diabetes and variations among the states of india: the global burden of disease study india state-level disease burden initiative cancer collaborators. the burden of cancers and their variations across the states of india: the global burden of disease study - laboratory supported case-based surveillance outcomes. front public health current status of dengue and chikungunya in india : epidemiology of an outbreak of an emerging disease how countries of south mitigate covid- : models of morocco and kerala what the world can learn from kerala about how to fight covid- . mit technology review aggressive testing, contact tracing, cooked meals: how the indian state of kerala flattened its coronavirus curve. washington post kerala's early experience: moving towards universal health coverage address to the legislative assembly tracking universal health coverage: first global monitoring report. geneva: world health organization achieving the targets for universal health coverage: how is thailand monitoring progress? who south-east asia j public health monitoring and evaluating progress towards universal health coverage in brazil better measurement for performance improvement in low-and middle-income countries: the primary health care performance initiative (phcpi) experience of conceptual framework development and indicator selection disaggregated data to improve child health outcomes. afr j prim health care fam med public health informatics: designing for change -a developing country perspective research methods used in developing and applying quality indicators in primary care the institutional analysis and development framework and the commons learning health systems: an empowering agenda for low-income and middle-income countries a framework for value-creating learning health systems the political economy of universal health coverage. montreux: health systems global the political economy of universal health coverage: a systematic narrative review. health policy plan strengthening accountability of the global health metrics enterprise measuring the performance of primary health care: a practical guide for translating data into improvement. arlington: joint learning network for universal health coverage new delhi: national health system resource centre monitoring and evaluation of health systems strengthening: an operational framework. geneva: world health organization global reference list of core health indicators. geneva: world health organization data source mapping: an essential step for health inequality monitoring wtequity study primary care indicators kerala wtequity study primary care indicators kerala mumbai: international institute for population studies health service coverage and its evaluation strengthening patient-centred care for control of hypertension in public health facilities in kannur district. prince mahidol award conference on the political economy of ncds: a whole of society approach prince mahidol award conference every newborn-birth" protocol: observational study validating indicators for coverage and quality of maternal and newborn health care in bangladesh, nepal and tanzania new delhi: national health systems resource centre. presentation at workshop on health information architecture, design, implementation, and evaluation measuring progress towards universal health coverage and post- sustainable development goals: the informational challenges best practices in scaling digital health in low and middle income countries standards: recipes for reality we thank the department of health and family welfare, government of kerala, the state health systems resource centre, kerala and the aardram task force. dn is affiliated to the faculty of medi- key: cord- -dwns l authors: rafiq, danish; suhail, suhail ahmad; bazaz, mohammad abid title: evaluation and prediction of covid- in india: a case study of worst hit states date: - - journal: chaos solitons fractals doi: . /j.chaos. . sha: doc_id: cord_uid: dwns l in this manuscript, system modeling and identification techniques are applied in developing a prognostic yet deterministic model to forecast the spread of covid- in india. the model is verified with the historical data and a forecast of -days ahead is presented for the most affected states of india. the major results suggest that our model can very well capture the disease variations with high accuracy. results also show a steep rise in the total cumulative cases and deaths in the coming weeks. the advent and spread of novel coronavirus (sars-cov- ) has posed a global health crisis with a sharp rise in cases and deaths since its first detection in wuhan, china, in december . the infection causes illness ranging from common cold to extreme respiratory disease and death [ ] . currently, the prime epidemiological risk factor for novel corona-virus disease includes close contact with infected individuals with an incubation period of − days [ ] . the case mortality rate is projected to range from to % [ ] . various drugs are being assessed in line with previous researches into therapeutic treatments for sars and mers, however, there is no robust evidence for any significant improved clinical outcome [ ] . apparent risk of acquiring the disease has led many governments to institute a variety of control procedures like quarantine, isolation and lock-down measures. despite rigorous global containment measures, the frequency of the novel corona-virus disease continues to rise, with over . million confirmed cases and over , deaths worldwide as on th may, [ ] . although countries around the world have enhanced capacity building of the laboratory systems and response procedures, yet, there is a need for proper disease surveillance systems. comprehending the initial transmission of the virus and analyzing the effectiveness of control measures are crucial in assessing the prospects for continued transmission in newer locations. this necessitates tracking the course of the pandemic to be able to foresee its emergence for a better response. prospective studies on modeling and forecasting of the epidemic have been carried out to provide analytical predictions on the size and end phase of the spread. wu, et al. [ ] have used a susceptible exposed infectious recov-email address: danish_pha @nitsri.net (corresponding author) (danish rafiq) ered (seir) meta-population model to simulate the epidemic across all major cities in china. early dynamics of transmission and control of covid- within and outside wuhan has also been studied using a stochastic transmission dynamic model [ ] . another study used the seir compartmental model to predict the feasibility for conducting the summer olympics of in japan [ ] . similarly, abdullah, et al. [ ] presented a stochastic sir model to predict the spread of covid- in kuwait. a classical seir type mathematical model is also presented in [ ] to study the qualitative dynamics of covid- in india. further work has been carried out in [ ] , with special focus on the transmissibility of super-spreader individuals in wuhan, china. besides the above mentioned compartmental models, some other methods have been used to model and forecast the covid- spread. for example, in [ ] , a data-driven estimation method like long short-term memory (lstm) is used for the prediction of total number of covid- cases in india for a -days ahead prediction window. in [ ] , daily forecasts of covid- activity from global epidemic and mobility model (gleam), an agent-based mechanistic model is used as an one of the inputs to produce stable and accurate forecasts two days ahead of current time. harun, et al. [ ] have used box-jenkins (arima) and brown/holt linear exponential smoothing methods to estimate and forecast the number of covid- cases in the g countries. al-qaness et al. [ ] have incorporated a modified version of flower pollination algorithm (fpa) coupled with the salp swarm algorithm (ssa) to forecast the number of confirmed cases of covid- for ten days in china. as on th may , india observed a total cases of , with , deaths [ , ] . the very first case was reported on th january , in a coastal state of kerela (southern india) when a student returned from wuhan, china. subsequently, the number of positive cases in in-dia rose rapidly due to the arrival of many passengers via airways [ ] . an overview of the spread of covid- in india is shown in figure ( ) . it can be easily seen that the virus has spread to entire country with the worst hit states being maharashtra ( , cases), gujarat ( , ), tamil nadu ( , ), delhi ( , ), rajasthan ( , ), and madhya pradesh ( , ). figures ( ) and ( ) show the trend of rising new cases and deaths in india. this manuscript demonstrates a control-theoretic, datadriven estimation technique to derive a time-series model from the historical data collected from [ , ] up-to th may . the model is then used for the prediction of the total number of cases and deaths in most affected states of india for the next days. the paper is sectioned as follows: section ( ) describes the system identification method employed. section ( ) presents the predicted cases and deaths along-with some discussions. finally, conclusions are presented in section ( ). to estimate the spread of covid- in india, we used a predictive error minimization (pem) based system identification technique to identify a discrete-time, single-input, single-output (siso) model [ ] [ ] [ ] . different models very identified for different states based on the data collected. the models were then verified on the testing data and upon validation, the models were used to predict the total number of cases and deaths for the next -days in the worst hit states in india. the discrete-time, identified model can be realized in the state-space from given as: where the y(t) represents total number of cases or deaths of a particular area which is proportional to system state vector x(t) ∈ r n , u(t) is the time series input and t s is the sampling interval. here, the unknowns to be identified are a ∈ r n×n , k ∈ r n× and c ∈ r ×n which are in canonical form. here, n is the dimension of the state-space model. the identification problem can thus be posed as to selecting a model set m (θ) (indexed by a finite dimensional parameter vector θ) and evaluating a member from the set which best describes the recorded input-output relation according to a given criterion. one such criteria as given in [ ] is defined as : where (t, θ) = (y −ŷ , ..., y n −ŷ n ) is referred as the prediction error, l(.) is a scalar measure of fit and z(t) = [y t (t), u t (t)] and n is length of data-set. typical choices of l(t, θ, ) can be seen in [ ] . the identified model thus minimizes the -step ahead prediction and the error (t, θ) between the measured y(t) and predicted valuesŷ(t) is used to make the future prediction about the system. the prediction error identification estimate is thus given as: here, we have taken: figures ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) show the dynamics of the forecasted response for most infected states of india along-with a step predicted response comparison with the validation data. further results are presented in table ( ). as seen from table ( ), maharashtra has recorded the highest number of covid- cases accounting for % of the total countrys caseload. it has also witnessed the sharpest rise in covid- deaths with mumbai being the epicenter of the pandemic in india. the constant influx of tourists, reliance on public transportation and population destiny have cumulatively made the metropolitan city hospitable for corona virus. even though the state is conducting more tests, the violation of physical distancing rules by individuals particularly in containment zones results in the mixing of infected with healthy population. moreover, unlike other red zones of maharashtra, mumbai faces shortage of icu beds and dedicated covid- hospitals. according to the prediction made herein, it would be inevitable that mumbai and its suburbs would continue to see an upsurge in the number of cases and deaths for at least up to th june . gujarat has recorded the second highest covid- mortality rate in the country in spite of reporting its first case as late as march . the covid- mortality rate of ahmedabad city is . %, which is double the national average. officials acknowledge that while gujarat had its guard up sufficiently fast, there was a delay in testing. even by mid of march, the daily average was as less as tests per day, going up to /day by the end of march. according to the data driven identification scheme employed herein, the mortality rate in gujarat may increase as high as . % up to th june . tamil nadu, although being the third worst hit indian state in terms of covid- cases has witnessed the least number of mortalities with among positive cases succumbing to the disease (see fig ) . this is attributed to its credibility as a trusted medical center of the country. chennai has the highest medical tourism in india with the states average being above the national average in the health sector. this may be the reason that the predictable mortality rate of tamil nadu projected in this study is least among the rest of the states in consideration (see table ( )). as per our prediction based on data up to th may , delhi along with other states would continue to see marginal surge in the number of covid- cases owing to the relaxations in lock-down measures. the impact of removing the curbs will be more evident by the mid of june . the under-funding of the healthcare system, paucity of testing labs, violations of the lock-down protocols and inadequate quarantine facilities arranged by states and union territories are the biggest hurdles in combating the spread. the study concerns the spread of covid- in india. a control-theoretic approach is used to develop an epidemic model to simulate and predict the disease variations of most affected states of india. results depict a rapid increase in the number of cases in the coming days. however, it is pertinent to mention that the future estimation provided, is subject to certain system parameters and can vary based on the external inputs like lock-down measures, social-distancing, vaccine/drug development, rapid testing, etc. information provided by our model could help establish a realistic assessment of the situation for the time-being and in the near future in order to apply the appropriate public health measures. the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. carlos,mild or moderate covid- three months of covid- : a systematic review and meta-analysis coronavirus: covid- has killed more people than sars and mers combined, despite lower case fatality rate clinical features of patients infected with novel coronavirus in wuhan, china, the lancet nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study early dynamics of transmission and control of covid- : a mathematical modelling study prediction of the epidemic peak of coronavirus disease in japan forecasting the spread of covid- in kuwait using compartmental and logistic regression models a model based study on the dynamics of covid- : prediction and control mathematical modeling of covid- transmission dynamics with a case study of wuhan prediction for the spread of covid- in india and effectiveness of preventive measures a machine learning methodology for real-time forecasting of the - covid- outbreak using internet searches, news alerts, and estimates from mechanistic models modeling and forecasting for the number of cases of the covid- pandemic with the curve estimation models, the box-jenkins and exponential smoothing methods optimization method for forecasting confirmed cases of covid- in china on the consistency of prediction error identification methods dynamical effects of overparametrization in nonlinear models improved structure selection for nonlinear models based on term clustering system identification -theory for the user, appendix a method for the solution of certain problems in least-squares algorithm for least-squares estimation of nonlinear parameters the levenberg-marquardt algorithm: implementation and theory, numerical analysis on the decay rate of hankel singular values and related issues ministry of human resource development (mhrd), new delhi, india, is duly acknowledged. . author would like to thank asiya batool for fruitful discussions. the authors declare no potential conflicts of interest regarding the publication of this paper. key: cord- -vk xy zn authors: prasad, narayan; hatt, mansi; agarwal, sanjay k.; kohli, h.s.; gopalakrishnan, n.; fernando, edwin; sahay, manisha; rajapurkar, mohan; chowdhary, arpita roy; rathi, manish; jeloka, tarun; lobo, valentine; singh, shivendra; bhalla, a.k.; khanna, umesh; bansal, s.b.; rai, p.k.; bhawane, amol; anandh, urmila; singh, ajit kumar; shah, bharat; gupta, amit; jha, vivekanand title: the adverse effect of covid pandemic on the care of patients with kidney diseases in india date: - - journal: kidney int rep doi: . /j.ekir. . . sha: doc_id: cord_uid: vk xy zn introduction: the coronavirus disease- (covid- ) pandemic has affected the care of patients with non-communicable diseases, including those suffering from kidney-related ailments. many parts of the world, including india, adopted lockdown to curb community transmission of disease. the lockdown affected transportation, access to healthcare facilities, availability of medicines, and consumables as well as out and inpatient services. we aimed to analyze the effect of lockdown imposed due to covid- pandemic on the care of patients with kidney diseases in india. methods: we surveyed major hospitals ( in public and in private sector) to determine the effect of lockdown on the care of patients with kidney disease, including those on dialysis after the first weeks of lockdown. results: the total number of dialysis patients in these centres came down from to . about ( . %) of patients missed one or more dialysis sessions, ( . %) required emergency dialysis sessions, ( . %) stopped reporting for dialysis, and ( . %) were confirmed to have died. outpatient attendance in the surveyed hospital came down by . %, and inpatient service reduced by %. tele-consultation was started but accessed by only a small number of patients. conclusion: lack of preparedness before lockdown resulted in an interruption in health care services and posed an immediate adverse effect on the outcome of dialysis and kidney disease patients in india. the long-term impact on the health of patients with less severe forms of kidney disease remains unknown. the coronavirus disease- pandemic, caused by a novel severe acute respiratory syndrome coronavirus- (sars-cov- ), has directly or indirectly affected everyone in the world ( , ). the million people suffering from kidney-related ailments, including the . million on regular dialysis and recipients of kidney transplantation will not be spared its effects ( ) . to curb the disease transmission, many countries have adopted the policy of lockdown, an action for mass quarantine. the government of india ordered a nationwide lockdown for weeks on th march , which was subsequently extended and still remains in effect with some relaxations at the time of writing ( , ) . the lockdown restricted the movement of . billion people at a time when the number of confirmed coronavirus cases in india was about . while its impact on the prevention of spread remains unclear, the lockdown severely limited the ability of patients with chronic diseases to access medical care. the impact was felt almost immediately by patients on dialysis. public and private transports were shut down, which prevented patients from reaching dialysis centers ( ) . lockdown also affected the availability of consumables for hemodialysis and peritoneal dialysis and essential medicines. regular outpatient services were suspended, and inpatient services severely curtailed. interruptions in supply chains and increased demand led to shortages of personal protective equipment (ppe), placing health care workers, including dialysis staff at undue risk. many hospitals and dialysis centers were ordered to close, and all staff quarantined for weeks after a sars-cov- positive patient was detected. to this was added social stigma associated with the care of covid patients spread through social media and word of mouth. this caused fear amongst the staff, leading to absenteeism. as with many national societies, the indian society of nephrology issued guidance (adopted by the indian ministry of health), and a hemodialysis preparedness checklist was developed for managing dialysis services during the pandemic ( , , ) . despite these efforts, reports of dialysis patients suffering extreme adversity and even deaths were reported in the lay press. however, the exact magnitude of service disruption remains unknown. we conducted a survey to ascertain the impact of covid pandemic on the care of non-covid patients with kidney disease during the first weeks of the lockdown. an online questionnaire was distributed through email to the director or the heads of the departments of public sector tertiary care teaching institutes and private sector corporate hospitals to complete the survey at the end of the first lockdown period, which lasted for weeks. the invited centers were distributed all over in northern, southern, western, and eastern regions of the country. the authors (np, ska, and mr) conceptualized and framed the questionnaire, and np and mb received answers to the survey questionnaire. np and vj performed the data analysis and manuscript writing. the manuscript was circulated to all authors for their feedback, comments and approval before submission for publication. the questionnaire, the list of the centres and the region of india to which these centres belong are shown in supplementary table s . data extraction and analysis: the data were extracted and entered into an excel sheet and subsequently transferred to the spss file (ibm spss . version) for analysis purposes. the data were analyzed to see the effect of lockdown in the public and private sector hospitals in terms of dialysis, opd and ipd related services by comparing data before and after the first lockdown period. a total of centres responded to the survey, which includes public and private sector hospitals from all parts of india. together, these centers had dialysis stations for maintenance hemodialysis: the public sector hospitals had stations catering to (range - ) patients, whereas the private sector hospitals had stations, servicing (range - ) patients on regular dialysis. thus, a total of patients were on regular dialysis at these centers before the lockdown. (table ) after lockdown, the number of serving dialysis stations declined from to , by in the public hospitals and in the private sector. the total number of patients on regular dialysis decreased from to (from to in public and from to in the private sector). (table ) a total of ( . %) patients missed one or more sessions of dialysis during these weeks of lockdown. of them, , ( in the public sector and in the private sector), missed dialysis sessions after informing the dialysis centre of their inability to report to the unit; and patients ( in the public sector and in the private sector) missed dialysis sessions without any information to their respective dialysis centers. another patients ( in public and in public sectors) were advised by the treating nephrologists to reduce dialysis frequency because of accommodating potential dialysis required for the covid- positive patients and curbs imposed by the hospitals (table ) . a total of ( . %) patients ( in the public sector and in the private sector) who missed dialysis landed in the emergency for dialysis. a total of ( . %) patients ( from public and from private centers) had stopped reporting to the dialysis centers permanently during these three weeks, and patients ( from public and from private) were known to have died. of note, only hospitals ( public and private) facilitated the travel of patients to the dialysis centre. the indian ministry of health and family welfare, government of india, and indian council of medical research, new delhi, issued guidance for testing sars-cov- , which have undergone modification since the initial announcement ( , ) . during the survey period, testing for covid- was suggested only for patients with symptoms or history of travel from other countries or contact with sars-cov- infected individuals. however, the survey showed heterogeneity in this regard, with some hospitals adhering to the advisory, whereas others used their own protocols. a total of centers ( %), each in public and private, had created cohorting solutions for dialysing sars-cov- positive or covid suspect patients, whereas centers did not have any mechanism to segregate or isolate covid patients. of the hospitals, ( . %) adopted isolation rooms with dedicated machines for dialysis, and ( %) had dedicated machines without isolation, and ( . %) had dedicated shifts. in the private sector hospitals, have isolated rooms with dedicated machines, and two centers had dedicated machines without isolating the patient for a suspect or positive patients. of the public sector hospitals, had isolated rooms with dedicated machines, and centers had dedicated machines without isolation, and one centre pooled all such patients of day to dialyse in a single shift. effect on peritoneal dialysis: the surveyed centers were managing a total of (range - ) patients on peritoneal dialysis, the public sector had a total of pd (range from - ) patients, whereas (range from - ) were being managed in private hospitals (table ) data on the impact of lockdown on opd services during the pandemic are presented in table . the total daily attendance in the opds in the surveyed centers decreased from a total of (range - ) on the day just before the lockdown to (range - ), on the day of the survey, representing a decline of . %. during this time, the government allowed telemedicine of the public sector hospitals, had the policy of testing themselves if they had flu-like symptoms, and two had adopted the policy of self-isolating. of the private sectors, had a policy of testing if they develop flu-like symptoms, and had self-isolation as per the survey report. this survey clearly demonstrates the impact of the covid- pandemic and lockdown on the care of patients with kidney diseases in india, a low-middle income country. we found a reduction in capacity to deliver lifesaving in-center hemodialysis, leading to a reduction in dialysis frequency and drop-outs directly attributable to these measures. although not captured fully, this is likely to have resulted in patient deaths. further, there was a large reduction in the number of kidney transplant surgeries and patients with kidney diseases that accessed regular outpatient and inpatient care. ever since the onset of the pandemic, the ability of countries to address the medical needs of patients with covid- has been under a scanner ( , ) . the discussion, however, has been around the adequacy of testing capabilities, availability of hospital beds, ventilators, and personal protective equipment (ppe) ( , ) . in recent weeks, concerns have been raised around the impact of such a drastic redesign of the healthcare system on the care of patients with chronic diseases ( , ) . using the lens of kidney disease, we provide for the first-time objective evidence of such a disruption in india. according to the global burden of disease study, ckd was responsible for , dalys in in india ( , ) . at the best of times, the indian healthcare system is unable to provide care to all the patients with this condition ( , , ) . a large number of patients with end-stage kidney disease are unable to get dialysis and die ( , ) . a recent estimate put the number of patients on dialysis at , , which gives a prevalence of about per million population -a figure that puts india amongst the bottom of the countries listed in the annual report of the us renal data system ( ) . we show direct evidence of adverse impact on the care of dialysis patients - . % were forced to miss their one or more dialysis sessions, in many cases requiring emergency dialysis. the reasons were both involuntary because of the patient's inability to reach the dialysis units because of lack of transport, and on medical advice because of reduction in capacity secondary to curtailment in the number of available dialysis stations in order to meet with the pandemic norms. these patients on regular dialysis do not normally absent themselves wilfully. it is theoretically possible that these patients could have gone to another dialysis unit. however, it is well-known that the number of dialysis units in india is low, and they are mostly located in urban areas. a recent study showed low population coverage of dialysis facilities in india. almost % lived more than km away from a health facility providing dialysis, and nearly a quarter lived more than km away from the facility ( ) . interestingly, we noticed relatively low impact of lockdown on pd, a home-based therapy. unfortunately, the penetration of pd in india is relatively low. however, a few patients may face problem with supplies for accessories used for the pd. we also note that patients in the public sector hospitals were more likely to miss dialysis or drop out completely. the majority of the indian population, especially those belonging to lowmiddle socioeconomic groups, depend on the public sector for usual care, including renal care. these people are more disadvantaged in terms of access to services during the lockdown. a large number of public hospitals were converted into covid care centers. in some instances, dialysis units were shut down, and patients forced to seek care in other facilities, which in most cases were already full ( , ) . in many private hospitals, services were affected due to lockdown restrictions, lack of internal protocols to handle the pandemic, fear of infection to medical staff, and an unwillingness to risk the business from non-covid patients ( ). in an attempt to prevent the inadvertent entry of sars-cov- infected patients, some hospitals adopted testing policies at variance from that issued by the governments, even requiring that all new patients first undergo testing for the infection irrespective of whether they met the recommended eligibility criteria for testing. since these patients did not meet the eligibility criteria set down by the government, they were put in an impossible situation, desperately seeking care in multiple hospitals, and needing emergency dialysis. until recently, anecdotal reports of interruptions in care leading to death of dialysis patients had been reported in the lay press ( , ) but we provide objective evidence for the same. deaths could be confirmed in about . %, whereas the outcome of the remainder remains unknown at the time of writing. the next most extreme impact was complete dropout, noted in about . % of patients. whereas the outcomes of these patients was not known, it is unlikely that patients on mhd could survive without dialysis beyond a few days. some of these deaths could have been prevented with adequate preparedness of dialysis units. since the lockdown was sudden, units had no time to set up screening areas, isolation rooms, testing facilities for covid and arrangement of accessories like n- mask, and ppe kits. it was only after reports of death and refusal of dialysis by many hospitals made it to the media ( , , ) , that the attention of the government was drawn, leading to the development of guidance specifically prohibiting denial of dialysis on the grounds of fear of covid ( , ) . kidney transplant services were suspended throughout the country as part of the suspension of all non-essential surgeries, as was done in other countries ( , ) . for some patients, early living donor transplant is critical for long-term survival because high-quality dialysis cannot be ensured, and delaying transplant can lead to an adverse outcome ( ) . although this aspect was not explored, transplant recipients are particularly vulnerable to interruptions in the availability of medications or laboratory monitoring. the regular out and in patient services were also affected. all opd services were suspended, and admitted patients were discharged due to a combination of factors such as lockdown restrictions and lack of internal protocols to handle the pandemic. the outpatient attendance declined by . %, and the number of patients admitted in the renal wards dropped drastically. the long-term impact on the interruption in care cannot be estimated at this time. even though the survey covered the first -week period, the lockdown has already gone on for weeks, and outpatient services have still not resumed in many locations. private hospitals are resuming service since this has a bearing on the hospital revenue. however, it is expected that the impact of covid on how services are run will last for several months. it will be a challenge to ensure compliance with practices needed to limit the spread of coronavirus like social distancing in heavily crowded public hospitals. many public sector hospitals were converted to covid hospitals, limiting regular services. lack of preparedness, anxiety about covid- , and preferential shifting of services from non-covid to covid care are reasons for non-resumption of services in the public sector hospitals. the pandemic saw the emergence of telemedicine services in india. new rules were formed and endorsed rapidly by the government and adopted quickly by hospitals ( ) . teleconsultations were provided using the existing videoconferencing tools rather than specialized telemedicine platforms. in addition, medical care, howsoever limited, continued to be provided through emails, phone calls, and messaging services like whatsapp. the impact of these services on the adequacy of care provided to the small number of patients who accessed it has not been evaluated we provide the first data on the impact of covid on the care of patients with chronic diseases in india. non-communicable diseases (ncd) are responsible for more than half of all premature deaths in india. even though we present data on renal care, patients with other chronic diseases are likely to have been similarly impacted. there is already evidence that care of patients being managed under the national tuberculosis control program has been affected ( ) . similar evidences about the care of cancer patients have emerged from developed ( , ) and developing countries including india ( ) . the overall toll of the collateral damage in the form of impact on people with non-covid conditions will take a long time to evaluate. our survey covers the range of healthcare facilities in all parts of india, both in the private and public sector. these are large facilities located in major cities with greater resilience compared to smaller hospitals and standalone dialysis units, which are likely to have been even more affected. we observed that many doctors were quarantined due to incidental exposure. however, the non-physician staff such as technicians and nurses were more likely to abstain due to a combination of ignorance, fear, and practical difficulties with transport due to lockdown. this study has a number of limitations. this survey was limited to hospitals and did not cover small facilities in remote locations. it is likely that services were even more badly hit in those areas. data collected in surveys are likely to be affected by recall bias. however, this survey collected actual data rather than respondents' opinions, which are unlikely to be affected. to conclude, the covid pandemic affected the non-covid patients in india, as shown by the bystander effect on patients with kidney diseases. director of nephrology, king edward memorial hospital, pune, maharashtra . professor and head, institute of medical sciences, bhu, varanasi, up . director of nephrology, sir ganga ram hospital opal hospital telangana references: . coronavirus disease (covid- ) pandemic severe acute respiratory syndrome coronavirus (sars-cov- ) and coronavirus disease- (covid- ): the epidemic and the challenges a single number for advocacy and communication-worldwide more than million individuals have kidney diseases covid- pandemic lockdown in india covid- : lockdown across india, in line with who guidance adding insult to injury: kidney replacement therapy during covid- in india indian society of nephrology -covid- working group guidelines hemodialysis unit preparedness during and after covid- pandemic covid- kidney health action group comparative performance of private and public healthcare systems in low-and middle-income countries: a systematic review quality of private and public ambulatory health 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during covid- pandemic: a systematic review of current evidence cancer management in india during covid- key: cord- -jrc hy b authors: sardar, shaheen; abdul-khaliq, iqra; ingar, aysha; amaidia, hanaa; mansour, noor title: ‘covid- lockdown: a protective measure or exacerbator of health inequalities? a comparison between the united kingdom and india.’ a commentary on “the socio-economic implications of the coronavirus and covid- pandemic: a review” date: - - journal: int j surg doi: . /j.ijsu. . . sha: doc_id: cord_uid: jrc hy b nan 'covid- lockdown: a protective measure or exacerbator of health inequalities? a comparison between the united kingdom and india.' a commentary on "the socio-economic implications of the coronavirus and covid- pandemic: a review" dear editor, we read with great interest the review by nicola et al on the socio-economic impact of the covid- pandemic ( ) . in this letter, we focus on how worldwide lockdown measures have been an exacerbator of these socio-economic inequalities. the covid- pandemic has been a source of considerable panic, concern, and feelings of uncertainty, with much ambiguity surrounding the virus remaining. the response to ensure public safety worldwide has been largely influenced by global and national politics most commonly leading to lockdowns on national levels with variable levels of success (success in this essay is defined as the overall biopsychosocial wellbeing of a people). whilst early containment measures have shown to reduce the number of patients who contract the virus ( ), it has also highlighted several hard truths surrounding socioeconomic and political inequalities on regional levels which have been exacerbated during the lockdown period. johnson et al ( ) describes that one of the six themes which make up influence global health is the socioeconomic and environmental determinants of health. this is influenced by patients social, political, economic, environmental and gender circumstances ( ) . the comparison of two countries with varying national economic income can be used as a means of demonstrating this theme within the context of covid- lockdown. lockdown measures had somewhat different levels of success in the united kingdom (uk) and india, which differ in their national economic income, with the latter considered a low-income and middle-income country (lmic) ( ) which may have been an influencing factor. as such, this essay aims to compare and critique the impact of lockdown measures within the uk and india and draw lessons on how this can impact individual everyday practise within the clinical environment. united kingdom: the uk government implemented lockdown measures on march rd , , putting in place restrictions on social contact, changes to working conditions, and a significant reduction to public services. these measures were considered to be successful in reducing transmission of covid- ; the scientific advisory group for emergencies (sage) reported that r at the beginning of the pandemic ranged from . - . depending on the region (i.e. on average one person with the disease would transmit it to approximately three others), as of the end of july, r has been reduced to . - . ( ). however, despite this success in the reduction of transmission, lockdown measures are considered to be a means of exacerbating health inequalities. one of the notable consequences of lockdown measures on the public was on their mental health (mh) ( ) . it has been noted that more demographic risk factors such as sex, age, and socioeconomic resources before the pandemic remain important determinants of individuals mental health during the pandemic ( ). however, mh changes during this time has been thought to not be evenly distributed amongst the population. additional factors that have also impacted susceptibility is acute financial difficulty (i.e. low income, unemployment), household environment (domestic abuse, living alone, or with young children) ( ) and being a keyworker with exposure to potential infection. protective factors have included those who live with higher levels of socioeconomic security; the reduction in commuting, alterations to education and work activities and more time with family may have decreased levels of stress and in fact promoted better mental wellbeing ( ) . this demonstrates that lockdown may be viewed as potentially a measure that benefits those socioeconomically privileged and detrimental to those underprivileged. gender and race inequalities have also been exacerbated during the pandemic. worldwide, women earn less and thus save less, and are more likely to work within the informal sector. in addition, they have less access to social protection measures and form most single parent households ( ) . consequently, women's capacity to withstand economic shocks is less than their male counterparts. in the uk this has been demonstrated with a report showing that mothers were . times more likely than fathers to have lost or quit their jobs within the quarantine period ( ), again demonstrating how lockdown measures can be considered somewhat unsuccessful due to its negative social implications and exacerbation of health inequalities. race inequalities were highlighted with the first individuals dying from covid- in the uk all being of black and minority ethnic backgrounds ( ). since its first case of covid- being reported on january th , india had worked rapidly to declare one of the world's largest nationwide lockdowns, impacting . billion individuals, which was praised by the world health organisation as being 'tough and timely' ( and ). despite these measures, however, it was reported that at one point, india was the third most infected country worldwide ( ) . it is worth asking, what factors may have contributed towards the failure of what initially looked like promising measures? in a country with much inter-city travel, the shutdown of public transport forced millions into makeshift shelters, leading to their relying on food handouts and the use of public toilets resulting in social distancing become difficult to implement ( ). additionally, it was noted that lockdown measures resulted in the poorest and most marginalised members of society (who make up approximately million informal workers), who have the least socioeconomic capacity to combat the pandemic without work and income, leading to deeper poverty and starvation ( ) . despite government promises to provide food and essential supplies to those in most need, these were often facilitated by informal supply chains that were easily disrupted during the quarantine period ( ) . this would in turn threaten to negatively impact adherence to social distancing and lockdown rules. in addition, another threat to the response to lockdown has been the spread of misinformation amongst the public driven by panic, stigma, and blame. on a community level, increasing levels of violence against healthcare workers and stigmatisation of individuals suspected or confirmed of having covid- may impact members of the public reporting symptoms and seeking help ( ) . societally, the pandemic has been used to exacerbate anti-muslim sentiment, following accusations of a gathering from the group tablighi jamaat being to blame for the spread of many cases ( ), again exacerbating a climate of stigmatisation and violence in a country where discrimination against religious minorities has been on the rise in recent years ( ) . these reflect the significance of political, social, and economic factors as determinants of the overall success of lockdown measures, which may have contributed towards the high rates of infection. both examples show that lockdown may be seen as a means of controlling an epidemic that has demonstrated a skewed success (in a biomedical, social and mental sense) towards the socioeconomically advantaged on an inter-country level (i.e. quarantine measures were less successful in reducing transmission rates in india, a lmic) and an intra-country level (as demonstrated with the mh and gender disparities in the uk). it is worth noting that outbreaks are not only public health emergencies, but also socioeconomic and political emergencies as well ( ) . both countries can be considered guilty of falling into viewing the crisis with a singularly biomedical lens in the name of protecting the population at the expense of social and political factors putting the most disadvantaged individuals of society at risk. to protect the public from being developing covid- (or any other communicable diseases), social, political, and psychological factors need to be addressed as these factors may hinder adherence to preventative and treatment advice. it may be possible that the governments in the uk and india may have been able to improve the success of lockdown measures if these factors were addressed alongside the implementation of social distancing rules. a lesson that clinicians can take from this on an individual level is to ensure that we see patients in a holistic manner, through the lens of the biopsychosocial model to ensure we are maximising improvements to their clinical outcome. further to this point, the importance of the collaborative process and open communication between local healthcare professionals and politicians who both adeptly adhere to the biopsychosocial model in the realms of public health to ensure the overall wellbeing of the public should be emphasised. this may have been beneficial to lmic's such as india who have been criticised by some media outlets for the implementation of a 'western-style lockdown' ( ) . in addition, the pandemic can be seen as deepening pre-existing inequalities, revealing vulnerabilities within social, political and economic systems, which consequently amplify the biomedical impact of the pandemic ( ) . whilst clinicians should focus on approaching individual patients in an holistic biopsychosocial manner, seeing that factors such as gender and race increased negative outcomes in the uk (increased rates of unemployment, mortality and deteriorating mental health) we should also strive to dismantle structures within the nhs and institutions that work to predispose and disadvantage certain groups to these outcomes. in conclusion, lockdown measures can be thought of as an effective biomedical measure to contain a pandemic in more affluent regions. however, more emphasis was required on the social, political, and economic factors of the public, which exacerbated the health inequalities that existed in both india and the uk. this reflects the requirement to broaden our definition of 'wellbeing' and 'health' to one that is more in line with the biopsychosocial model. bibliography: the socio-economic implications of the coronavirus and covid- pandemic: a review the -ncov pandemic in the global south: a tsunami ahead. eclinicalmedicine global health learning outcomes for medical students in the uk. the lancet an appeal for practical social justice in the covid- global response in low-income and middleincome countries. the lancet global health scientific advisory group for emergencies. the r number in the uk. the r number in the uk mental health before and during the covid- pandemic: a longitudinal probability sample survey of the uk population. the lancet psychiatry data resource profile: adult psychiatric morbidity survey (apms) how are mothers and fathers balancing work and family under lockdown?". institute for fiscal studies the indirect impact of covid- on women. the lancet infectious diseases uk government urged to investigate coronavirus deaths of bame doctors. the guardian india under covid- lockdown how india is dealing with covid- pandemic. sensors international covid- and the world of work the citizenship (amendment) bill, : international law on religion-based discrimination and naturalisation law how india's lockdown restrictions have affected the poorest in the community this work is original and is not being considered for potential publication elsewhere, nor has it been published previously.all authors have contributed significantly and are in agreement with the content of the manuscript. there are no conflicts of interest in association with this paper. key: cord- -kthqb fs authors: rajkumar, r. p. title: the relationship between demographic, psychosocial and health-related parameters and the impact of covid- : a study of twenty-four indian regions date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: kthqb fs objectives: the impact of the covid- pandemic has varied widely across nations and even in different regions of the same nation. some of this variability may be due to the interplay of pre-existing demographic, psychological, social and health-related factors in a given population. methods: data on the covid- prevalence, crude mortality and case fatality rates were obtained from official government statistics for regions of india. the relationship between these parameters and demographic, social, psychological and health-related indices in these states was examined using both bivariate and multivariate analyses. results: a variety of factors - state population, sex ratio, and burden of diarrhoeal disease and ischemic heart disease - were associated with measures of the impact of covid- on bivariate analyses. on multivariate analyses, prevalence and crude mortality rate were both significantly and negatively associated with the sex ratio. conclusions: these results suggest that the transmission and impact of covid- in a given population may be influenced by a number of variables, with demographic factors showing the most consistent association. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint been observed across nations and regions. demographic, social and health-related factors have been implicated in this variability. this study suggests that factors such as population, sex ratio, and prior burden of certain communicable and non-communicable diseases may influence this variability within a given country. these findings may shed light on integrated biological and psychosocial approaches to minimize the spread and mortality due to the covid- pandemic. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the global pandemic of acute respiratory illness caused by the novel betacoronavirus sars-cov- , officially designated covid- , has emerged as perhaps the most significant health crisis of our times. an unexpected observation in the context of this pandemic has been the existence of wide variations in the prevalence, mortality and case fatality rates across affected countries, , , which cannot be wholly explained on the basis of differences in the virulence of sars-cov- strains. , while some of this variation may reflect variations in health care and testing capacity across nations, it remains important to examine the role of other factors in causing this variability, particularly socioeconomic determinants of health. there is already evidence that social factors, such as perceived sociability, socioeconomic disadvantage, health literacy, trust in regulatory authorities, and the speed and stringency of measures instituted to control the spread of covid- , can crucially influence these variables. , , these social factors interact with individual psychological responses to influence behaviour either positively or negatively: for example, an adaptive ("functional") level of fear of covid- was associated with better adherence to public health safety measures in an international sample of adults, while self-reported depression had the opposite effect. preliminary research has found that demographic and socioeconomic factors can influence variability in the spread and impact of covid- not only between countries, but within a given country; in an ecological analysis of data from the united states, poverty, number of elderly people and population density were positively correlated with covid- incidence and mortality rates. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint at the time of writing this paper, india ranked fourth among all nations in terms of the total number of confirmed cases of covid- , behind the united states, brazil and russia, with over , cases reported as of july , . following the initial identification of positive cases, the indian government instituted a nation-wide lockdown for a period of days, which began at midnight on march , , and was gradually relaxed over the next two months. data from the initial phase of the lockdown suggested that this measure significantly reduced the transmission of covid- ; however, this number rapidly increased in subsequent months. this rapid increase was not uniform: across the states and territories of india, certain states have reported over , cases, while others have reported far lower numbers despite their geographical proximity to these states. besides the demographic and socioeconomic variables discussed above, an important factor that may influence such variations in the indian context is the availability and quality of health care. health care facilities in india are unevenly distributed, with a significant urbanrural divide, and this inequality has been further exacerbated by the covid- pandemic. keeping the above in mind, an exploratory study was conducted to examine the relationship between demographic, socioeconomic and health-related indices and measures of the spread and impact of covid- across the different states of india. the current study was an exploratory, cross-sectional study based on data officially released by the government of india. information related to covid- was obtained from the website of the ministry of health and family welfare (https://mohfw.gov.in), which provides information on the total number of cases, active cases, recovered cases and deaths for each state and territory of india and is updated every hours. data for this study was recorded from the above source on june , . out of the . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint states and territories, only the regions which reported at least cases and one or more deaths were selected, to permit a meaningful computation of covid- -related indices. after obtaining information on the population of each region from the government of india's official census data (available at https://censusindia.gov.in/census_and_you/area_and_population.aspx), the following indices related to covid- were calculated for each state: • the prevalence rate, defined as the total number of cases (active, recovered and deceased) per million population • the crude mortality rate, defined as the total number of reported deaths due to covid- per million population • the case fatality rate, defined as the ratio of deaths to all cases with outcomes (death or recovery), expressed as a percentage. demographic information. details on population per state were recorded using the census data cited above, while information on population density was obtained from the national institution for transforming india (niti-aayog), the government of india's official source of data on demographic and socioeconomic variables. as age and male sex have both been associated with mortality due to covid- , , mean life expectancy for each state and sex ratio per state, defined as the number of women per men, were obtained from the same source. socioeconomic variables. information on literacy rates and female literacy rates per state was obtained from official census data, while information on poverty, defined as the percentage of people living below the poverty line in each state, was obtained from the data published by . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . data analysis. data was analyzed using the statistical package for social sciences, version (spss . , ibm corporation). prior to bivariate analysis, all study parameters were tested for normality. as the covid- indices -prevalence, mortality and case fatality ratewere not normally distributed (p < . for all indices, shapiro-wilk test), spearman's rank correlation coefficient (ρ) was used to test the hypothesis of a monotonic relationship between these indices and the aforementioned demographic, socio-economic and health-. cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint related indices. in view of the exploratory nature of our study, a conservative significance level of p < . was used for all bivariate analyses, and all tests were two-tailed. to confirm the strength of these associations, multivariate linear regression was carried out for each of the individual covid- indices. only those variables which were associated with these indices at least at a trend level (p < . ) were included in the multivariate analyses. data was obtained for indian states and one territory (delhi). the mean and standard deviation values of prevalence, crude mortality rate and case fatality rate for the entire sample is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint poverty line (ρ = - . , p = . ). no significant correlations were observed between covid- mortality and case fatality rates and any socioeconomic parameter. was significantly and negatively correlated with the burden of diarrheal disease per state (ρ = - . , p = . ) and showed trend-level associations with the maternal mortality rate (ρ = - . , p = . ) and the burden of ischemic heart disease (ρ = . , p = . ). in contrast, the mortality rate showed a significant positive correlation with the burden of ischemic heart disease (ρ = . , p = . ) and trend-level relationships with maternal mortality rate (ρ = - . , p = . ), under-five mortality rate (ρ = - . , p = . ), and burden of diarrheal disease (ρ = - . , p = . ). none of the health-related variables were significantly associated with the case fatality rate. multivariate analyses. all variables that were significantly associated with covid- indices at p < . or lower were selected for multivariate linear regression analysis. for covid- prevalence, only the sex ratio remained significantly and negatively associated with this parameter on multivariate analysis (t = - . , p = . ). a similar result was obtained for the covid- mortality rate, with the sex ratio remaining significantly and negatively associated with this variable (t = - . , p = . ). as only a single study variable, namely the population size, was associated with the case fatality rate, multivariate analyses were not carried out in this case. the results of this preliminary analysis found that certain demographic, socioeconomic and health-related variables were significantly related to the variability in covid- prevalence, mortality and case fatality rates across different regions of india. in particular, covid- prevalence was associated with the sex ratio and the burden of diarrheal disease as measured . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint by the percentage of dalys associated with this disorder; covid- mortality was associated with the burden of ischemic heart disease; and covid- case fatality rate was associated with the total population of each region. on multivariate analysis, only the negative association between the sex ratio and covid- prevalence and mortality remained significant. the association between the sex ratio and measures of the impact of covid- is in line with existing research findings. several clinical case series, both from india and other countries, have reported a preponderance of male patients in hospitalized samples, as well as a link between male sex and mortality due to , , this phenomenon may be partly explained by sex differences in the immune and inflammatory response to sars-cov- infection ; however, in the indian context, this relationship could also be influenced by traditionally-defined gender roles. these are associated with comparatively greater freedom of movement for men, which places them at a higher risk of exposure to infection. similarly, the link between state-wide differences in the burden of ischemic heart disease and mortality due to covid- is supported by clinical research, which has found an association between the presence of ischemic heart disease and the severity of covid- . , moreover, ischemic heart disease is commonly associated with other medical conditions, such as systemic hypertension and chronic renal disease, which themselves worsen the outcome of covid- , and covid- has been documented to trigger myocardial injury in patients with pre-existing coronary artery disease. no such significant association was found in this study for other medical comorbidities, such as diabetes mellitus (ρ = . , p = . ) or chronic obstructive pulmonary disease (ρ = . , p = . ), suggesting a certain degree of specificity for this association. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint though this could not be confirmed by multivariate analysis, population was positively correlated with the case fatality rate across the different regions of india. this association does not appear to be mediated solely by over-crowding, as no significant association was found between population density and case fatality (ρ = . , p = . ). a possible explanation for this finding is the unequal distribution and accessibility of healthcare facilities in india, particularly in highly populated or rural areas; , such inequalities may lead to delays in obtaining appropriate treatment. the negative association found between the burden of diarrheal disease and the prevalence of a number of other associations were observed at a trend level. while the direction of these associations was unexpected in some cases -such as a positive association between covid- prevalence and literacy, and a negative association between covid- and levels of poverty and maternal and under-five mortality rates -these findings must be interpreted with caution, owing to their low statistical significance and the large number of potential confounding factors, as well as the possibility of type i error. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint the results of this study must be viewed in the light of certain limitations. first, data on demographic, socioeconomic and health-related was obtained from official government statistics and populations which preceded the onset of the covid- outbreak by a period of three to six years. therefore, some of this information may not accurately reflect the contemporary situation in the different states of india. second, this study did not take into account other factors that could influence the spread of covid- , such as cultural norms and practices, local variations in climate and temperature, and the efficiency of implementation of quarantine and related measures. , third, the data analysis did not take into account the confounding effects of other variables on the bivariate analyses. fourth, due to logistic and manpower constraints on testing and case finding, the officially reported statistics on covid- may underestimate the true scope of this problem in india. , finally, owing to the cross-sectional nature of this study, it was not possible to assess the relationship between the study variables and trends in the spread of covid- , such as the rate of increase in the number of cases. the results of this study, though preliminary and limited by the nature of the exploratory analyses, suggest that some of the factors that have been found to influence the outcome of covid- at a clinical level, such as male sex and comorbid ischemic heart disease, also have an impact at the population level. other unexpected findings, such as the link between population and case fatality and between diarrheal disease burden and covid- prevalence, may represent potential socioeconomic or biological mechanisms that require further elucidation. further longitudinal research with more sophisticated statistical modelling and up-to-date data may clarify the role of these and other demographic, socioeconomic and health-related variables in moderating the impact of covid- within nations, and may inform future strategies to curtail the impact of this pandemic. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint the data that support the findings of this study are derived from the following sources available in the public domain: the author declares no potential conflicts of interest with respect to the research, analysis, authorship or publication of this article. the author reports no sources of funding for the work presented in this article. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint regulation and trust: -month follow-up study on covid- prevalence and fatality rates of covid- : what are the reasons for the wide variations worldwide as covid- cases, deaths and fatality rates surge in italy, underlying causes require investigation cross-country comparison of case fatality rates of covid- /sars-cov- . osong public health res perspect distinct viral clades of sars-cov- : implications for modeling of viral spread the many estimates of the covid- case fatality rate importance of collecting data on socioeconomic determinants from the early stage of the covid- outbreak onwards author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted functional fear predicts public health compliance in the covid- pandemic spatial disparities in coronavirus incidence and mortality in the united states: an ecological analysis as of an interactive web-based dashboard to track covid- in real time covid- : india imposes lockdown for days and cases rise epidemic trend of covid- transmission in india during lockdown- phase the rise and impact of covid- in india retaining health workforce in rural and underserved areas of india: what works and what doesn't? a critical interpretative synthesis cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted considering how biological sex impacts immune responses and covid- outcomes public health foundation of india, and institute for health metrics and evaluation. india: health of the nation's states -the india state-level disease burden initiative meta-analysis investigating the relationship between clinical features, outcomes, and severity of severe acute respiratory syndrome coronavirus (sars-cov- ) pneumonia the burden of mental disorders across the states of india: the global burden of disease study - clinical characteristics, associated factors, and predicting covid- mortality risk: a retrospective study in wuhan, china covid -clinical profile, radiological presentation, prognostic predictors, complications and outcome: a perspective from the indian subcontinent international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted risk factors for mortality in patients with covid- in new york city epidemiological and clinical features of novel coronavirus diseases (covid- ) in the south of iran relevance of gender-sensitive policies and general health indicators to compare the status of south asian women's health women's freedom of movement and participation in psychosocial support groups: qualitative study in northern india impact of cardiovascular disease on clinical characteristics and outcomes of coronavirus disease (covid- ) risk factors of critical and mortal covid- cases: a systematic literature review and meta-analysis age and multimorbidity predict death among covid- patients: results of the sars-ras study of the italian society of hypertension. hypertension prognostic significance of cardiac injury in covid- patints with and without coronary artery disease. coron artery dis a composite indicator to measure universal health care coverage in india: way forward for post- health system performance monitoring framework. health policy plan factors affecting the choice of health care utilisation between private and public services among the elderly population in india combating covid- : health equity matters tmprss and tmprss promote sars-cov- infection of human small intestinal enterocytes cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprintthe copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint key: cord- -m vlv q authors: ogundokun, r. o.; awotunde, j. b. title: machine learning prediction for covid pandemic in india date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: m vlv q background: coronavirus was detected in december in a bulk seafood shop in wuhan, china. the original incident of covid- pandemic in india was conveyed on th january instigating from the nation called china. as of th april , the ministry of health and family welfare has established a total of , incidents, , recuperation including relocation, and demises in the republic. objective: the objective of the paper is to formulate a simple average aggregated machine learning method to predict the number, size, and length of covid- cases extent and wind-up period crosswise india. method: this study examined the datasets via the autoregressive integrated moving average model (arima). the study also built a simple mean aggregated method established on the performance of regression techniques such as support vector regression (svr, nn, and lr), neural network, and linear regression. result: the results showed that covid- disease can correctly be predicted. the result of the prediction shows that covid- ailment could be conveyed through water and air ecological variables and so preventives measures such as social distancing, wearing of mask and hand gloves, staying at home can help to avert the circulation of the sickness thereby resulting in reduced active cases and even mortality. conclusion: it was established that the projected method outperformed when likened to previously obtainable practical models on the bases of prediction precision. hence, putting in place the preventive measures can effectively manage the spread of covid- , and also the death rate will be reduced and eventually be over in india and other nations. coronaviruses are a wide intimate of diseases, few of which lead to disease in humans and the remaining which mingle between animals and natures. animal coronaviruses will occasionally transmit to individuals and only transmit to humans [ ] . in recent years, zoonotic coronaviruses have formed triggering humanoid outbursts for instance coronavirus ailment (covid- ) , severe acute respiratory syndrome (sars), as well as a respiratory syndrome in the middle east (mers). the human disease occurs often as a lung infection, or occasionally as a stomach infection. the clinical range of disease ranges from no signs or moderate breathing problems to extreme, increasingly progressing pneumonia, severe breathing suffering condition, infected tremor, or death-induced multiple-body part catastrophe [ ] . as of april , india registered more than , established crisis of . around , individuals are now in good health from these, whereas crises have led to death. the sum of individuals afflicted with the disease was increasing in the south asian nation which led to the government swinging into action to further curb the outbreak's spread. as of mid-april , more than two million cases of coronavirus have been identified worldwide. a sikh preacher who, bearing the virus, returned from traveling to italy and germany, became a "mega propagator". he was present at a sikh commemoration in anandpur sahib from th to th of march [ , ] . cases of covid- were backtracked in the direction of him [ ] . on march more than , residents were quarantined in villages in punjab to control the circulation of the disease [ , ] . on st of march, an occasion of a spiritual assembled group of people in tablighi jamaat that happened in delhi at the beginning of march arose as a novel disease asperity next multiple crisis around the world were backtracked toward the occasion [ ] . more than thousand proselytizers might have joined the service, accompanying the bulk arriving from different nations in india [ , ] including nine hundred and sixty from forty republics abroad [ ] . as reported by the office of health and family wellbeing, this incident was related to , out of , confirmed cases in twenty-three indian cities including unified terrains before the th of april [ ] . on the th of april , nurses and physicians were found to have been diagnosed with the virus in mumbai's wockhardt hospital. hospitals were locked down immediately, and a safety region was professed. health treatment incompetence was responsible for the infections [ ] . in india, covid- infection rates are estimated towards . , slightly lesser than in the worst-pretentious nations [ ] . the outburst had proclaimed a widespread in over nations as well as unification terrains, where requirements of the infectious ailments act were applied, and public institutions and other business enterprises were on standstill. indian had revoked entirely every traveler entry permit since most reported cases have been related to other countries [ ] . on march , at prime minister narendra modi's say, india implemented a -aera community restriction. the government responded with movement restriction in areas wherever covid- events and all major cities had taken place [ , ] . also, the prime minister ordered a -day national shutdown on march, affecting india's entire . billion population [ , ] . the prime minister extended the current national lockout until may on april [ ] . michael ryan, chief executive officer of the healthiness emergencies program of the world health organization, said that india has "great potential" to cope with covid- epidemic as per the next most populated nation, would possess a significant effect proceeding the ability of the globe to cope with the disease [ ] . many analysts were apprehensive concerning the financial destruction instigated via the lockout, having immense consequences on migrant employees, large as well as trivial initiatives, agriculturalists, and entrepreneurial individuals, who were abandoned without an income in the nonappearance of transport and consumer contact [ , ] . spectators noted the lockout reduced the pandemic's progress frequency by april to double every six days [ ] and by april to double every eight days [ ] . founded on statistics from seventy-three nations, the oxford covid- régime response tracker (oxcgrt) states that the indian government has reacted to the pandemic more rigorously than other nations. this acknowledged the fast intervention of the government, emergency policymaking emergency healthcare spending, budgetary initiatives, expenditure in vaccine development and successful reaction towards the crisis, and rated india with a " " aimed at her firmness [ , ] . india registered the first covid- case in kerala on january, which grew to incidences by rd february ; altogether were undergraduates who came back from wuhan, china [ , ] . the remainder of february showed no noticeable increase in events. on the th of march , twenty-two fresh incidence was discovered together with those groups of visitors from italy involving of the participants contaminated [ ] . the spread intensified in mid-march, amid news of multiple cases around the world, several of which were related to individuals with itinerant antiquity to pretentious nations. on the th of march, an individual of age who had come back from saudi arabia turned out to be the country's primary survivor of the covid- disease [ ] . confirmed deaths reached a hundred on th march , [ ] thousand by th march , [ ] thousand by th of april , [ ] thousand by th april [ ] . demise toll passed by st april [ ] then by th april [ ] . with covid- no additional antiviral therapy is recommended. infected patients should provide medical medication to help in pain relief. in extreme cases, the function of vital organs should be protected. [ ] sars-cov- is currently not available as a vaccine. evitement is the primary form of deterrence. numerous international projects have quickly arisen to identify and evaluate the efficacy of antivirals, immunotherapies, monoclonal antibodies, and vaccines. pharmacotherapy protocols and reviews for covid- have been written. [ , [ ] [ ] [ ] . transmission of infectious disease is a dynamic mechanism of transmission that happens within the crowd. frameworks can be developed for this method to potentially examine and test the propagation mechanism of infectious diseases [ ] so that we can forecast correctly the future pattern of infectious diseases [ ] . therefore, to monitor or reduce the damage of infectious diseases, the study and review of predictive models for infectious diseases have been a hot topic of science [ ] . therefore, the study projected a simple average aggregated scheme, and the aggregated system has been established by aggregating three regression methods which include support vector regression, linear regression as well as artificial neural network. the variables utilized for the formulation of an aggregated method are the figures of covid- cases. the dataset was gathered and collated from statistica.com from january to april gathered monthly. the study predicted the values from the previous covid- incidents and values of environment variables such as water and air. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the authentic datasets of covid- have been gathered from https://www.mygov.in/ and https://www.pharmaceutical-technology.com/ the dataset is publicly available on cases from india from the first case index on january . the datasets gathered were in a monthly form that is january to april . table displays the scenario of covid- incidents in india from january to april . as at th april covid- dataset includes accumulated , total samples, confirmed cases of , , recovered cases of , ; death cases and migration. is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint there are numerous diverse methods utilized to perform machine learning tasks. machine learning approaches require certain types of algorithmic approaches. according to dataquest, , there are three types of machine learning algorithms and they are: i. supervised learning algorithms such as classification, regression, and ensemble ii. unsupervised learning algorithm such as association, clustering, dimensionality reduction iii. reinforcement learning the utmost extensively anns utilized in the estimation problem is multi-layer perceptions (mlps), which employs the solitary tiers feed-forward network [ ] . this method is categorized by a system of layers. the nodes in several tiers are as well identified as altering fundamentals. the outcome of the method is calculated employing the subsequent mathematical expression in statistics, linear regression is the scheme for demonstrating the association amid the scalar or reliant variables and solitary or additional self-determining variables [ , , , , ] . the circumstance of the descriptive variables is termed a simple linear regression while in the circumstance of greater than single descriptive variables the procedure is referred to as multiple linear regressions. the mathematical formulation of the linear regression is as specified beneath. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . support vector machines (svm) are a supervised learning scheme which could be employed for the classification as well as regression glitches (adikari et al., ; shanthi et al., ) . the core impression of svm once employed to dual categorization difficulties is to discover an established manic level that excellently splits the assumed clusters of tutoring models. in circumstances where data points are not linearly divisible, a lenient border manic level classifier is created as below to employ svmr, as in the categorization difficulty this belongs to a few clusters, for instance, a and a in the circumstance of regression and support vector machine at this point is the actual figure and additional variables are equivalent as for the categorization glitches [ ] . regression techniques are one of the prevailing methods for the prediction of specific datasets. in this study, the authors formulated a simple mean aggregated method by combining popular regression models and predicted the sum of covid- in india. authors such as [ ] and [ ] have employed the regression method predominantly to communicable datasets and as well hypotheses an ensemble model typically with estimation approaches. there is a key challenge in the study of prediction predominantly in the relation of predicting an occurrence of a specific illness as it had been stated earlier. . employing the independent variables, this revert them to discover the estimation by employing svr, lr, and ann . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . ܰ is the overall scope of crises. this section describes the objective of finding the equivalence between the figures of covid- cases with environmental variables such as water (sewage overflow) and air (air streams or wind). in this study, ecological variables play an important role in the spread of covid- diseases. to accomplish this objective the authors have applied a statistical p-value test to determine the equivalence between the figure of covid- cases. after examination by the pvalue test, it was concluded that water is a protuberant ecological variable for the incidence of covid- incident in india. many authors have found the equivalence between infectious diseases and ecological variables by p-value test [ , ] . the application of the p-value test accomplishes that ecological variables like water and air had a positive equivalence with the occurrence of several cases for the period since this disease started. the statistical implication was measured p< . . the study discards the null hypothesis. the equivalence of covid- cases with water and air is substantial table . tables - displays the evaluation of the prediction precision in terms of root mean square error, mean scaled error and mean absolute error. for the confirmation of our postulated aggregated system, one instantaneous series dataset was utilized in this research. these are the numeral of covid- crises in india and these datasets were gathered on statistica.com. the explanation of period series datasets is obtainable in table . . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . the figures of all these errors are anticipated is to be as low as probable for improved prediction accuracy. . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . figure of recorded covid- crises as of january to april as a substitute for epidemiologic spread procedure, the study employed aggregated methods svr, nn, and lr to predict the instantaneous movement of the conveyance dynamics and generate the real-time predictions of covid- disease transversely the metropolises of india. the finding presented that the precision of estimation and succeeding multiple-process prediction was extreme. it was revealed that predicting enhanced when aggregating regression models together compared to when used individually. the postulated system appraised the possible period when there will be decreasing evolution of fresh established cases crosswise the metropolises and the extent of covid- disease across india and the minute the figure of the accrued established incident of covid- would spread to the upland of their accrued crises. the core intention of this investigation is to formulate a simple mean aggregated method for the estimation of covid- disease in india. to formulate this, the study first computed the revert figures of the covid- disease from the whole separate regression procedure followed by their amalgamation in an aggregated method. in the second stage of formulating the method, the study intention is to decrease the prediction errors of covid- in india and these errors include rmse, mae, and mape. each time a certain method gives a greater prediction error compared to alternative methods its weightiness in the aggregate is diminished and vice versa. this study has joined the employed methods and presented the data for covid- disease in india as stated below. in this study, the formulation of aggregated methods illustrates a substantial enhancement in the prediction of the covid- disease in india. the postulated aggregated method is likened with the separate prediction of these methods. the attained covid- prediction precision attained for the entire approach is represented in the table - . the obtainable outcome of covid- disease is shown in table which demonstrates that our postulated aggregated system delivered the least prediction error amid the entire separate fitted methods. the study delivered a substantial enhancement in prediction precisions for covid- disease in india when the postulated aggregated system was employed. if the datasets are dependable and there exist no subsequent outbreak, the aggregated methods predicted that covid- outburst in india could end by may ending. the aggregated methods permit entering the interferences information as well as examining the influence of interferences on the extent of the disease outburst and the ending period if the covid- epidemic. employing the assumed original extents of the covid- outburst, the study utilized the aggregated methods (svr, nn, and lr) with identified framework and model to evaluate the extent of the outburst in time to come and excite the influence of the interferences on the magnitude and asperity of the pandemic. approbatory to the individually used methods for the conveyance of the covid- diseases, the aggregated methods (svr, nn, and lr) provide real-time predicting instruments used for shaping and tracking covid- disease in india, . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint reckoning the covid- disease, obtaining covid- disease asperity, predicting the extent of the pandemic together with supporting government and health staffs to constitute strategy and competent verdicts towards the eradication of the covid- diseases in india. the integration of the prediction from diverse methods substantially decreases prediction errors and consequently makes available advanced precision. a few decades back, several researchers' studies have suggested several statistical methods. the study postulated a simple-mean aggregated method for the prediction of covid- disease in india. the projected aggregated approach investigated separate predictions and therefore the prediction of covid- disease in india is formulated with very recognized methods: neural network, support vector regression, and linear regression. the result indicates that the postulated method outperformed based on prediction precision of the covid- disease in india when likened to currently existing applicable methods. in the future the competence of the postulated method could be as well as be investigated and some other regression models or algorithms can be used and evaluated. the authentic datasets of covid- have been gathered from https://www.mygov.in/ and https://www.pharmaceutical-technology.com/ the dataset is publicly available on cases from india from the first case index on january , . cc-by . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint effectiveness of n respirators versus surgical masks in protecting health care workers from acute respiratory infection: a systematic review and meta-analysis effectiveness of surgical and cotton masks in blocking sars-cov- : a controlled comparison in patients coronavirus disease (covid- ) situation report - . world health organization novel coronavirus ( -ncov) in the u.s. centers for disease control and prevention (cdc) wuhan virus: what clinicians need to know us now has more coronavirus cases than either china or italy mmwr morb mortal wkly rep northern california coronavirus patient wasn't tested for days. the washington post early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia a familial cluster of pneumonia associated with the novel coronavirus indicating person-to-person transmission: a study of a family cluster covid- ): covid- situation summary impact of non-pharmaceutical interventions (npis) to reduce covid- mortality and healthcare demand cdc: first person-to-person spread of novel coronavirus in us reports its first case of person-to-person transmission. the new york times covid- ): people at higher risk novel coronavirus the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention lost sense of smell may be peculiar clue to coronavirus infection. the new york times epidemiological characteristics of pediatric patients with coronavirus disease in china clinical and epidemiological features of children with coronavirus disease (covid- ) in zhejiang, china: an observational cohort study interim healthcare infection prevention and control recommendations for patients under investigation for novel coronavirus novel coronavirus covid- treatment: a review of early and emerging options. open forum infectious diseases (ofid) novel coronavirus aerosol and surface stability of sars-cov- as compared with sars-cov- stability of sars-cov- in different environmental conditions. the lancet microbe virological assessment of hospitalized patients with covid- clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study viral dynamics in mild and severe cases of covid- presumed asymptomatic carrier transmission of covid- a familial cluster of infection associated with the novel coronavirus indicating potential person-to-person transmission during the incubation period sars-cov- viral load in upper respiratory specimens of infected patients respiratory virus shedding in exhaled breath and efficacy of face masks infectious diseases society of america guidelines on the treatment and management of patients with covid- pharmacologic treatments for coronavirus disease (covid- ): a review review of emerging pharmacotherapy for the treatment of coronavirus disease analysis and projections of transmission dynamics of ncov in wuhan reporting, epidemic growth, and reproduction numbers for the novel coronavirus ( -ncov) epidemic real-time forecasting of infectious disease dynamics with a stochastic semi-mechanistic model retrieved on th forecasting strong seasonal time series with artificial neural networks dimensionality reduction for indexing time series based on the minimum distance work watermarking mpeg- d mesh animation with time-series analysis an evaluation of neural network ensembles and model selection for time series prediction prediction of blood glucose concentration ahead of time with feature based neural network an empirical application of linear regression method and fir individual versus super ensemble forecasts of seasonal influenza outbreaks in the united states ensemble method for dengue prediction classification of dengue illness based on readily available laboratory data predicting the severity of dengue fever in children on admission based on clinical features and laboratory indicators: application of classification tree analysis the author declared that they didn't receive any funds from any organization. authors declared that there is no conflict of interest key: cord- - bijio authors: eltom, kamal h.; samy, abdallah m.; abd el wahed, ahmed; czerny, claus-peter title: buffalopox virus: an emerging virus in livestock and humans date: - - journal: pathogens doi: . /pathogens sha: doc_id: cord_uid: bijio buffalopox virus (bpxv) is the cause of buffalopox, which was recognized by the fao/who joint expert committee on zoonosis as an important zoonotic disease. buffalopox was first described in india, later in other countries, and has become an emerging contagious viral zoonotic disease infecting milkers with high morbidity among affected domestic buffalo and cattle. bpxv is a member of the genus orthopoxvirus and a close variant of the vaccinia virus (vacv). recent genome data show that bpxv shares a most recent common ancestor of vacv lister strain, which had been used for inoculating buffalo calves to produce a smallpox vaccine. over time, vacv evolved into bpxv by establishing itself in buffaloes to be increasingly pathogenic to this host and to make infections in cattle and humans. together with the current pandemic of sars-cov /covid , bpxv infections illustrate how vulnerable the human population is to the emergence and re-emergence of viral pathogens from unsuspected sources. in view that majority of the world population are not vaccinated against smallpox and are most vulnerable in the event of its re-emergence, reviewing and understanding the biology of vaccinia-like viruses are necessary for developing a new generation of safer smallpox vaccines in the smallpox-free world. buffalopox virus (bpxv)-the etiological agent of buffalopox-is member of the genus orthopoxvirus, subfamily chordopoxvirinae, family poxviridae https://talk.ictvonline.org/ictv-reports/ ictv_ th_report/ [ ] . bpxv is a close variant of the vaccinia virus (vacv), the type-species of the genus orthopoxvirus (opxv). buffalopox was first described in india [ ] [ ] [ ] and further reports on the disease came from other countries [ ] [ ] [ ] . discovery of the virus was achieved around the time of smallpox epidemics and the beginning of vaccination programs with vacv. the first isolation of the virus was made in northern india in the year and the virus continued to cause sporadic outbreaks in asian buffaloes (bubalus bubalis) in bangladesh, india, indonesia, pakistan, egypt, russia, and italy [ ] , figure . in the same year of the first isolation of the virus, the disease was recognized by the fao/who joint expert committee on zoonosis as an important zoonotic disease [ ] . forty years buffalopox virus resembles vacv in terms of its size, shape, structure, physico-chemical properties, and autonomous replication in "viroplasm zones" [ , ] . buffalopox virus replicates in a wide range of cells [ ] [ ] [ ] [ ] [ ] . cell cultures of bovine and monkey origins are most frequently used for virus propagation, accompanied by a cytopathic effect (cpe). whole-genome restriction fragment length polymorphism (rflp) studies have indicated genetic similarity between vacv and bpxv [ ] . phylogenetic analysis based on some genes sequences [ , ] and complete genomes [ , ] revealed that bpxvs clustered closely with vacv rather than with other opxvs. furthermore, phylogenomics data support the hypothesis that vacv lister and allied vaccine strains (western reserve, copenhagen, etc.) share a most recent common ancestor with bpxv to the exclusion of other vacv strains [ ] . analysis of the available complete genomes of four isolates (three from india and one from pakistan) confirmed the monophyly bpxvs [ ] . epidemiology of buffalopox should be reconsidered more than years after cessation of smallpox eradication campaigns [ ] . bpxv resembles vacv in its pathogenesis, pathology, and histology. after recovery from infection, animals and humans are protected by both cell and antibody-mediated immunity. neutralizing, hemagglutination-inhibiting, and precipitating antibodies are important for protection; they appear after days approximately following experimental infection and maternal antibodies are transferred to the newborn animals via colostrum [ ] . many authors guessed that bpxv is likely to have emerged from the lister vaccine strain of vacv, the strain that had been used in buffalo calves in india to produce smallpox vaccine [ , , ] . support for this has been provided by analyzing the complete genomes of bpxvs sequenced so far [ , ] . the emergence of bpxv occurred by gradual adaptation of the vaccine strain in buffaloes [ ] until it converted to pathogenic, leading to outbreaks in this new host. consequently, buffalopox outbreaks occurred frequently in many parts of india, affecting both buffaloes [ , , ] and humans [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . reports on zoonotic outbreaks of buffalopox have been made from pakistan as well [ , ] . subsequently, reports on bpxv cases in other hosts, such as cattle, have also been made [ ] . transmission of the virus to cattle and humans is alarming as it might have serious public health implications, in the view that no more vaccination against smallpox is practiced since after its eradication [ ] . the products of host-range genes have been demonstrated to affect the infecting ability of the virus for cells by subverting immune responses of the host [ ] . the most important host-range genes of opxvs that have been sequenced for bpxv strains are e l, k l, c l, and b r, which are implicated in altering the antiviral defense mechanism of the host cell. the full-length sequences of these four genes of bpxvs-obtained from outbreaks in buffaloes, cattle, and humans in india-were analyzed, to investigate their evolutionary relationship to other opxvs circulating in the world vis-à- buffalopox virus resembles vacv in terms of its size, shape, structure, physico-chemical properties, and autonomous replication in "viroplasm zones" [ , ] . buffalopox virus replicates in a wide range of cells [ ] [ ] [ ] [ ] [ ] . cell cultures of bovine and monkey origins are most frequently used for virus propagation, accompanied by a cytopathic effect (cpe). whole-genome restriction fragment length polymorphism (rflp) studies have indicated genetic similarity between vacv and bpxv [ ] . phylogenetic analysis based on some genes sequences [ , ] and complete genomes [ , ] revealed that bpxvs clustered closely with vacv rather than with other opxvs. furthermore, phylogenomics data support the hypothesis that vacv lister and allied vaccine strains (western reserve, copenhagen, etc.) share a most recent common ancestor with bpxv to the exclusion of other vacv strains [ ] . analysis of the available complete genomes of four isolates (three from india and one from pakistan) confirmed the monophyly bpxvs [ ] . epidemiology of buffalopox should be reconsidered more than years after cessation of smallpox eradication campaigns [ ] . bpxv resembles vacv in its pathogenesis, pathology, and histology. after recovery from infection, animals and humans are protected by both cell and antibody-mediated immunity. neutralizing, hemagglutination-inhibiting, and precipitating antibodies are important for protection; they appear after days approximately following experimental infection and maternal antibodies are transferred to the newborn animals via colostrum [ ] . many authors guessed that bpxv is likely to have emerged from the lister vaccine strain of vacv, the strain that had been used in buffalo calves in india to produce smallpox vaccine [ , , ] . support for this has been provided by analyzing the complete genomes of bpxvs sequenced so far [ , ] . the emergence of bpxv occurred by gradual adaptation of the vaccine strain in buffaloes [ ] until it converted to pathogenic, leading to outbreaks in this new host. consequently, buffalopox outbreaks occurred frequently in many parts of india, affecting both buffaloes [ , , ] and humans [ , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . reports on zoonotic outbreaks of buffalopox have been made from pakistan as well [ , ] . subsequently, reports on bpxv cases in other hosts, such as cattle, have also been made [ ] . transmission of the virus to cattle and humans is alarming as it might have serious public health implications, in the view that no more vaccination against smallpox is practiced since after its eradication [ ] . the products of host-range genes have been demonstrated to affect the infecting ability of the virus for cells by subverting immune responses of the host [ ] . the most important host-range genes of opxvs that have been sequenced for bpxv strains are e l, k l, c l, and b r, which are implicated in altering the antiviral defense mechanism of the host cell. the full-length sequences of these four genes of bpxvs-obtained from outbreaks in buffaloes, cattle, and humans in india-were analyzed, to investigate their evolutionary relationship to other opxvs circulating in the world vis-à-vis the vaccine strains. sequences of these genes revealed a higher degree of similarity to those of vacv strains [ ] . the functions of the vacv e l gene were studied extensively in deletion mutants, which caused abortive replication and expression of only a subset of viral genes in most mammalian cell lines [ , ] . e l encodes a -kda and a -kda protein that suppresses the antiviral response of the host cell by inhibiting both protein kinase and rnasel [ , ] . the k l gene confers interferon resistance and was shown to repress activation of the protein kinase (pkr) and phosphorylation of eif α in mammalian cells [ ] , which can result in inhibiting the antiviral defense mechanism. the c l gene is conserved in all opxv genomes [ ] and causes inhibition of apoptosis [ ] and blockage of antiviral effects by antagonizing interferons (ifn) [ ] . the b r gene is essential for the formation of extracellular virus particles (ev) [ ] and is involved in viral evasion from the immune response of the host [ ] . when this gene was deleted from vacv strain wr, it resulted in a decrease in ev production, reduction in the plaque size in vitro and in high attenuation of the virus in vivo in comparison with the parental strain [ ] . point mutation of at least one amino acid was observed within this gene in cattle and human isolates of bpxv [ ] , which also occurred when a bpxv isolate was passaged times [ ] . some of these mutations might be critical for the virus to adapt to new hosts and can be implicated in the zoonotic nature of this virus [ ] . clinical signs of buffalopox resemble those of vacv infections. characteristic signs in buffaloes include a local pox exanthema (pustulation with central necrosis) and localized pock-lesions on the muzzle, udder, teats, inside of the thighs, scrotum, base of the ears, inner surface of earflap, and eyes in the mild form [ ] . the disease may also proceed to severe systemic disease of a cyclical pattern with generalized lesions in individual cases [ ] . although buffalopox does not occur very frequently, the disease is economically important in countries where buffaloes are reared. the disease has a negative impact on the dairy industry as a consequence of reduced productivity ( - % reduction) of affected milking animals when severe local pocks affect the udder and teats, which in turn may lead to mastitis [ , ] . humans in close contact with affected animals can get infected by the virus. in humans, infection with bpxv was manifested as pox lesions in the flexor aspect of distal forearms, in the hand, dorsae of hands, wrist fingers, and thumbs, right preauricular area, right angle of mandible, right ala of nose, and forehead with or without swelling of the regional lymph nodes, general malaise, and fever [ , , , , , ] . several reports on bxpv outbreaks involving both animals and humans or infections of individual cases were made from india. an outbreak of buffalopox in animals and humans in maharashtra state of india in was reported. it involved herds and resulted in % overall morbidity; some animals also exhibited lesions on their hindquarters, suggesting secondary or even a generalized infection. milkers suffered pox-like local lesions on their hands, forearms, and forehead, presented with pyrexia, axillary lymphadenopathy, and general malaise [ , ] . further similar outbreaks had also been described also in animals and humans [ , ] and a recent case report on human infection with bpxv was made on an indian milkman and owner [ ] . manual milking with bare hands exposed these individuals to the infection. a report on laboratory-acquired bpxv infection in humans was also made in india, highlighting the need for observance and enforcement of strict biosafety measures within laboratories [ ] . in pakistan in - , reports were made describing a nosocomial outbreak of bpxv in humans in the five major burn units in karachi. here, patients developed pox lesions at burn wounds and the intact skin surrounding them. the source of infection was vacv-contaminated buffalo fat, which had been used as a first-aid medication for dressing the burns. this event showed an indirect mode of transmission of an opxv [ , ] . although outbreaks of orthopoxvirus infections-unique to the indian subcontinent region-were repeatedly described and significant veterinary research work was conducted in this respect, limited diagnostic tools were developed [ ] . clinical examination and collection of specimens (swab and serum) from both animals (buffaloes, cattle) and humans are the first steps of diagnosis. these samples are then subjected to electron microscopy examination, inoculation in cell culture for isolation of the virus, plaque reduction and neutralization test, pcr, and partial genome sequencing [ , ] . like other opxvs, bpxv can be isolated from the lesion scabs of animals and humans by inoculation in embryonated chicken eggs as well as in a number of cell lines including chick embryo fibroblast cells, pup kidney cells, vero cells and baby hamster kidney cells [ ] [ ] [ ] [ ] [ ] . cytopathic effects can be observed in - days. bpxv is serologically uniform and cross-reacts with both vacv and cpxv, as well as with other opxvs. therefore, serological assays are not advantageous for virus differentiation unless a targeted monoclonal antibody is used. classical assays used to distinguish bpxv from other opxvs would be double immunodiffusion (id), complement fixation (cf), and immunoelectrophoresis (ie). today, enzyme-linked immunosorbent assay (elisa), immunofluorescence assays (if), and western blotting (wb), together with neutralization and plaque reduction tests (nt/prt) are more commonly used. earlier investigations with monoclonal antibodies have shown that bpxv is serologically more closely related to vacv than to other opxvs [ , ] . recent attempts were made for specific detection of bpxv and differentiation from other opxvs. monoclonal antibodies against the bp strain of bpxv were produced and used in antigen capture elisa. although these monoclonal antibodies differentiated the bpxv from other opxvs, only two of them significantly bound different bpxv strains; none of them had virus-neutralizing abilities; furthermore, they did not bind the polypeptides shared by other bpxv strains in western blotting [ ] . therefore, they are of no use for serodiagnosis of bpxv infections. some recombinant proteins antigens were evaluated for the specific detection of bpxv [ , ] ; they cross-reacted with other opxv as they were based on conserved proteins (a l and h l) in opxv. however, their potential use in diagnostic assays of bpx infections was not evaluated. primers for the c l gene of opxv were used in conventional pcr, duplex pcr, and real-time pcr [ ] for the detection of bpxv. the primers amplify a bp pcr product unique for bpxvs. in duplex pcr, using these primers together with those for the dna polymerase (pol dna), opxv species, as well as capripox and parapox viruses, amplified only a bp amplicon of the pol dna, whereas bpxv amplified both the bp and pb pcr products. the sensitivity of real-time pcr, however, was times more than the conventional pcr [ ] . currently, no licensed specific antivirals are available for the treatment of bpxv infections in humans and animals. if possible, acute infections can be curtailed with immune sera; but, in the case of immunosuppressed individuals, serum therapy does not prevent the local infection from developing into a generalized systemic disease [ , , ] . however, reservations against polyclonal human immune sera arise due to safety reasons, as their biological compounds are not characterized very well [ ] . for the prevention of secondary bacterial infections, symptomatic treatment is provided. because bpxv is closely related to vacv, the antivirals cidofovir and st may be effective for local and systemic treatment in humans and animals. recently, a new series of thiazolo [ , -a] pyrimidine- -carboxylate derivatives a-f and a-f were synthesized and characterized [ ] . the compounds were tested for in vitro antimicrobial and antiviral activities. the probable mode of action of these active compounds was determined through in silico docking study by docking the receptor methionyl-trna synthetase and human inosine- -monophosphate dehydrogenase (impdh) for antibacterial and antiviral activities, respectively. of these compounds, c elicited excellent in vitro antimicrobial activity against all tested strains. on the other hand, compound a elicited . % and . % inhibition of the camelpox virus (cmlv) and bpxv, respectively. moreover, this compound exhibited minimum docking and binding energy along with the maximum hydrogen/hydrophobic interaction with impdh [ ] . recently, some protein kinase inhibitors were tested for antiviral activity. among these, the kinase inhibitor cgp , which blocks the mitogen-activated protein kinase (mapk) interacting kinase (mnk ), was found to be promising as an antiviral agent against bpxv. in in vivo studies, this compound was found to decrease the synthesis of the viral genome and to reduce synthesis of viral proteins, whereas in in ovo studies it prevented the formation of pock lesions on the chorioallantoic membrane (cam) as well as associated mortality of the chick embryos [ ] . no specific vaccine against bpxv infection is available. however, prophylactic control and protection of animals in an infected herd is possible with a live vaccine based on an attenuated vacv strain. vaccinia virus vaccines were initially produced in buffaloes (dermo-vaccine) in india [ ] . later cell culture adapted strains were used. the program resembles that of vaccinia and cowpox prophylaxis. however, the protective efficacy of the third generation vaccinia based vaccines has been tested in animals (mice, rabbit, and monkeys) [ ] . in addition to the safety of these vaccines, the elicited immune responses provided protection against challenge with the respective virus. the use of these vaccines would be advantageous for use in buffalo and humans in contact with buffalo, as no data is available about prophylaxis in humans at risk of bpxv infections. recombinant dna vaccines from the envelope proteins (a l and hl) of opxv-derived from a bpxv strain-were tested in animal models [ , ] . an increase in antigen-specific serum igg level as well as in neutralizing antibody titers was observed in the recombinant vaccines. in passive protection experiments in suckling mice, hyperimmune sera of the recombinant a l vaccine conferred % protection [ ] , while % protection was reached with anisera of the h l [ ] . a combined vaccine containing both a l and h l recombinant proteins elicited a high immune response in mice measure by specific igg titers in elisa and neutralizing antibody titers. in addition, complete protection of mice vaccinated with this combination was seen when they were challenged by virulent virus strain [ ] . over time, bpxv evolved from vacv and established itself in buffaloes to be increasingly pathogenic to the new host, i.e., buffaloes, and further to make infections in cattle and humans [ ] . the emergence of a pathogenic opxv, which can spread efficiently from human-to-human, should be considered an immediate public health risk [ ] [ ] [ ] . together with the current pandemic of sars-cov /covid , bpxv infections in india [ , , ] illustrate how vulnerable the human population is to the emergence and re-emergence of viral pathogens from unsuspected sources. a deep understanding of the underlying molecular mechanisms, that control the species tropism of poxviruses in non-evolutionary hosts is of utmost importance [ ] . as more information becomes available on tropism determinants of poxviruses, new strategies will likely be developed to control zoonotic infections. raising awareness, improvement of diagnostic techniques, education, and preparedness for early intervention, and development of disaster guidelines are necessary given the potential disease outbreak, in case it happens in the future [ ] . like most opxvs and other zoonotic poxviruses reservoir host(s) that maintain bpxv in the environment did receive attention and yet is unknown-although it is thought to be most likely rodents [ ] ; knowledge on this respect is essential for the prevention of introduction of the virus in naïve buffalo and cattle populations and for designing eradication and control programs. increasing incidences of opxv infections are being reported across the world: bpxv in asia, vacv and vacv-like viruses (vlvs) in 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virus, a zoonotic indian vaccinia-like virus immunogenicity and protective efficacy of recombinant major envelope protein (rh l) of buffalopox virus in animal models animal poxviruses transmitted from cat to man: current event with lethal end fatal cowpox-like virus infection transmitted by cat in vitro and in silico biological studies of novel thiazolo[ , -a]pyrimidine- -carboxylate derivatives mnk inhibitor as an antiviral agent suppresses buffalopox virus protein synthesis comparison of dried vaccine with fresh indian buffalo-calf lymph in revaccination against smallpox summary report on first, second and third generation smallpox vaccines; world health organization co-administration of recombinant major envelope proteins (ra l and rh l) of buffalopox virus provides enhanced immunogenicity and protective efficacy in animal models an emergent poxvirus from humans and cattle in rio de janeiro state: cantagalo virus may derive from brazilian smallpox vaccine passatempo virus, a vaccinia virus strain aracatuba virus: a vaccinialike virus associated with infection in humans and cattle novel orthopoxvirus infection in an alaska resident human monkeypox: current state of knowledge and implications for the future human infection with a zoonotic orthopoxvirus in the country of georgia fatal outbreak in tonkean macaques caused by possibly novel orthopoxvirus novel orthopoxvirus and lethal disease in cat we acknowledge the support of the open access publication funds of the university of goettingen. the authors declare no conflict of interest. key: cord- -ggcpsjk authors: radhakrishnan, chandni; divakar, mohit kumar; jain, abhinav; viswanathan, prasanth; bhoyar, rahul c.; jolly, bani; imran, mohamed; sharma, disha; rophina, mercy; ranjan, gyan; jose, beena philomina; raman, rajendran vadukkoot; kesavan, thulaseedharan nallaveettil; george, kalpana; mathew, sheela; poovullathil, jayesh kumar; govindan, sajeeth kumar keeriyatt; nair, priyanka raveendranadhan; vadekkandiyil, shameer; gladson, vineeth; mohan, midhun; parambath, fairoz cheriyalingal; mangla, mohit; shamnath, afra; sivasubbu, sridhar; scaria, vinod title: initial insights into the genetic epidemiology of sars-cov- isolates from kerala suggest local spread from limited introductions date: - - journal: biorxiv doi: . / . . . sha: doc_id: cord_uid: ggcpsjk coronavirus disease (covid- ) rapidly spread from a city in china to almost every country in the world, affecting millions of individuals. genomic approaches have been extensively used to understand the evolution and epidemiology of sars-cov- across the world. kerala is a unique state in india well connected with the rest of the world through a large number of expatriates, trade, and tourism. the first case of covid- in india was reported in kerala in january , during the initial days of the pandemic. the rapid increase in the covid- cases in the state of kerala has necessitated the understanding of the genetic epidemiology of circulating virus, evolution, and mutations in sars-cov- . we sequenced a total of samples from patients at a tertiary hospital in kerala using covidseq protocol at a mean coverage of , x. the analysis identified unique high-quality variants encompassing novel variants and new variants identified for the first time in sars-cov- samples isolated from india. phylogenetic and haplotype analysis revealed that the circulating population of the virus was dominated ( . % of genomes) by three distinct introductions followed by local spread, apart from identifying polytomies suggesting recent outbreaks. the genomes formed a monophyletic distribution exclusively mapping to the a a clade. further analysis of the functional variants revealed two variants in the s gene of the virus reportedly associated with increased infectivity and variants that mapped to five primer/probe binding sites that could potentially compromise the efficacy of rt-pcr detection. to the best of our knowledge, this is the first and most comprehensive report of genetic epidemiology and evolution of sars-cov- isolates from kerala. the covid- pandemic has seen a widespread application of genomic approaches to understand the epidemiology and evolution of sars-cov- . the accelerated efforts to sequence genomes of clinical isolates of sars-cov- from across the world picked up pace following the initial genome sequencing of the virus from a patient in wuhan, the epicenter for the pandemic [ ] ). as the virus evolves through the accumulation of mutations, it has split into major lineages with strong geographical affinities [ ] . the availability of the genome sequences in the public domain has provided a unique view of the introduction, evolution, and dynamics of sars-cov- in different parts of the world [ ] . a number of approaches have emerged for rapid and scalable sequencing of sars-cov- from clinical isolates. this includes direct shotgun approaches as well as targeted amplicon-based and targeted capture-based approaches [ ] [ ] [ ] . sequencing based approaches provide a unique opportunity for high fidelity of detection and for understanding the genetic epidemiology of sars-cov- [ ] . additionally, the genetic variants could offer insights into the mutational spectrum, evolution, infectivity, and attenuation of the virus [ , ] . additional analyses on genomic variants have also provided useful insights into the efficacy of primer/probe-based diagnostic assays as well as immune epitopes and resistance to antisera [ , ] . an approach for high-throughput multiplex amplicon sequencing of sars-cov- has been previously reported from our group [ ] . kerala is a unique state in india with a population of million people and extensively connected with the global populations through over . million expatriates, apart from being a traditional trade post and a global tourist destination. the state is therefore in a distinct position, affected by local as well as global epidemics. in fact, the first identified case of covid- in india was from kerala, early in the epidemic. the patient had traveled from wuhan, china [ , ] . the initial genomic identity of the virus was also established which mapped to the b superclade of sars-cov- [ ] . further introductions into the state during the later days of the pandemic through international and regional travel could have contributed to the spread of the epidemic in the state and the pool of circulating genetic lineages or clades. while a number of studies on the genetic epidemiology of sars-cov- from different states in india have emerged [ ] [ ] [ ] [ ] , there has been a paucity of information on the genetic architecture and epidemiology of sars-cov- isolates in the state of kerala. we intended to fulfill the gap in knowledge on the identity of the circulating genetic lineages/clades contributing to the epidemic in the state of kerala. to this end, we employed a high-throughput sequencing-based approach for the genetic epidemiology of sars-cov- . to the best of our knowledge, this is the first comprehensive overview of the genetic architecture of sars-cov- isolates from the state of kerala. the institutional human ethics committee approved the project (gmc kkd/rp /iec ). rna samples were isolated from nasopharyngeal/oropharyngeal swabs of patients presenting to government medical college, kozhikode, a major tertiary care center in kerala. rna extraction was done using magmax viral/pathogen nucleic acid isolation kit in thermo scientific kingfisher flex automated extraction system according to the manufacturer's instructions. all the rna samples were transferred within hours of collection at a cold temperature ( - °c) and were stored at - °c until further processing. sequencing was performed using the covidseq protocol as reported previously [ ] . briefly, this protocol involved multiplex amplicon sequencing on the illumina novaseq platform. the base calls generated in the binary base call (bcl) format were demultiplexed to fastq reads using bcl fastq (v . ). for reference-based assembly, we followed a previously defined protocol from poojary et al. [ ] . as per the protocol, the quality control of fastq reads was performed using trimmomatic (v . ) at a phred score of q [ ] with adapter trimming. these reads were further aligned to the severe acute respiratory syndrome (sars-cov- ) wuhan-hu- reference genome (nc_ . ) using hisat - . [ ] . the human reads were removed using samtools (v . ) [ ] . the samples with coverage > % and < % unassigned nucleotides underwent variant calling and consensus sequences generation using varscan (v . . ) [ ] and samtools (v . ) [ ] , bcftools (v . . ), and seqtk (v . -r ) [ ] respectively. variants were annotated using annovar [ ] employing a range of custom annotation datasets and tables. all the variants identified were systematically compared with a compendium of other indian and global variants. a total of , complete sars-cov- genomes deposited in the global initiative on sharing all influenza data (gisaid) database till september , were used for comparative analysis. summary of the sample details along with their originating and submitting laboratories are provided in supplementary table . viral genomes with a pairwise alignment ≥ % and gaps < % with the reference genome (nc_ . ) were considered for further variant calling using snp-sites [ ] . genetic variants compiled from a total of , high-quality genomes from india and , global genomes were considered for analysis. phylogenetic analysis was performed according to the pipeline provided by nextstrain [ ] . the dataset of , complete sars-cov- genomes deposited in the gisaid database from india was used for the analysis supplementary table , along with genomes from the current study which have % coverage and at least % pairwise alignment with the reference genome (nc_ . ). genomes having more than % ns or missing dates of sample collection were excluded from the analysis. the phylogenetic tree was constructed and refined to a molecular clock phylogeny using the augur framework provided by nextstrain and was visualized using auspice. the phylogenetic assignment of named global outbreak lineages (pangolin) package was used to assign lineages to the genomes from this study [ ] . the lineages were visualized and annotated on the phylogenetic tree using itol [ ] . for haplotype analysis, the genomes were aligned to the wuhan-hu- (nc_ . ) reference genome using mafft [ ] and problematic genomic loci (low coverage, high sequencing error rate, hypermutable and homoplasic sites) were masked from the alignment [ ] . the aligned sequences were imported into the dna sequence polymorphism tool (dnasp v . . ) [ ] to generate haplotypes. a tcs haplotype network [ ] for the genomes was constructed using the population analysis with reticulate trees software (popart v . ) [ ] . times to the most recent common ancestor (tmrca) for the haplogroups were computed following the bayesian markov chain monte carlo (mcmc) method using beast v . . [ ] . the analysis was performed using a coalescent growth rate model along with a strict molecular clock and the hky+Γ substitution model with gamma-distributed rate variation (gamma categories= ). mcmc was run for million steps. the output was analyzed in tracer v . . [ ] and burn-in was adjusted to attain an appropriate effective sample size (ess). further, we have evaluated the sars-cov- variants based on their functional relevance. we curated a comprehensive compendium of sars-cov- variants of functional relevance as well as variants that are associated with increased infectivity and attenuation of sars-cov- from literature and preprint servers. the variants were systematically annotated and mapped to the reference genome coordinates and their respective amino acid changes. this variant compendium encompassed about variants curated from publications. the variants in this study were compared with the genomic variants generated using bespoke scripts. we were also interested to evaluate the effect of sars-cov- variants on the efficacy of rt-pcr detection. we took a compiled list of primer/probe sequences widely used in the molecular detection of sars-cov- around the globe [ ] . in our analysis, we mapped the sars-cov- genetic variants obtained from kerala genomes to the primer or probes sequence and calculated the melting temperature (tm) of the mutant with the wild type sequence. the length of primers in the curated list is greater than nucleotides. the formula applied for calculating melting temperature is tm= . + *(yg+zc- . )/(wa+xt+yg+zc) where w, x, y, and z are the number of a, t, g, and c nucleotides respectively [ ] . figure summarises the schematic for the overall data analysis. a total of isolates of sars-cov- from kerala were processed for genome sequencing. the genomes were sequenced using covidseq protocol [ ] and generated approximately . million raw reads per sample. the reads were subjected to quality control and resulted in approximately . million reads per sample, of which around . million reads per sample aligned to the sars-cov- reference genome (nc_ . ). the reads had a mapping percentage of . % and mean , x coverage. the data has been summarized in supplementary table and the mean coverage of the sample across the amplicons has been represented in figure . of the isolates of sars-cov- sequenced, a total of samples had > % coverage and < % unassigned nucleotides across the genome. these samples were further processed for variant calling and consensus generation. our analysis identified a total of unique variants, with a median variant count of per sample. variant quality has been ensured with the average variation percentage across genomes ≥ . of the total unique variants, were categorized as high-quality variants. the detailed information on variant quality is provided in supplementary table . the distribution of variants across the sars-cov- genomes used in the study was analyzed. also, the proportional distribution of variants for every bps across the genome was calculated and compared among various datasets. variant distribution across genomes and comparison of variant proportions across genome datasets are represented in figure . out of the high-quality unique variants, variants were found to be reported for the first time in the global compilation of variants table . we have also added new variants ( . %) to the indian repertoire of genetic variants. details of these variants are systematically compiled in supplementary table . the overlap in the variants between the present study of kerala, other indian, and global datasets is summarized in supplementary figure . out of the novel variants, variant in the s gene, g>a, was a personal variant and was not shared by any other isolate. the remaining three novel variants were shared variants and were present in different genes (orf b, orf a and s). of the total high-quality unique variants, variants were located in the protein-coding regions while variants mapped to either downstream or upstream regions. of the total variants in protein-coding regions, variants were non-synonymous, were synonymous, and variants resulted in stopgain mutation. these two stopgain variants were found in orf a ( :g>t) and orf ( :g>a) genes and were present in one individual each. the annotation of the variants based on the location and consequence is represented in figure . the phylogenetic tree was constructed using the genome wuhan/wh (epi_isl_ ) as root and genomes from india which met the inclusion criteria (ns < %, no missing/ambiguous date of sample collection) including genomes sequenced in this study. all genomes from this study were found to cluster under the globally predominant clade a a (gisaid clade g and gh). in contrast, one of the previous genomes available from kerala (epi_isl_ , submitted by national institute of virology, pune, india), which is also one of the first sars-cov- genomes sequenced in india, belongs to the clade b [ ] . haplotype analysis was done using a dataset of sars-cov- genomes from india (including genomes from kerala) that fell under clade a a in the phylogenetic tree and clustered close to the genomes from kerala. among the genomes, there were variable sites and unique haplotypes supplementary figure summarizes the haplotype network of the a a clade genomes. may) for the three major haplogroups k , k , and k respectively. taken together, the analysis suggests that the majority of the sars-cov- isolates are outcomes of limited introductions early in the epidemic followed by local circulation. annotating the variants for their functional consequences using custom annotation datasets, revealed a total of genetic variants that were predicted as deleterious by sift [ ] . the filtered variants were found to span unique protein domains as per uniprot [ ] annotations. we found and genetic variants that mapped back to potential b and t cell epitopes from the immune epitope database (iedb) [ ] respectively. in addition, variants were found to span predicted error-prone sites including sequencing error sites, homoplasic positions, and hypermutable sites. functional annotation details of all the filtered variants are summarised in supplementary table . we also explored whether the variants mapped to the rt-pcr primers and probes sites. on mapping the genetic variants with the curated primers and probes, we found unique variants at unique primer or probes binding sites. a total of four unique variants had allele frequency > % at unique primer binding sites. summary of novel variants and diagnostic primer/probe spanning variants are compiled in table and table respectively. details on the read count and depth of coverage of these variants are systematically documented in supplementary table .a and . b . with the view of identifying potential functionally relevant variants, we overlapped the variants obtained from the present study with a manually curated compilation of functionally relevant sars-cov- variants. our analysis identified variants in the s gene which were reported to be associated with increased infectivity. l f, a variation co-occurring with d g was earlier demonstrated to possess increased infectivity [ , ] using cell line studies. in our study, a>g (d g) and c>t (l f) mutations were observed at frequencies of . % and . % respectively in the genomes. the combination of these variations was found to occur at a higher frequency in genomes from kerala. [ ] and therefore leaves the mutational fingerprint which is widely used for tracing the spread of the virus [ ] . the availability of high-throughput sequencing approaches has enabled researchers to sequence genomes as the pandemic progressed in their respective countries. a number of methods have been adopted for rapid high throughput sequencing of sars-cov- including shotgun sequencing [ ] , pcr amplicon, and hybridization/capture-based enrichment and sequencing [ ] [ ] [ ] . genome sequencing of sars-cov- in various countries [ ] has led to to insights into the temporal and geographical spread of the virus [ ] , introductions, and spread of the virus through travelers [ , ] , local transmission, and dynamics [ ] , investigating the origin of outbreaks [ ] , just to name a few. by virtue of its connectivity to major cities through its expatriate population, trade and tourism is uniquely poised in this pandemic. it is not surprising therefore that the first case of covid- in india, early in the pandemic, was reported from the state [ , ] . the genome of the isolate suggested it originated from china [ ] . the following months have seen the number of cases increase to over thousand in the state with a paucity of information on the origin, spread, and dynamics of the virus [ https://dashboard.kerala.gov.in/ ]. in this present study, we performed sequencing and analysis of sars-cov- isolates from kerala which revealed unique patterns of the transmission. these genomes are clustered into a monophyletic group mapping to the a a clade. the a a clade is also marked by the d g variant, which is suggested to confer higher infectivity to the virus in experimental in vitro settings [ , ] and is therefore thought to have emerged globally as the predominant clade [ ] , though the cause-effect relationship still remains speculative. haplotype analysis suggests that three major haplogroups with distinct ancestry groups encompass the majority of the isolates. the haplotype analysis in the context of other genomes from india suggests the introductions were from inter-state travel. the prevalent haplotypes were not found in any of the global genomes, supporting this observation. this also suggests that focussed testing, tracing and quarantine of expatriates and international travelers implemented during the epidemic would have been effective in curbing the spread from international travelers. the genome clusters also suggested polytomies, suggesting a recent outbreak [ ] . close follow-up of the cluster members confirmed the potential source of the outbreak, suggesting genetic epidemiology could be used in conjunction with case follow-ups to uncover potential outbreaks and possibly connect outbreaks which are apparently not related. this study uncovered a total of novel genetic variants and variants which were identified only in kerala and not in the rest of india. the genome sequences could also uncover insights into the variants of functional relevance. one of the variants of significance is a stopgain variant ( :g>a) in the orf gene. variants including deletions in orf have been suggested to attenuate the virus [ , ] . similar variants have also been identified in other related viruses like the sars-cov and mers-cov [ , ] . a variant c>t (l f) in the s gene associated with increased infectivity of the virus [ ] was present in . % of the genomes sequenced. following recent reports which suggest variants in the primer/probe binding sites could impact the efficiency of rt-pcr assays [ , , ] , we explored whether any of the variants in the present study mapped to the primer/probe binding sites. we identified unique variants in unique binding sites. the maximum number of variants were the primer set published by won et al. [ ] spanning multiple genes, apart from the -ncov-nfp ggggaacttctcctgctagaat binding sites in the n gene [ https://www.who.int/docs/default-source/coronaviruse/whoinhouseassays.pdf?sfvrsn=de a aa_ ]. the latter is part of the china centers for disease control and prevention (cdc) protocol with variants in . % in genomes from kerala. we have earlier reported variants in this primer site in . % of the genomes from india [ ] and . % [ ] of global genomes. this information would be potentially valuable for laboratories in selecting reagents for screening and diagnosis. the study has two caveats; first is that the samples were collected from a single major tertiary care center in north kerala. however, the center caters to a large population and region and has close proximity to an international airport. secondly, the sampling was limited to a short period of time, thus enabling only a cross-sectional view of the epidemic and precluding an accurate and temporal view of the dynamics of the epidemic in the state. nevertheless, this provides a unique opportunity to create a snapshot of the epidemic in time and space. notwithstanding the limitations, this is the first and most comprehensive overview of the genetic epidemiology of sars-cov- in the state of kerala. while providing insights into the epidemiology of the epidemic, the study also enabled tracing outbreaks thereby highlighting the utility of genome sequencing as an adjunct to high-throughput screening and testing. it has not escaped our mind that scalable technologies that can combine both the approaches [ ] could potentially find a place in understanding epidemics better. a new coronavirus associated with human respiratory disease in china evolutionary history, potential intermediate animal host, and cross-species analyses of sars-cov- global initiative on sharing all influenza data -from vision to reality rapid implementation of sars-cov- sequencing to investigate cases of health-care associated covid- : a 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assist genomic epidemiology interactive tree of life (itol) v : recent updates and new developments recent developments in the mafft multiple sequence alignment program issues with sars-cov- sequencing data dnasp : dna sequence polymorphism analysis of large data sets tcs: a computer program to estimate gene genealogies popart : full-feature software for haplotype network construction bayesian phylogenetic and phylodynamic data integration using beast . posterior summarization in bayesian phylogenetics using tracer . hybridization of synthetic oligodeoxyribonucleotides to phi chi dna: the effect of single base pair mismatch sift: predicting amino acid changes that affect protein function uniprot: the universal protein knowledgebase the immune epitope database (iedb): update the impact of mutations in sars-cov- spike on viral infectivity and antigenicity genome-wide analysis of sars-cov- virus strains circulating worldwide implicates heterogeneity. sci rep cog-uk) consortiumcontact@cogconsortium.uk. an integrated national scale sars-cov- genomic surveillance network geographical and temporal distribution of sars-cov- clades in the who european region rapid sars-cov- whole-genome sequencing and analysis for informed public health decision-making in the netherlands whole genome and phylogenetic analysis of two sars-cov- strains isolated in italy in genomic epidemiology of sars-cov- in guangdong province clinical features of patients infected with novel coronavirus in wuhan the d g mutation in the sars-cov- spike protein reduces s shedding and increases infectivity d g mutation of sars-cov- spike protein enhances viral infectivity. microbiology. biorxiv; identification of unique mutations in sars-cov- strains isolated from india suggests its attenuated pathotype biorxiv effects of a major deletion in the sars-cov- genome on the severity of infection and the inflammatory response: an observational cohort study deletion variants of middle east respiratory syndrome coronavirus from humans newly emerging mutations in the matrix genes of the human influenza a(h n )pdm and a(h n ) viruses reduce the detection sensitivity of real-time reverse transcription-pcr the impact of primer and probe-template mismatches on the sensitivity of pandemic influenza a/h n / virus detection by real-time rt-pcr development of a laboratory-safe and low-cost detection protocol for sars-cov- of the coronavirus disease (covid- ) presence of mismatches between diagnostic pcr assays and coronavirus sars-cov- genome authors thank anjali bajaj for editorial assistance. aj, md, bj acknowledge research fellowships from csir. ds acknowledges a research fellowship from intel. authors acknowledge funding for the work from the council of scientific and industrial research (csir), india through grants codest and mlp . the funders had no role in the design of experiment, analysis, or decision to publish . supplementary table : gisaid acknowledgment table for global genomes used in the study supplementary table : gisaid acknowledgment table for genomes from india considered for phylogenetic analysis supplementary table : data summary of the samples sequenced by covidseq protocol and processed using a custom pipeline. table . summary of quality details of the variants identified in the study key: cord- -fn o id authors: kotian, rahul p; faujdar, disha; kotian, sneha p; d’souza, brayal title: knowledge and understanding among medical imaging professionals in india during the rapid rise of the covid- pandemic date: - - journal: health technol (berl) doi: . /s - - - sha: doc_id: cord_uid: fn o id during the first week of march, the surge of coronavirus disease (covid- ) cases reached all over the globe with more than , cases. healthcare national and international authorities have already initiated awareness and lockdown activities. a poor understanding of the disease among medical imaging professionals (mips) may result in rapid spread of infection. this study aimed to investigate the knowledge and understanding of mips about covid- . a cross-sectional, web-based study was conducted among mips about covid- during the fourth week of march . an online sample of mips was successfully recruited via the authors’ networks in india using data collection tool – write google forms. a self-developed online kap questionnaire was completed by the participants. the knowledge and understanding questionnaire consisted questions regarding the clinical characteristics and transmission routes of covid- . assessment on practices towards covid- included questions on techniques while imaging against covid- suspected patients. of participants, a total of mips completed the survey (response rate: . %); . % were males, . . % were aged – years, and most were undergraduates ( . %) and postgraduates ( . %). regarding covid- , most of the participants answered correctly ( . %) on symptoms, ( . %) time interval for visible symptoms, ( . %) transmission and ( %) airborne transmission respectively. a significant proportion of mips ( . %) had poor knowledge about wearing multiple masks as an effective measure against coronavirus infection. most of the respondents ( . %) incorrectly considered x-ray as the reliable method of diagnosis for suspected covid- patients. . % of the respondents lacked knowledge about the steps involved in hand washing technique which is one of the most important safety practice methods in medical imaging to prevent spread of infection. factors such as age and occupation were associated with inadequate knowledge and poor perception of covid- . as the current global threat of covid- continues to emerge, it is crucial and critical to improve the knowledge and understanding of mips. educational videos and live webinars are urgently needed to reach mips and further detailed studies are the need of the hour. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. coronavirus disease (abbreviated "covid- ") is a life threatening respiratory disease caused by a novel coronavirus and was first detected in december in china. the disease is considered highly infectious, with clinical symptoms of fever, dry cough, fatigue, dyspnea and myalgia. in india, approximately patients were tested positive with covid- by the first week of april, and deaths reported. clinical data have shown that the overall death rate of covid- is between . % to . % in india, much lower than those of sars ( . %), mers ( . %), and h n ( . %) ( ) ( ) ( ) ( ) . the covid- was declared pandemic on march th by who and by then had inflicted countries and caused deaths. the world health organization immediately responded to this serious situation and declared it as a public health emergency of international concern on january and requested for collaborative efforts of all countries in the world to prevent the rapid spread of covid- ( ) . india, has also been seriously hit by the covid- pandemic. some unprecedented measures have been adopted by our prime minister shri narendra modi to control the covid- transmission in india including complete lockdown with stay at home policy in the country from march rd, till april , . the fierce battle against covid- is still a matter of major concern in india. to guarantee the final success, adherence to these control measures by the medical imaging healthcare providers are essential, which is largely affected by their knowledge, attitudes, and practices (kap) towards covid- in accordance with kap theory because imaging diagnosis is the second step for covid- confirmation after blood test. lessons learned from the sars outbreak in suggest that knowledge and attitudes towards infectious diseases is of utmost importance which can further complicate attempts to prevent the spread of the disease ( ) . to facilitate outbreak management of covid- in india, there is an urgent need to understand that the medical imaging professionals (mips) awareness of covid- at this critical moment. in this study, we investigated the kap towards covid- of mips during the rapid rise period of the covid- outbreak. an online cross-sectional survey during the rapid rise period of the covid- outbreak was used to assess the knowledge and understanding among mips on covid- in india between march , to april , , the second week after the national lockdown. this was an online survey as it was not convenient and feasible to do a community-based national sampling survey due to the global emergency. the questionnaire were sent to participants via google forms, the identity of the contributors were kept anonymous. the minimum eligibility to participate in the survey was that the respondents were from the medical imaging fraternity. the questionnaire used in the present study was formed by referring information about covid- on website of world health organization, centre for disease control and prevention (cdc), expert discussion and their opinion. the questionnaire was then given to five experts in the field of medical imaging, public health and community medicine with more than five years of experience for content validity. confidentiality of the study participants' information was maintained throughout the study by making the participants' information anonymous. an informed consent was obtained from each participant prior to participation. the data collection was done between st march to th april . the questionnaire was administered after by government of india had declared the lockdown. the details of the study was provided to the participants before beginning the survey. the questionnaire was administered in english language. the questionnaire consisted of items to assess their knowledge and attitudes of covid- which took approximately min to complete. the questionnaire consisted of two parts namely: demographics and kap. demographic variables included age, gender, education and occupation. the overall questionnaire had questions (table ) : regarding clinical presentations, regarding transmission routes and regarding prevention and control during medical imaging procedures of covid- . attitudes towards covid- were assessed through questions about training and safe use of personal protective equipment. the assessment of practices were through questions on various imaging procedures. these questions were answered on a multiple choice option, true/false basis with an additional "not so sure" option. the data analysis was done using descriptive statistics of mean & sd for continuous variables and for disc rete variables frequency and percentage was used. the responses obtained in the study was analysed using spss . . a total of mips were requested to participate in the study by sending questionnaire through e-mails and social media whatsapp application and responded (response rate . %). majority of them ( . %) had undergraduate qualification in medical imaging, . % had postgraduate qualification in medical imaging, . % had diploma in medical imaging, . % had distance education in medical imaging and . % had phd in medical imaging. a total of participants completed the survey questionnaire. among this final sample, the average age was . years (standard deviation [sd]: . , ( . %) were men and ( . %) were women. other demographic characteristics are shown in table . most of the respondents answered correctly on ( . %) symptoms, ( . %) time interval for visible symptoms, ( . %) transmission however it was low for airborne transmission respectively ( %). most of the respondents ( . %) wrongly considered wearing multiple masks as an effective measure against coronavirus infection. the ideal distance to be maintained from a person infected with covid- was rightly answered by only ( . %) of the respondents. when it came to steps involved in handwashing, it was observed that only . % respondents were fully aware about this technique. most of the respondents ( . %) incorrectly considered x-ray as the reliable method of diagnosis for suspected covid- patients. about ( . %) of the respondents were also aware about infection control at the radiology department after imaging suspected covid- patients. the most preferred investigation of choice for covid- suspected patients as portable x-ray was answered only by ( . %) mips. majority of respondents ( . %) considered computed tomography as the preferred investigation for covid- suspected patients. while analysing questions pertaining to attitude of medical imaging professionals, it was found that in majority ( . %) underwent training for the safe use of personal protective equipment (ppe). the questions regarding practices followed by the imaging professionals on considering air-exchange rate in imaging rooms, after scanning a suspected covid- patient was unclear with respondents having mixed responses ( . %) min, ( . %) min, ( . %) and ( . %) hour respectively. the right answer was one hour of air exchange after imaging suspected covid- patients. while analysing question pertaining to awareness about two radiographers using the 'one clean, one in contact with patient system ( . %) were aware about this technique. interestingly, it was observed that ( . %) respondents were aware about the use of lead gown before wearing the ppe. lastly, ( . %) respondents were very well aware about the necessary steps to limit covid- transmission. the detailed summary of the results are depicted in table to the best of our knowledge, this is the first study in india examining the kap towards covid- among mips. currently, covid- is a topic of global discussion in the media and among the public, especially among mips and patients. with the current case surge of covid- transmission raising tensions for everyone, including health officials and national health systems, an important question arises regarding how to disseminate information to help frontline mips in times of public health crisis. for this reason, we investigated their knowledge and understanding on the precautions and control of covid- during a global epidemic. the finding of a high correct rate of covid- knowledge in mips was unexpected, because this epidemiological survey was conducted during the very early stage-ii of the pandemic. we consider that this is primarily due to the sample characteristics: . % of the study respondents held an bachelor's degree and . % of the respondents held a postgraduate degree. because of the serious situation of the pandemic and the overwhelming news reports on this public health emergency, this population would actively learn knowledge of this infectious disease from various tv and news channels and the official website of the national health commission of india. the levels of education and covid- knowledge scores supports this speculation. however when it came to questions pertaining to practices during medical imaging procedures of suspected covid- patients, most of the mips have insufficient knowledge about dealing with covid- suspected patients and managing the radiology imaging room. interestingly, as most of the respondents answered correctly about the symptoms of covid- , majority of the respondents % answered incorrectly about the airborne transmission of covid- virus. the coronavirus infection can be transmitted through small droplets from nose or mouth of an infected covid- individual and this might have caused confusion among the respondents about its airborne transmission route. the findings about lack of knowledge about steps involved in hand washing technique was a vital finding of this study and needs to be corrected immediately if we want to contain the spread of covid- infection in india as mips are the first line healthcare providers. . % of the respondents lacked knowledge about the steps involved in hand washing technique which is one of the most important safety practice methods in medical imaging to prevent spread of infection. blood test is the first and most reliable method of diagnosis for suspected covid- patients. however, x-ray investigation can only be used as a supplementary measure for confirming covid- . majority of the respondents . % wrongly answered that x-ray can be regarded as the reliable method of diagnosis for suspected covid- patients. the preferred imaging modality of choice to screen a suspected covid- patient is portable x-ray because it is easy to follow infection control measures and the radiology imaging room will also not be contaminated. it is also easy to disinfect and clean the portable x-ray unit and the isolated room where the imaging procedure was done. however, most of the respondents . % considered computed tomography (ct) scan as the preferred modality in order to screen a suspected patient for covid- . ct may provide the following vital findings in covid- positive cases: ground glass opacities in the lungs, air space consolidation, crazy paving appearance and broncho-vascular thickening in the lesion ( ) ( ) ( ) ( ) . hence, we presume that the respondents might have gone through these studies and hence they considered were also unaware about two radiographers using the 'one clean, one in contact with patient' system while imaging suspected covid- patient. the strength of this study lies in its large sample recruited during a critical period, the early stage of the covid- outbreak in a given allied health speciality. given the significant associations between these demographic variables and kap towards covid- revealed in this study, we may have overestimated knowledge and rates of preventive practices and underestimated rates of positive attitudes towards covid- of mips. the present study was conducted in a standardized manner. the authors used a questionnaire which was developed through stages of item development, content validation and test-retest reliability. however, the study had few inadvertent limitations. to improve response rate, the number of questions were kept limited. hence, the knowledge, attitude and practice of the mips cannot be fully determined. in addition, the data presented in this study are selfreported and partly dependent on the participants' honesty and recall ability; thus, they may be subject to recall bias. there may be a responder bias as only respondents who have better knowledge of covid- may have responded. finally, due to the four-week closure of higher educational institutions in india during the covid- outbreak, the institutional review board was not approached. despite these limitations, the present study provides vital information about the knowledge and understanding of medical imaging professionals during the rapid rise period of covid- . in summary, our findings suggest that mips, have poor knowledge, attitudes, and appropriate practices towards covid- during the rapid rise period of the covid- outbreak. however, the mips had good knowledge about the symptoms and general awareness on covid- . hopefully, under the combined efforts of indian authorities and all indian residents, india surely will win the battle against covid- in the near future. epidemiological and clinical characteristics of cases of novel coronavirus pneumonia in wuhan, china: a descriptive study a novel coronavirus emerging in china -key questions for impact assessment knowledge, attitudes, and practices towards covid- among chinese residents during the rapid rise period of the covid- outbreak: a quick online cross-sectional survey novel coronavirus pneumonia emergency response epidemiology team. [the epidemiological characteristics of an outbreak of novel coronavirus diseases (covid- ) fahmi #covid coronavirus disease national center for inectious diseases/sars community outreach team b, et al. fear and stigma: the epidemic within the sars outbreak radiological findings from patients with covid- pneumonia in wuhan, china: a descriptive study time course of lung changes on chest ct during recovery from novel coronavirus (covid- ) pneumonia clinical characteristics of hospitalized patients with novel coronavirus-infected pneumonia in wuhan, china covid- pneumonia: what has ct taught us? lancet infect dis acknowledgements the authors thank all the medical imaging professionals involved in this study for their cooperation and support.availability of data and material the datasets used and/or analysed during the current study is made available by the corresponding author and attached in the supplementary files. health technol.authors' contributions rk conceptualized the study. df and spk have given inputs in study design. rk and df collected the data. rk analysed the data and wrote the first draft of manuscript and all co-authors contributed in critical review of data analysis and manuscript writing. rk will act as guarantor for this paper. ethics approval and consent to participate the study protocol followed was reviewed and approved by the research committee of srinivas university telephonically and approved online. the consent to participate approval was also taken.ehical approval reference number not applicable. a detailed explanation about the study was given by the principal investigator after which they provided consent for publication. all the patients included in this research gave written informed consent to publish the data contained within this study.competing interests the authors declare that they have no competing interests in this study. the authors declare that they have no competing of interests. key: cord- - ngcwdln authors: laxminarayan, ramanan; jameel, shahid; sarkar, swarup title: india’s battle against covid- : progress and challenges date: - - journal: am j trop med hyg doi: . /ajtmh. - sha: doc_id: cord_uid: ngcwdln india's battle against covid- : progress and challenges. india was fortunate not to be among the first countries hit by covid- . the first reported case of infection with the sars-cov- , the virus that causes covid- , in india was reported on january , in an indian student evacuated from wuhan, and the first death was reported on march , . although it is possible that the sars-cov- was circulating in india earlier, the first known secondary transmission of the virus within india was reported only in early march. even when the case load was low, india was predicted to be at high risk for covid- for a number of reasons. a dense population, especially in urban settings, could exacerbate the spread of sars-cov- . the indian population has high rates of uncontrolled hypertension and diabetes, both of which have been shown to be risk factors for severe covid- and mortality. although children were found less likely to be infected in china and other countries, it was unclear how children in india, who have high levels of stunting and early exposure to infections, would fare against sars-cov- . on the plus side, it was hypothesized that india's relatively young population- % of india's population is younger than years, and only % is older than years-would be spared high mortality from a disease that targets the elderly. in comparison, % of the population of italy and % of that of china are older than years. how did india respond and how has it fared? the indian government responded to covid- with temperature screening of incoming passengers on flights from east asia. large public events, including one to greet u.s. president donald trump, were held as late as february , although disease transmission was well underway in europe at that time. on march , a national lockdown was announced with hours' notice. although a state-level or more localized lockdown would have been preferable, the precise locations of disease hotspots were unknown because of low levels of testing. the sudden lockdown imposed a significant burden on the urban poor and migrants, who found themselves both out of work and with no means to return to their villages. at the time of the lockdown, india had officially counted about cases of covid- and deaths because of the contagion. the lockdown represented a law-and-order solution to a problem for which india was poorly equipped from a public health standpoint. at that time, india had approximately . million hospital beds, , intensive care unit (icu) beds, and , ventilators, against a need of , icu beds under an optimistic scenario of covid- burden. the lockdown was essential to buy time to prepare for the eventual flood of cases. model-based estimates produced in march had indicated that a national lockdown could reduce the number of infections at the peak of the pandemic-expected in early may-by - %, depending on the degree of public compliance with physical distancing. these projections estimated that, in the absence of any intervention, india could expect to see - % of its urban population infected in a first wave. , at an overall mortality rate of %, the death toll could climb to hundreds of thousands, if not higher. by all accounts, the national lockdown was tightly enforced and has been described as one of the harshest in the world. since late june, the lockdown has been lifted in stages and has transitioned to state-level lockdowns that have been largely reactive to local caseloads at any given time. some form of restrictions on movement exists in most states. however, universal adherence to masking and social distancing has been difficult to enforce, and compliance has varied across states and districts. physical distancing is not practicable in many lowincome communities where there is significant crowding both within households and in public spaces. as of august, schools, colleges, movie theaters, places of worship, and most other places of mass gathering remain closed. the future outlook for reopening is unclear at this time. caseloads and deaths are now increasing at the fastest rate of any large country, and india currently records more than covid- deaths every day (figures and ). as of august , , india was third in the world in the number of reported sars-cov- infections ( , , ) and fourth in the number of reported covid- deaths ( , ). both infections and deaths are likely underestimated because of the low levels of testing in india. mortality rates (based on reported cases and deaths) appear to be low in india, as they are in most countries in the region, perhaps indicative of both limited testing and other unexplained factors. india was slow to provide testing despite significant capacity for reverse transcription-polymerase chain reaction (rt-pcr) testing in both public and private laboratories. testing in the early days of the epidemic was limited to a few public laboratories. private laboratories, which typically provide the bulk of pathology services, were not allowed to test at all. the restriction was not only ostensibly to maintain quality but presumably also to control information. testing for covid- in india continues to rank among the lowest in the world on a per-capita basis. testing rose from , tests per day on march , (approximately per million population) to more than , per day ( per million) in august (figure ), although much of this increase was due to the introduction of rapid antigen tests that have far lower sensitivity than rt-pcr. at the current time, india has conducted approximately , tests per million population, a rate that is a third that of south africa, about % that of nepal, and among the lowest of any large country. testing rates have been highly variable across states. daily testing in delhi, the capital city, was around per million at the end of july, comparable to that in the united states, but rates elsewhere were much lower. as of august , the state of bihar was conducting just , tests per day, for a population of million ( per million). the low level of testing nationally has likely led to a large number of infections being missed. as a consequence, reported infections in india are likely indicative of only a small proportion of the total infections. according to a serological study based on , samples conducted by india's national cdc from june to july , % of the population of delhi had been infected. the number of seropositives-roughly . million-was approximately times greater than the reported cumulative number of infections in delhi, indicating that a large number of infections were likely missed by the testing process. another unpublished seroprevalence study conducted in mumbai in early july indicated that % of those living in slums had antibodies to sars-cov- , compared with % of those residing in other parts of the city. unpublished data from the indian council of medical research indicated that million people ( . % of the indian population) had been infected through early may, at a time when fewer than , cumulative infections had been reported. similar undercounts by a factor of - have been uncovered by comparing seroprevalence data with reported infection data. an important caveat is that the seroprevalence data have yet been published in the peer-reviewed literature. despite the size of the covid- problem, there has been limited published epidemiological or clinical research emerging from india. preliminary data from comprehensive surveillance in the indian states of tamil nadu and andhra pradesh (home to ∼ million people) from a cohort of , index cases and , contacts found that the risk of transmission from an index case to a close contact ranged from . % in the community to . % in the household; these results did not differ with respect to the age of the index case. this finding indicated an important role for children and young adults in transmission, with a third of infected individuals younger than years. early analysis from this contact-tracing dataset, which represents one of the largest prospective studies of infections among exposed individuals to date, found that superspreading events were the rule, rather than the exception. prospective follow-up testing of exposures revealed that % of infected individuals did not infect any of their contacts, whereas % accounted for % of observed new infections. unlike in high-income countries, where deaths are mostly in the age-group older than years, covid- -related deaths were concentrated at ages - years, and the incidence of reported cases did not increase with older age. strikingly, these differences cannot be fully accounted for by differences in population age distributions. contrary to the long hospital stays reported in high-income settings, the median time to death was days following admission. the study also found substantial reductions in the reproduction number associated with the implementation of india's countrywide lockdown. india is a large country, and it does not face a single homogenous epidemic. currently, % of cases are reported from < % of its districts. the epidemic is in different stages in different parts of the country, but the response has been driven by a national, overarching centralized strategy instead of being locally owned. although opportunities for containment of infections are limited, given the tremendous economic and human cost of lockdowns, a number of measures could help reduce the mortality rate and facilitate a quicker exit from the pandemic. . an important aspect of covid- management is averting deaths. the current national guidelines do not prioritize high-risk individuals for early testing, and this is a missed opportunity for averting deaths in vulnerable populations of the elderly and those with comorbidities. . reporting of deaths is incomplete, and because many individuals die without a covid- test, the number of reported deaths is likely an underestimate of the true numbers. identification of deaths offers an opportunity to learn about the disease and, thereby, prevent future cases and deaths. a formal system of mortality surveillance, specifically to measure the additional mortality attributable to covid- , needs to be put in place. . the epidemic response should be data driven and locally owned. more granular data and greater openness to data sharing and coordination would enable surveillance data to be used for management decisions, including planning regarding personal protective equipment, medicines, supplies, and, most importantly, icu capacity and healthcare personnel. this would provide a clear picture of the impact of covid- to the public and could encourage greater compliance with personal protection and distancing. . nongovernmental organizations and civil society have been largely missing from the response to the pandemic and should be involved in helping mitigate the continued effects of the lockdown and enabling access to health care. should be updated rapidly, consistent with global research findings, and communicated clearly to clinicians. despite national guidelines, there is confusion about how best to care for patients at home with asymptomatic infection, in hospital with mild-to-moderate disease, with serious disease requiring high flow oxygen, and with severe disease requiring mechanical ventilation. . india is now in a season during which other diseases including dengue, chikungunya, malaria, and seasonal influenza have symptoms that are similar to those of covid- . as these diseases are likely to have overlapping spread in the country, a clinical and testing strategy to enable distinction between the diseases is needed. the covid- pandemic is an opportunity to invest in the public health infrastructure of india, an area of systemic neglect over the past few decades. in the short-to-medium term, developing protocols for clinical trials to investigate candidate vaccines, drugs, and monoclonal antibodies against sars-cov- infection will be critical to ensure optimal preventive and therapeutic management of the disease, particularly to protect those at high risk of death. in the long term, a blueprint should be developed to empower and strengthen india's national and state level mechanisms for public health research, surveillance, and policy activities. as was the case in other countries, india's pandemic preparedness plan was largely abandoned in the face of a real pandemic. the response to covid- has been driven by political priorities rather than by public health and epidemiological expertise. given the country's size and its large global diaspora, india's battle with covid- will play a large role in the fate of the pandemic. as the world's largest vaccine producer, india will likely be a major supplier of vaccines against covid- , if and when they are approved. the country's largest vaccine manufacturers are gearing up to produce covid- vaccines at scales that have not been attempted before. if india's vaccine industry is successful, then it will help ensure that these vaccines will be available not only to those who can pay for them but also to the hundreds of millions of impoverished people in india and in other low-and middle-income countries who need a vaccine. india stands at a critical juncture. although covid- is exacting a significant health and economic impact on the country, it offers an opportunity to rethink india's approach to public health. if done correctly, the legacy of covid- could be a much needed public investment in health, a wellequipped workforce to respond to future pandemics, and system capacity for surveillance, contact tracing, research, disease modeling, and response. emerging trends in hypertension epidemiology in india government survey found . % prevalence of diabetes in india epidemiological characteristics of pediatric patients with coronavirus disease in china risks to children under-five in india from covid- . medrxiv coronavirus in india: modi orders total lockdown of days. the new york times state-wise shutdowns may be only way to prepare for spike in covid- jopinion. india news, hindustan times statewise estimates of current hospital beds, intensive care unit (icu) beds and ventilators in india: are we prepared for a surge in covid- hospitalizations? medrxiv covid- in india: potential impact of the lockdown and other longer-term policies. center for disease dynamics prudent public health intervention strategies to control the coronavirus disease transmission in india: a mathematical modelbased approach oxford covid- government response tracker coronavirus cases coronavirus: india is turning to faster tests to meet targets sero-prevalence study conducted by national center for disease control ncdc, mohfw the hindu, . coronavirusj % of mumbai slum population has developed antibodies: study. the hindu. available at just . % of people exposed, but india still susceptible to covid epidemiology and transmission dynamics of covid- in two indian states. medrxiv incidence, clinical outcomes, and transmission dynamics of severe coronavirus disease in california and washington: prospective cohort study the indian council of medical research (icmr), . icmr press statement tracking covid- mortality in india, where deaths aren't registered properly. the wire science covid- and dengue fever: a dangerous combination for the health system in brazil the pandemic pipeline this is an open-access article distributed under the terms of the creative commons attribution (cc-by) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. key: cord- - x k authors: cilloni, lucia; fu, han; vesga, juan f; dowdy, david; pretorius, carel; ahmedov, sevim; nair, sreenivas a.; mosneaga, andrei; masini, enos; sahu, suvanand; arinaminpathy, nimalan title: the potential impact of the covid- pandemic on the tuberculosis epidemic a modelling analysis date: - - journal: eclinicalmedicine doi: . /j.eclinm. . sha: doc_id: cord_uid: x k background: routine services for tuberculosis (tb) are being disrupted by stringent lockdowns against the novel sars-cov- virus. we sought to estimate the potential long-term epidemiological impact of such disruptions on tb burden in high-burden countries, and how this negative impact could be mitigated. methods: we adapted mathematical models of tb transmission in three high-burden countries (india, kenya and ukraine) to incorporate lockdown-associated disruptions in the tb care cascade. the anticipated level of disruption reflected consensus from a rapid expert consultation. we modelled the impact of these disruptions on tb incidence and mortality over the next five years, and also considered potential interventions to curtail this impact. findings: even temporary disruptions can cause long-term increases in tb incidence and mortality. if lockdown-related disruptions cause a temporary % reduction in tb transmission, we estimated that a -month suspension of tb services, followed by months to restore to normal, would cause, over the next years, an additional ⋅ million tb cases (crl ⋅ – ⋅ ) and , tb deaths (cri – thousand) in india, , ( , – , ) tb cases and , deaths ( . – . thousand) in kenya, and , ( – , ) cases and , deaths ( – , ) in ukraine. the principal driver of these adverse impacts is the accumulation of undetected tb during a lockdown. we demonstrate how long term increases in tb burden could be averted in the short term through supplementary “catch-up” tb case detection and treatment, once restrictions are eased. interpretation: lockdown-related disruptions can cause long-lasting increases in tb burden, but these negative effects can be mitigated with rapid restoration of tb services, and targeted interventions that are implemented as soon as restrictions are lifted. funding: usaid and stop tb partnership the emergence of the novel virus sars-cov- has caused morbidity, mortality and societal disruption on a global scale. in the absence of pharmaceutical interventions, many countries have resorted to population-wide lockdowns to slow the spread of the virus and to allow their health systems to cope [ ] . these lockdowns have had an important effect on sars-cov- transmission [ , ] . however, unintended consequences are inevitable with such sweeping measures. in low-and middle-income countries with health systems already under strain, the adverse effects of disruptions in health services (for example, ongoing transmission of infectious diseases) can last far beyond the period of the disruptions themselves [ À ] . in the present study we focus on tuberculosis (tb) -globally, the leading cause of death due to an infectious disease [ ] . in recent decades tb incidence and mortality have been steadily declining, reflecting ongoing improvements in diagnosis, treatment and prevention [ ] . however, in march a rapid analysis conducted by the stop tb partnership brought attention to severe impacts of covid-related lockdowns on tb care in different countries [ ] . for example, in the weeks following the imposition of a nationwide lockdown on march , , india reported an % drop in daily notifications of tb [ ] relative to average pre-lockdown levels. similar changes have been reported elsewhere, for example with south africa reporting a drop in numbers tested for tb by almost a half [ ] . such declines may be partly due to delays in reporting but are also likely to reflect reductions in access to diagnosis and treatment, potentially having a lasting impact on tb burden at a country-wide level. missed diagnoses would mean increased opportunities for transmission, while worsened treatment outcomes increase the risk of death from tb. therefore, while lockdowns are an important measure to mitigate the immediate impact of covid- , it is critical to anticipate (i) the potential long-term impact of these measures on tb and other diseases, and (ii) how this impact might be stemmed, in the short term, by appropriately targeted investment and effort. we therefore aimed to examine these questions using mathematical modelling of tb transmission dynamics. building on earlier modelling conducted for the lancet commission on tuberculosis [ , ] , we modelled the potential tb-related impact of covid-related lockdowns -and mitigating effects of potential post-lockdown interventions -in three focal countries: india, the republic of kenya, and ukraine. it is not possible to predict the extent or depth of lockdowns in any given country, let alone their impact on tb services. therefore, the primary purpose of our analysis is not to predict future tb trajectories, but rather to identify the critical drivers through which a lockdown can lead to elevated tb incidence and mortality, and to apply these insights to understand how best mitigate the long-term adverse impact of any lockdown-related disruptions. for each country we drew from previously published models of m. tuberculosis transmission [ ] , which were designed to capture essential features of the tb care cascade. for the current analysis, this approach allowed us to model the impact of disruptions acting at multiple points in the care cascade. the three country settings offer examples of contrasting types of tb care cascade: for india we incorporated the dominant role of the private healthcare sector in providing tb care; [ ] for kenya, the role of hiv in driving tb dynamics; [ ] and for ukraine, the burden of drug resistance [ ] . the overall model structure is illustrated schematically in fig. s in the appendix. as noted above, the purpose of the analysis was not to predict tb trajectories in these three countries, but rather to examine the importance of different types of disruptions (i.e. acting at different stages of the tb care cascade), thus providing insights that could be relevant to other high-burden countries sharing similar characteristics. we calibrated each country model to the available data on tb burden, including who estimates of tb incidence and mortality [ ] , and on the burden of drug resistance (see table s ). full details of each model are provided in the supporting information. calibration was performed using markov chain monte carlo (mcmc) simulation [ À ], whereby we allowed model parameters to vary over pre-specified prior distributions, using a likelihood function based on the calibration targets listed above to weight simulations according to their fit to the observed data. for each country, we drew samples from the weighted (posterior) density of simulations following burn-in and thinning as described in the supporting information. we then performed model projections on the basis of each of these samples, under the lockdown scenarios described below. for any model projection (for example, incidence over time), we estimated bayesian credible intervals as Á th and Á th percentiles, and central estimates as th percentiles, of the corresponding posterior density. disruptions to tb services can act at all stages of the tb care cascade. during a lockdown, movement restrictions would curtail opportunities for those experiencing tb symptoms to seek care. even once these people are able to visit a provider or health facility, the diagnostic and laboratory capacity needed to support tb diagnosis may be severely reduced À for example, with molecular diagnostic tools for tb being repurposed for covid- [ ] or tb laboratory staff being redirected to covid- efforts. national tb programmes are investing significant effort to continue supporting those already on tb treatment, but there are also concerns that lockdown conditions may interfere with the continued supply of drugs [ ] . to capture this range of possible disruptions, we performed a rapid consultation amongst experts at the stop tb partnership and the united states agency for international development (usaid). table lists those experts' consensus opinion as to the degree to which tb services could be disrupted by covidrelated lockdowns, at each step of the care cascade. there is substantial uncertainty around these possible impacts, and as described below, a key part of this analysis is to resolve the specific disruptions that would have the greatest influence on long-term tb burden. depending on its readiness, a country tb programme may take weeks or months to restore tb services to normal after a lockdown. this process may be delayed if, for example, laboratory capacity for diagnosis needs time to be reconstituted for tb, or indeed if there evidence before this study we searched both the published and grey literature for relevant studies in this context, using the terms "(sars-cov- or coronavirus or covid- ) and tuberculosis," limited to publications in english. one modelling study found it unlikely that tb transmission reductions could compensate for the adverse impacts of disrupted tb services. another study used approaches relating notifications to tb mortality, to estimate the excess tb deaths that could occur globally, under different lockdown scenarios. we found no studies examining the potential impact of disruptions at different stages of the tb care cascade, nor for post-lockdown strategies for reconstituting tb services. we focused on india, kenya and ukraine, three high-burden countries, representing contrasting epidemiological conditions. in each country we modelled the impact of a range of lockdown scenarios, informed by expert consensus on the potential effects of a lockdown at various points in the tb care cascade. for each country we additionally examined which type of disruption (i.e. acting at which point on the care cascade) would be most associated with excess tb burden. using insights from this analysis, we identified potential strategies for high-burden countries to bring their tb responses back on track. even short-term disruptions can trigger escalations in tb burden that can take years to return to pre-lockdown levels. such increases can be explained by an accumulating pool of undetected, untreated tb during a lockdown. accordingly, country preparedness should involve 'catch-up' plans to intensify screening, evaluation and treatment of 'missed' cases of tb, immediately upon lifting a lockdown. remains a reluctance to seek care amongst those with tb symptoms, as a consequence of fear and stigma caused by the covid- pandemic. accordingly, to model the impact of the lockdown and its aftermath, we assumed two phases: a 'suspension' period of given duration, during which all impacts listed in table are in full effect, followed by a 'restoration' period, during which tb services are gradually (for simplicity, linearly) restored to normal. the suspension period is expected to last for as long as the lockdown is in effect, and potentially for longer: even once restrictions are eased, it may take some time for the reconstitution of tb services to begin, and for normal careseeking to begin resuming. we also assumed that tb transmission would revert to normal at the end of the suspension period, as a result of contact rates in the community rapidly being restored to normal. this assumption may be appropriate in high-burden, lowincome settings where physical distancing is less feasible than in high-income settings, but also where there are strong economic incentives to restore livelihoods as soon as possible. we present results for two disruption scenarios: a 'mild' scenario consisting of a -month suspension followed by a -month restoration period for tb services, and a 'severe' scenario consisting of a -month suspension followed by a -month restoration period. in each scenario we simulated the excess tb cases and deaths that would arise, over the period from À , compared against a situation where tb services continue as normal over this period. in doing so, we ignore potential expansions in tb care in our comparator scenario, for example the scale-up of engagement with the private sector in india that was ongoing prior to the covid- pandemic [ ] . our analysis therefore does not include the foregone benefits from continuing these expansions, and so we expect our model projections to be conservative with respect to the excess tb burden arising from the lockdown. we also extrapolated estimates from our three focal countries to the global level using a simple approach, detailed in the supporting information (section ). we used the india model to inform projections for countries with high tb burden and private sector involvement; the kenya model to inform projections for countries where hiv is a driver of the tb epidemic; and the ukraine model to inform projections for countries with a high proportion of drug-resistant tb, and hospital-based care delivery systems. countries not in these groups were assigned the average impact of the three country models; we then aggregated country-level results to the global level. we conducted a 'leave-one-out' analysis, in which we simulated the impact of the lockdown, but in the absence of a single element in table (for example, a scenario where all impacts are in full effect with the exception of diagnosis, which remains at pre-lockdown levels). this analysis allows an assessment of how excess tb burden may vary under more limited disruptions than the full set of scenarios identified in table . in doing so, this analysis also helps to identify which types of disruption have the strongest contribution to excess tb burden. by performing a 'leave-one-out' simulation for each row of table in turn, we aimed to estimate the influence of each type of disruption. additionally, while many of the assumptions in table can be refined as further data become available, the effect of reduced contact rates in particular will be challenging to measure empirically. recent analysis has examined the potential impact of different levels of transmission reduction [ ] , finding, for example, that these are unlikely to counterbalance the effects of disruptions in tb services. our current analysis complements this work by capturing details of tb services. as discussed below, there is wide uncertainty around footnotes: scenarios were constructed through a rapid consultation with experts in the stop tb partnership and usaid, the former using information from a rapid survey of national tb programmes . the scenarios listed here are not predictive, but illustrative on the basis of current information: they offer a basis for examining the potential impact of different types of disruption. for the initial levels and uncertainty intervals of these parameters in each country, see tables s Às (entries highlighted in yellow) in the supporting information. lockdowns would have the effect of reducing transmission in the community level, but also intensifying and prolonging exposure at the household level. as our models do not incorporate household vs community structure, these scenarios instead aim to capture the net effect of changes in household vs community transmission. in urban slums in particular, where tb transmission is strongest, overcrowding may tend to reduce the effect of any lockdown on community transmission. in section in the supporting information, we present corresponding sensitivity analyses to these assumptions. the initial patient delay is an assumed interval of active, infectious tb, prior to a patient's first presentation for care. it is calibrated to match epidemiological data (see table s for data, and tables s Às for parameter estimates). for simplicity, only the kenya model incorporates the role of hiv/tb coinfection, which is estimated to account for % of incident tb. however, we note that ukraine has a high burden of hiv as well; in the present study, our focus in ukraine is on the role of drug-resistant tb. potential tb transmission reductions during a lockdown. there is evidence for contact rates being reduced by lockdown, even in informal settlements in kenya [ ] , and masque use may further decrease transmission [ ] . however, it is not yet known how strong these transmission-reducing effects might be for tb, for example when weighed against the potential for prolonged and intensified exposure within the household. we therefore adopted a central estimate of % (see table ), while also adopting a wide range of scenarios from % to %. under each scenario we calculated the excess cases and deaths that would occur between and . role of the funding source sam, am, em and ss are employed by the stop tb partnership, and sa is employed by usaid. the funders of the study otherwise had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript. the corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. all authors approved the final version of the manuscript submitted for publication. figures s À s , and tables s À s in the supporting information, show the model calibrations to each of the targets shown in table . on the basis of these calibrations, following a mild disruption we projected that between and , in india there would be an increase of , tb cases ( % bayesian credible interval (cri) À thousand) and , tb deaths ( % cri . À . thousand). likewise, in kenya there would be an additional cases ( % cri À À ) and deaths ( % cri À ), and in ukraine an additional cases ( % cri À À ) and deaths ( % cri - ) (see figs. and , andtable ) . although these results suggest the possibility of a net reduction in tb incidence in kenya and ukraine (as a result of the assumed % reduction in transmission during the lockdown), such reductions only manifest under this mild scenario: in the case of a severe disruption, results suggest that tb incidence could increase by À % between and , and that tb deaths could increase by À % in this same period. in terms of the monthly dynamics, figs. and illustrate that increases in incidence and mortality typically last longer than the duration of disruption. indeed, in india, incidence was projected to remain at least % higher than a "business-as-usual" baseline for a period of months, even in the mild scenario of a two-month suspension followed by two-month restoration (fig. s ) . in india, the three specific service disruptions having the most effect on incidence and mortality are, in order: the increase in the initial patient delay before first presenting to a provider; the probability of diagnosis per visit to a provider; and the drop in treatment initiation ( fig. : leaving aside transmission, which we address below). likewise in kenya, the same three factors appear as most influential on the impact of the lockdown, on both tb incidence and mortality. in ukraine, a setting with a high burden of drug resistance, the drop in second-line treatment completion was far more influential on overall impact, the drop in drug sensitivity testing, and the drop in the probability of tb diagnosis per visit to a provider were also important considerations. fig. . the potential impact of a lockdown on tb incidence in india, kenya and ukraine. shown is monthly tb incidence in each country, in and , for two disruption scenarios: (i) a 'mild' scenario with a -month lockdown and a -month restoration (orange), and (ii) a 'severe' scenario with a -month lockdown and a -month restoration (red). bars labelled with 's' and 'r' denote, respectively, the suspension and restoration periods, with numbers giving the duration in months in each period. as described in the main text, we assume that the disruptions in table are in full effect during the suspension period, and that they are reduced to zero in a linear way over the restoration period. shaded intervals show % bayesian credible intervals, reflecting uncertainty in pre-lockdown model parameters. cumulative excess tb incidence over the period À is given in table . the effect of disruptions in diagnosis, as well as in care-seeking and treatment initiation, is an expansion of the pool of individuals with undetected and untreated tb. fig. shows how the size of this pool grows over time; the right-hand panel illustrates the potential impact of a two-month campaign to reduce the prevalence of untreated tb in india through expanded case finding to reach an monthly notification target of per , population per month, immediately upon easing of lockdown restrictions (i.e., implemented alongside the restoration of tb services). depending on disruption severity and duration of restoration, such a two-month campaign could, pre-emptively, fully avert the adverse impact of the lockdown, by bringing -year incidence trends back to pre-lockdown levels. below we discuss potential approaches for implementing these post-lockdown measures. in addition to service disruptions, fig. illustrates that transmission reductions are also influential in the excess tb burden caused by a lockdown. we therefore conducted additional analyses to examine how model projections are affected by our assumptions for transmission. fig. shows estimates for excess incidence and mortality in all three countries, illustrating overall that, although it is possible for transmission reductions to give rise to net reductions in cumulative tb burden, this effect only occurs under the mildest disruption scenario (orange curve), and under the heaviest transmission reduction scenarios. additional analyses, provided in the supporting information (section ), extrapolates from these three focal countries to the global level. this approach suggests, for example, that a severe suspension scenario could lead to an additional , tb cases, and an additional , tb deaths worldwide between and (table s ) . the potential impact of a lockdown on tb deaths in india, kenya and ukraine. as for fig. , but showing monthly tb deaths in each country. as in fig. , bars labelled with 's' and 'r' denote, respectively, the lockdown and restoration periods, with numbers giving the duration in months of each period. shaded intervals show % bayesian credible intervals, reflecting uncertainty in pre-lockdown model parameters. excess tb deaths over the period À are listed in table . table the left-hand panel shows, in the example of india, the growth in the prevalence of undetected and untreated tb during the lockdown period, taking the example of a -month lockdown followed by a -month restoration. as described in the text, this expanded pool of prevalent tb is a source of short-term increase in tb mortality, as well as seeding new infections of latent tb that manifest as incident tb disease over the subsequent months and years. the right-hand panel shows the effect of 'supplementary measures' that are instigated immediately upon lifting the lockdown, and that operate over a two-month period to reach these missed cases and initiate them on treatment as rapidly as possible. in practical terms, such efforts could be guided by notification targets. shown in the figure is the example of a mild lockdown scenario, followed by supplementary measures that aim to reach a peak target of ( %cri À ) monthly notifications per , population. this modelling analysis in three key countries illustrates that even short covid-related lockdowns can generate long-lasting setbacks in tb control. our results suggest that, in a severe disruption scenario, over the next five years tb deaths could see increases of À %, while tb incidence could see increases of À %, in the three countries studied here (figs. and , and table ). our work also illustrates some differences between country settings, in the potential impact of lockdowns. for example, percentage increases in tb burden tend to be higher in india than in kenya and ukraine (table ). on the one hand, our estimates for the initial delay before first presentation for care are substantially higher for kenya than for india (respectively, over a year and around months respectively À see tables s and s ). if the majority of transmission has already occurred by the time a symptomatic first presents for care, then service disruptions may have only limited impact on tb burden; we expect the same to apply in any high-prevalence setting, with prolonged pre-careseeking delays. on the other hand, ukraine is a setting with substantially lower incidence than india or kenya, and therefore weaker transmission: overall, we might expect lockdown-related increases in longterm incidence and mortality to be exacerbated in settings with higher levels of tb transmission, and vice-versa. our overall projections are broadly consistent with other, recent modelling work that also aimed to assess the potential impact of lockdown-related disruptions, on tb control [ , ] . however, our work complements these analyses by paying specific attention to the tb care cascade in different countries. while it is not possible to predict the trajectories of lockdowns, or associated disruptions in health services in any country, our work instead aims to identify the specific types of disruptions that would be most influential for long-term tb burden. these insights can be valuable in informing planning for post-lockdown tb measures in any country setting beyond those that we have examined here. in particular, fig. illustrates that the specific disruptions posing the greatest risk for long-term increases in tb incidence and mortality are those that permit an expansion in the pool of undetected, untreated tb: that is, disruptions hindering access to care amongst tb symptomatics, as well as the availability of diagnostic capacity when patients do access health faciities. our analysis highlights how the expanded pool of undetected tb may continue to seed new infections of latent tb, many of which would take years to manifest as incident tb disease. consequently, service disruptions give rise to a short-term escalation of tb mortality (fig. ) , followed by a prolonged increase in incidence that could take years to undo (fig. ) . it follows that the adverse, long-term impact of these disruptions could be averted through focused efforts to address the problem of undetected tb, immediately upon lifting restrictions. in fig. we illustrate one scenario, where such supplementary measures aim to reach a target of notifying cases per , population, per month. we have not aimed here to define how such targets might be reached since optimal approaches are likely to vary across different settings. for example, it is likely that such supplementary measures would involve some form of active case-finding, [ , ] including contact tracing with longitudinal follow-up [ ] . at the same time, in settings where careseeking rapidly restores to normal, it is possible that the manifestation of 'pent-up demand' could contribute substantially towards this target. in this scenario, it is important for tb programmes to retain the capacity needed to meet this post-lockdown surge in demand. in practice, a combination of both approaches may fig. . sensitivity analysis to the extent of tb transmission reduction during the suspension period. in other figures we assume that transmission is reduced by % (see table ), and here we examine the potential implications of more substantial reductions. lines show the percent increase in cumulative incidence (upper row) and cumulative tb mortality (lower row) between and , compared to a baseline of tb services continuing indefinitely at pre-lockdown levels. the horizontal dashed line in each figure indicates zero overall change; the region above this line corresponds to a net increase in tb burden over the next years, and vice versa. overall, and in agreement with recent analysis [ ] , the figure illustrates that tb transmission reductions are likely to lead to overall reductions in tb burden only when strong transmission reductions are combined with mild disruptions (orange lines, at > % transmission reductions for kenya, and > % transmission reductions for india and ukraine). be needed, even at a time when tb programmes are operating under severe constraints in human and material resources. in the face of these constraints, anticipating the need for these concentrated efforts will be invaluable for planning, both by country programmes and by international donors who could support these efforts. on the patient side, covid- and pulmonary tb are both associated with respiratory symptoms. if, during the current pandemic, covid- comes to be seen as a "tb-like" disease, public recognition of the importance of recognising tb symptoms may wane once covid- is thought to be under control. additional efforts may therefore be needed to address these misperceptions. an additional concern is that covid- may carry stigma in many communities, and this stigma may transfer to individuals with tb as well [ ] . conversely, there may be opportunities to leverage synergies between the two diseases; for example, integrated tb and covid- screening and testing algorithms or combined contact investigation strategies. any such strategies based on respiratory symptoms could use similar infrastructure and staff to mitigate both the direct impacts of sars-cov- transmission and the indirect effects of augmented m. tuberculosis transmission. we emphasise that, readiness to restore tb services as rapidly as possible, combined with focused efforts to 'catch up' on missed diagnoses, will be critical in limiting any long-term setback to tb care efforts as a result of the covid- response. one important uncertainty is the potential impact of the lockdown, on tb transmission. assuming a % reduction in transmission, our results suggest the possibility of a mild disruption to yield a net reduction in -year incidence, in kenya and ukraine (fig. , and table ). more broadly, our sensitivity analysis (fig. ) illustrates that transmission reductions would only lead to a net decrease in tb burden over the next five years if these reductions are relatively strong, coupled with disruptions to tb services that are relatively mild. these results are in agreement with recent modelling analysis, that similarly showed how transmission reductions are unlikely to outweigh the negative impacts of disruptions to tb services [ ] . we caution that À as with any models not fully capturing household and other population structures -these simulations are likely to overestimate the rate-of-change in tb incidence over short timescales, such as the drop in tb incidence shown during the lockdown period. nonetheless, these and similar results remain qualitatively illustrative of the potential importance of changes in transmission. a key implication of our scenario analysis is the centrality of establishing surveillance and other data systems to inform the extent of lockdown-associated disruptions in tb care. for example, tb notifications (e.g., ref [ ] ) can be monitored in real time at a national and subnational level, to evaluate the depth and duration of any reductions in tb diagnosis at different stages of any lockdown. if these indicators suggest persistent declines in notifications and/or falling levels of treatment success, targeted interventions (e.g., active case finding, treatment support, or expanded access) can be rapidly implemented. as contact investigation for tb is implemented, surveillance of infection and active tb can be established and time trends can be used to inform whether household transmission has increased and/or access to care has declined, again at the local, subnational, and national levels. in the longer term, community-based surveys (e.g., serial surveys of tb infection in young children [ ] , can be conducted to explore the impact of lockdowns on tb transmission more broadly. we note that the present analysis does not address the potential for direct interactions between tb and covid- (for example, increased risk of covid- mortality amongst individuals with tb). for this reason, our estimates for excess mortality in particular are likely to be conservative. for example, early evidence suggests that existing tb infection, whether latent or active, can be a strong risk factor for severe disease resulting from sars-cov- infection [ ] , although this association may vary by setting [ , ] . moreover, through pre-existing lung damage [ ] , past tb infection might also predispose individuals to poorer outcomes from covid- . further evidence on both potential impacts, particularly from longitudinal cohorts) [ ] , would be invaluable for future work examining these potential pathogen-pathogen interactions. as with any modelling study, our analysis involves several simplifications. our models do not distinguish age structure, nor pulmonary versus extrapulmonary tb, instead taking an average over these distinctions. for our modelling of kenya, for simplicity we have only captured the transmission dynamics of tb, treating hiv incidence as pre-specified. our model therefore does not capture the potential tb implications of disruptions in hiv care, and for this reason may be conservative. lockdowns are likely to reduce community transmission but at the expense of intensifying and prolonging household and congregate setting exposure. faithfully capturing household contact structure is generally not feasible in compartmental models such as in the current analysis, and instead we have taken a simple approach of an assumed overall net reduction in transmission. finally, while our work has concentrated on three country settings capturing key challenges in the tb care cascade, future work should address other settings (such as in south america), as well as the effect of disruptions at the subnational level, if lockdowns against covid- increasingly become implemented at city-and provincial-levels. in conclusion, our analysis illustrates how increases in tb burden can take months to manifest, but years to undo. even if a lockdown is a period of curtailed programmatic activity, our results also highlight how this period might be used by country programmes and international agencies to prepare for the timely restoration of tb control activities and even "catch-up" campaigns upon easing of restrictions, to prevent such long-term negative impacts from taking hold. the resilience of systems to end tb worldwide will depend critically on readiness to restore, supplement and monitor tb services as rapidly as possible. all data used and generated in this study is available in the manuscript and supporting information. sa is employed by usaid and san, am, em, and ss are employed by the stop tb partnership. the other authors declare no conflicts of interest. this work was supported by the stop tb partnership, and by usaid. na gratefully acknowledges additional support from the bill and melinda gates foundation, and the uk medical research council. ss, sa, and na conceived the study, and na, dd, and cp designed the approach. sa, san, am, em, and ss provided expert input in constructing the model assumptions, and validated model findings. lc, hf, jfv, and cp performed the analysis, and all authors contributed to the interpretation. lc, hf, na, and dd wrote a first draft of the manuscript, and all authors contributed to the final version. all estimates are over the period from the beginning ( jan) of to the beginning of . percentages show increases in cases and deaths relative to a baseline of no disruption how will country-based mitigation measures influence the course of the covid- epidemic estimating the number of infections and the impact of non-pharmaceutical interventions on covid- in european countries the effect of control strategies to reduce social mixing on outcomes of the covid- epidemic in wuhan, china: a modelling study malaria morbidity and mortality in ebola-affected countries caused by decreased healthcare capacity, and the potential effect of mitigation strategies: a modelling analysis health in financial crises: economic recession and tuberculosis in central and eastern europe effects of response to - ebola outbreak on deaths from malaria, hiv/aids, and tuberculosis world health organization. global tuberculosis report . world health organization tuberculosis : burden, challenges and strategy for control 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for sars-cov- in the who european region tuberculosis and hiv responses threatened by covid- joint effort for elimination of tuberculosis the potential impact of covid- -related disruption on tuberculosis burden the impact of covid- control measures on social contacts and transmission in kenyan informal settlements surgical face masks worn by patients with multidrug-resistant tuberculosis predicted impact of the covid- pandemic on global tuberculosis deaths in turning off the tap: stopping tuberculosis transmission through active case-finding and prompt effective treatment how much is tuberculosis screening worth? estimating the value of active case finding for tuberculosis in south africa, china, and indi household-contact investigation for detection of tuberculosis in vietnam world health organization. social stigma associated with covid- central tb division india. nikshay dashboard decreasing household contribution to tb transmission with age: a retrospective geographic analysis of young people in a south african township active or latent tuberculosis increases susceptibility to covid- and disease severity clinical characteristics of covid- and active tuberculosis co-infection in an italian reference hospital tuberculosis, covid- and migrants: preliminary analysis of deaths occurring in patients from two cohorts tuberculosis and lung damage: from epidemiology to pathophysiology active tuberculosis, sequelae and covid- co-infection: first cohort of cases we gratefully acknowledge support from sara gonzalez andino and shinichi takenaka from stop tb partnership, in the process of development of modelling assumptions. supplementary material associated with this article can be found, in the online version, at doi: . /j.eclinm. . . key: cord- -wxsbbl r authors: bindra, vimee title: telemedicine for women’s health during covid- pandemic in india: a short commentary and important practice points for obstetricians and gynaecologists date: - - journal: j obstet gynaecol india doi: . /s - - - sha: doc_id: cord_uid: wxsbbl r background/purpose of study: in view of restrictions on patients because of covid- pandemic, face-to-face consultations are difficult. this short commentary tells us about the feasibility of telemedicine in this scenario in obstetrics and gynaecology. methods: the database from our teleconsultation application (apollo and askapollo) was analysed to assess feasibility of telemedicine and to design a triage pathway to reduce hospital visits for non-emergency situations and also to identify emergency cases without delay during this lockdown phase. existing guidelines by ministry of health and family welfare (mohfw), government of india, were accessed. results: this was a single-doctor experience of consultations done over days. we also designed a triage pathway for obstetrics and gynaecology cases, and we discussed general practice for obstetricians and gynaecologists with its utility and limitations. conclusion: telemedicine has provided us the opportunity to manage women health problems and pregnancy concerns during this pandemic of covid- , except a few instances where face-to-face consultation or hospital visit is must. if we implement the triage pathway, we can minimize the risk of exposure for both patients and healthcare teams during covid- pandemic. disasters and pandemics pose a great challenge to health care delivery for an already burdened healthcare system. when the whole world is fighting with an invisible enemy, there is a major shift in routine patient care. who declared covid as pandemic on march , [ ] . many hospitals and practices had to cancel routine out-patients visits and out of necessity, most of the practices have been encouraged to use telemedicine as a method of continuity of care. while writing this article, there were already , , cases globally and , , deaths [ ] . india had reported , cases and deaths [ ] . pregnant women are the vulnerable population hence guidance and support through telemedicine will go a long way in reducing complications and timely intervention during this pandemic. known consequences of delayed access to healthcare due to lockdown and pandemic situation on pregnant women could be delay in identifying the warning signs, more maternal and neonatal deaths, less access to abortion facilities as patients are also scared to visit hospitals because of fear of contracting the infection. during these times telemedicine came as a boon for our patients when govt of india and medical council of india released their new guidelines for use of telemedicine during this pandemic [ ]. our hospital telemedicine services came to our rescue and through our applications apollo and ask apollo we could serve a large number of women in need during this pandemic situation. a total of tele consults (single doctor experience) happened during th march to st may. the age range of patients who consulted via telemedicine were - years. dr. vimee bindra ms (gynaecology and obstetrics) is a consultant gynaecologist and obstetrician at apollo hospitals, hyderabad, india. * vimee bindra vimee.bindra@gmail.com apollo hospitals, hyderabad, india % of patient who consulted through telemedicine were from a nearby location and % were outstation from remote locations or cities where nearby clinics and outpatient facilities were closed. the new patients who consulted for the first time constituted . % of total consults, while follow up patients constituted . % of the tele consults. (new patients mean they did not have any face to face consultation in the past months and follow up patient had at least one face to face consultation in the past months.) out of consultations, % consultations happened for one time, % for two times, and rest of the consultation that is % happened for three or more than three times. multiple consultations for same patients were mostly for pregnant patients. as we know significant number of covid- infections are caused by asymptomatic carriers, decreasing in person contact with patients is of vital importance [ ] . the described triage pathway (figs. , ) for teleconsultation allows for necessary urgent and emergent obstetric or gynaecologic care and helps in minimizing the exposure that would be associated with standard obstetric and gynaecology consultations. many specialties like orthopaedic and urology are using telemedicine extensively [ , ] . before covid- pandemic, telemedicine had not been widely used by indian physicians. it is there for distant telehealth services where rural areas are connected to hospitals through telemedicine. women's health especially pregnant women can utilize this facility and avoid contracting the infection. for gynaecological disorders if no emergency can also be managed through telemedicine from the comfort of their homes. gynaecologists and obstetricians can interact with patients, gather complete history, educate them regarding the warning signs in pregnancy and give advice and instruct them to come for physical consultation if needed. telemedicine in india can go a long way in future at least for non-emergencies and low risk pregnancies. also, not only covid- , this can help to reduce transmission of many diseases and reduce overall disease burden on healthcare. the following points can be useful practical guide for telemedicine for registered medical practitioners. few • for gynaecological patients with heavy menstrual bleeding not responding to medication, suspected ovarian torsion, acute pelvic inflammatory disease and others. by utilizing telemedicine for non-urgent gynaecologic and obstetric consultations, we were able to provide appropriate care and counselling, while reducing the surge of outpatient gynaecologic and obstetric visits and care following covid- crisis. telemedicine has provided us the opportunity to manage women health problems and pregnancy concerns during this pandemic of covid- , except a few instances where face to face consultation or hospital visit is must. if we implement the triage pathway we can while minimize the risk of exposure for both patients and healthcare teams during covid- pandemic. more robust data is needed to evaluate the effectiveness of telemedicine to manage antenatal women and general gynaecological issues in india and this can be utilized in future too for continuity of care. world health organization. coronavirus disease (covid- ) pandemic ministry of health and family welfare govt substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (sars-cov ) telemedicine in the era of covid- : the virtual orthopaedic examination managing urology consultations during covid- pandemic: application of a structured care pathway publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations acknowledgements i express my thanks and acknowledge mr. atulya (apollo app) and mr. bhaskar (ask apollo) for providing me with the data from app for analysis. ethical statement this article does not contain any studies with human participants by any of the authors.informed consent all patients who were consulted through telemedicine had consented to teleconsultation and they understood the nature of consultation as compared to physical consultation. she has a keen interest in the field of gynecological endoscopy specially endometriosis excision surgeries and fertility enhancing surgeries. she has received her advanced reproductive technology (art) training from, homerton university hospital, london (uk). she has done her fellowship in cosmetic gynaecology from american aesthetic association. she was awarded "vaidya sree award in " and "best emerging gynaecologist of the year" in . she is an author of three well known medical books in the field of gynaecology and obstetrics. key: cord- -cxc k d authors: saha, jay; chouhan, pradip title: indoor air pollution (iap) and pre-existing morbidities among under- children in india: are risk factors of coronavirus disease (covid- )?() date: - - journal: environ pollut doi: . /j.envpol. . sha: doc_id: cord_uid: cxc k d globally, the coronavirus disease (covid- ) outbreak is linked with air pollution of both indoor and outdoor environments and co-morbidities conditions of human beings. to find out the risk factor zones associated with coronavirus disease among under-five children using pre-existing morbidity conditions and indoor air pollution (iap) environmental factors and also with current fatality and recovery rate of covid- disease in india. data was utilized from the th round of the national family health survey (nfhs), – , and from the ministry of health and family welfare (mohfw) on th may . mean, standard deviation, and z-score statistical methods have been employed to find out the risk factor zones i.e. to execute the objective. findings of this study are, the states and uts which have more likely to very higher to higher risk factors or zones of coronavirus disease (covid- ) are mizoram ( . ), meghalaya ( . ), uttarakhand ( . ), west bengal ( . ), uttar pradesh ( . ), jammu and kashmir ( . ), odisha ( . ), madhya pradesh ( . ), jharkhand ( . ), bihar ( . ), maharashtra ( . risk score), compared to uts like assam (- . ), rajasthan (- . ), goa (- . ), manipur (- . ), chandigarh (- . ), haryana (- . ), delhi (- . ) have moderate risk factors of covid- , and the states and uts like daman and diu (- . ), sikkim (- . ), andaman and nicobar islands (- . ), kerala (- . ), dadra and nagar haveli (- . ), arunachal pradesh ( .- ), karnataka (- . ), and nagaland (- . ) have very low-risk zones of covid- deaths. from a research viewpoint, there is a prerequisite need for epidemiological studies to investigate the connection between indoor air pollution and pre-existing morbidity which are associated with covid- . well-built public health measures, including rapidly searching in high focus areas and testing of covid- , should be performed in vulnerable areas of covid- . coronavirus disease outbreak is a global pandemic frightening the whole world amid unexpected emergence and massive spreading of novel coronavirus ( -ncov) or the severe acute respiratory syndrome coronavirus (sars-cov- ) (who, a (who, , b al-dadah & hing, ; cucinotta & vanelli, ; jin et al., ; lai et al., ; peeri et al., ; saha et al., ; singhal, ; sohrabi et al., ; stahel, ; wang et al., ) . the covid- is a vastly contagious disease rapidly spreading from its origin in wuhan city, hubei province of china to the rest of the world in december . as of may , , the covid- outbreak has hit south-east asia with , confirmed cases; india has the th-largest number of confirmed cases ( , cases), already crossing china (who, a (who, , b . in indoor air pollution (iap), from the indoor biomass combustion, the air pollutants which are emitted include suspended particulate matter (spm), nitrogen oxides (nox), carbon monoxide (co), benzene (c h ), , -butadiene (c h ), methanol (ch o), polycyclic aromatic hydrocarbons (pahs), and several toxic organic compounds (world health organization, ; sukhsohale et al., ; chakraborty et al., ; air quality expert group, ) . the cooking fuels which are generally burned for cooking mostly in a rural home and also in urban areas are coal, lignite, charcoal, wood, straw/shrubs/grass, agricultural crop, animal dung, etc. (iips, ) which are sufficient for the concentration of indoor air pollutants. smoking of cigarettes, bidis, and pipes within the home or indoor environment are also other responsible factors for the increase of smoky indoor environment (bruce et al., ; gilmour et al., ; chaouachi, ), a risk factor of the coronavirus disease among under-five children. the acute respiratory infection (ari), i.e. executes signs like short and rapid breaths (iips, ), cold & cough, and fever among human beings are the primary symptoms of the coronavirus disease and the severe acute respiratory syndrome coronavirus (sars-cov- ) which have widespread effects because it is hazardous or risk factor for children and human beings health having a weak immune system (jin et al., ; lai et al., ; peeri et al., ; singhal, ; wang et al., ; who, a who, , b . these symptoms are quite common among under-five children of developing countries and also in india which have impacts on children's health (ramani et al., ; thota et al., ; krishnan et al., ) . globally, and also in developing countries like india, the under-five children are most vulnerable groups compared to the other age classes, so we considered only underfive age group and in an estimated . million children under the age of years died (unicef, ), mostly from preventable childhood morbidities. for that very reason, areas with these symptoms are vulnerable/risk zone for the covid- deaths in the coming days. several previous studies that have analyzed the indirect effect of the covid- on-air (fattorini & regoli, ; bashir et al., ; collivignarelli et al., ; zambrano-monserrate et al., ) and few studies specifically from that have analyzed the effect of lockdown during the covid- pandemic on air quality in india i.e. pm . had the highest reduction in most of the regions amid the covid- lockdown (sharma et al., ) ; again, pm and pm . concentrations over megacity delhi, have reduced by above % in comparison to the before-lockdown period in india i.e. improvement of air quality during the covid- lockdown (mahato et al., ) . so, compared to the other previous studies in india, this type of study is yet not done, considering this huge research gap and novelty, this study also aims to find out the risk factors associated with the coronavirus disease (covid- ) among under-five children using pre-existing morbidity conditions and indoor air pollution environmental factors which are solid biomass cooking fuel and indoor smoking cigarettes and also with current case fatality ratio (cfr) and recovery rate (rr) of the covid- disease in the high focusing states and union territories of india which are in a risk zone. this very research would be helpful for policymakers, strategy developers, environmentalists, and public health workers to combat the future pandemic situation. for this study, data were utilized from the th round of the national family health survey, e , consisting of nationally representative sample surveys. a total of , living children ( e months) were surveyed by the national family health survey (nfhs)- , among them the under-five children having preexisting morbidities and indoor air pollution characteristics of the states and union territories of india were considered for this study (iips, ) . the data used for this study were retrieved from the public domain after describing the objective of the study. data on the covid- is use from the https://www.mohfw.gov. in/naming 'covd- state-wise status', provides the most updated figures on the daily and a total number of confirmed cases, recovered or cured cases, and deaths (mohfw, ) for each affected states and union territories of india. this data is provided by the ministry of health and family welfare (mohfw), government of india. we have collect information on confirmed cases, the number of deaths, and cured cases as on may , , : ist (gmtþ : ) of affected states and union territories of india. for the analysis of the study, a selection of pre-existing morbidities indicators and indoor air pollution or domestic smoky environmental indicators among under-five children household and recent covid- rates were included. pre-existing morbidities indicators include symptoms of acute respiratory infection (ari) in the two weeks before the survey, the prevalence of cold and cough, and the prevalence of fever among under-five children. indoor domestic smokes indicators include children's family used smoky domestic cooking fuel and children's mother smoke cigarettes and recent covid- rates include case fatality ratio (cfr) and recovery rate (rr) of different affected states and union territories of india ( fig. ). the prevalence of pre-existing childhood morbidities and the percentage of children's family used indoor domestic smokes were computed using the statistical package and data science software stata version . (statacorp lp, college station, tx, usa). after that, the case fatality ratio has been calculated as the ratio of the total figure of deaths due to covd- to the total figure of confirmed cases of the covid- . likewise, the covid- recovery rate is calculated as the ratio of the total figure of recovered cases of the covid- to the total figure of confirmed cases of the covid- . for identification of risk factors zone of the coronavirus disease, the mean composite z-score technique has been employed. all the factors which are taken for this study are positively influenced by the covid- except the factor recovery rate of the covid- . for composing, all the selected variables must be working unidirectional manner. so, the factor recovery rate has been converted into a non-recovery rate i.e. each recovery rate of the covid- of all states and uts is subtracted from . after that, for each variable (x or x and so on) number of observations (states and uts) are sum up and mean was calculated, then standard deviation was calculated as the root mean square deviation from the mean. the zscore i.e. risk score also be calculated for identification of risk or vulnerable zones of the covid- using the following formula- all the z-score values of all variables for each state and uts have been calculated then mean was calculated using total z-score value. high z-score value indicates high-risk factors of the covid- and vice versa. . . indoor air pollution and pre-existing prevalence of morbidities among under-five children and case fatality ratio and recovery rate of the covid- table represents the percentage of under-five children with indoor domestic smokes and pre-existing childhood morbidities and the covid- cfr and rr in states and uts of india. symptoms of ari was higher in the states like meghalaya ( . %), jammu and kashmir ( . %), uttar pradesh ( . %), uttarakhand ( . %), punjab fig. (a) ) compared to the states and uts like assam (À . ), rajasthan (À . ), goa (À . ), manipur (À . ), chandigarh (À . ), haryana (À . ), delhi (À . ) have moderate risk factors of the covid- , showed in color ramp of light yellow to light yellow-greenish ( fig. (a) ) and the states and uts like daman and diu (À . ), sikkim (À . ), andaman and nicobar islands (À . ), kerala (À . ), dadra and nagar haveli (À . ), arunachal pradesh ( .- ), karnataka (À . ), and nagaland (À . ) showed in color ramp of green to light greenish-yellow ( fig. (a) ) have very low-risk factors of covid- . the states and uts with to < . composite score i.e. high ( to À . ), moderate (À . to À . ), and low to very low (À . to À . ) risk score factors of the coronavirus disease ( fig. (b) ). worldwide, till may , as of : p.m. cest, , , confirmed cases of the coronavirus disease, including , deaths have been reported and countries, territories have been affected by the covid- pandemic (who, a (who, , b . in india, as of may , as of : ist (gmtþ : ), ministry of health and family welfare, the government of india reported, a total of , , confirmed cases and deaths have been reported speeded over states and uts (mohfw, ). the present study has examined the risk factors of the coronavirus disease . as the coronavirus has been associated with indoor air pollution and a smoky environment, so, there has a relationship between indoor cooking fuel used with biomass and the coronavirus disease (covid- ) (afshari, ) . the under-five children living in indoor smoky environmental conditions are most vulnerable and risk of the coronavirus disease. this study is consistent with the study done by ahmed et al. ( ) , and a significant relationship between exposure to air pollution and deaths due to the covid- was found in united states . they use of solid biomass for cooking fuels and burning inside their houses with poor vitalization system and no chimneys were found to direct the smoke outside in urban slums of bangalore, india (ghergu et al., ) . so, we found that these indoor air pollution conditions are extremely at risk or vulnerable to the covid- infection. those people staying in an area with intense high amounts of pollutants are, therefore, more likely to develop severe respiratory conditions and also at risk of any infective disease (conticini et al., ) . in this study among children's mothers with smoking cigarettes is a risk factor of the covid- among under-five children in india. this finding is in agreement with another study conducted in china, where hospitalized patients of the covid- with smoking behavior were times high likely to expire or die compared to the patients those were non-smokers (liu et al., ) , and in saudi arab (alraddadi et al., ) . the states and uts with high case fatality ratio and air pollution are risk factors of the covid- in affected states and uts of india. this finding was similar to another study in the people's republic of china i.e. the high prevalence of confirmed/infected cases and deaths of severe acute respiratory syndrome coronavirus (sars-cov- ) were associated with air pollution (cui et al., ) and in northern italy, higher prevalence and mortality of the covid- was also associated with air pollution (conticini et al., ) . indoor air pollution or indoor domestic smoky environment and pre-existing morbidities are the risk factors of health among children with under-five age. indoor air quality directly linked to the respiratory system of living peoples and dependence on hard biomass for cooking and burning or heating exposes respiratory health problem of children of developing countries as well as in india due to use lofty levels of indoor air pollution (padhi and padhy, ; bruce et al., ; mandal et al., ) . pre-existing morbidities like acute respiratory infection (ari), cold & cough, and fever among under-five children in india have also risk factors of the coronavirus disease . in earlier studies, it is found that pre-existing co-morbidities among children are risk factors of the covid- death (sinha et al., ; shekerdemian et al., ) . the measurement of cfr amid the covid- outbreak is not very suitable, because it is sensitive to under-reporting, testing of the covid- cases and moment of reporting and robust estimation of cfr is likely possible only at the end of the covid- pandemic. recovery rate also varies and daily changes during the pandemic situation, so these are few limitations of this study. surveyed women have self-reported about their children's pre-existing childhood morbidities, so there is a possibility of recall bias during the collection of information about children. from a research viewpoint, there is a prerequisite for epidemiological studies to investigate the relationship between indoor air pollution and pre-existing morbidity which are associated with the covid- . more focus needs to place on improving cooking stoves and use clean indoor cooking fuels should become a top concern in the high focus vulnerable region. the children should be kept away from the kitchen during the cooking and burning of fuels. the kitchen room should have extensive space so that air pollutants smokes are not being capable to concentrate within the room for a long period, which reduces indoor air pollution, which is the risk factor of the covid- . smokers of the family should also stay away from indoor house environment when smoking. finally, well-built public health proceedings, including rapidly searching in high focus areas and testing of the covid- , should be performed in vulnerable areas of the covid- . credit authorship contribution statement jay saha: conceptualization, data curation, formal analysis, investigation, methodology, software, supervision, validation, visualization, writing -original draft, writing -review & editing. pradip chouhan: conceptualization, formal analysis, investigation, methodology, software, supervision, validation, visualization, writing -original draft. the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. indoor air quality and severity of covid- : where communicable and non-communicable preventive measures meet why inequality could spread covid- the potential air quality impacts from biomass combustion. department for environment, food and rural affairs novel coronavirus (covid- ): a global pandemic risk factors for primary middle east respiratory syndrome coronavirus illness in humans correlation between environmental pollution indicators and covid- pandemic: a brief study in californian context. environmental 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outbreak of global health concern who coronavirus disease (covid- ) dashboard. world health organization. world health organization air quality guidelines: global update : particulate matter, ozone, nitrogen dioxide, and sulfur dioxide. world health organization situation report exposure to air pollution and covid- mortality in the united states indirect effects of covid- on the environment supplementary data to this article can be found online at https://doi.org/ . /j.envpol. . . key: cord- -yjxbm tn authors: correa, m.t.; grace, d. title: slum livestock agriculture date: - - journal: encyclopedia of agriculture and food systems doi: . /b - - - - . - sha: doc_id: cord_uid: yjxbm tn slums are unplanned squatter human settlements in peri-urban and urban areas where more than million people live. these densely populated areas lack basic public services. livestock raised in these conditions compete with humans for space and water, and pose a risk to human and animal health. notwithstanding the risk of disease transmission, slum livestock agriculture plays an essential role in the livelihoods of people and deserves consideration in urban planning and policy making. slums are human settlements developing in peri-and urban areas. often not recognized as part of planned urban environments, slums continue to grow in number and size around the world. there are now million to a billion people living in slums, a large percent of the seven billion worldwide. slums are difficult to define based on a single characteristic because they are not homogeneous within cities in a country or among countries; their unique milieu depends on the geographical location of the settlement, the socioanthropological background of the dwellers, and the history of its development. notwithstanding the sociocultural differences, slums have some common characteristics: poor housing, often illegitimately built on private or public land with poor drainage and unfit for agriculture; overcrowded conditions; limited access to potable water; poor sanitation and lack of sewage or waste removal; high numbers of domestic pets; and clandestine keeping of livestock. slums originate from the need of people for a place to live after displacement due to drought, famine, or wars, and migration from the countryside into the cities by the push of rural unemployment and the pull of urban opportunities. this migration from rural to urban areas populates informal settlements in the periphery of cities and towns in many countries (united nations, ) . demographic information from slums is only as good as the reports governments make. less than countries report data on slum human population, and from those, indicate they have more than % of the population living in slums. one country reported that % of the population lives in slum conditions (united nations, ) . in the census in india, million people were identified as living in slums (government of india, ) , which is probably an underestimate. in lesser developed countries, the increase in the urban population dating from the s is parallel to the decrease of the rural population. demographers expect that % of the world's population will live in urban areas by the year and billion people will be living in slums (united nations, ) . in africa, the population in urban areas increased sevenfold in years. population density in some slums has reached people per square kilometer, as in bangladesh (huque, ) . with one in every seven people living in a slum, ensuring sufficient food becomes a concern; slum livestock agriculture could be part of the solution to fulfill the nutritional needs of that many people (united nations human settlements programme, ) . production of food in slums is clearly different from rural, peri-urban, or other types of urban agriculture developing in many industrial countries. urban agriculture had been characterized as a decentralized supply system composed of small and scattered production units (mougeot, ) . there are other classifications of urban agriculture, only some of which include slum agriculture (egbuna, ) . slum livestock keeping is especially difficult to classify. the lack of basic resources to maintain and exercise good agricultural practices coupled with unsanitary slaughter is likely to render slum livestock agricultural products unfit for human consumption. however, despite all the negatives, slum livestock agriculture is a means of securing food, earning income, and supporting livelihoods of slum dwellers. slum agriculture benefits from a large market close at hand, low transportation costs, availability of production inputs, the ability to make use of waste foods and water, and low entry costs to setting up production (food and agriculture organization, ) . informal markets for real estate and goods develop in slums, including markets for processed and unprocessed animal products (potsiou and ioannidis, ) . peri-urban and urban livestock agriculture is a complex and multifaceted activity developing in an environment often unfit for human habitation. roaming chickens, pigs, and goats are a common sight in slums, and even cows and animals used for transportation or hauling such as donkeys and horses can be seen. in different regions of the world, different animal species are popular: goats and sheep are more common in africa and southeast asia, and pigs are more common in latin american slums. food animals in slums are a public health concern due to their potential for transmitting zoonotic diseases, unsafe food products, the risk of physical injuries and traffic accidents, and environmental contamination. animal products processed locally enter the general population food chain through peri-urban and urban food markets. owing to the lack of a proper waste disposal, animal and human waste mixes in the streets with leftover water from household activities. stagnant water and waste, garbage, and other contaminants develop a foul smell and attract vermin and insects. untreated wastewater flows into local waterways and is drunk by roaming animals. this gray water is often used for urban vegetable or crop farming. there are few estimates of the volume of animal or vegetable products originating from slums used to supplement the family diet or entering the food chain through peri-urban or urban markets. in ghana, % of the lettuce consumed in accra is produced in urban and peri-urban areas (amoah et al., ) . in the chimbote slum in lima, peru, where people live, it has been estimated that there are swine production units (chimbotenlinea.com, ) . that is approximately % of the households in the slum assuming there are four members per household. the food and agriculture organization of the united nations has conducted technical consultations and extensive studies on urban and peri-urban agriculture. thirty percent of the meat and % of eggs produced in the world is associated with urban production (food and agriculture organization, ) . it is not clear if slum agriculture production is included in these estimates. slum livestock keeping is typically smaller scale than the peri-urban and nonslum urban agriculture. however, slum agriculture has rarely been the focus of systematic evaluations and studies. the complexity of this type of slum livestock agriculture and its implications in the social and political arena is, however, getting recognition (international livestock research institute, ; lemma and rao, ) , and some evidence is emerging on scale and importance. in maputo ( . million inhabitants), mozambique, more than one in three households in urban areas raises livestock (international livestock research institute, ) . in ibadan in southern nigeria, one in three urban households kept livestock, whereas in kaduna in northern nigeria nearly half the households kept livestock (international livestock research institute, ) . livestock production in slums is typically small to medium scale and low technology. chickens and pigs seem to be ubiquitous in latin american slums, whereas goats and rabbits are favored in africa and southeast asia. cows are noticeable in india and nepal where, for religious reasons, they cannot be slaughtered. some animals in slums are allowed to roam and scavenge whereas others are confined in unsuitable small spaces shared with humans. the scale of this agricultural activity varies in type and size and it can range from subsistence to small-to medium-size commercial enterprises with hundreds of small animals. in more densely populated slums, fewer animals are kept and enterprises are likely to be small scale; where more land is available, livestock keeping is more common and on a larger scale (box ). chickens are animals most commonly raised in slums. one or two hens and one rooster roaming free with a few chicks is a common sight. it is not uncommon to find medium ( - box livestock keeping in dagoretti district, nairobi, kenya dagoretti district lies to the west of nairobi city, km from nairobi city center. it is one of urban districts in nairobi and has around onetenth of the total population. most inhabitants live in tin-roofed timber houses with inadequate access to piped water, sanitation, and electricity. unemployment (approximately %), human immunodeficiency virus-acquired immune deficiency syndrome, crime, and homelessness are persistent problems. dagoretti was originally outside the city of nairobi, but when the boundaries were extended in , it became part of the city. dagoretti district has both government and ancestral land. some ancestral land has been sold to migrants, and government land has also been allocated to individuals. in some areas, squatters live on land temporarily leased out by landlords, a loose agreement, which can be revoked at any time. the population in the last available census was up from in , a vivid illustration of the rapid growth of cities. of the population, % are below years of age, an age distribution that is also typical of developing countries. a recent survey characterized livestock keeping in dagoretti. more than half the households kept animals: in order of declining popularity: dogs ( %); poultry ( %); cats ( %); sheep and goats ( %); pigs ( %); and cattle ( %). a few households kept other animals including, rabbits, donkeys, doves, turkeys, ducks, and geese. dogs were kept mainly for security, cats for vermin control, donkeys for work, geese for security and food production, and the other species were kept mainly for food production. in addition, cattle manure is a valuable by-product used for urban crop and vegetable production, and livestock are an easily liquidated asset that can be sold to meet urgent household needs or act as pledge enabling access to credit. moreover, farmers report deriving social and psychological benefits from livestock keeping. the study focused on dairy cattle kept by in households in dagoretti. farmers kept an average of three cattle. nearly all households kept productive breeds, used artificial insemination, and zero grazing. farms produced approximately l of milk a day, and % of this was sold with the rest being consumed in the household. most of the milk produced is sold in the community through informal markets. all sales of milk earn farmers in dagoretti approximately us per year. farmers reported that both demand and production are increasing. chickens) to larger layer flocks (up to chickens) in confined spaces. chickens are the most versatile of poultry, given the value added of egg production and the worth of the animal, live or processed. in slums with limited electricity or where the cold chain is not available, chickens and eggs are a quick and easy source of protein and income generation. chickens have an additional value because they are used in religious ceremonies and offerings (alves et al., ) . the breeds of chickens vary from region to region and some commercial breeds are seen in slums. scavenging chickens are fed in the morning with leftover food and possibly with added corn or poultry meal. during the day, chickens eat insects, garbage, and organic matter found in empty lots or by the side of the road. housing is rudimentary and may consist of hay or rice husks arranged in cardboard or wooden boxes and placed off the ground for protection from dogs and predators mostly during the night. raising chickens is considered an easy activity requiring minimal labor and is usually performed by women and children (food and agriculture organization, ). backyard flocks requiring additional attention compete for space with humans and other animals and are more laborintensive requiring feeding, watering, and pen cleaning. noise levels and manure disposal become a problem with larger flocks and are a deterrent for keeping them in small and crowded spaces. larger flocks are more common in peri-urban areas than slums, but broiler chickens keepers may have more than birds, as in the case in the mombasa slum in bangladesh where a bird keeper is reported to have between and birds (sabuni, ) . live chickens are transported in cages or burlap bags to nearby food markets. these markets are located at walking distance from the dwelling where the animals are raised, although sometimes birds are transported in cages on top of buses or trucks to other urban markets. chickens are sold live or slaughtered on site at the buyer´s request. eggs have a longer shelf life (lasting - weeks without refrigeration depending on environmental conditions) than poultry meat. eggs are wrapped in newspaper and kept in the shade to prolong their shelf life. they may be sold to neighbors in small numbers, as needed, for income generation or in larger numbers at markets. other poultry kept in slums include turkeys, geese, doves, pigeons, quail, and guinea fowl. rabbits are gaining popularity in slums in africa. they can be kept in small spaces in crates, either individually or in small groups. rabbit crates are easy to build and can be kept stacked up against each other or leaned against a wall to occupy less space. these animals require more attention than scavenging or backyard flocks of chickens for feeding, watering, and cage cleaning. however, it is a profitable and uncomplicated business as evidenced by the number of rabbits a person can keep. one resident in the kahawa soweto slum in nairobi has more than rabbits in a shed (kelto, ) . rabbits are fed greens collected locally and supplemented with vegetable leftover from markets or pelleted food. this is a small species that can reach to kg of weight and can easily be processed locally as chickens for sale or family consumption. in a space of  feet, slum residents can raise more than rabbits of different breeds. more unusual animals are also kept: a survey in nigeria reported snails, grass cutters, and antelope among a total of species kept. pigs adapt easily to urban conditions. one sow can produce - piglets twice or three times a year if their reproductive cycle is timed properly (pregnancy lasts months, weeks, and days). selling the piglets before birth is not uncommon at certain times of the year for events or festivities where pork is commonly consumed. pigs are considered a form of saving account because piglets can be sold for cash or given in exchange for the boar´s service (the piggy bank). boars can grow tusks and become very large and aggressive, requiring confinement to protect people and other animals. this is why fewer people keep boars compared to sows. rearing of pigs in slums in small numbers (one to five) is often done by women and larger herds by men (food and agriculture organization, ) . piglets are easy to manage because they can roam during the day searching for food and come back to their home space at night. they can also be tethered and kept close to the dwelling, or housed in makeshift pens behind or in the confines of the human dwelling. nowadays pigs are ubiquitous to slums in latin america and present even in countries with muslim and hindu population such as india and nepal (rajshekhar, ) . it is difficult to establish the genetics of pigs commonly reared in slums. these are smaller and more adaptable to the local conditions than large commercial breeds. pigs revert to wild type very quickly and grow hair and tusks adapting to the environment. however, pigs kept in confined spaces in and small numbers are usually larger commercial breeds requiring more attention and feeding. the creole pig from haiti was an example of a small hairy dark pig well adapted to the environment, eating garbage and fallen rotten fruit. they had sociocultural value and were considered to have an important role in recycling waste. issues associated with swine fever in the late s and early s prompted the united states department of agriculture and other international organizations to develop and conduct an eradication program. the sociocultural value of these animals was not clearly understood. people were given large commercial breeds as substitutes for the creole pig and asked to pen the pigs. the larger breeds had to be fed and cared for and were not allowed to roam, which resulted in detrimental conditions of the environment in which people lived (ebert, ) . goats are adaptable to urban environments. they are known for eating almost anything, including bark from trees and shrubbery, garbage from streets and land fields, or clothes hanging to dry. these animals require attention, given their inquisitive nature and destructive eating habits. usually people keep a couple of female goats for their milk with the offspring. in slums close to peri-urban areas people keep the goats in pens or house patios during the night and walk them to pasture at different locations during the day. in the urban environment, and in particular in slums, goats roam the streets in search of food, and it is common to see them searching for food with pigs (diogo et al., ) . goats can decimate green areas very quickly, causing damage to vegetables growing by the side of the roads or public open spaces. they require more attention than chickens or pigs and they need shelter from the rain. goats' milk is nutritious and can be easily transformed into yogurt and cheese to extend the shelf life of an otherwise perishable product. in some large slums such as in delhi, india, slum goats' sightings have become a tourist attraction and are offered as part of city tours (news.com.au, ) . mixed bos taurus taurus and bos taurus indicus cattle are let free in search of food or water or walked to pasture in the mornings and brought back at night. in countries with a predominantly hindu population cows are sacred and only the milk is consumed. oxens are mainly kept for draught power; they are used for plowing and also transport. owing to religious reasons female cattle cannot be disposed of after their productive lives have ended. older unproductive animals may be abandoned and may die of diseases, hunger, intoxication from garbage, or get involved in traffic accidents. there are also many goshalas in india where abandoned cattle are looked after. milk is a valued product that contributes to food security in slums. but it is perishable and has to be consumed quickly or transformed into a variety of cheeses, yogurt, or sour milk. naturally fermented sour milk is popular in east and west africa; fermenting also removes lactose, which makes it easier to digest for populations that do not have lactase enzymes persisting in adulthood. tending larger animals is time consuming and may involve walking long distances to find a place to feed away from the city or to cut grass that can be brought back to the animal. this is easier to do when the slum is located in the periphery of a city compared to an urban-area slum. often cattle are confined to a small space or their mobility may be limited by tethering them close to the dwelling. studies of peri-urban dairying in east africa found that nearly all cattle were 'zero grazed,' that is, kept inside all the time (figure ) . cow dung in india is also a valuable fuel: it is collected, reshaped into cake-like forms, and dried. in india and elsewhere cattle dung is also used as a building material mixed with mud and other substances. livestock value is more than monetary; it is a symbol of social status and social identity both individually and collective (comaroff and comaroff, ) . the value of livestock and the production parameters used elsewhere (such as in the industrial countries) need to be revaluated because a cow or goat whose production is low may still be providing useful services (dutta, ) . in slums, an intricate relationship exists between poverty, food security, livestock keeping, and the environment. enforcing livestock regulations becomes a difficult task when animal ownership is clandestine. in many countries regulations cover animal health and welfare issues, the disposal of dead animals, slaughter procedures, and environmental contamination, but in practice they are not enforced in slums. in other cases, regulations are used for 'rent-seeking' by authorities: that is police or other officials will confiscate animals and not give them back unless a bribe is paid. keeping animals in cities undoubtedly creates environmental problems. for example, in kisumu, kenya, keeping animals is illegal. the city has six slums and enforcing animal farming law is a challenge. the dung of the animals becomes a problem when the rain washes it and contaminates the city water supply. the city lacks the infrastructure to recycle the dung and % of it is not utilized (new agriculturist, ). yet the draconian response of banning livestock from cities may not be the most appropriate. in kampala, uganda, a process lasting several years has recently led to new city ordinances that seek to support urban agriculture as an important economic activity, while regulating against the potential adverse effects. animals of the same or different species in slums are in proximity with each other and with humans. contagious diseases can spread rapidly under these conditions. additionally, slum-raised animals suffer from malnutrition coupled with an adverse environment that makes them more susceptible to disease or injury (food and agriculture organizations, ). some problems are associated with animals living in areas with poor waste disposal. pigs and goats eat plastic bags and these are common findings at slaughter or necropsy. the bags fill the stomachs impeding food digestion and nutrient absorption. rwanda banned nonbiodegradable plastic bags in , an excellent example for other african countries where plastic waste is ubiquitous. the health of animals in slums requires attention, but estimating disease and its impact is difficult. both zoonotic (diseases transmitted from animals to people) and nonzoonotic animal diseases need to be considered. reportable, zoonotic, and production diseases are discussed elsewhere in this encyclopedia. some of these diseases are of national public health interest or are of international trade importance requiring immediate reporting through specific official public health channels and to the world organisation for animal health, one of the three sisters of the world trade organization. reportable diseases of animals are those with the potential to cause epidemics or pandemics that cause serious disease in people, as is the case of the severe acute respiratory syndrome known as sars, the h n (pathogenic avian), and h n influenza virus (known as swine influenza) (gauthier-clerc et al., ; girad et al., ) . public health resources and market inspections are deployed for some of these diseases, but control is often ineffective in poor countries. determining the public health penetration of these programs in slums has been highlighted as a need (unger and riley, ) . risk communication in a crisis situation involving the livestock population in a slum may require additional resources and targeted programming. the lack of information of the size and location of the avian and swine population may impede the progress of disease control measures. public awareness programs or the application of rigid standards for disease control without consideration of the sociocultural and economic value of the animals for people may also decrease compliance (box ). references to the flu pandemic are always brought to light in the media as the possible serious consequences of disease spread and death. however, public health crisis response is different today and includes emergency and disaster preparedness, first responders training programs, and damage mitigation and relief. nonetheless robust economic estimates by the world bank suggest that the cost of an epidemic originating in animals could be a trillion dollars (world bank, ). there are approximately zoonoses or diseases transmitted from animals to humans. disease transmission may be direct through contact with infected animals or its fluids, or through contaminated animal products, water, or objects contaminated with infectious material (center for disease control and prevention, cdc / , ). especially important for poor countries are the so-called neglected zoonoses often associated with poverty, poor hygiene, and poor understanding of disease transmission. the rest of the article discusses some neglected zoonoses that are known or likely to be a problem in slums. brucella melitensis, the cause of brucellosis, is very pathogenic to humans (center for disease control and prevention, ). it is transmitted from goats and sheep to humans through direct or indirect contact. unpasteurized milk or contact with body fluids of infected animals are considered the most common transmission routes. there are other brucellae affecting swine, cattle, and dogs, but melitensis is associated with the more severe forms of the disease. flaying and skinning sheep by blowing air through a cut in the skin exposes people to body fluids and inhalation of bacteria from infected animal, and hence is not recommended. cysticercosis is a disease caused by the larval stage of the tapeworm taenia solium. the disease is sometimes wrongly known as the 'the pig tapeworm,' but humans are the definitive host for the adult form of the parasite, not the pig. the adult parasite releases segments daily containing thousands of eggs into the gut. these eggs pass into the environment with the feces. humans and pigs become infected and develop cysticercosis by ingesting the parasite eggs. pigs are coprophagic and human defecation in open spaces is one of the main forms of transmission of the disease from humans to pigs. when eaten by pigs, the eggs develop into cysts within the pig (figure ). if people eat meat containing viable cysts these can develop to tapeworms in the human host, thus completing its cycle. human to human transmission occurs when people harboring the parasite contaminate food due to poor hand hygiene (garcia et al., ; carrique-mas et al., ) . autoinfection can also occur following improper hand washing after a bowel movement. after humans consume eggs, cysts start to develop in any organ of the body, including the brain. when cysts develop in the brain, the disease is known as neurocysticercosis. it is considered as one of the most common infestations of the brain in humans. the main manifestation of the disease is epilepsy (garcia et al., ) . studies from a slum in india revealed that . % of people in the studied sample who had active epilepsy had antibodies to t. solium (singh et al., ) . cysticercosis in pigs may reach % prevalence or more in some countries where pigs are allowed to roam and human defecation is done in the open (carrique-mas et al., ; fleury et al., ; flisser et al., ) . even with low human taeniasis in the order of - %, the prevalence of cysticercosis in pigs can be high. this is mainly due to the fact that only adult parasite can live in the intestine of the host for years and release thousands of eggs into the environment. hepatitis e virus is an enteric disease transmitted from different species of animals including pigs to humans; it can be transmitted between humans through contaminated water and food. the seroprevalence in the human population unexposed to swine is % whereas the seroprevalence in swine workers or other swine-exposed populations is % (whithers et al., ) . data from a study of a pediatric population in karachi with access to municipal piped water and nonflush toilets in a slum in india showed a high seroprevalence for hepatitis e virus (jafri et al., ) . the exposure to hepatitis e virus seems lower than hepatitis a (mohanavalli et al., ) . hepatitis e is a disease that can cause severe gastrointestinal symptoms and has been associated with high death rates of pregnant women in lesser developed countries. in some peri-urban farms pigs are raised close to ponds where fish are kept. the pig feces are washed down to the ponds for the fish to eat. the virus seems to be ubiquitous in swine populations and undistinguishable even in samples from different countries. this was the case in hepatitis e study in two farming communities (not slum conditions), in north carolina and costa rica (whithers et al., ; kase et al., ) . hepatitis e is a zoonosis, but the importance of animals in its maintenance and transmission has not been fully established. a pandemic of h n influenza was declared in . this disease originated in pigs but subsequently was maintained entirely by human to human transmission. in response to the pandemic, the government of egypt ordered all of the country's pigs to be slaughtered. because humans can only get the new flu from other humans this was not effective as a control response. it also had far-reaching and unintended consequences on the cities' waste management. cairo's garbage collectors used to feed the city's organic waste to pigs and their livelihood became endangered while the streets of the capital filled up with trash. source: adapted from the new york times article, mona el-naggar contributed reporting, september . available at: http://www. nytimes.com/ / / /world/africa/ cairo.html_r= &scp= &sq= michael% slackman% cairo% pigs&st=cse& (accessed . . ). cryptosporidium is associated with cattle and causes diarrheal disease in humans and cattle. although extensively studied in developed countries, it has not been diagnosed until recently in slums. surveyed households in the nairobi´s dagoretti district, kenya, determined the extent of cattle keeping and the prevalence of cryptosporidiosis. with a prevalence of % in urban cattle, this parasite could be a major contaminant of water sources and disease that needs further consideration (international livestock research institute, ) (figure ) . antibiotics and other veterinary drugs administered to animals without proper veterinary supervision can have direct and indirect consequences for human health. after administration of an antibiotic there is a period of time when the animal product should not be consumed. this period known as the withdrawal period is to allow the drug in question to clear the animal's system because it may have harmful health effects if consumed by people who are allergic or sensitive to the drug. for example, clenbuterol is commonly used as a growth promoter (often illegally), and several outbreaks of illness have occurred when people consume livestock products from animals treated with clenbueterol. of potentially greater importance than sickness as the result of consumption of residues is the risk of bacteria developing resistance to antibiotics because of their use in agriculture. as a result of these concerns, many countries require that antibiotics and some other animal health drugs should only be prescribed by veterinarians. however, this is not practicable in most slums. veterinary services may be out of reach for many people in slums either because of distance or cost. in some cases, livestock owners may visit a veterinary office and explain the symptoms of the disease to the veterinarian, but without proper examination of the animal and the information received, the medicines may not be appropriately prescribed. the livestock owner may not fully understand how to administer the medicines and use a single dose of a medicament keeping the rest in case the animal does not improve. getting advice from another family member or neighbors, purchasing a single dose of an antibiotic from a street vendor, or using leftover medicines from a previous case is not uncommon. veterinary services are often expensive and out of reach of the poor (ahuja et al., ) . in addition, farmers may use drugs for nonhealth purposes. in khartoum, the practice of adding antibiotic to milk to preserve it was reported, and this could have health consequences such as allergy in the people ingesting the product (hassabo et al., ) . in china, melamine was added to milk so that it would appear to have higher protein levels. this lead to one of the largest food safety events of recent years resulting in the death of six infants; the children died from kidney stones and thousands were hospitalized as a result of drinking the contaminated milk (wei and liu, ) . slum agriculture and associated markets are part of the informal sector of the economy. it is a business model based on necessity, mostly home-based, and often clandestine. when there is no proper access to water and refrigeration, meat and eggs must be consumed rapidly, processed, and sold close to the place of origin. markets in slums are public places where vendors congregate. products may also be sold by hawkers moving from door-to-door or as requested. in many cities in developing countries milk is sold in this way. it is not uncommon to sell products from homes through modified window sills, from makeshift sale racks in corridors between houses, or on top of blankets or plastic sheets in the floor in open spaces. slum dwellers acquire knowledge of who produces and sell different items. prices vary based on perceived notions of quality, hygiene, or availability. the exchange of money is not always the norm for payment and people engage in bartering or exchanging products for services. agricultural markets in slums differ from municipal markets where there is an operational legal framework and the state is responsible for the enforcement of public health and food safety regulations. however, the great majority of food sold in municipal markets lack any structured sanitary inspection. this does not mean that the markets in slums lack internal form of self-regulation, they have a sui generis operational business model. although these markets are outside the purview of state regulation and disease control and preventative measures, the prevailing food-safety actions are based on accepted cultural norms. these norms are developed by the people who live, sell, and purchase products under these conditions or based on religious beliefs or restrictions (rheinländer, ) . the number, identification of species, and location and ownership of animals in a slum is not usually performed. the lack of census data and owner identification poses a challenge for the implementation of national disease control or eradication programs. required reporting of diseases and animal or product traceability to origin may be impossible in case of a food-related outbreak. this is contrary to the application of the sanitary and phtyo-sanitary measures of the world trade organization. most countries agree to adhere to these measures when they join the world trade organization. conducting an animal census in a slum is challenging but without knowing how many animals there are, vaccine campaigns or eradication programs cannot be conducted. however, the legally ambiguous position of livestock in slums mean owners are reluctant to incur official notice. the inspection of animal facilities and product transformation industries destined for human consumption is highly regulated. although in many developing countries animals must be processed in municipal slaughterhouses, at home and clandestine slaughter are common. in bolivia, some of the municipal slaughterhouses are rudimentary and managed by the local communities. the official veterinarian is allowed to inspect the animals preslaughter and outside the facility. the inspection concerns mostly reportable diseases of national importance. inside the slaughterhouse, skilled butchers castrate male pigs, and these and other animals bleed on the floor as part of the exsanguination process. once the internal organs are removed the carcass is hung on a wall hook and employees rub the pigs´canal with a rag. the same rag and water stored in a bucket is used to wash several carcasses. an inquiry into the practice revealed the employees neither understood why they were doing the cleaning nor how it was supposed to be done (correa et al., ) . in ibadan, nigeria facilities are even less developed. approximately - cattle are slaughtered daily; more are slaughtered on weekends, and fewer during muslim holidays. cattle are kept in pens, then moved to the slaughter slab. they are tied down at the slab and killed by cutting the throat. the dead cattle are then dragged on the ground to the abattoir area. this is simply a shed with a concrete floor and open sides. removal of the intestines and quartering is done on the floor. portions of the carcass are then carried to the adjacent butchers' stalls where they are sold. the abattoir is under municipal management and officers collect tax and tariffs on each cow amounting to us$ per animal. the role of environmental sanitary officers is to inspect slaughter slabs and the general environment and ensure the area is clean. however, the filthy conditions of the market witness the challenges they face in carrying out their work. the veterinary department is supposed to check animals before slaughtering and inspect meat after slaughter, but many animals escape inspection, and even when problems are found veterinarians find it difficult to ensure condemned meat is discarded. most butchers kill only one animal a day, and if this is condemned by veterinarians as unfit for human consumption they lose their entire day's earnings. hence, they strongly resist attempts to condemn meat (grace et al., ) . slaughter practices are probably clearly specified in pertinent regulations, but without oversight or evaluation by competent authorities, wrongly learned and applied practices may never be corrected. new employees learn from other employees and the practice is passed down, transformed, and perpetuated. the 'trichina inspectors' in livestock markets in bolivia are lay people trained by other people to inspect the tongue of pigs in order to detect cysts associated with cysticercosis. trichina is a different parasite and the tongue inspection is not associated with this parasite, but t. solium. the wrong parasite reference has prevailed and the practice continues unchecked for efficiency in preslaughter diagnosis of cysticercosis in pigs. in ecuador´s countryside, a traveling butcher works at the community slaughterhouses at scheduled days and times of the week and processes the carcasses of mainly large species at the municipal facility. this is a trained person who can condemn carcasses from sick animals and has an important food safety role. however, the most predominant form of slaughter in slums is the one done at home, in the streets, between or behind buildings. usually for smaller species the head is removed using a sharp knife or axe against a hard surface like a piece of wood or the stump of a tree. the internal organs are removed swiftly; sometimes the esophagus and the rectum are tied to avoid intestinal content spillage and contamination. animals processed in this manner are not properly exsanguinated. raw offal may attract dogs and vermin. the meat, without refrigeration must be consumed immediately or it is left to dry on racks. meat maybe carried to markets in small carts, buckets, or burlap bags and sold in small pieces or cut by the client´s request. the meat is not inspected when sold in the slums to neighbors or at smaller slum markets. in nepal, animal parts are sold with other identifiable body parts like a hoof or horns in order to guarantee that the species being sold is the actual species. in many cases the meat is covered in turmeric, reported to be done to decrease contamination (oral tradition reported to authors by street vendors). interestingly, homeopathy studies suggest that turmeric can help combat bacterial infections (krup et al., ; vasavda et al., ) . slum livestock agriculture interweaves its existence with the geographic location and culture of the population. people take advantage of their new environment and recreate a way of living based on their upbringing, including raising and processing livestock. the main motivations for this activity are family subsistence, income generation, and social status. slum livestock agriculture activities range from subsistence to semicommercial production. it plays a role in the livelihood of millions of people providing animal protein and generating income. however, it lacks technical sophistication and typically operates outside regulatory purview, and its practice overlooked and tolerated by local authorities. animals pose a risk to human health and other animals, are a public nuisance, and contribute to the waste accumulating on streets and the run off contaminating the environment and water sources. livestock products, raw or processed are sold in street markets and may enter the urban food chain. animal ownership is difficult to establish in slums and livestock population difficult to determine. under these circumstances, veterinary services and disease-control programs may be hard to implement. good hygiene, good manufacturing practices, and animal slaughter inspection turn into an impossible task to implement and enforce. disaster and white-coat diplomacy practices combined with information and communication technologies should be considered in the planning and implementation of public awareness and outreach programs (lemery, ; lin and heffernan, ) . the elimination of the slums is not feasible. the magnitude of the animal population in slums is unknown, but its food security importance is getting recognition from public and private organizations. there is a need for a community-led approach in collaboration with private and public institutions, academic, international, and nongovernmental organizations to find sustainable solutions. the delivery of veterinary services to poorer communities: the case of rural orissa. revue scientifique et technique de l commercialization of animal-derived remedies as complementary medicine in the semi-arid region of northeastern brazil irrigated urban vegetable production in ghana: microbiological contamination in farms and markets and associated consumer risk groups an epidemiological study of taenia solium in rural population in the bolivian chaco center for disease control and prevention, cdc / , . when humans and animals intersect criaderos clandestinos de cerdos se incrementan en pueblos jóvenes goodly beasts, beastly good: cattle and commodities in a south african context proceedings of the th international symposium on veterinary epidemiology and economics. available at: www.sciquest.org.nz resource use efficiency in urban and peri-urban sheep, goat and cattle enterprises the problem of huge unproductive livestock population in india north american 'swine aid' and economic disaster for haitian peasants urban agriculture: a strategy for poverty reduction in nigeria spotlight issues in urban agriculture studies suggest that up to two-thirds of city and peri-urban households are involved in 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country isolation, detection and characterization of swine hepatitis e virus from herds in costa rica livestock in the slum: a visit to an urban farm in kenya. farming livestock in african slums pharmacological activities of turmeric (curcuma longa linn): a review of a case for white coat diplomacy environmental and social sustainability of urban and periurban agriculture (upa) in selected towns of ethiopia creating the livestock guru: icts to enhance livestockrelated knowledge among poor households in orissa prevalence of antibodies to hepatitis a and hepatitis e virus in urban school children in chennai urban agriculture: definition, presence, potentials and risks available at cleaning up its act: recycling livestock waste slum tour in dharavi, mumbai with reality tours and travel informal settlements, real estate market need for good land administration and planning epidemiology of taenia solium taeniasis/cysticercosis in india and nepal street food quality. a matter of neatness and trust broiler chicken market in slums association between epilepsy and cysticercosis and toxocariasis: a population-based case-control study in a slum in india slum health: from understanding to action world urbanization prospects. economic and social affairs united nations human settlements programme pharmacological activities of turmeric (curcuma longa linn): a review review of melamine scandal: still a long way ahead antibody levels to hepatitis e virus in north carolina swine workers, non-swine workers, and murids growing greener cities in africa proper slaughter and flaying of sheep and goat. ethiopia sheep and goat productivity improvement program key: cord- - m iu j authors: singh, awadhesh kumar; misra, anoop title: impact of covid- and comorbidities on health and economics: focus on developing countries and india date: - - journal: diabetes metab syndr doi: . /j.dsx. . . sha: doc_id: cord_uid: m iu j background and aims: presence of comorbidities in patients with coronavirus disease (covid- ) have often been associated with increased in-hospital complications and mortality. intriguingly, several developed countries with a higher quality of life have relatively higher mortality with covid- , compared to the middle- or low-income countries. moreover, certain ethnic groups have shown a higher predilection to contract covid- , with heightened mortality. we sought to review the available literature with regards to impact of covid- and comorbidities on the health and economics, especially in context to the developing countries including india. methods: a boolean search was carried out in pubmed, medrxiv and google scholar databases up till august , using the specific keywords to find the prevalence of comorbidities and its outcome in patients with covid- . results: all available evidence consistently suggests that presence of comorbidities is associated with a poor outcome in patients with covid- . diabetes prevalence is highest in indian covid- patients compared to other countries. majority of the patients with covid- are asymptomatic ranging from to %. conclusions: universal masking is the need of hour during unlock period. low-income countries such as india, brazil and africa with less resources and an average socio-economic background, must adopt a strict policy for an affordable testing programs to trace, test, identify and home quarantine of asymptomatic cases. despite the huge number of covid- patients, india still has low volume research at the moment. since the coronavirus disease (covid- ) outbreak started in wuhan in december , it has spread across every corner of the world including lowincome countries. two low-income countries that bear the major brunt and tops the list along with usa with regards to the number of reported cases of covid- include brazil and india. brazil has reported nearly . million covid- cases with more than thousand deaths, while india has also crossed over . million reported cases with more than thousand deaths, as of august , . although both brazil and india are placed currently at second and third position respectively just after the usa with more than . million reported cases, india is currently reporting highest number of new cases of covid- day-wise, globally [ ]. africa has crossed over . million reported cases of covid- with more than thousand deaths, as of august , [ ] . emerging data clearly suggests, that associated comorbidities such as hypertension, diabetes, obesity, cardiovascular disease (cvd), cerebrovascular accident (cva), chronic obstructive pulmonary disease (copd), asthma, chronic kidney disease (ckd) and malignancy are often associated with increase in severity and or mortality in patients with covid- . we aimed to look at the impact of comorbidities in patients with covid- across the world and present a descriptive analysis on health and economics with a special emphasis on low-income countries like india, brazil and africa. a boolean search was carried out to find the prevalence of comorbidities and its outcome in patients with covid- in pubmed, medrxiv and google scholar j o u r n a l p r e -p r o o f databases up till august , using the specific keywords that include "sars-cov " or "covid- ", and "risk", "severity", "mortality", "obesity", "diabetes", "hypertension", "cardiovascular disease", "chronic kidney disease", "cancer", "chronic pulmonary disease", "developing countries". full text of all the related articles in english language with supplementary appendix were retrieved. we selected the single largest data published from each country for the descriptive analysis that reported the prevalence and outcomes of comorbidities in patients with covid- . the descriptive analysis of overall result was also presented whenever meta-analysis included the pooled data of largest study representing each country that studied the prevalence of comorbidities and its outcome. we excluded smaller case series or retrospective cohort studies from the descriptive analysis whenever the largest data was available, in order to avoid overlapping. in addition, we excluded studies that did not report the prevalence of comorbidities and its outcome. several meta-analyses have reported the prevalence of comorbidities in patients with covid- [ ] [ ] [ ] [ ] [ ] [ ] [ ] . however, many of them have included studies only from china and notably, several chinese studies included have apparently overlapped data that can limit any conclusions [ ] . in this regard, our recent meta-analysis table summarizes the prevalence of comorbidities in patients with covid- from the largest reported data from china, usa, uk, italy, mexico, spain, kuwait and india [ ] [ ] [ ] [ ] [ ] [ ] [ ] . unsurprisingly, diabetes prevalence is highest in indian covid- patients compared to other countries. interestingly, as many as . % ( % ci, . - . ) patients in the study from india were asymptomatic and had no symptoms at the time of diagnosis [ ] . a similar finding of disproportionately higher asymptomatic ( . %) covid- patients were also observed from kuwait [ ] . in contrast, studies from taiwan study from italy that analyzed and differentiated pre-symptomatic to asymptomatic cases reported a . % ( . - . ) prevalence of asymptomatic cases [ ] . collectively, these findings suggest a large proportion of patients with covid- could be asymptomatic and therefore a due care is urgently required to recognize these cases though trace, test and treat (quarantine) approach [ ] . study has clearly shown that universal use of mask effectively reduces the chance of contracting covid- amongst the health workers [ ] . the largest chinese data found significantly increased case-fatality rate (cfr) in presence of any comorbidity. although overall cfr was . % for overall population (n= , ), the presence of comorbidities such as cvd, diabetes, copd, hypertension and cancer increases the cfr to . %, . %, . %, . %, . uk data also found chronic cardiac disease, copd, ckd, obesity and liver disease to be associated with significant increase in mortality, apart from male sex and increasing age [ ] . several meta-analyses have shown a significant increase in severity and mortality in individuals with comorbidities with covid- , apart from increasing age [ , , , , ] . our metaanalysis that pooled the studies from china, usa and italy found a significant . to -fold increase in severe covid- associated with either hypertension or diabetes or cvd or copd or ckd and or cancer. similarly, patients with covid- with cvd or hypertension or diabetes had a significantly -fold increase in mortality [ ] . in addition, other studies from usa and uk have also found obesity to be associated with a significant increase in mortality [ , ] . no large published data is currently available from the developing countries with regard to the association of comorbidities to mortality. detailed available data of deceased from a total reported cases of deaths as of april , from india found . % of the deceased had one of these preexisting comorbidities, of which diabetes was present in . % ( / ), hypertension in . % ( / ), respiratory disease (copd and asthma) in . % ( / ) and cvd in . %. notably, while % of the deceased had both diabetes and hypertension, . % had all the three comorbidities (diabetes, hypertension and cvd). thus, diabetes was the leading comorbidity present in deceased covid- individuals from india [ ] . a latest report of july , by the integrated disease surveillance [ , ] . notwithstanding, the consistent association between bcg vaccination and reduced severity of covid- observed in epidemiological explorations, there is still insufficient evidence to establish causality between bcg vaccination and protection from severe covid- . to this end, two randomized placebo-controlled clinical trials are currently ongoing with bcg vaccine in health workers in holland and australia that will determine to what extent bcg vaccination in adults can confer protection from the covid- [ , ] . meanwhile, it appears that the "trained immunity" gained over the years, defined as an enhancement of innate immune response due to repeated exposure to the subsequent repeated infection (viral, malarial, bacterial infections in developing countries) which is achieved through a metabolic programming of j o u r n a l p r e -p r o o f immune cells as well as epigenetic factors, along with the universal bcg vaccination that has provided cellular immunity, both combined together, might be offering some role in having less severe covid- , as well as lesser mortality in developing countries including india [ , ] . the national surveillance agencies of two countries usa (centers for disease control and prevention) and uk (public health england) have assessed the outcomes of covid- based on ethnicity. while a systematic review from initial pre-print studies from both usa and uk found that the risk of infection, hospitalization, severe covid- were higher in blacks and minority ethnic (bame) groups, the risk of mortality was also higher in bame population in uk and in particular in blacks in usa [ ] . in addition, several recent cross-sectional, prospective-observational and retrospective studies from uk have also consistently found a significant greater mortality in bame groups including the south asians (bangladeshi > pakistani > indians) [ ] [ ] [ ] [ ] [ ] [ ] . it should be recalled that migrant south asians have been found to have a several fold increase in obesity, diabetes, heightened cardiovascular risk, associated complications and mortality from noncommunicable diseases. moreover, the latest morbidity and mortality weekly report (mmwr) from cdc (july , ) also found that non-white and black populations are more affected with covid- , especially in < years of age [ ] . while several hypothetical reasons for the heightened rate of infection and mortality with covid- in the bame group has been hypothesized by the researchers [ , ] , one potential contributing factor that could be the most likely explanation seems to be a higher percentage of bame population engaged in certain occupations such as service industry or essential activities or paramedical j o u r n a l p r e -p r o o f or frontline staffs that may preclude physical distancing. future research is further required for understanding the mechanism and further steps are needed to prevent devastating outcomes in the minor ethnic community. the latest estimates of international diabetes federation (idf), diabetes atlas th edition, , suggests that worldwide nearly million adults in the age of - year have diabetes, of which nearly % of them live in low-or middle-income countries and nearly % of them are asians. the estimates also found, in adults have diabetes and in of the people with diabetes in the world come from south-east asia, and in adults with diabetes in the world come from india [ ]. these large numbers pose a major challenge in managing diabetes during the covid- pandemic. expectedly, a large chunk of patients with diabetes have increased snacking/carbohydrate intake and decreased physical activity during the lockdown period that have resulted in weight gain and de-stabilize the glucose control which might results in a likely increase in diabetes-related complications [ ] . moreover, as per one estimate, weight gain during lockdown may increase prevalence and impact of cardiovascular metabolic diseases on covid- in china prevalence of comorbidities in the novel wuhan coronavirus (covid- ) infection: a systematic review and meta-analysis prevalence of underlying diseases in hospitalized patients with covid- : a systematic review and meta-analysis prevalence and severity of corona virus disease (covid- ): a systematic review and meta-analysis prevalence and ethnic pattern of diabetes and prediabetes in china in effects of hypertension, diabetes and coronary heart disease on covid- diseases severity: a 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patients in india who died had no comorbidities: govt analysis chronic heart diseases as the most prevalent comorbidities among deaths by covid- in brazil global, regional, and national estimates of the population at increased risk of severe covid- due to underlying health conditions in : a modelling study ethnic and socioeconomic differences in sars-cov- infection: prospective cohort study using uk biobank bcg vaccine protection from severe coronavirus disease (covid- ) the bcg world atlas: a database of global bcg vaccination policies and practices reducing health care workers absenteeism in covid- pandemic through bcg vaccine (bcg-corona) innate immune memory: a paradigm shift in understanding host defense the impact of ethnicity on clinical outcomes in covid- : a systematic review opensafely: factors associated with covid- -related hospital death in the linked electronic health records of million adult nhs patients type and type diabetes and covid- related mortality in england: a whole population study ethnicity and risk of death in patients hospitalised for covid- infection: an observational cohort study in an urban catchment area ethnicity and outcomes in patients hospitalised with covid- infection in east london: an observational cohort study ethnicity and outcomes from covid- : the isaric ccp-uk prospective observational cohort study of hospitalised patients covid- in black, asian and minority ethnic populations: an evidence review and recommendations from the south asian health foundation is ethnicity linked to incidence or outcomes of covid- ? covid- and ethnicity: a novel pathophysiological role for inflammation effects of nationwide lockdown during covid- epidemic on lifestyle and other medical issues of patients with type diabetes in north india increase in the risk for type diabetes due to lockdown for covid pandemic in india: a cohort analysis estimation of effects of nationwide lockdown for containing coronavirus infection on worsening of glycosylated haemoglobin and increase in diabetes-related complications: a simulation model using multivariate regression analysis acceptability and utilization of newer technologies and effects on glycemic control in type diabetes: lessons learnt from lockdown diabetes technol ther roadblock in application of telemedicine for diabetes management in india during covid pandemic the links between covid- and diabetes, known and unknown diabetes during the covid- pandemic: a global call to reconnect with patients and emphasize lifestyle changes and optimise j o u r n a l p r e -p r o o f glycemic and blood pressure control covid- in people living with diabetes: an international consensus scoring systems for predicting mortality for severe patients with covid- does communicable diseases (including covid- ) may increase global poverty risk? a cloud on the horizon addressing covid- impacts on agriculture, food security, and livelihoods in india | ifpri the potential impact of the covid- epidemic on hiv, tb and malaria in low-and middle-income countries j o u r n a l p r e -p r o o f key: cord- - tmtvw r authors: singh saraj, k.; mishra vishal, a.; jha vikas, c. title: modification of neurosurgical practice during corona pandemic: our experience at aiims patna and long term guidelines date: - - journal: interdiscip neurosurg doi: . /j.inat. . sha: doc_id: cord_uid: tmtvw r background: first case of covid- was confirmed on (th) january, in india. our state, bihar reported its first confirmed case of covid on (nd) march at aiims patna. for safety, electives surgeries and outpatient department was suspended temporary since (th) march. standard operating procedure (sop) was framed for covid suspected, covid positive and negative patients. neurosurgery department formulated their own strategy for successful and covid free management of neurosurgical patients along with zero transmission rate among doctors and staff. methods: all neurosurgical patients who got attended, admitted and operated from (th) march to (th) june (period of lockdown) were taken in this study. categorizations of the patients were done according to the urgency and elective nature of pathology after corona screening and rt-pcr testing of covid- . a proper training to all neurosurgical staff and residents were given for management of patients (admission to operation to discharge). results: total patients were attended and were admitted. we operated cases (major - , minor – ) during the lockdown period. out of this were corona positive (both eventually succumbed) and rest was corona negative. one patient who was operated with corona negative report became positive after days of surgery inward. all the residents, faculty and nursing staff remain asymptomatic throughout the lockdown period with zero infection rate and zero transmission rate. conclusion: following a properly made standard operating procedure and strictly implementing it can avoid any type of misadventure in neurosurgery during corona pandemic. key message: adequate planning and sufficient training is necessary to avoid any untoward incident of infection. proper utilization of limited human resources and infectious kit is needed at this time. the first case of covid- was reported in india on january . as of th may , the ministry of health and family welfare have confirmed a total of , cases, , recoveries (including migration) and , deaths in the country. [ ] india currently has the largest number of confirmed cases in asia with number of cases breaching the , mark on th may and million in august. [ ] after successful trial of brief curfew on nd march, indian prime minister narendra modi followed it with complete nationwide lockdown from th march for days. the period of lockdown was subsequently increased three times in two months. [ , ] first proven case of covid in bihar was reported on nd march at our institute, all india institute of medical sciences, patna. he was -yearold male with a travel history to qatar. [ ] the virus has spread in districts of the state, of which patna has the highest number of cases. [ ] the state with a population of more than million people was under complete lockdown from th march to st may. it remained in partial lockdown status till st july . approximately , people got infected with covid till th june . after th june our hospital got converted into covid dedicated hospital. the state government has responded to the outbreak by following a contact-tracing, testing and home to home surveillance model. all outpatient services were shut down in our hospital since th march . however emergency services were continued and standard operating procedure (sop) was made both for the institute and our department. as our department is the only neurosurgical unit dealing vascular neurosurgery in the whole region of million, our responsibility was more as compared to other hospitals. to avert crisis during such pandemic, hospital and department both need a strategy to meticulously manage their staff, emergency, operation theatre complex (otc), intensive care unit (icu) and wards. here we are discussing our department response, guidelines, drawbacks and analysis of one of the most important emergency services at aiims patna with safe execution and management of neurosurgical patients. we also finalized a roadmap for future management of neurosurgical patients for next few months till this pandemic gets over. consecutive patients of neurosurgery (both traumatic and non-traumatic) at our institution were considered for the study. all patients who attended, admitted and operated from th march to th june (period of lockdown) were taken in this study. all all admitted patients were categorized on the basis of emergency for intervention data collection methods: data was collected prospectively when the patient was in emergency and trauma in the form of demographic profile at the time of admission and operation, comorbidity, gcs at the time of surgery. all patients were assessed on the basis of severity and admission was done. all admitted patients were categorized on the basis of protocol we made for department. (table no ) management was done on the basis of this protocol. along with urgency of the cases. in category i, patients were operated in emergency within hours with only corona screening. in these patients, nasopharyngeal swab were sent before taking up for surgery. external ventricular drain insertion, vp shunting (ventricularperitoneal shunting), edh (extradural hematoma) evacuation and decompressive craniotomy were included in this category. in category ii, patients were operated on urgent basis within - days after admission. results of rt-pcr were assessed before taking up for surgery. category ii was formalized by keeping incubation period of covid - in minds ( - days the surgeries needing more than - hours of exposures were categorized in major group and less than hour were categorized in minor group. in emergency, total patients were attended during lockdown period. out of this, were admitted in which were female and were male. mean age was . years. total patients underwent procedures/operations. (table no (table no )out of patients that got admitted, two came out as positive and rest were negative. one was having hypertensive bleed with intraventricular extension. in this patient evd was inserted after wearing full ppe kit. other was chronic sdh with severe mass effect which came with poor gcs (gcs- ). here twist drill was done and hematoma evacuated. but both the patients eventually succumbed. one covid negative patient became covid positive at th postoperative day on routine testing. however she was asymptomatic. she was transferred to covid positive ward and discharged from there after testing negative on rt-pcr. after lockdown from th march, the whole outpatient department (opd) was closed. all patients with minor ailments were advised to stay at home and only emergency patients were getting attended at trauma and emergency. from the beginning, contact details of the department were getting circulated in local newspapers for benefit of the patients. for initial to days, patients having traumatic head injury and spinal injury were getting admitted. than later on stroke, aneurysm rupture and large intracranial space occupying lesions also started arriving in emergency. after triage from institute, our department was also categorizing the patient on the basis of severity. it was observed that just by differentiating the cases into emergency and elective procedure, we are just avoiding the bay and not the storms. most of patients with benign intracranial or spinal pathologies will land up in emergency within days or months. so by doing triage we are just segregating emergency and urgent cases at that particular point of time. even after development of vaccine, covid- is going to stay for a longer period of our life. so we needed a triage system where we can deal with all types of cases with avoidance of covid exposure. the study from italy has provided a framework for creating an emergency task force, streamlining a stringent protocol and adequate training to achieve zero infection and transmission rate. [ , ] they have created treatment hubs with interchanging of neurosurgeons along with transport of patients from one hospital to other hospitals. they also created a task force which helped in reducing non-urgent cases. most of the urgent neurosurgical procedures were performed by a strict number of operators. [ ] it was not possible for us, because our institution is the only institution where active and specialized neurosurgical procedures is happening presently in the whole state of bihar having a population of more than million. . our team was composing of seven junior residents, four senior residents and two actively working faculties. we made a team of seven residents who were attending and admitting the patients from emergency. all emergencies were first attended by our junior residents. one resident was given an emergency duty of hours followed by days off. they were exempted from duties of ward and icu. each resident was covered by senior resident and one faculty on alternate days. . all senior residents were rotated weekly. one resident was fixed for taking rounds of covid negative patients in the ward and icu for week. in second week he got shifted to total junior residents everyone attending emergency one day/week duty off for next days operation theatre. his assistance was utilized for week. during third week he got shifted to covid ward and he was taking rounds of covid positive/ covid suspected patients followed by week of quarantine. above mentioned cycle was followed by each resident and it got repeated every month. . two faculties were actively working in the department. both of them took alternate turns for operation theatre/ ward rounds. faculty a was posted on st and rd week, faculty b on nd and th week. both the faculties were getting week of quarantine. following this protocol we maintained minimal interaction between faculties, senior residents and junior residents. it was followed till th june, . after that our hospital got converted from covid care center into covid dedicated hospital and all emergency services were closed. week - week - week - week - mask, head and shoe cover, goggles). (figure ) lifesaving procedures were done in corona suspected ward, bed side only like evd (external ventricular drain) insertion, twist drills. if rt-pcr comes positive, then patient is shifted in corona ward/ corona icu for further management. category i patients were planned for urgent surgeries and category ii patients were planned for surgery within - days. these patients were operated under strict covid protocol and again shifted back to covid icu. a dedicated transportation route is recommended during this covid pandemic. [ , ] and our department complied with it and neurosurgical patients were carried to operation theatre complex (otc) from different route. the whole route was sanitized once the transportation was completed. it is advised to do ct chest for all the patients. [ , , , ] nasopharyngeal swab for all the patients were sent. in trauma ward / icu total admissions took place. on rt-pcr all came out as negative. negative patients were shifted to neurosurgical ward/ neurosurgical icu. sensitivity of rt-pcr of different body fluids had been analyzed and published in jama. in this bronchoalveolar lavage fluid is the most sensitive specimen ( %), followed by sputum ( %), nasal swab ( %), fibrobronchoscope brush biopsy ( %), pharyngeal swabs ( %), feces ( %), and blood ( %). [ ] but we don't recommend multiple testing from different sites even if it can improve sensitivity and reduces false-negative results. however we recommend multiple modalities of investigations like chest x ray, rt-pcr from swab along with thermal screening and most important clinical assessment. at our institution only corona screening, chest x ray and rt-pcr for nasopharyngeal swab was done for all the patients. recent guidelines at present recommend a single upper respiratory nasopharyngeal swab for suspect cases. [ ] also a recent survey has indicated that, nasopharyngeal swab was the preferred method for screening ( %), followed by ct scan ( %), and chest radiograph ( %). some respondents indicated more than one screening method, especially those from italy ( %) and india ( %), where the most common combination was the nasopharyngeal swab with chest radiograph. [ ] the most important thing during preoperative period is mobilization of patients. it is the most important factor as patient can acquire these infections from hospital surroundings. we suggest that mobilization should be grossly restricted. radiological investigations like chest x ray, ct, mri and dsa should be done after keeping in mind the usefulness of these in planning surgery. if possible, all should be done in single transportation and sittings. [ , ] all patients were operated under strict covid operating room protocol. training -it has been shown by hoz et al that without sufficient quantity of ppe kit and also without adequate training, the whole system will collapse and staff will suffer along with the patients. [ ] so a proper training is mandatory for the whole surgical team before going for any surgery. a rigid training was given to all dedicated neurosurgical staff, technicians, residents and faculties to prepare for emergency cases. all steps (in sequence) were revised for many days in a dummy class by neurosurgical residents and faculties. multiple classes were taken for proper donning and doffing sequence of ppe kit for all the staff. already neurosurgical procedure needs a very smooth coordination of staff and operating surgeon which was stressed during this pandemic. movement of technicians and staff were kept very minimal. and neurosurgical nursing staff was allowed to assist only on the allotted specific days for surgery for a week followed by quarantine on next week. for initial month preferably accidental cases were taken for surgery, as this surgery needs less expertise from neurosurgical point of view. it will also give neurosurgical team and staff to acclimatize to work in pandemic atmosphere. avoiding surgeries is neither beneficial for the surgeons and nor for the patient. so battling the fear and rigorous training can only help us achieving zero infection rates with good post-operative results. needed during such pandemic to avoid transmission of infection. [ , , ] it was advised to have dedicated operation theatre for neurosurgery during this pandemic. [ , ] but survey has indicated that majority of institutions and centers had not done it. [ ] however as it was getting not possible in our institute, we opted for high air flow otc to reduce viral load. after each operation the otc was fumigated twice with sodium hypochlorite ( %) before taking up another case. in otc, all major neurosurgical equipment was covered with sterile covers. operating microscope was covered with drape and vision guard. c-arm was draped with sterile covers. equipment (ppe). patient face was covered with square transparent box during intubation. as anesthetist are in direct contact, risk of aerosol dispersion is maximum during intubation, hence it has been suggested that the whole face area may be covered by a transparent sheet and the hands may be inserted under the sheet to intubate the patients, while the edges should be stuck to the surface. a preferred protocol is the use of a separate room for intubation and then bringing the patient to the or, so the risk is minimized to the surrounding health personnel. [ , ] however as it was not possible at our center, our anesthetist opted for intubation after wearing ppe kit and head shield. during anesthetic procedure (intubation, arterial line insertion, central line insertion), all neurosurgical team was advised to stay outside. operative procedure -patient positioning was done after wearing n mask and head shield. during initial phase while we were not having any ppe kit for otc, we utilized "universal precaution kit" for performing surgeries. later on we switched over to ppe kit. it has been advised that surgical procedure should be performed after wearing level - protections kit. [ , , , ] only disposable items were utilized in surgeries like coverings, draping and gowns at our center. it is mandatory to wear two layers of surgical gloves to avoid infection from breakage of gloves. all surgeries should be performed after proper distribution of various stages to different surgeons. aerosol dispersal and blood spillage should be minimal. [ , ] at our center, only one surgeon at a time was involved in operative procedure. opening and closure was done by senior residents. middle portion of surgery was performed by the faculty. for complicated and long procedure, other faculty was kept on standby. during macroscopic phase (craniotomy, laminectomy) of surgery, head shield and eye goggles were utilized. (figure ) throughout the drilling process, copious irrigation was continued to allow minimal dispersal of aerosols. drilling was kept at minimal level to avoid dispersal of aerosol. operative procedure was done slowly and meticulously, especially the opening phase to avoid blood loss and spillage. (figure a and b) craniotomy utilizing hudson burr and gigli wire/saw should be avoided. it causes inappropriate dispersal of bone dust and blood. also it is very cumbersome to use and injury prone. transnasal vs transcranial approach -throughout the pandemic and even after opening of lockdown, we are continuously giving transnasal approach (both microscopic and endoscopic) a back seat. transcranial and spinal procedures are considered as safe. csf dissemination of virus has been rarely reported. only one case from china and one from japan has been reported with covid meningitis. [ ] however during pandemic, we should treat all cases of neurosurgery as covid positive case. by avoiding transnasal route we are also nullifying the chances of invasive covid meningitis. operative time -many of the neurosurgical procedures needing longer stay in otc can be deferred. however some of them needing urgent intervention like giant craniopharyngiomas, skull base tumors (giant vestibular schwannonas, glomus jugulare), bypass for giant aneurysms, multiple intracranial tumors (neurofibromatosis) and multiple aneurysms can be staged. longer contact period with the patient on ot table is one of the factors for surgeons getting infected with covid. [ , ] young neurosurgeons with good experience, precision and adequate speed should perform major surgeries, as they can sustain longer time and contact period in otc. neurosurgeons with comorbidities (like copd, hypertension, and diabetes mellitus) and age more than years should not opt for performing major surgeries at this time of pandemic. however trainees should be given a back seat at this moment of epidemic. postoperative period -ideally all post-operative patients should be categorized as covid suspected. they should be quarantined in ward. it has been recommended to take throat swab and do a ct chest at least thrice weekly. [ , , ] majority of the patient in neurosurgery get shifted in icu. so ventilators and monitors are necessary equipment. also nutritional support is very important to regain natural immunity in post-operative period. [ , , ] at our center, all patients were shifted to neurosurgical icu in post-operative period. air duct of ventilators were getting replaced daily. nasopharyngeal swab was sent and chest x ray also done but only once in two weeks. we avoided unnecessary mobilization of patient postoperatively for multiple investigations. all the patients were started with early feeding, either orally or ryle's tube feeding. immunosuppressive drugs like steroids were avoided in majority of the patients in post-operative period. mobile ct machine and mobile x ray machines should be used aggressively during this pandemic and cover should be destroyed after each round of utilization. [ , , ] we kept a separate x ray machine and technician for neurosurgical icu. as mobile ct was not available, timing slots were given to respective departments. our patients were mobilized for postoperative or preoperative ncct head or mri / dsa at allotted time slots. none of the patients came positive on immediate postoperative swab. however one patient of ica cavernous segment aneurysm (ica trapping was done) came positive in the ward after days. on repeating pcr of rest of the patients in adjacent bed, it came negative. we fumigated that section of ward covered with glass shield. multiple articles have suggested that patients with stable condition should be postponed. [ , , , , , , , , ] the covid- outbreak had a relevant impact on surgical planning. in survey by fontanella et al most have responded with a significant change in surgical activity in their institutions ( %). [ ] the majority ( %) performed only urgent and emergency procedures; with few had ( %) completely closed the entire neurosurgical department. there is % reduction of surgical interventions. delaying elective procedures will contain the spread of sars-cov- by reducing no of visits and it will also reduce possibility of treating asymptomatic carriers. [ , , ] by following this zero infection and transmission rate can be achieved. however, as ours is an apex center catering around million population, we developed our own triage system. we categorized the patients according to the condition of the patient. stable patients were postponed but not cancelled indefinitely. they were taken up at later date after doing an rt-pcr of nasopharyngeal swab just before the operative procedure. at our department, the number of cases dipped minimally. however, number of elective cases went down but emergency cases went up significantly. as most of the private hospitals in our state got closed, our load remained fairly constant. academic activities -intra-hospital and intradepartmental movements were restricted and minimum residents were kept for functioning of the department. it is suggested that all the academic activities like mortality meetings, journal club, and case discussions should be done through video conferencing and webinars. it is also recommended that physical distancing should be maintained during rounds and departmental meetings also. [ ] we strictly adhered to it. however from st july, all rounds, operative teachings and classes were suspended. all the residents came into common pool and got involved in covid patient care only. but we are still continuing with webinars and online classes. future plan-it has been outlined that telemedicine and telephonic communication is the future. [ , ] our department is planning to initiate telemedicine for patients both telephonically and on video calls. it will help us to follow our post-operative cases. through this assessment of preoperative cases can be also be done and they can be given appointment for surgeries especially elective cases. semi urgent cases can be followed weekly and in case of deterioration they can be called up to emergency directly. our department is already having policy of giving contact details of our common duty mobile number to all our preoperative and post-operative patients and their relatives. during this pandemic we encouraged these types of communications significantly. this cell phone is carried by neurosurgical resident and covered by one of the faculty daily. it was planned to give dates to all elective cases, so that they can plan their transportation and safety before arriving in opd. they will come one day before opd and get themselves tested for covid- . maximum new cases and old cases will be entertained per day. we have planned to erect glass shield along with microphones so that clinical history can be taken maintaining physical distancing. clinical examination will be done after wearing protection kit. mri, ct scan, dsa will be done at our center. it will minimize our contact with fomites. if already done outside, every patient will be advised to carry dvd / cd of their imaging. majority of these things we had already started and practicing in our institute and department. however due to conversion of hospital into covid dedicated center, it took back seat. as patients are piling up, sooner we will restart our department and center with same protocol. however as more cases of covid related encephalitis are getting reported, it may get delayed. [ ] during corona pandemic, it is advised to do meticulous triage of neurosurgical patients. home | ministry of health and family welfare | goi hindustan times india to go into nationwide lockdown india's coronavirus lockdown: what it looks like when india's . billion people stay home india reports seven coronavirus deaths as die in mumbai what are red, orange, green zones". the times of india neurosurgery during the covid- pandemic: update from lombardy, northern italy neurosurgical practice at the time of covid- neurosurgical practice during the severe acute respiratory syndrome coronavirus (sars-cov- ) pandemic: a worldwide survey preliminary recommendations for surgical practice of neurosurgery department in the central epidemic area of coronavirus infection preparing for a covid- pandemic: a review of operating room outbreak response measures in a large tertiary hospital in singapore neurosurgery and neurology practices during the novel covid- pandemic: a consensus statement from india detection of sarscov- in different types of clinical specimens covid- ) neurosurgery in iraq at the time of corona roadmap for restarting elective surgery during / after covid- pandemic letter: safety instructions for neurosurgeons during covid- pandemic based on recent knowledge and experience letter: the coronavirus disease global pandemic: a neurosurgical treatment algorithm covid- in neurosurgery news, guidelines and discussion forum american college of surgeons. covid- : recommendations for management of elective sources of support (if applicable): none conflict(s) of interest: none key: cord- - s ap authors: sundaram, sridhar title: covid testing before every endoscopy: is india ready for primetime? date: - - journal: gastrointest endosc doi: . /j.gie. . . sha: doc_id: cord_uid: s ap nan to the editor, the first case of sars-cov infection in india was reported on the january , from kerala. the disease since then has increased manifold to reach figures of over , infections across the country, significantly impacting healthcare with drastic changes in clinical practice. multiple society guidelines have been published since the outbreak of the virus, with a major focus on screening and precautions for patients undergoing endoscopy. continuing hospital services in a smooth and effective manner while taking care of patient and caregiver safety remains a priority. covid has had its economic impact with hospitals cutting down on elective procedures, impacting patient care and also the revenue generated. one question that has remained largely unanswered in all guidelines is whether we should routinely test for covid before elective and semiurgent endoscopies. india is a unique healthcare setting with costs of healthcare interventions being very low. average upper gi endoscopy costs in india is between rs. to rs. (~ to u.s. dollars). colonoscopy costs are between rs. to rs. (~ to u.s. dollars). meanwhile, average testing cost for novel coronavirus pcr is rs. (~ - u.s. dollars) in private laboratories. also, the report may not be available right away considering pool testing done at various centers. the low endoscopy costs and higher pcr test costs may not justify testing for all with pcr. the population prevalence in india is approximately . per , as compared with per , in the study by corral et al. the chances of disease detection fall significantly, considering the low prevalence. the disease prevalence in high-risk pockets like mumbai are close to per , population, which is much less than the prevalence in the study previously quoted. however, an important consideration becomes the fact that disease prevalence is likely to increase further. hence, testing for all may not be the right strategy at the moment. however, constant appraisal of the situation will guide us better for further policy decisions on testing. adequate screening before patient assessment and endoscopy remains the cornerstone for prevention. clinical judgement should take credence over laboratory investigations to decide necessity of investigations. the prudent use of ppe appropriate to the risk setting remains imperative and cannot be overemphasized. we designed an algorithm for restarting semiurgent and elective procedures once there is de-escalation of isolation measures (fig. ). our reliance on pcr makes it difficult to test all individuals, considering the logistic and financial difficulties. serological tests with antibody testing may be the solution, where tests can be offered for all individuals. however, current first-generation elisa tests for covid igm and igg are still in the stages of evolution and require validation in our setting. the caveat is also that patients may not get detected in the early stages of the disease, leading to increased infections in the hospital. the american enterprise institute has provided a roadmap to reopening after the coronavirus pandemic. india is likely to go from phase to phase after lockdown measures are relaxed. despite our slogan being "go corona go," i guess the virus is here to stay. what remains crucial is to build our disease surveillance, testing, and treatment capacity to smoothen the transition. to conclude, we may still not be ready for primetime with pcr testing for all patients, largely because we may not need it in the first place at the moment. full-genome sequences of the first two sars-cov- viruses from india covid- polymerase chain reaction testing before endoscopy: an economic analysis unit cost of medical services at different hospitals in india the promise and peril of antibody testing for covid- national coronavirus response: a road map to reopening figure legend figure : algorithm for testing before endoscopic procedures. high-risk clinical setting includes symptomatic with severe acute respiratory syndrome or influenza-like illness or asymptomatic contact of positive patient. high-risk epidemiologic setting includes hailing from a high-prevalence area/hotspot/containment zone key: cord- -l yz ude authors: sharma, shubham; zhang, mengyuan; anshika; gao, jingsi; zhang, hongliang; kota, sri harsha title: effect of restricted emissions during covid- on air quality in india date: - - journal: sci total environ doi: . /j.scitotenv. . sha: doc_id: cord_uid: l yz ude the effectiveness and cost are always top factors for policy-makers to decide control measures and most measures had no pre-test before implementation. due to the covid- pandemic, human activities are largely restricted in many regions in india since mid-march of , and it is a progressing experiment to testify effectiveness of restricted emissions. in this study, concentrations of six criteria pollutants, pm( ), pm( . ), co, no( ), ozone and so( ) during march th to april th from to in cities covering different regions of india were analysed. overall, around , , , and % decreases in pm( . ), pm( ), co, and no( ) in india were observed during lockdown period compared to previous years. while, there were % increase in o( ) and negligible changes in so( ). the air quality index (aqi) reduced by , , , and % in north, south, east, central and western india, respectively. correlation between cities especially in northern and eastern regions improved in compared to previous years, indicating more significant regional transport than previous years. the mean excessive risks of pm reduced by ~ % nationwide due to restricted activities in lockdown period. to eliminate the effects of possible favourable meteorology, the wrf-aermod model system was also applied in delhi-ncr with actual meteorology during the lockdown period and an un-favourable event in early november of and results show that predicted pm( . ) could increase by only % in unfavourable meteorology. this study gives confidence to the regulatory bodies that even during unfavourable meteorology, a significant improvement in air quality could be expected if strict execution of air quality control plans is implemented. • the effect of restricted human activities due to the covid- pandemic in india on air quality in cities was estimated. • pm . had maximum reduction in most regions. • correlation between cities especially in northern and eastern regions improved in compared to previous years. • the substantial reduction in concentrations resulted in a times reduction in total er. • pm . could increase due to unfavourable meteorology but the average concentration would still be under cpcb limits. a b s t r a c t a r t i c l e i n f o air pollution has come up as a growing concern all over the world, especially in developing nations like india. india witnessed economic growth, rapid expansion of cities, industrialization, and fast-paced development of infrastructure since liberalization during the s. simultaneously, the level of air pollution in india has increased to a major health risk and cause of large premature mortality. approximately one million people died in due to ambient particulate matter (pm) pollution alone in india (guo et al., ) . indian cities have been always making into the top most polluted cities of the world for the past few years and exceeding the ambient air quality standards recommended by the world health organization and central pollution control board (cpcb) kota et al., ; mukherjee and agrawal, ) . pm, the most dominant pollutant, in major parts of india has major contributions from vehicles, residential, energy, industrial and dust (guo et al., ; guo et al., ) . to control the severe air pollution in the country, the national clean air programme (ncap) launched a five-year action plan was launched in with a goal of reducing pm by % nationwide (moefc, ). are effective strategies followed up by efficient implementation can reduce the air pollution as expected? it is an open question as atmospheric processes that determine concentrations of air pollutants are nonlinear and changing meteorology plays significant roles in pollution formation. for example, the chinese five year clean air action plan resulted in improved air quality in china (j. li et al., ) . however, the peak pm . concentrations during episodes in winter did not reduce due to unfavourable meteorology (wang et al., ) . similarly, zhang et al. ( ) estimated~ % reduction in nitrate in eastern us by emission control was offset by meteorology. a simulation done in china showed that metrology played very important role in air pollution formation and severe air pollution was not avoided during the lockdown in january and february (wang et al., ) . the spread of coronavirus disease (covid ), which was initially identified in wuhan of china, resulted in more than one million cases worldwide within the first four months. this has resulted in lockdown in many nations worldwide. while, the first confirmed case in india was on january th, , the first international travel advisory posing restrictions on travel to china, republic of korea, iran, italy and japan was issued on march th of after the country saw sudden jump in covid- cases on march th (https://www.mohfw.gov.in/). southern state of india, kerala, which was initially the most effected state imposed curtails on mass gatherings on march th. starting from march th all places of mass gatherings such as institutions, shopping malls and theatres were closed across the country. the first nationwide lockdown for fourteen hours was on march nd, which was followed by days lockdown starting from march th. this lockdown enforces restrictions and self-quarantine measures, which reduce emissions from transportation and industries. the changes in air pollution in this lockdown period can provide an insight into the achievability of air quality improvement when there are significant restrictions in emissions from many sources and gives regulators better plans to control air pollution. in this paper we analysed the variations in ground-based air quality and meteorological data obtained from a network of air quality monitoring stations across different cities in india for the past four years ( - ) for the time period of march th to april th. comparison of data in the last four years helps in understanding the potential effect of change in emissions during days with similar meteorology. this paper also explores the possible scenario which could result in national capital region if similar control on anthropogenic emissions occurs in worst meteorology conditions using weather research forecasting (wrf)-air quality dispersion modelling system (aermod). to study the changes in air quality during the lockdown period, the data from cities covering different regions of india were analysed, i.e. bhopal and dewas in centre, jorapokhar, patna, gaya, brajrajnagar and kolkata in the east, faridabad, amritsar, jodhpur, delhi, agra, kanpur and varanasi in the north, amravati, bengaluru, thiruvananthapuram and chennai in the south, as well as ahmedabad, mumbai, nagpur and pune in the west. concentrations of the different pollutants for the time period of march th to april th from to were analysed. the hourly concentrations of seven air pollutants including particulate matter (pm . and pm ), nitrogen oxides (no x , no and no ), sulfur dioxide (so ), ozone (o ) and carbon monoxide (co) along with meteorological parameters including wind speed, wind direction, temperature and relative humidity were obtained from the cpcb online portal for air quality data dissemination (https://app. cpcbccr.com/ccr/#/caaqm-dashboard-all/caaqm-landing). to understand the overall improvement in air quality, air quality index (aqi) was computed. the details of aqi are available elsewhere (cpcb, ; sahu and kota, ) , and only briefly summarized here. aqi uses pm , pm . , no , o , co, so , nh and pb, of which minimum concentrations three pollutants should be available, with at least one being either pm . or pm . the concentrations are converted to a number on a scale of - . the sub index aqi (aqi i ) for each pollutant(i) is calculated using eq. ( ) where, c i is the concentration of pollutant 'i'; b hi and b lo are breakpoint concentrations greater and smaller to c i and in hi and in lo are corresponding aqi values. the overall aqi is the maximum aqi i , and the corresponding pollutant is the dominating pollutant. the aqi is divided into five categories: good, satisfactory, moderate, poor, very poor and severe depending on whether the aqi falls between - , - , - , - , - and - , respectively. the potential health benefits in different cities due to change in concentrations were estimated using the excess risks associated with the pollutant loads during similar periods with and without lockdown. the relative risks of a pollutant are calculated using eq. ( ). where rr i is the relative risk of pollutant i, β i is the exposure-response coefficient indicating the additional health risk (such as mortality) caused by per unit of air pollutant i, when it exceeds a threshold concentration. the β values are . %, . %, . %, . % and . % for m , pm , so , no and o per μg/m respectively, and for co, it is . % per mg/m (hu et al., ; shen et al., ) . c i, is the threshold concentration, meaning that when the concentration of pollutant i is below or equal it has no excess health risk. the excess risk (er) from pollutant i and the total er of all pollutants are estimated using eqs. ( ) and ( ). . . wrf-aermod modelling system the effect on meteorology on the pm . concentrations in national capital region (ncr) of delhi was studied using the air quality dispersion modelling system (aermod). required meteorology data was simulated by the weather research forecasting (wrf) model version . . with initial and boundary conditions from fnl (final) operational global analysis data on . × . degree grids from ncar for every h (http://dss.ucar.edu/datasets/ds . /). the × m gridded emissions for delhi-ncr by the safar-indian ministry of earth sciences for (beig and sahu, ) (http://safar.tropmet.res.in/) was used to drive the model. . . variation in meteorology during the analysis period fig. shows the wind rose plot for march th to april th of , , and for five different regions in india. except central india, the wind pattern in most of the years during the analysis period was similar. in north india, south and southwest are the predominant wind direction with average wind speed of~ . ms − . in southern, eastern and western india, while predominant wind direction was south and southeast, the average wind speeds were~ ms − ,~ . ms − and . ms − , respectively. however, in central india, even though wind speeds in all the years were similar (~ . ms − ), wind direction in (southeast), (west) and (southwest) were different. furthermore, there were negligible variations in temperature in different regions during this period. for example, the average temperature in north india was . °c (coefficient of variation~ %). overall, it can be concluded that the meteorology in the analysis period during to was similar. fig. shows the temporal change in the average concentrations of the six criteria pollutants in the five regions. overall, around , , , and % decreases in pm . , pm , co, and no were observed during lockdown period compared to the previous years. while there were % increase in o and negligible change in so . the higher decrease in pm compared to pm . could be due to its greater contribution from anthropogenic sources (klimont et al., ) . significant decreases in concentrations of pm . , pm , no and no were observed in north india. for example, compared to an average decrease of % in the previous years, pm . concentration in decreased by %, clearly indicating the effect of lockdown. similar conclusions can be derived for pm . and pm in other regions. a slight increase in so concentrations was observed in compared to previous year. this could be due to no restrictions on power plants in northern india and using coal powered energy an essential commodity during lockdown period. a decrease in o was observed in compared to , while compared to last three years averagely, the concentrations in were % higher. in east india, while there was a decrease in co concentration, an increase in other gaseous pollutants was observed in compared to . o had % increase compared to and % increase compared to the average concentration in to . in southern india, clear decrease in no, no and o was observed during the lockdown period, while increase in co was observed. increases in o and co and decreases in no and no were observed in central india. most cities in northern, western and southern regions are voc limited (sharma et al., ) , thus this increase in o could be due to more decrease in nox compared to voc. furthermore, this could also be attributed to decrease in pm concentrations, which can result in more sunlight passing through atmosphere encouraging more photochemical activities and thus higher o production (dang and liao, ; k. li et al., ) . excessive risks (er) associated with the criteria pollutants during the lockdown compared to the same period in the previous three years are included in fig. . as per who air quality guidelines (who, ) , the threshold values of μg/m ( hour mean), μg/m ( hour mean), μg/m ( hour mean), μg/m ( hour mean) and μg/m ( hour mean) for pm . , pm , o , no and so were considered for t calculation. for co, the recommended air quality guidelines of cpcb, mg/m ( hour mean), were used. overall, significant health risks due to pm . and pm were obtained in all the regions even during lockdown period. however, the mean er due to pm reduced by~ % on an average in the country. except so in north india and o in east india, er for all pollutants in every region reduced during lockdown period. this overall reduction in er in india during the lockdown period (~ times) could save~ . million deaths in india in a year. fig. shows the change in aqi and the corresponding dominant pollutant during the analysis period in indian cities. overall, a significant improvement is observed in during the lock down period in the entire country compared to the previous years. % reduction in aqi was observed in the analysis period of compared to the previous years. about , , , and % reductions in aqi were observed in north, south, east, central and western regions. delhi observed the maximum reduction of % in aqi. this reduction in aqi was also associated with a change in dominant pollutant in many cities. while in gaya, kolkata, kanpur and nagpur, the dominant pollutant during the lockdown period changed to o , it changed to no for agra and patna. this is expected as the maximum reduction was observed for pm . among all pollutants. correlation between aqi of cities in four different regions, north, east, west and south, during the analysis period is shown in fig. . correlation between cities especially in northern and eastern parts of the country improved in compared to previous years. for example, the correlation between the largest city in north india, delhi with other cities increased by a factor of . to . . the best correlation ( . ) between the two central indian cities bhopal and dewas was observed in . this clearly indicates that the increased dominance of regional transport compared to local contributions in the cities during lockdown period. furthermore, this betterment of overall air quality could be due to more dispersion during the pre-monsoon period when this lockdown happened. similar lockdown in china did not result in significant improvement in air quality due to unfavourable meteorology (wang et al., ) . to understand this effect, two simulations were carried out. while in simulation the actual meteorology during the analysis period in was used, in simulation the meteorology pertaining to worst case during early november of was used (beig et al., ) . in both cases the emissions from all sources but energy, residential and windblown dust in delhi ncr was zeroed out to predict pm . . the model performance in observations stations in the city are shown in table . results indicate that except in eight sites, the mean fractional bias (mfb) falls under the usepa criteria of ± . (epa, ). the relative change in concentration in simulation compared to simulation is also included in table . in sites an increase in concentration was observed due to unfavourable meteorology. on an average the concentration in simulation in sites with good model performance increased by % compared to simulation . this indicates that even the meteorology was not favourable, the average daily pm . concentration in delhi-ncr would increase to μgm − , which is less than the cpcb standard ( μgm − ) and . times more than the corresponding who standard. however, this increase might not be accurate in the air pollution episode during november, even though similar restrictions on human activities are implemented, as the residential emissions increase in north india mainly due to space heating (guo et al., ) . the effect of restricted human activities due to the covid- pandemic in india since mid-march of was studied by analysing concentrations of six criteria pollutants during march th to april th from to in cities covering different regions. among all pollutants, pm . had maximum reduction in most regions. in contrary, in most regions an increase in o was observed, which could be due to the decrease in pm in addition to decrease in nox. this substantial reduction in concentrations resulted in a times reduction in er. as expected, a significant reduction in aqi was observed in compared to previous years. however, four cities had o as their dominant pollutant instead of pm . , suggesting that attention should also be given to decreasing emissions of precursors to secondary pollutants in addition to controlling primary pm. correlation between cities especially in northern and eastern regions improved in compared to previous years, indicating more significant regional transport than previous years. further analysis on actual and unfavourable meteorology using wrf-aermod modelling system concluded that even the predicted pm . could increase due to unfavourable meteorology, the average concentration would still be under cpcb limits. this study gives confidence to the regulatory bodies that a significant improvement in air quality in india could be expected if strict execution of air quality control plans is implemented. note: mfb not following the us epa criteria limit was underlined and the values where the concentrations in worst meteorology is lower than base case is shown using italics. the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. safar-high resolution emission inventory of mega city delhi - . moes objective evaluation of stubble emission of north india and quantifying its impact on air quality of delhi radiative forcing and health impact of aerosols and ozone in china as the consequence of clean air actions over - guidance on the use of models and other analyses for demonstrating attainment of air quality goals for ozone, pm . , and regional haze a review of air quality modeling studies in india: local and regional scale source apportionment of pm . in north india using source-oriented air quality models contributions of local and regional sources to pm . and its health effects in north india characterizing multi-pollutant air pollution in china: comparison of three air quality indices global anthropogenic emissions of particulate matter including black carbon year-long simulation of gaseous and particulate air pollutants in india severe particulate pollution days in china during - and the associated typical weather patterns in beijing-tianjin-hebei and the yangtze river delta regions anthropogenic drivers of - trends in summer surface ozone in china ministry of environmenta, forest and climate change air pollutant levels are times higher than guidelines in varanasi, india. sources and transfer significance of pm . air quality at the indian capital sensitivity analysis of ground level ozone in india using wrf-cmaq models temporal variations of six ambient criteria air pollutants from to , their spatial distributions, health risks and relationships with socioeconomic factors during in china. environ responses of pm . and o concentrations to changes of meteorology and emissions in china severe air pollution events not avoided by reduced anthropogenic activities during covid- outbreak source apportionment of sulfate and nitrate particulate matter in the eastern united states and effectiveness of emission control programs authors would like to thank the central pollution control board, ministry of environment, forest and climate change (moefcc) and ministry of human resources and development, government of india. key: cord- -z zoogs authors: neve, d.; patel, h.; dhiman, h. s. title: on modeling of covid- for the indian subcontinent using polynomial and supervised learning regression date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: z zoogs covid- , a recently declared pandemic by who has taken the world by storm causing catastrophic damage to human life. the novel cornonavirus disease was first incepted in the wuhan city of china on st december . the symptoms include fever, cough, fatigue, shortness of breath or breathing difficulties, and loss of smell and taste. since the devastating phenomenon is essentially a time-series representation, accurate modeling may benefit in identifying the root cause and accelerate the diagnosis. in the current analysis, covid- modeling is done for the indian subcontinent based on the data collected for the total cases confirmed, daily recovered, daily deaths, total recovered and total deaths. the data is treated with total confirmed cases as the target variable and rest as feature variables. it is observed that support vector regressions yields accurate results followed by polynomial regression. random forest regression results in overfitting followed by poor bayesian regression due to highly correlated feature variables. further, in order to examine the effect of neighbouring countries, pearson correlation matrix is computed to identify geographic cause and effect. on december , in wuhan city, hubei province of china cases of unknown virus were detected. from december through january , a total of casepatients of unknown etiology were reported to who by the national authorities in china. the authorities in china identified a new type of virus called coronavirus, which was isolated on january . on and january , who received detailed information from the national health commission of china that the outbreak of virus is originated from the unhygienic wet seafood market in wuhan city. on january , china shared the genetic sequence of the novel coronavirus. [ ] covid- is an infectious disease caused by severe acute respiratory syndrome coronavirus (sars-cov- ). common symptoms include fever, cough, fatigue, shortness of breath or breathing difficulties, and loss of smell and taste. [ ] while most people have mild symptoms, some people develop acute respiratory distress syndrome (ards) possibly precipitated by cytokine storm, [ ] multi-organ failure, septic shock, and blood clots. the incubation period may range from one to fourteen days. [ ] the first case of covid- in india, which originated from china, was reported on january . india currently has the largest number of confirmed cases in asia, [ ] and has the second-highest number of confirmed cases in the world after the united states, [ ] [ ] with the number of total confirmed cases breaching the , mark on may, [ ] and , , confirmed cases on july . on august , india recorded the global highest single-day spike in covid- cases with , cases, surpassing the previous record of , cases recorded in the us on july . [ ] india currently holds the single day record for largest increase in cases, set on september , with an additional , . [ ] the world health organization declares covid- a pandemic, which is defined "an epidemic that has spread over several countries or continents, and most people do not have immunity against it". at this point, more than , , people were infected and over , died globally. to reduce corona virus cases, india government introduced days lockdown on march with several special rules. the lockdown was extended till may with several changes in guidelines. the government of india has proposed multiple lockdowns to curb the spread of this virus. due to these lockdowns, there has been a decrease in the number of cases from . % to . % daily. but the government cannot shut the entire nation forever as the economy may fall drastically. due to lockdown the country is facing job crisis and unemployment. the gdp has also decreased to - . %. the tourism sector had been highly affected due to lockdown. also, textile industry is highly affected. according to world trade organization (wto) and organization for economic cooperation and development (oecd) have indicated covid- pandemic as the largest threat to global economy since the financial emergency of - . this emergency has been the largest emergency till date. so, covid- has undoubtedly put forth a remarkably adverse effect on the day to day life of the entire human society and on world economy. medical researchers throughout the globe are currently involved to discover an appropriate vaccine and medications for the disease. on march, the national task force for covid- constituted by the icmr recommended the use of hydroxychloroquine for the treatment of high-risk cases. since there is no approved medication till now for killing the virus so the governments of all countries are focusing on the precautions which can stop the spread. in india serum institute of technology is working on clinical trial to discover corona vaccine. machine learning (ml) has proved itself as a prominent field of study over the last decade by solving many very complex and sophisticated real-world problems. these prediction systems can be very helpful in decision making to handle the present scenario to guide early interventions to manage these diseases very effectively. to contribute to the current human crisis our attempt in this study is to analyze covid- spread in india. hence a verified and proved vaccine of this coronavirus is not found and many researches and scientific experiments are undergoing and some vaccines are still in trial stage so to utilize the available resources and to deal with the current ongoing pandemic, modelling the situation and analyzing the outcome the future can be predicted. all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . in this study first we studied the growth curve of the current situation. then different regression models like polynomial regression, forest regression, support vector regression, naive bayes, were used to predict the situation till september , and an optimal model was proposed. this is especially useful for government and health workers to analyze current situation and predict the situation up to few weeks. this helps them to take necessary precautions and actions to curb the spread of disease. we have divided data set into regions to understand which polynomial curve fits best. we have also compared our results with neighboring countries like pakistan, sri lanka, and bangladesh for better analysis. in this section, several methods based on machine learning regression and polynomial regression are discussed. the analysis is carried out for pan india cases where the data is acquired from [ ] [ ] . the experiments for regression analysis are carried out on python platform. regression models are statistical sets of processes which are used to estimate or predict the target or dependent variable based on dependent variables. regression may be linear or nonlinear. a model is said to be linear when it is linear in parameters. for example, the second-order polynomial in one variable y = + t + + ε ( ) and the second-order polynomial in two variables y = + + + + + + ε are also the linear model. in fact, they are the second-order polynomials in one and two variables, respectively [ ] . polynomial regression is a special type of regression which works on the curvilinear relationship between the dependent values and independent values. for covid we have used polynomial regression with only one variable. polynomial with one variable equation shows the relationship between a dependent and independent variable in polynomial regression. in equation ( ), x is the independent variable and is the bias also the intercept and , … . are the weight or partial coefficients assigned to the predictors and n is the degree of polynomial. the polynomial regression used in the study includes transformation of data into polynomials and applying linear regression to fit the parameter. a polynomial all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . regression with degree equal to is a linear regression. choosing the value of a degree is a challenging task. if the degree of polynomial is less, it will not be able to fit the model properly and if the value of degree of polynomial is greater than actual, it will overfit the training data. the mean squared error (mse) is an unbiased estimator of the variance σ of the random error term and is defined in equation where are observed values and ̂are the fitted values of the dependent variable y for the ith case. since the mean squared error is the average squared error, where averaging is done by dividing by the degrees of freedom, mse is a measure of how well the regression fits the data. the square root of mse is an estimator of the standard deviation σ of the random error term. the root mean squared error rmse= √ is not an unbiased estimator of σ, but it is still a good estimator. mse and rmse are measures of the size of the errors in regression and do not give a indication about the explained component of the regression fit. random forest is an ensemble method that generates something akin to a forest of trees from a given training sample. ensemble-based models are far more accurate than a single method owing to advantages like capturing linearity and nonlinearity of time series obtained from individual methods [ ] . a random forest begins with splitting the input features into a group of subsets that essentially form a tree. a particular tree is characterized by a node that leads to a number of branches, as depicted in figure. all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . in random forest regression, the number of trees and the number of random features in each tree decomposition are the parameters that decide the performance of regression. at each decision tree, a fitting function is created, which acts on the random features selected. finally, at the end of the training process a random forest model is created. it is worth noting that during the training process, each tree is created from randomly selected input vectors and thus is called a "random" forest. mathematically, the estimated output of a random forest regression is given as where ( , ) is the representative tree at the end of training process, x is the set of input feature vectors, t is the collective set representing an input-output pair the predicted output is averaged over k decision trees. decision trees are sensitive to the data on which they are trained. changing the training data can change the predictions. meanwhile a common problem of overfitting persists in machine learning regression models when a well-trained model captures the noise component as well. to reduce the complexities posed by overfitting, a random forest makes a compromise between flexible and inflexible models. in the training phase, each regression tree repeatedly draws a sample from the feature set. this ensures that even though the tree may possess a high variance, the overall variance of the forest may be low. a random forest works on the principle of bagging, which combines the predictions from different tree models to give an overall insight to the data under training. this also helps to reduce the potential overfitting caused by supervised machine learning models. the main objective of svm is to find the optimal hyperplane which linearly separates the data points in two component by maximizing the margin [ ] . consider a set of data( , ) , ( , ) … ( , ) ⊂ x x r, where x denotes the input feature space of dimension . let y = ( , … . ) denote the set representing the training output or response, where i = , ,..., n and ∈ r. this type of svr uses an ε-insensitive loss function that intuitively accounts for sparsity similar to svr by ignoring errors less than ε. ε-svr aims to find the linear regressor for prediction, where x ∈ x is the input set containing all the features, w is the weight coefficient related to each input xi, and b is the bias term. the objective is to find f (x) with maximum deviation ε from the respective feature sets while being as flat as possible. in case of covid - features sets might not be able to linearly separable. to handle such nonlinearities in the feature sets, the so called kernel functions are used to transform data to a higher-dimensional space ("kernel trick"). after transformation via a suitable mapping function φ : rn → z, the data become linearly separable in the target space (high-dimensional space), that is, z. the inner product < ,φ(x)> in the target space can be represented by perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint where α and * represent the positive and negative lagrange multipliers such that * = , i = , ,..., n. the regressor f (x) can be written as the complexity of this regressor is independent of the dimensionality of the feature set and only depends on the number of support vectors, which are nothing but the data points that separate the feature sets from each other. however, the performance of the svr also depends on the choice of a kernel function and helps in reducing the computation time of the regression. naive bayes assigns a probability to every possible value in the target range. the resulting distribution is then condensed into a single prediction. in categorical problems, the optimal prediction under zero-one loss is the most likely value-the mode of the underlying distribution. however, in numeric problems the optimal prediction is either the mean or the median, depending on the loss function. these two statistics are far more sensitive to the underlying distribution than the most likely value: they almost always change when the underlying distribution changes, even by a small amount. therefore, when used for numeric prediction, naive bayes is more sensitive to inaccurate probability estimates than when it is used for classification consider the problem of predicting a numeric target value y , given an example e. e consists of m attributes x , x , . . . , xm. each attribute is either numeric, in which case it is treated as a real number, or nominal, in which case it is a set of unordered values. if the probability density function p(y |e) of the target value were known for all possible examples e, we could choose y to minimize the expected prediction error. however, p(y |e) is usually not known, and has to be estimated from data. naive bayes achieves this by applying all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . bayes theorem and assuming independence of the attributes x , x , . . . , xm given the target value y . bayes' theorem states that where the likelihood p(e|y ) is the probability density function (pdf) of the example e for a given target value y , and the prior p(y ) is the pdf of the target value before any examples have been seen. naive bayes makes the key assumption that the attributes are independent given the target value, and so equation can be written instead of estimating the pdf p(e|y ), the individual pdfs p(xi |y ) can now be estimated separately. this dimensionality reduction makes the learning problem much easier. because the amount of data needed to obtain an accurate estimate increases with the dimensionality of the problem, p(xi |y ) can be estimated more reliably than p(e|y ). we have analyzed the data from january , to september , . figure and illustrate that new cases of covid- , the rate of total confirmed cases and recovered was increasing at a slow pace but after april , there was an exponential growth in both total confirmed cases and recovered cases. as number of deaths increases up to , . however confirmed cases rise increases , , while recovered cases rise , , till september , . figure showcase statistical analysis of all variables of covid- . from figure , we can see that daily confirmed cases, total confirmed cases, daily recovered, total recovered, daily death and total death are highly dependent on each other. all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint we applied polynomial regression to find relationship between total confirmed cases verses number of days. for linear, cubic, quadratic and quartic accuracy was . %, . %, . % and . % respectively. as earlier discussed regarding overfitting in polynomial regression and degree was observed as the best fit polynomial which otherwise would not be observed with degree due to overfitting. all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint here we applied naive bayes regression between total confirmed cases and number of days. we get accuracy around . %. from figure we can see that naïve bayes regression failed to fit the graph and does not show linear relationship. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint in figure , we have applied random forest regression between total confirmed cases and number of days. random forest has successfully fit the growth curve with . % accuracy. but when we predict further value for day , and , we are getting . for all. technically as number of days increases total confirmed cases cannot be constant so we can observe data overfitting. we apply machine learning models to data set for predicting future values. random forest failed for future predictions due to overfitting. in figure , we converted number of days and total confirmed cases in standard scalar form for performing better support vector regression. by applying radial basis function (rbf) kernel we got an accuracy of . %. figure : support vector regression all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . for better understanding among total confirmed cases and number of days we divided total number of days in regions. first region ranges from january to march . second region ranges from march to may . third region ranges from may to july. fourth region ranges from july to september . for figure , the regression analysis of each region is illustrated in subsequent figures. first region consists of samples from january to march . in beginning cases increases exponentially of order . accuracy of model is found to be . %. figure illustrates quadratic curve with an accuracy of . %. in second region, degree of polynomial decreases from to . now, if we increase value of degree predicted curve will overfit the data. further for region and they show quadratic curve with . % and . %. all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . https://doi.org/ . / . . . doi: medrxiv preprint for all three cases total confirmed, total recovered and total death value pearson coefficient values are majorly dependent on each other. the output data frame can be interpreted as for any cell, row variable correlation with the column variable is the value of the cell. we have calculated the pairwise correlation of all columns in the data frame. figure - illustrate the pearson correlation matrix between india and neighbouring countries. it is observed that for total confirmed cases, a high correlation coefficient is observed between india and bangladesh compared to pakistan and sri lanka. similarly, the correlation coefficient between india and neighbouring countries is observed to be high and indicates a strong geographic influence in covid- transmission. all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted october , . . covid- (coronavirus) has affected day to day life and is slowing down the global economy. this pandemic has affected thousands of peoples, who are either sick or are being killed due to the spread of this disease. regression analysis is a statistical tool for the investigation of relationships between variables. by applying various regression models from january , to september , we found that polynomial regression and support vector regression have performed exceptionally well. but in case of polynomial regression, the curve witnessed exponential increase which is not fails to explain the realtime scenario as the total number of confirmed cases will cease in magnitude with improved medication. naive bayes regression failed due to less accuracy and random forest ended up overfitting the data set. in case of support vector regression with radial basis function kernel, graph decreases after achieving its peak value. so, we can conclude that support vector regression is best among all methods we applied. in beginning covid cases grow at order of from jan to march. from march , to may , covid- cases has increases in order of due to imposition of lockdown. strict rules were followed during this period. similar curve has been seen from may , to september , . as the lockdown has uplifted and the life had come to normalcy and as the government has given authority to open multiplex and cinema halls and slowly and steadily soon the educational institutes will also reopen so, there will be a possibility in sudden spike in the number of cases. compared to neighboring countries like bangladesh, nepal and pakistan india is worst affected with covid - . however, this is due to india's high population density, increase in testing, large economy activities there is surge in corona virus cases. as sri lanka is away from india geographically it is comparatively less affected. we also observe that india and bangladesh are highly correlated in terms of total confirmed, total recovered and total death. this study is limited to cases because if any government imposes special rule or restriction on international flights than scenario might be different. this study was limited to data-driven models using the total covid- cases. in the future studies, the other co-factors (associated with the demographics, social, cultural, and medical infrastructure, etc.) can be taken to considerations. modeling and forecasting of covid- growth curve in india. transactions of the indian national academy of engineering introduction to time series and forecasting. springer texts in statistics using autoregressive integrated moving average (arima) models to predict and monitor the number of beds occupied during a sars outbreak in a tertiary hospital in singapore analysis and forecast of covid- spreading in china, italy and france regression analysis of covid- spread in india and its different states prediction of new active cases of coronavirus disease (covid- ) pandemic using multiple linear regression model regression model based covid- outbreak predictions in india fractal kinetics of covid- pandemic modelling using polynomial regression covid- pandemic: power law spread and flattening of the curve decision tree ensemble-based regression models. supervised machine learning in wind forecasting and ramp event prediction supervised machine learning models based on support vector regression. supervised machine learning in wind forecasting and ramp event prediction data. . coronavirus source data novel corona virus key: cord- - m sqwq authors: kumar, harender; azad, amaanuddin; gupta, ankit; sharma, jitendra; bherwani, hemant; labhsetwar, nitin kumar; kumar, rakesh title: covid- creating another problem? sustainable solution for ppe disposal through lca approach date: - - journal: environ dev sustain doi: . /s - - - sha: doc_id: cord_uid: m sqwq amid covid- , there have been rampant increase in the use of personal protective equipment (ppe) kits by frontline health and sanitation communities, to reduce the likelihoods of infections. the used ppe kits, potentially being infectious, pose a threat to human health, terrestrial, and marine ecosystems, if not scientifically handled and disposed. however, with stressed resources on treatment facilities and lack of training to the health and sanitation workers, it becomes vital to vet different options for ppe kits disposal, to promote environmentally sound management of waste. given the various technology options available for treatment and disposal of covid- patients waste, life cycle assessment, i.e., cradle to grave analysis of ppe provides essential guidance in identifying the environmentally sound alternatives. in the present work, life cycle assessment of ppe kits has been performed using gabi version . under two disposal scenarios, namely landfill and incineration (both centralized and decentralized) for six environmental impact categories covering overall impacts on both terrestrial and marine ecosystems, which includes global warming potential (gwp), human toxicity potential (htp), eutrophication potential (ep), acidification potential (ap), freshwater aquatic ecotoxicity potential (faetp) and photochemical ozone depletion potential (pocp). considering the inventories of ppe kits, disposal of ppe bodysuit has the maximum impact, followed by gloves and goggles, in terms of gwp. the use of metal strips in face-mask has shown the most significant htp impact. the incineration process (centralized− kg co eq. and decentralized− kg co eq.) showed high gwp but significantly reduced impact w.r.t. ap, ep, faetp, pocp and htp, when compared to disposal in a landfill, resulting in the high overall impact of landfill disposal compared to incineration. the decentralized incineration has emerged as environmentally sound management option compared to centralized incinerator among all the impact categories, also the environmental impact by transportation is significant ( . kg co eq.) and cannot be neglected for long-distance transportation. present findings can help the regulatory authority to delineate action steps for safe disposal of ppe kits. in december , a pneumonia type outbreak was reported in wuhan, china (new york times ) which was traced to a novel strain of coronavirus (who a). during january who declared coronavirus disease (covid- ) as a pandemic disease (who b), which spread very rapidly from human to human by personal contact, contact with air-water droplets during sneezing, and coughing of coronavirus affected person (bherwani et al. a; nair et al. ; wathore et al. ; gupta et al. ) . as of june , there have been at least , , confirmed deaths, and more than , , (covid- dashboard csse) confirmed cases under covid- pandemic. since to date, there is no vaccine identified yet (who a, b, c, d, e; healthline ) for the effective prevention of covid- disease, thus other measures recommended by who to mitigate the spread of covid- (who c) become very vital for peoples among this pandemic (kaur et. al. ) . the adverse impacts of covid- on human and planetary health will arise from different sources during the response (unep ). as per a who estimate, million medical mask, million examination gloves and . million goggles are required for the covid- response each month (who e) for which the manufacturing capacity should ramp by %, to meet the rising global demand (park et al. ) . with reported cases of covid- infected health and sanitation workers (satheesh ; hindustan times ; new india express ), waste management of used infectious safety gears has become a critical component to restrict the spread of novel coronavirus (bherwani et al. b; vanapalli et al. ) . according to wwf report (italy wwf ) , "if only % of the masks were disposed of incorrectly and perhaps dispersed in nature, would result in million masks per month in the environment". across the globe, an unprecedented rise in the covid- cases, the amount of waste of infectious waste generated, far exceeds the available capacity for treatment. worldwide waste management systems have already been unable to deal with existing waste satisfactorily, the imminent surge in the volume of waste from covid- pandemic threatens to overwhelm existing waste management systems as do healthcare capacity. the directives from who, which mandate incineration of ppes and other infectious wastes, especially made from plastic, has increased the load on the incineration facilities (who a, b) . in china, with % rise in hubei province and with % rise in wuhan, i.e., from a normal level to t/day to about a peak t/day, exceeding the maximum incineration capacity available with the country (jiri et al. ; ivy s. ; klemeš et al. ) . similar, the waste agency of catalonia (arc), spain, has noticed a % increase in medical waste with added tons/month more than usual (acr ). in the usa, a multi-fold increase in from ppes has been reported (justine ). in india, gurugram city has seen two times increase in the quantity of covid- related bmw with a prediction of over a ton of covid- related bmw every day (prayag ) . the north delhi municipal corporation (ndmc), india, has also observed an additional . tons of hazardous waste from households (abhimanyu c. ) , and ahmedabad's apollo hospital gave reported a . fold increase in bmw in comparison to normal of - kg per day (yahoo ) . the effective management of coronavirus infectious waste, including ppes, has been identified by as a key area of concern by regulatory agencies in india, with the release of waste handling-treatment-disposal guidelines generated during treatment-diagnosis-quarantine of covid- patients (cpcb revision ; aggarwal ). unlike india, other countries like eu member countries have made changes in waste management in the context of the coronavirus crisis (virjinijus s. ). some european municipalities have suspended the plastic recycling industry with the fear that workers getting infected as the virus remains on the surface of waste bags and materials when they are collected (zero waste a; zero waste b) the use of personal protective equipment (ppe) has emerged as the most reliable and visible preventive control safety gear to keep the covid- transmission at bay (herron et al. ) . typical ppes, also referred as ppe kits, are made of over % plastics (which takes up to years to degrade) like pp, pc, and pvc, etc., includes surgical face mask with metal strip, gloves, goggles, full-body suits containing pant, gown with head cover and shoe cover (park et al. ). national disaster management & safety protocols have advised the use of ppes, by attending physicians and all the healthcare-nursing staff, funeral workers including visiting families etc., who are directly or indirectly in contact of any covid- (confirmed or suspected) patients (selvakumar et al. ; who d; nmpa ) . in the wake of necessary preventive control measures, it is evident that the used ppes waste is likely to increase multiple folds and will stress the current waste management systems, and now pose a grave threat to the environment, if not tackled properly (ict ) . in developing countries, with lack of complete connectivity and waste handling capacities in existing centralized bio-medical waste treatment facilities (cbmwtf), the covid- infectious waste handling has become a grave concern (henam and shrivastav ; who a, b; cpcb ). in india, practical implementation of effective covid- waste management guidelines, with multiple cares at each step, including containers/bins/ trolleys be disinfected daily, use of double-layered bags (using bags) of collection, regular sanitization of workers, and vehicle sanitization etc. (cpcb ; aggarwal ) becomes looming and challenging. in populous countries like india of crore people (worldometer ) and having fifth-highest number of confirmed cases in the world (the guardian ), with overcrowded hospitals, large cities only connected to cbmwtf and lack of training of health workers (who a, b) and having institutional and residential quarantine centre's staff, adds to the challenges. there have been reports of dumping of masks and medical waste, leading to unknowing containmination of workers with coronavirus from various cities of india (abhimanyu c. ; the new york times ). hence, in consideration with the above, it becomes essentially important to explore and encourage decentralized disposal techniques, with treatment and disposal at source, of effective waste management, considering handling, storage and transportation-related risks. from table , it can be inferred that majority of the previous research works focused on the alternatives to use and reuse ppes and to minimize its requirement as well as waste generation through methods like disinfection by ultraviolet rays or treating used ppes with hydrogen peroxide. but these studies lacked in considering other vital environmental impact parameters, during manufacturing and disposal of ppes waste to the environment. the current research focused on the cradle to grave analysis of ppes for environmentally sound and sustainable management of these wastes, which has not been reported till date. thus, our present study on life cycle assessment of ppes for disposal of infectious ppe waste becomes very vital for environmentally sound management of ppe waste. the present work has tried to evaluate different disposal options for ppe kits, i.e., landfill, centralized incinerator and decentralized incinerator, with a view to promote environmentally sound management of waste. the study entails an assessment of all the life cycle stages including raw material extraction, material processing, production, use, disposal of ppe kits, using life cycle assessment (lca) tools, with an idea to transform the country's waste management sector into a secondary resource recovery sector, coupled with its integration with the manufacturing sector, to implement and promote a circular economy and ecosystem services conservation approach through a life cycle approach (bherwani et al. c; draft nerp ) . lca is defined as "a tool to assess the potential environmental impacts and resources used throughout a product's life cycle, i.e., from raw material acquisition, via production and use stages, to waste management" (iso ) . lca enables the estimation of the cumulative and realistic environmental impacts resulting from all the stages of a product life cycle, while also including impacts which are sometimes not included in the conventional analysis. in the current research, lca is conducted according to the iso , and iso , standards. the main goal of this study is to evaluate the relative human health and environmental impacts caused by raw material extraction, production, use, and disposal of ppe kit. amid the analysis is done in the form of three case studies namely case-i, case-ii, and case-iii as shown in fig. , based on disposal options. • case-i: centralized incineration waste management system refers to the system in which the common facility of waste treatment is considered. the waste is collected from the source of waste generation and is transported to the waste disposal site with the help of compacted trucks. the distance from nagpur city to bhandewadi yard, site for waste disposal is km, and therefore, this distance has been taken for centralized system analysis (arcadis ). • case-ii: a decentralized incineration waste management system is about each community managing and processing their waste in their locality and not sending it to a centralized large processing facility or often landfill (agrawal and jadon . • case-iii: comprising of landfill disposal technique for ppe. the three case studies are so designed to estimate, compare, and evaluate the environmental and health impacts caused by the transportation activity as well as by landfill and incineration process. the functional unit refers to a quantified description of the primary function of the system under study. the functional unit adopted for this study is the ton of ppe kit (babu et al. ). the ppe kit comprised of the goggles, gloves, shoe cover, mask, and overall suit, comprising of gown and pant. all the above-mentioned components of the ppe kit were precisely measured and weighed with the help of a weighing balance. all the items of the disposable ppe kit were one-time use only except goggles, which can be reused for days (mohfw). the reusability of goggles has been taken in this study as well (mohfw ) after following proper precaution and disinfection guidelines as stated by the world health organization (who guidelines ). figure gives details about the ppe kits configuration and composition. the material that comprises of these products were identified primarily based on manufacturer specification and through peer-reviewed literature (marcin ; seemal et al. ; halyard; paho ; the conversation ). the system boundary is the set of criteria specifying which activities are part of the studied system and which resource use and emissions associated with them are included in the study. the system boundary of the lca study includes all direct and indirect resources use and emissions, like manufacturing, suppliers, along with the use and endof-life phase. in this study, materials like polypropylene (pp), nitrile butadiene rubber (nbr), polycarbonate (pc), and metal strip used in the manufacturing of ppe kit were included in the system boundary. also, the use of ppe by frontline workers, vehicles used in transportation, and ppe disposal are also incorporated under the system boundary as shown in fig. environmental impacts are calculated in terms of gwp (kg co equivalent), ap (kg so equivalent), ep (kg po equivalent), http (kg dcb equivalent), faetp (kg dcb equivalent) and pocp (kg ethane equivalent). the life cycle inventory (lci) model aims to link all unit processes that are required to deliver the product studies in an lca. in the current study, all flows of the materials, energy, and all the waste streams related to the functional unit were identified and quantified. the study focused on the total impact caused by the ppe kit from their process of "cradle to grave". the impact categories are selected in a way that laid more emphasis on the environment and human health. since there were only a few inventories contributing to other impacts, they are not considered in this study. the six impact categories chosen for this study are mainly global warming potential (gwp), human toxicity potential (htp), acidification potential (ap) eutrophication potential (ep), freshwater aquatic ecotoxicity potential (faetp), and photochemical ozone creation potential (pocp) (rejane et al. ) . the emission from the incineration process may give negative values due to application of heat recovery systems (jeswani et al. ; parkes et al. ) . while conducting lca, material wise. after running lca in gabi, the inventory results were analyzed for the ppe kit. the inventory analysis for this study was based on centrum voor milieuwetenschappen (cml -jan. ) methods. the cml method is one of the strongly preferred methods followed by edip and ecoindicator (hand book of life cycle assessment ). it focuses on a series of environmental impact categories expressed in terms of emissions to the environment or resource use. the cml method groups the result into midpoint categories (klemeš et al. ) , the cml impact category used in this study were: gwp, htp, ep, a.p, faetp, and pocp. the impact assessment of the case-i revealed that the highest gwp impact was caused by ppe suit among all the inventories, with a total of , . kg co eq. emission. the ppe suit is made of pp fabric resulting in emission during the manufacturing with a total of kg co eq, and additional emissions of co eq were observed through masks. the details of the impact profiles are shown in fig. . . kg co eq. emission occurred during the incineration process of ppes which contributed as the second-highest gwp related emissions. the gwp impact was from gloves with a total of . kg co eq. emission. the details reveal that manufacturing of gloves resulted in more gwp, due to a large amount fig. an illustration of the lca of ppe kit of energy being consumed during its steam cracking process (design life cycle ). the transportation by trucks for a payload of ton ppe waste and km travel to a disposal site, resulted in total gwp impact of . kg co eq, which is inclusive of diesel mix at the refinery. the htp, faetp, and ap values are also reported to be very high for ppe suit and mask, while negative values for incineration were observed probably due to heat recovery. case ii results are similar to case i result, except for transportation. while most of the values are same, it is to be noted that impact categories values have reduced due to reduced transportation. the benefit may seem to be minuscule for the considered case; however, the large-scale operations lead to evident differences and reduced environmental and health footprint. the results are showcased in fig. . the reduced transportation is also better due to multiple reasons other than reduced lca-related impacts. the number of direct and indirect people handling also reduces significantly, which reduces fatalities and morbidities. case iii is analyzed with respect to cradle to grave boundaries, with grave being the landfilling of the ppe. it can be seen from fig. , the impact categories have shown a drastic increase except for gwp, which is lower due to the reduced amount of heat input in the disposal process. in case iii, transportation is also included till the landfill site. the values of ep, faetp, htp and pocp are higher than cases i and ii, while ap values seem to remain constant across all the cases. it is worthwhile to note that there is no negative value for landfill cases except for transportation pocp, which is negligible. at present, the whole worlds are fighting a war against covid- with countries implementing various measures to ensure reduced fatalities and morbidity from this novel coronavirus sars-cov- . while this battle is being fought against a micro-sized with these changing habits, the use of ppes have increased drastically, especially by medical practitioners, in order to safeguard themselves and humanity from this novel coronavirus. while the use is absolutely essential and justified, it is to be noted that disposal of these ppes might become a problem in the near future, for which we should finding solutions today. in the current analysis, we have explored various options of disposing of these ppes through lca approach. three cases with different disposal options are considered. two of them include centralized and decentralized incineration, and one is landfill. the complete environmental footprint is considered through the cradle to grave in order to understand the detailed impact magnitude from each of the steps during the life cycle of ppes. the results are collated and presented in table . from table , it is evident that decentralized incineration seems to be a viable option for disposal of ppes both in terms of environment and health. the least viable option is landfill based disposal with all impact categories on a higher side except for gwp. the decentralized incinerator has a lower footprint in terms of ep, htp, pocp, and gwp when compared to centralized incinerators. at the same time, it produces almost similar impact in terms of ap and faetp. decentralized incinerator is a viable option because of additional reasons as well which are not considered in the scope of these impacts. the centralized incinerator adds number of people handling the ppes which might be infected by sars-cov- . right from local disposal to centralized collection facility, there are additional number of people handling the waste and hence have higher chances of contracting the disease which can be avoided if decentralized systems are put in place. considering the above, it is important to note that lca impact categories have produced high footprint values for decentralized system as well, hence there is always a need to improve the systems at hand to reduce the overall impacts. given the above results, it is important to create strategies of handling such type of wastes in advance given that times are changing fast and policy decisions are to be taken with speed and scientific accuracy to reduce the impact on human lives. the lca approach in the present work has demonstrated that it can be used as an important tool in such decision making and that environmentally sound and sustainable strategies can be devised using it. furthermore, in addition to preparing for the future with respect to increase in generation of biomedical waste, there is a need to educate people who are handling it. the pandemic has altered the waste generation dynamics, creating distress among workers involved in sanitation and policymakers. covid- times have shown that microbes can be very deadly if proper hygiene is not followed, and one of the important components of hygiene is the proper handling of waste. while efforts are being made to make people understand the severity of this virus, there is a need to educate and inform these front line workers who are handling this waste as well. the results from the research can be used for decision making to plan future strategies for environmentally sound management of covid- infected ppe waste. fighting from the bottom, india's sanitation workers are also frontline workers battling covid municipal waste 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unep's covid- response challenges and strategies for effective plastic waste management during and post covid- pandemic report on health-care waste management status in countries of the south-east asia region understanding air and water borne transmission and survival of coronavirus: insights and way forward for sars-cov- safe management of wastes from health-care activities: a summary coronavirus disease (covid- ) advice for the public: mythbusters statement regarding cluster of pneumonia cases in wuhan report: laboratory testing of human suspected cases of novel coronavirus (ncov) infection covid- ) advice for the public rational use of personal protective equipment for coronavirus disease (covid- ) and considerations during severe shortages ahmedabad hospitals shell out rs /kg for disposal of covid- bio-waste zero waste europe statement on waste management in the context of covid- the authors greatly acknowledge the support of council of scientific and industrial research (csir) and director, csir-neeri under the major laboratory project number mlp- . the manuscript is checked for plagiarism using licensed version of ithenticate software with assigned manuscript reference number as csir-neeri/krc/ /july/csum-drc-ermd-dir/ dated july . publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. harender kumar · amaanuddin azad · ankit gupta , · jitendra sharma · hemant bherwani , · nitin kumar labhsetwar , · rakesh kumar , csir-national environmental engineering research institute, csir-neeri, nagpur, maharashtra , india academy of scientific and innovative research [acsir], ghaziabad, uttar pradesh , india key: cord- -djp onk authors: verma, v. r.; saini, a.; gandhi, s.; dash, u.; koya, d. m. s. f. title: projecting demand-supply gap of hospital capacity in india in the face of covid- pandemic using age-structured deterministic seir model date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: djp onk background: due to uncertainties encompassing the transmission dynamics of covid- , mathematical models informing the trajectory of disease are being proposed throughout the world. current pandemic is also characterized by surge in hospitalizations which has overwhelmed even the most resilient health systems. therefore, it is imperative to assess supply side preparedness in tandem with demand projections for comprehensive outlook. objective: hence, we attempted this study to forecast the demand for hospital resources for one year period and correspondingly assessed capacity and tipping points of indian health system to absorb surges in demand due to covid- . methods: we employed age- structured deterministic seir model and modified it to allow for testing and isolation capacity to forecast the demand under varying scenarios. projections for documented cases were made for varying degree of mitigation strategies of a) no-lockdown b) moderate-lockdown c) full-lockdown. correspondingly, data on a) general beds b) icu beds and c) ventilators was collated from various government records. further, we computed the daily turnover of each of these resources which was then adjusted for proportion of cases requiring mild, severe and critical care to arrive at maximum number of covid- cases manageable by health care system of india. findings: our results revealed pervasive deficits in the capacity of public health system to absorb surge in demand during peak of epidemic. also, continuing strict lockdown measures was found to be ineffective in suppressing total infections significantly, rather would only push the peak by a month. however, augmented testing of , tests per day during peak (mid-july) under moderate lockdown scenario would lead to more reported cases ( , , - , , ), leading to surge in demand for hospital resources. a minimum allocation of % public resources and % private resources would be required to commensurate with demand under that scenario. however, if the testing capacity is limited by , tests per day under same scenario, documented cases would plummet by half. coronavirus disease (covid- ) is a contagious disease caused by a novel strain of coronavirus (sars-cov- ) which was first informed as the cluster of viral pneumonia cases of unknown etiology detected in wuhan city, hubei province, china. coronaviruses are enveloped, positive single-stranded large rna virus that infect humans, but also a wide range of animals ( ) . amongst humans, they have known to cause myriad of illness with varying degree of severity ranging from relatively benign common cold to more severe forms like sars (severe acute respiratory syndrome) and mers (middle east respiratory syndrome). however, illness onset among rapidly increasing number of people and mounting evidence human-to-human transmission suggests that sars-cov- is more contagious than its predecessors ( ) . following the outbreak of covid- , the who emergency committee declared it a global health emergency on january , and a pandemic on march , . within a short span of time, a localized outbreak evolved into pandemic with three defining characteristics: a) speed and scale-the disease has spread quickly to all corners of the world, and its capacity for explosive spread has overwhelmed even the most resilient health systems b) severity-overall, % cases are severe or critical, with a crude clinical case fatality rate currently of over %, increasing in older age groups and in those with certain underlying conditions c) societal and economic disruption-shocks to health and social care systems and measures taken to control transmission having deep socio-economic consequences ( ) . currently, approximately , , confirmed cases of covid- has been reported including an estimated , deaths in countries and territories as on may , . around three months have elapsed since the first case of covid- was reported in india on january , . since then, the number of cases have surged to , with , deaths as on may , . as part of the pandemic preparedness, in the absence of vaccines or antivirals, india adapted gamut of nonpharmaceutical interventions such as lockdown, quarantining and tracing and testing concomitantly to alter the trajectory of pandemic. these interventions encompassed two types of strategies a) suppression, which aims to reverse epidemic growth, by minimizing the effective reproduction number (average number of secondary cases each case generates), r, to below and thus, reduce case numbers to low levels and maintaining that indefinitely b) mitigation, which aims to slow the spread of epidemic with the rationale of preventing significant overload on health system and gradually allowing the population to develop herd immunity ( ) . who enforced a binding instrument of international health regulation (ihr) in to prevent, detect and respond to public health emergencies. the ihr monitoring and evaluation framework includes state party annual reporting tool (spar) which underscores capacity indicators to gauge the preparedness of nations to mitigate the effect of public health emergencies, including the emergence of novel pathogen (who, ) . in , although india's spar composite score ( . ) was above the international average ( . ), albeit, the scores for indicators pertaining to health service provisioning and laboratory capacity were incongruous as india had only half the average readiness in these indicators as compared to international scores. therefore, it is imperative to unravel the supply side readiness especially, with regards to infrastructural capacity of india to handle the surge of hospitalization cases. demand for hospitalization services for covid- can be estimated by analyzing the interface between transmission curve, age-structure, contact patterns and morbidity status of population. disease progression is characterized by myriad of uncertainties and the trajectory of an epidemic is defined by some key factors and parameters. specifically, for a novel infection whose disease dynamics are still unclear, mathematical models are thus, pertinent to understand the mechanics of transmission. deterministic compartmental models such as susceptible-exposed-infectious and recovered (seir) are widely used to provide insight into disease progression and can be chosen over complex models due to minimum number of assumptions. yet, there is a caveat in using the baseline seir model as it doesn't incorporate the testing capacity in the model which punctuates the dynamics in two ways. firstly, in basic model, the undetected yet infectious individuals are not accounted in determining probability of infection and potential transmissibility and secondly, there's reduced transmissibility from confirmed positive cases which no longer transmit the disease once they are tested and isolated. modelling exercises allowing for testing and isolation capacity and undetected cases are rather scarce. further, covid- has differential impact on different age groups and additionally, heterogeneities in contact networks have a major effect in determining whether pathogen can become epidemic or persist at endemic levels. consequently, mathematical models of disease transmission incorporating age and social contact structures are more congruous to the reality. therefore, in this study we have attempted the short and long term prediction of transmission of covid- using age-structured compartment based model allowing heterogeneities in contact networks and simulating for varying assumptions and scenarios around containment and mitigation strategies. drawing from international experience and literature on covid- , we determined the proportion of high-risk population with underlying conditions in india who are more vulnerable to progress into severe condition upon infection that can guide triage and targeted intervention decisions. further, we assessed the capacity and tipping points of indian health system to absorb surges in the number of people that will need hospitalization and critical care because of covid- based on varying scenarios. the objectives of the study can be elucidated as follows: -a) estimate the projected demand for hospital resources under various mitigation strategies of reduced social mixing and varying levels of testing capacity in india. b) analyze the hospital surge capacity of the indian health system to absorb the surge in demand under different scenarios. the spread of any virus is incumbent upon the infectivity of pathogen and the pool of susceptible population. we formulated the transmission dynamics model for the outbreak of covid- in a heterogeneously mixing population. compartmental disease models divide population into groups (or compartments) based on each individual's infection status and track the corresponding population sizes through time. seir model in which the population was divided according to infection status into susceptible(s), exposed (e), infected (i) and removed(r) was employed in the study. susceptible individuals become infected at a given rate when they interact/contact with an infectious person and enter the exposed state. these exposed pool transition to infectious state after a latency period and later either recover or die. however, it is crucial to consider host age structure to enable realistic modelling for disease prevention policy. also, the spread of an infectious disease is sensitive to the contact patterns in the population as person-to-person transmission is largely driven by who interacts with whom. the agespecific mixing patterns of individuals in age group i alter their likelihood of being exposed to the virus given the extent of infections in the group. the assumption of homogenously mixing population can lead to an overestimation of the final epidemic size and magnitude of interventions needed to stop an epidemic ( ) . contrarily, including contact patterns that vary across age and locations (e.g. home, work, and schools) as predictors in transmission dynamic model improves the model's realism. thus, we investigated the impact that different mixing assumptions have on the spread of covid- in an age structured seir model with infectivity in both latent and infectious period described by a system of ordinary differential equations. our model incorporates two sections as illustrated in figure where left part represents the classic seir model with additional post latency node accounting for infections in the terminal stage of incubation period. the transmission dynamics is further branched out into asymptomatic, symptomatic, severe and critical on the right-hand side constrained by the testing coverage. following equations represents the dynamics of the model. where β' is the probability of infection upon contact with infectious people, n is the total number of considered age groups, cij is the number of age wise interaction between infectious and susceptible population. where si, ei, li, ii and rui are the susceptible, exposed, post latency, infectious and undocumented recovered group of people of age group i. rate constant k = t_latency is defined by time from exposure to onset of infectiousness (latent period), k ' and k ' are rate for testing, k is defined by part of incubation time after latent period and k is rate at which undocumented infectious people recover or die. documented cases in the model are determined and constrained by the testing. positive cases can be presymptomatic, symptomatic and asymptomatic. pre-symptomatic and symptomatic may progress to severe and critical state before either recovery or death. whereas true asymptomatic positives recover without exhibiting any symptoms over the course of illness. where tpi is tested positive, asi is asymptomatic, ssi is symptomatic, svi is severe, cri is critical, di is dead and rdi is documented recovered for age group i. rates of progression are given as follows . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . to account for the mitigation factor such as social distancing, the contact matrix is divided into household contacts, workplace contacts, school contacts and other contacts using the following form where tw, ts and to can range from to allowing various degree of interactions of contacts delineating the impact of same on progression of the epidemic. main parameters of the model are surmised in table which were extracted/estimated from various sources. population age distribution for india was obtained from website of population pyramid ( ) and social contact matrices were adapted from state-of-the-art compilation by prem et. al in which matrices were projected by bayesian hierarchical model for countries using contact surveys and demographic data ( ) .time parameters were extracted from a recently published systematic review which synthesized parameters using meta-analysis of studies on covid- ( ) . further, age-distributed data from u.s. was used to estimate the epidemiological parameters in the study. as reported in table , age wise fractions of transition from one state to another and case fatality ratio (cfr) was calculated from the report published by u.s. center for disease control ( ), as currently in india (as of nd may), cfr is analogous to that of usa when cdc carried out the study. also, we collated the data on confirmed positive cases, hospitalizations, recovery and deaths from publicly available time series data of usa published by u.s. cdc ( ) to estimate the probability of infection β'. remaining model parameters such as latency rate, testing rate and rate of recovery/death were estimated using crowdsourced indian data ( ) from th march till nd may, while incorporating mitigation strategies of lockdown starting from th march to rd may and current social distancing guidelines based on the zones which is issued by indian government starting from rd may to th may. three scenarios of mitigation measures were modeled -(a) full lockdown (assuming closure of schools, workplace and community spaces and doubling of contacts in households) (b) social distancing measures and moderate lockdown (assuming closure of schools, staggered opening of workplace and community spaces with half strength and social distancing of vulnerable population including aged above years and people with at-least one underlying high risk chronic condition with % compliance) post th may, and (c) no lockdown (assuming % contacts in schools, workplace, community spaces and households). the model is augmented to incorporate the testing coverage and test to positive (ttp) ratio of % till may nd in india. the underlying set of assumptions characterizing the transmission dynamics are elucidated as followsi) india was assumed to be a closed system with constant population size of . billion (s+e+l+i+r= . billion) throughout the course of epidemic. ii) different inflows and outflows and imbalance by demographics, migration etc. is not considered. iii) seasonal effects, weather conditions like temperature and humidity and mutations not included in the model. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint iv) heterogeneous mixing in the contact networks is assumed and interactions at four spheres are considered: home, work, school and other locations. v) infectivity from latency period is considered, a latent individual can transmit the disease to the susceptible, i.e., individual has force of infection in both latent and infectious period. vi) asymptomatic transmission from truly asymptomatic cases is accounted in the model. vii) positively diagnosed cases are documented and isolated from rest of the susceptible pool, thus, less likely to spread the infection. viii) the recovered individuals develop the immunity and do not revert back to the susceptible pool. multi country evidence suggest that there are certain underlying conditions most associated with severe and critical cases of covid- . in conjunction with elderly, younger and working population group with chronic health conditions are also vulnerable and can be classified as high risk for developing complications. u.s. center for disease control and prevention in its morbidity and mortality weekly report ( )divulged that as of march , , % hospitalized non-icu cases and % icu cases had one or more precondition. similarly, evidence from italy ( ) affirmed that in a sample of deaths in italy, . % patients had some pre-condition(s). overall, among dead, . % had single disease, . % had diseases and . % had or more underlying diseases in italy. therefore, analyzing the prevalence of highrisk underlying condition associated with covid- is germane to understand the progression of cases from mild to severe/critical stage and identify the vulnerable population to design more effective interventions. hence, we used the information on burden of chronic diseases from a study conducted by london school of hygiene and tropical medicine ( ) therefore, we used the information on prevalence of these underlying conditions in india (table ) by culling out information from above-mentioned study to estimate proportion of population with at-least one underlying condition. data on indian health infrastructure was coalesced from different sources. information on beds in public hospitals (phc+chc+dh) and medical college hospitals was extracted from national health profile, ( ) . however, there was missing information in this data source for some states and colleges, which was then scrapped individually from websites of the colleges. beds under ayush, defense, railways and esi corporation are also incorporated in the analysis as india is likely to rope in beds from these institutions during surge in demand. the data for bed availability in these institutions was taken from national health profile, ( ) . further, due to absence of veritable data available on private sector, approximations using utilization rates for hospitalizations in private hospitals from recently released national sample survey organization th round ( ) was used and crude estimations were made based on proportion of . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint inpatients treated in private hospitals. further, there is major lacunae in credible data availability for icu beds and ventilators required for critical care. henceforth, another assumption was made that only % of total beds are icu beds and % icu beds are equipped with ventilators in india. health system's capacity to accomodate the increasing number of covid- patients was computed using an open access tool developed by giannakeas et al ( ) ( ) . this tool enables the modelling of steady state patient flow dynamics that can guide the tipping point of health care system in terms of the availability of hospital beds, icu beds and mechanical ventilators. entire dynamics of supply side readiness is explained in figure . the left-hand panel in the figure is representative of the current health capacity with total number of hospital beds, icu beds and ventilators. average length of stay determining the daily turnover rates for mild, severe and critical cases were set as . days, . days and . days respectively (parameter values from model). using population-weighted age-stratified probabilities, number of cases requiring hospital beds, icu beds and ventilators was estimated. further, the daily turnover of each of these resources was measured by dividing the number of available resources with average length of stay for that resource. thereafter, the daily turnover rates were divided by the proportion of cases requiring mild, severe and critical care to arrive at the maximum number of covid cases manageable by health care system of india. three distinct cases based on the allocation of resources were made to discern the surge capacity for each of these cases. in all three cases, we assumed that public health facilities dedicate fixed % of their hospital beds, icu beds and ventilators for covid- patients since existing bed occupancy rate of public hospitals in india is around % ( ) . however, for private sector hospitals, varied assumptions pertaining to allocation was made. under case , the provision of private infrastructure was assumed to be . whereas, the allocation of hospital beds, icu beds and ventilators in private hospitals was % under case and further expanded to % under case- main findings of the study are presented in this section. figure encapsulates various transmission curves under the scenario of ramping up of testing coverage (number of individuals tested daily) and increased ttp from % to % when the pandemic reaches final stage of community transmission. the impact of other non -pharmaceutical interventions like social distancing and lockdown is also explicated in the figure. while the lockdown was effective in slowing down the infection rate and shifting the peak to later months of the year , it perpetuated heavy socio-economic costs in india. therefore, it is pertinent to compare how continuing with moderate lockdown or lifting the restrictions completely would impact the number and spread of total covid- cases in india. the detailed representation of our modelling results is exhibited in figure . our modelling exercise revealed that with the current testing rate of , individuals tested daily on an average in india from th march, till nd may and % ttp ratio, the estimated total documented covid- infections in india would not exhibit any significant difference ( , to , in an year) across the scenarios of no lockdown, full lockdown and moderate lockdown guidelines. lifting the lockdown completely after th may would hasten the surge in demand to th july as compared to rd august if the full lockdown . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . continues for one year. although, moderate lockdown would push the peak to early august, total number of infections will not plummet by this intervention. current ttp ratio in india is around % which is exiguous as compared to ttp in usa of %. there could be plethora of reasons for low ttp in india such as absence of widespread-community spread, untargeted testing or less sensitivity of diagnostic kits. however, we estimated the number of total infections and peak time for surge in demand for expanded testing coverage of , and , tests per day at current % ttp as well as for % ttp modelling for worst case scenario. assuming no/limited community spread with ttp of % and augmenting the testing to , , in the absence of lockdown, our model estimated the peak to be around mid-july with total documented cases ranging from , to , during peak time. however, continuing moderate lockdown (with % contacts in schools, workplaces and others), estimated number of documented cases would be around , at the peak time of th july. with this increased testing of , individuals per day, surge in demand would be highest (~ , , ) if stringent lockdown measures are imposed after th may. this is because complete lockdown will delay the overall community spread and more people will be diagnosed and tested positive during peak time. under the worst case scenario of widespread community spread in india with ttp of %, peak will be witnessed around early july to mid-august . total documented infections under moderate lockdown scenario will range from , , to , , around rd july if , individuals are tested daily. however the total documented infections will increase with higher testing rate of , individual per day ranging from , , to , , cases around peak time on th july. in a no lockdown situation during worst case scenario with ttp %, number of cases will peak a week ahead around th july with similar number of infected cases in moderate lockdown. our analysis indicated paucity of resources in india to handle surge in demand during the peak time for both mild infections and severe cases. the capacity of indian healthcare system to absorb increases in caseload is constrained by availability of beds and ventilators. india has a total (public +private) bed capacity of , , which can be allocated for covid- infections according to existing bed occupancy rate and government guidelines. the availability of health care infrastructure which is collected from multiple sources is presented in table . according to case- where no allocation is made by private sector and only % resources are dedicated in public infrastructure, actual availability of hospital beds, icu beds and ventilators is , , , and , respectively. the estimated inflow/outflow of mild, severe and critical cases per day are , and . under this scenario, india has the capacity to accommodate only , mild cases, , severe and critical new covid cases every day. however, leveraging upon expansive private health care system in india can bolster the capacity. the tipping point for beds and ventilators increases significantly when % (case ) and % (case ) private health care resources were assumed to earmarked to accommodate covid- patients. for example, under case- , we found that the surge capacity of health system for mild, severe and critical care is distinctly higher than case as can be seen in figure and figure . moreover, when the allocation of private infrastructure increases by %, the capacity to manage new covid cases doubles. we computed the surge capacity, which is determined by trajectory of cases and infrastructure dedicated to covid- patients by accessing the time period around which indian hospitals will face serious crisis in terms of availability of beds and ventilators. the demand-supply gap during peak time if the moderate lockdown is continued after th may for mild, severe and critical cases is presented in the form of heat map ( figure ). green coloured boxes are indicative of the availability of infrastructure during peak time in respective scenarios, whereas non-green coloured boxes suggest the extent of health infrastructure that has to be upgraded to meet the real demand during peak time. as mentioned earlier, surge capacity is likely to vary across different testing scenarios. for example, when the partial lockdown is considered with increased testing coverage of , and , per day and ttp of %, our demand and supply side projections indicate that the indian health care system is likely to face a huge deficit in terms of the availability of health care infrastructure, especially for severe and critical case. assuming the community spread and scaling up of testing to , tests per day with ttp of %, under case- , india will have to increase the availability of icu beds by more than five times ( %) and availability of ventilators by . times( %) before th july . however, under current scenario where ttp is %, if we increase testing to , cases per day, we will have to ramp up the availability of icu beds by . % and ventilators by . % before th july . under case- , where % of capacity in public facilities and % in private facilities is apportioned for covid- , and testing coverage is , per day with ttp of %, the estimated demand for severe and critical cases can only be met if supply of icu beds and ventilators is increased by . % and . % before th july . however, increasing the testing even further to , , number of icu beds must double, and supply of ventilators must be increased by . % before th july. therefore, necessary steps must be made to include private-sector hospitals in the treatment of covid- patients in order to be prepared for the widespread community transmission and increase in detected cases due to aggressive testing. time to surge in capacity or tipping point will occur much earlier than the peak. hence, this analysis delineates an urgent need of procuring the ventilators and upgrading the capacity in this months window. our study calibrated the model to preliminary data arising from outbreak in india in order to project the demand for hospital resources under three transmission curve scenarios: no lockdown, moderate lockdown and full lockdown across varying testing coverage. we also evaluated the extent to which the full lockdown and moderate lockdown delays the peak of outbreak, thereby, prolonging the window of time to augment the health-system capacity in order to accommodate the surge in demand during peak period. our analysis of indian healthcare system's preparedness to absorb surges for infected cases exhibited pervasive deficits. there was a substantial variation in tipping points of supply side capacity across the assumptions on resource allocation in private sector to accommodate covid- patients. one of the important finding of our analysis is relative ineffectiveness of further extending the strict lockdown measures, as full lockdown is likely to push the surge in demand for hospital resources by a month without suppressing the total number of cases significantly. india was amongst the countries to implement lockdown early with highest stringency in the world which is also indicated by the stringency index of lockdown ( % for india) prepared by university of oxford ( ) . due to the high costs of lockdowns, there's a policy conundrum if the countries should quarantine everyone at a large social cost or test everyone and apply quarantine in a more directed fashion. the increase in documented cases with augmented testing in our study suggests that lockdown should be replaced gradually with more thrust on public health intervention of testing, tracing and isolating in conjunction with surveillance and real time data. more targeted sequestering of infected case(both symptomatic and asymptomatic) aided with increased random testing, along-with the social distancing measures for containment zones with higher incidence of cases and isolating vulnerable with underlying conditions and aged population is recommended rather than stringent lockdown in order to prevent the negative shock from deepening further. our analysis underscored the absence of surge capacity for severe and critical cases under all of the transmission and testing scenario. there is some capacity available for mild cases, provided documented cases are constrained by testing capacity, albeit, in an event of expanded testing and community transmission, mild cases will also be subjected to deficit of beds. the shortage of beds for even mild and asymptomatic cases can be corroborated with the recent reports from indian cities of chennai ( ) and mumbai ( ) where government hospitals are running out of beds due to explosion of cases. many countries are resorting to home isolation of mild and asymptomatic cases, a measure which union health ministry of indian government has also announced recently. however, we recommend to ramp up institutional capacity to isolate infected cases under institutional care as india's congested housing conditions are not conducive to quarantining at home. the national sample survey office data ( ) reveals that for % indians, per capita space available is less than a single room leading to unprecedented challenges for effective home isolation. our model didn't consider the potential staff shortages in transmission dynamics and capacity readiness due to uncertainty around their predictions and unavailability of quality data. age-distributed data on severe, critical and recovered cases is rather sparse in india, therefore, we adapted/estimated some parameters from detailed data released by other countries. modelling is rather a necessary input to guide policy decisions, however, a more comprehensive approach incorporating stakeholder's analysis, case studies and triangulating information across multitude of sources should be adapted for nuanced decision making. the study can be further extended to map the geographical accessibility of facilities providing covid- care, specifically spatial accessibility for critical care needs to be explored. also, rapid health facility assessments for covid- preparedness unravelling mean availability of tracer items for emergency response should be conducted for targeted interventions at hospital level. finally, study can be extended at more granular level to inform demand-supply gap so that resources can be mobilized in commensuration with demand at more local level, thereby enabling local government systems to combat covid- in india. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . the covid- epidemic method study design [internet]. cdn.onb.it mise à jour de la stratégie covid- impact of non-pharmaceutical interventions (npis) to reduce covid mortality and healthcare demand mathematical models of mixing patterns between age groups for predicting the spread of infectious diseases. pdfs.semanticscholar.org [internet projecting social contact matrices in countries using contact surveys and demographic data epidemiological characteristics of covid- ; a systemic review and meta-analysis . medrxiv.org [internet preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease -united states covid- india tracker case-fatality rate and characteristics of patients dying in relation to covid- in italy. jamanetwork how many are at increased risk of severe covid- disease? rapid global, regional and national estimates for . medrxiv.org [internet directorate general of health services m of h and fw. national health profile directorate general of health services m of h and fw estimating the maximum capacity of covid- cases manageable per day given a health care system's constrained resources utilization pattern and financing of public hospitals: a report ^ variation in government responses to covid- bed-medical-personnel-shortage-as-cases-rise/story/ .html . ministry of statstics and programme implementation. drinking water, sanitation, hygiene and housing condition in india updated rapid risk assessment from ecdc on the novel coronavirus disease (covid- ) pandemic: increased transmission in the eu/eea and the uk. ncbi.nlm.nih.gov key: cord- -ydkv m authors: patra, apurba; ravi, kumar satish; chaudhary, priti title: covid reflection/experience on teaching–learning and assessment: story of anatomy teachers in india date: - - journal: anat sci int doi: . /s - - - sha: doc_id: cord_uid: ydkv m nan as the world is suffering from an ongoing and serious pandemic, i felt it necessary to comment, from the perspective of a teacher, on the impact this pandemic has had and is having on anatomical education (franchi ) in india. my concerns are basically about the implications it might have on the future of current anatomy students. so, here i wish to present some of my experiences on this matter. readers must be aware of the fact that the outbreak of the novel coronavirus began in wuhan, china, in late december (zhu ) . the world health organization named the disease caused by this severe acute respiratory syndrome coronavirus (sars-cov- ) as covid- on th february (who a), and subsequently labelled it a pandemic on th march (who b). on nd april, the number of cases reported worldwide crossed million, with countries and territories affected (worldometer ) . in india, country-wide lockdown was imposed on rd march, and since then the majority of universities and medical colleges had suspended face to face teaching, forcing teachers and students to move to online distance learning for an indefinite period. however, the teaching-learning of anatomy with cadaveric dissection has become almost non-existent in most medical schools due to the lack of the number of corpses compared with the growing number of students. in india, the scenario is completely different from european countries; till date, most of the indian medical schools use cadaveric dissections as the prime source of teaching anatomy. so, the covid- pandemic situation has hit us hard and created a lot of ruckus in medical teaching. specifically, if we talk about teaching anatomy, the magnitude of its impact is many folds, because our curriculum is practical work based, which is not possible at the present. although medical teachers are trying their best to teach students using different online platforms available, practical work is missing. being a teacher in anatomy, initially it was really impossible for us to teach the subject in this pandemic period. in regular days, we used to do dissection of a particular region in the morning session so that students can see and feel the anatomical structures. on the same afternoon, we used to conduct lecture on the same topic. however all of a sudden, we have entered into a virtual world of teaching and learning after a country-wide lockdown was announced. neither could we do dissection nor take lectures in a lecture theatre in front of the students. the situation was really extraordinary and no one had any clue how to continue the teaching-learning process. initially, few faculty started with sending ppts and youtube links to make the process fruitful, but the students did not find it useful and there was lot of confusion regarding the method of teaching to be adopted. few institutes started with online teaching using platforms such as zoom, webex and google meet. we also thought of doing the same in our institution (all india institute of medical sciences, bathinda), but before starting we thought of taking students' opinion regarding such method of teaching. after getting their views, we found that most of the students were not in favour of online platforms and the reasons cited were network issues, as most of our students were from either rural or suburban areas. now, we were left with only one feasible option: that was making video lectures with recorded narration. initially, it was the department of anatomy that started such a method of teaching and luckily our students found it very innovative and useful. we started getting a huge response from our students. side by side, we started online discussions using google classroom, followed by online assessment like quiz competition. the students were really happy with this method. it was like a gush of fresh air for all of us in the middle of the covid- pandemic situation. gradually, other departments acknowledged our efforts and few started doing the same. despite the advances in technology, we believe that cadaveric dissection is the ideal and the most (ghosh ) , as it is one of the methods of training hands and fingers for future surgical procedures on living human beings (ajita and singh ) . government of india, ministry of health and family welfare, recently have issued guidelines of dead body management in view of covid- pandemic understanding the significance of dead body (ravi ) . now when i am writing our story, it is already months in this virtual world of anatomy and we all are eagerly waiting to go back to the d-hall 'where death laughs to teach the living'. funding this study was not funded. conflict of interest the authors declare that they have no conflict of interest. body donation and its relevance in anatomy learning-a review the impact of the covid- pandemic on current anatomy education and future careers: a student's perspective cadaveric dissection as an educational tool for anatomical sciences in the st century dead body management in times of covid- and its potential impact on the availability of cadavers for medical education in india who ( ) world health organization. who director-general's remarks at the media briefing on -ncov on who ( ) world health organization. who director-general's opening remarks at the media briefing on covid- - covid- coronavirus pandemic china novel coronavirus investigating and research team. a novel coronavirus from patients with pneumonia in china key: cord- -i oprni authors: mahajan, ashutosh; sivadas, namitha a; solanki, ravi title: an epidemic model sipherd and its application for prediction of the spread of covid- infection in india date: - - journal: chaos solitons fractals doi: . /j.chaos. . sha: doc_id: cord_uid: i oprni originating from wuhan, china, in late , and with a gradual spread in the last few months, covid- has become a pandemic crossing million confirmed positive cases and thousand deaths. india is not only an overpopulated country but has a high population density as well, and at present, a high-risk nation where covid- infection can go out of control. in this paper, we employ a compartmental epidemic model sipherd for covid- and predict the total number of confirmed, active and death cases, and daily new cases. we analyze the impact of lockdown and the number of tests conducted per day on the prediction and bring out the scenarios in which the infection can be controlled faster. our findings indicate that increasing the tests per day at a rapid pace ( k per day increase), stringent measures on social-distancing for the coming months and strict lockdown in the month of july all have a significant impact on the disease spread. india where it has reached at alarming level.  impact of lockdown and the number of tests conducted per day on predictions of containment is studied.  purely asymptomatic cases and spread from them as well as exposed in incubation period considered.  increasing the tests per day by k every day, stringent measures on social-distancing and strict lockdown in july have significant impact on the disease spread. the outbreak of novel corona virus disease (covid- ) caused by severe acute respiratory syndrome coronavirus (sars-cov- ), originated from a wet market in wuhan, china, is now widespread in the world and has severely affected many counties including india. the first case of covid- in india was reported on january, at thrissur, kerala, in a student who had returned from china. india has reached the fourth position in the world in the number of confirmed covid- cases and presently has , confirmed cases and , deaths as of june , , which is really an alarming situation. social distancing is the best method for mitigating this pandemic until an effective medicine or vaccine is invented [ ] . the first nationwide lockdown is ordered by the prime minister on march for ladays and further extended the lockdown till may by relaxing certain substantial fields [ ] . later, though the lockdown period is extended to june , the freedom is given to the states to impose restrictions assessing the situations in the respective states. mathematical modeling and simulation are helpful for predicting the transmission of the epidemic and to implement necessary actions for its control. mathematical models for the epidemic have a major role to make predictions of the transmission dynamics of the disease and thus assist the authority to take necessary movements for the containment. several epidemic models are already reported in the literature, however, the covid- is different type of infection showing certain special characteristics. the transmission of the disease from the persons who are infected without showing any symptoms (asymptomatic cases) is one of the special characteristics of this disease [ ] and to be considered in the modeling. also, the disease can be spread from the infected who is in the incubation period [ ] . in this study, we present a new mathematical model named sipherd, incorporating the aforementioned characteristics of the covid- . many mathematical models for the infectious disease spread are reported in the literature, and the classical and widely used method is sir model described in [ ] . an approximate spatial epidemiological model of the covid- , is initially proposed in [ ] in which the spread of the disease within between and the countries is analysed. the infected and undetected cases and the spread of covid- from those persons are incorporated in [ ] but this study is associated with only china. a modified compartmental sir model is discussed in [ ] . in this study, the total population of the country is divided into eight compartments, and this work is carried out only for italy, and also, the model does not undertake the purely asymptomatic cases of infected. a different compartmental model seir [ ] predicts the dynamics of the transmission of the covid- for certain countries, and the impact of quarantine of the infected persons are also studied in it. another improved sir model is depicted in [ ] , and the time dependency of the parameters of the sir model is also examined in this. prediction of transmission of covid- using curve fitting algorithms are reported in [ ] , [ ] and [ ] . a stochastic mathematical model is proposed in [ ] to analyse the impact of covid- on the healthcare system in india. assessment of the preventive measures of covid - such as lockdown and prediction of its spread in india is studied in [ ] . the seir epidemic and regression model is extended for predicting and evaluating the transmission of covid- in india [ ] . progression of the epidemic in india is also determined using the mathematical modelling in [ ] and [ ] . in india, complete lockdown is limited to the containment zones and hotspots from june on-wards. the forbidden activities in the places outside the containment zones are re-opened in a phased manner with the conditions to follow the standard operating guidelines given by the health ministry of india. inter-state and intra-state travel is allowed in the present situation without any pass/permission, religious places, restaurants, shopping malls and hospitality facilities are allowed to open whereas the educational institutions, entertainment zones, international air travel and railway services remain prohibited as of june . despite all these restrictions, the infection is growing exponentially, and policymakers need to consider different ways for the containment of the disease. the most hit cities in india by covid- pandemic are mumbai, delhi and chennai with a collective population of around million. in this paper, we bring out different possible ways for better control of the infection spread. we employ an improved mathematical model sipherd [ ] for the covid- pandemic embedding the purely asymptomatic infected cases and the transmission of the disease from them. the model simulations bring out the efficacy of different ways for the containment, by predicting the total number of active and confirmed cases, total deaths, and daily new positive cases considering various social distancing/lockdown conditions and the number of tests done per day. we model the evolution of the covid- disease by dividing the population into different categories as listed below which is described in detail in [ ] [ ] . the sipherd model equations are for the defined entities (s,i,p,h,e,r,d) are a set of coupled ordinary differential equations ( to ). the population is divided into different categories, as susceptible (s), exposed (e), symptomatic (i), purely asymptomatic (p), hospitalized or quarantined (h), recovered (r) and deceased (d). where, tr and td are the delay associated with the recovery and death respectively with respect to active cases h. the various parameters seen in fig and their optimized values for india covid- data are listed in table i.all fractions add up to unity that can also be seen from summing the above equations. the detection of the asymptomatic and symptomatic cases can be taken dependent on the number of tests done per day (tp d ). where, µ , µ , ν , and ν are positive constants. the effectiveness of the tests increases if contact tracing is performed. so far in india contact tracing is performed well, we assume that the increased tests are also performed on the suspects more carefully and the detection probability increases with increasing tests linearly. since the severe cases are going to approach for the tests, one component of the detection probability is not taken dependent on the number of tests. recovery of asymptomatic cases is taken faster than the symptomatic cases. the total confirmed cases are the addition of the active cases, extinct cases, and a part of the recovered that were detected. this can be written as the set of coupled ordinary differential equations for the model can be solved numerically for a given set of parameters and initial values. it is however important that the parameters are determined accurately so that the model demonstrates the real situation of the infection spread. we take into account the data sets of the total number of confirmed cases, active cases, cumulative deaths and tests done per day, and find the model parameters that generates the best possible match between the actual data and model. for this purpose, a cost function is written in terms of errors between the actual and solver data sets. the minimizer of the cost gives the optimized set of parameters. the model and the optimization codes are implemented in matlab. the number of total positive or confirmed cases, present active cases and deaths are collected from [ ], [ ] , and the number of tests per day from [ ], which is plotted in supplementary material fig.s a. the parameters determined by our model for covid- spread in india are listed in table i and the simulation data from the model is compared with the actual data in supplementary material fig.s . the parameter values related to the characteristics of the disease are discussed in more detail in [ ] . for the available data till june , , we run the model for first days i.e. till june to extract parameters listed in table i, and then with the extracted parameters, the model is run for days starting from march . the current increase in tests per day is around . k, we assume the same trend for the test per day and take the current value of transmission rate to generate the simulated data for the prediction. two scenarios are considered for lockdown and social distancing conditions. one possible scenario is that the conditions are kept the same, and the second one is that they are made stricter by taking into account some measures after june such that the transmission rates α and β decrease by % . these measures can include restrictions on travel, large gathering of people for social events, distribution of low-cost masks and hand sanitizers in hot spots. test per day assumed to be increased by . k, which is close to the current trend and taken saturated at million for both the scenarios. the mortality rate is calculated from the data and is improved in steps from initial value . e- , . e- , . e- , . e- on march to june as seen in supplementary material fig.s .b. for the future, mortality rate is taken improved to a fixed value e- . a comparison of the predictions for the two scenarios i.e. with and without the stringer measures is plotted in fig. . reproduction number variation with time and evolution of the undetected infected cases can be seen in supplementary material fig.s . the total number of reported cases is predicted to be around million. this number appears very high. however, compared to the usa reported cases . million, the number is reasonable, given the fact that india's population is roughly four times higher. we also study one more possible scenario in which a total lockdown is imposed for july . the rate of transmission of infection is going to decrease in the imposed lockdown, and we take the α and β values to decrease by % from the current value. the prediction with . k increase in tests per day and saturation at million tests, is compared in fig. a,b and in fig. d , we plot the prediction for the daily new cases. detailed plots and evolution of infected can be seen in supplementary material fig.s for this condition of stricter lockdown for july and relaxed after that. we compare the effect of testing on the prediction of total, active and death cases in fig. a,b. total, active and extinct cases are plotted for the coming months if tests per day are increased by . k, k and k per day after june and saturated at million as seen in the initial reproduction number . is seen go down to . after the imposition of lockdown on th day i.e. march . after the second lockdown on th day i.e. april it has reached . . it shows a downward trend further and goes below on october , . if tests per day are increased k per day, then the reproduction number comes below one on july, , which can also be seen in fig. c . the reproduction number is seen to go below one on july if the transmission rate decreases by % due to lockdown in july. the initial basic reproduction number . is in the range of the mean reported value [ ] [ ] . a sensitivity study is carried out for the different parameters, as seen in supplementary material fig.s and s . the parameters are increased and decreased by % from the optimized values to see the changes in the outcomes. it can be seen in supplementary material fig.s that the model prediction are most sensitive to the transmission rates α ,β and γ . just a % change in these estimated parameters gives a huge change in total, active and extinct cases. supplementary material fig.s v. conclusion sipherd model is employed for covid- spread that considers purely asymptomatic category of infected cases in addition to the symptomatic, and the disease spread by the exposed. the effect of lockdown on the rates of transmission of infection and the influence of tests per day on detection rates has been incorporated in the model. with the current trend, total infections would be million when disease ends and can lead to k total deaths. our findings suggest that increasing the number of tests at k per day with highly efficient contact tracing, rather than the current . k per day rise leads to a reduction of million reported cases and reduction of k in total extinct cases. in the absence of a vaccine, the infection can last long till the end of this year and number of deaths could be around k if social distancing conditions and increase in tests remain at the current trend. age-structured impact of social distancing on the covid- epidemic in india assessment of days lockdown effect in some states and overall india: a predictive mathematical study on covid- outbreak estimating the asymptomatic proportion of coronavirus disease (covid- ) cases on board the diamond princess cruise ship, yokohama, japan, transmission of -ncov infection from an asymptomatic contact in germany containing papers of a mathematical and physical character application of the be-codis mathematical model to forecast the international spread of the - wuhan coronavirus outbreak mathematical modeling of the spread of the coronavirus disease (covid- ) considering its particular characteristics. the case of china a sidarthe model of covid- epidemic in italy on an interval prediction of covid- development based on a seir epidemic model a time-dependent sir model for covid- with undetectable infected persons preliminary estimation of the basic reproduction number of novel coronavirus ( -ncov) in china, from to : a data-driven analysis in the early phase of the outbreak predictions of -ncov transmission ending via comprehensive methods artificial intelligence forecasting of covid- in china healthcare impact of covid- epidemic in india: a stochastic mathematical model prediction for the spread of covid- in india and effectiveness of preventive measures seir and regression model based covid- outbreak predictions in india predictions for covid- outbreak in india using epidemiological models prediction of covid- disease progression in india: under the effect of national lockdown estimation of undetected symptomatic and asymptomatic cases of covid- infection and prediction of its spread in usa an epidemic model sipherd and its application for prediction of the spread of covid- infection for india and usa the reproductive number of covid- is higher compared to sars coronavirus novel coronavirus -ncov: early estimation of epidemiological parameters and epidemic predictions ☒ the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.☐the authors declare the following financial interests/personal relationships which may be considered as potential competing interests: eclaration of interest statement key: cord- -lhqvi j authors: barman, manash pratim; rahman, tousifur; bora, krishnarjun; borgohain, chandan title: covid- pandemic and its recovery time of patients in india: a pilot study date: - - journal: diabetes metab syndr doi: . /j.dsx. . . sha: doc_id: cord_uid: lhqvi j background and aims: covid- virus started from wuhan, china and has brought the world down to its knees. it has catapulted as a venomous global phenomenon. this study focuses on the covid- situation in india and its recovery time. method: the study period is from march , to april , . a random sample of individuals found positive with covid- from march , to st march is included in the study which is followed up april , . there is a male preponderance in the sample with % of the covid- patients being male and about % being female. kaplan-meier product limit estimator, kaplan-meier survival curve and log-rank test are used to analyze the recovery time of covid- patients. result: from the results of the study, it is found that the average recovery time of covid- patients in india is days ( % c.i. days to days). only % of the patients get cured after days of treatment. the recovery time of male and female patients is not statistically different. recovery time of patients belonging to different age groups is also not statistically significant. conclusion: this information on recovery time of covid- patients will help planners to chalk out effective strategies. the study period is from st march to th april . a random sample of individuals found positive with covid- from st march to st march is included in the study which is followed up th april . there is a male preponderance in the sample with % of the covid- patients being male and about % being female. kaplan mankind has, more often than not, been at the receiving end of certain unprecedented events that have hogged the limelight and become history [ ] . diseases which were never there in the past have gained currency and become a part of the popular parlance. plagues, flu etc. have battered humanity from time to time and the casualties have been of no small dimension. as of now, it is covid- caused by sars-cov- which is doing the rounds and have brought the world to a deadening standstill [ ] . regarded as a family of viruses, the corona viruses cause cold, cough, and respiratory problems [ ] . known as the sars-cov- , this virus is life threatening and can take a heavy toll in terms of morbidity and fatalities [ ] . the global headcount as of on may st , , is about . million which presents a staggering picture indeed [ ] . in india, with reports of the first case reported way back in january , , the headcount as of may st , , stands about , which is likely to increase exponentially the beginnings of which are to be located in fateful wuhan in china [ ] , the disease gradually spread across the globe with the initial hotspots being italy, france, germany, england et al and of course, the united states of america and india. it finally turned its ugly head to become a global phenomenon which the world is now trying to grapple with and thereby eke out a solution in the form of a vaccine. even as the efforts towards finding a vaccine are underway, there have been simultaneous efforts to reach out to those huge groups of people which have been by now affected. the process being undertaken by governments is to trace, test, isolate and quarantine. the mechanism currently in place to contain or rather to flatten the curve is hard and fast social distancing, using of masks and frequent hand washing [ ] . by now, a few countries have endorsed and ramped up rapid testing to contain the spike and spiraling of covid- . meanwhile, various studies have been undertaken to understand the nitty-gritty of this venomous disease. these studies have been of variegated nature. instead of creating health burden, this pandemic has a great impact on the economic downturn which has seriously affected people from the lower socio-economic stratum (ses) [ ] . research also shows that the different meteorological factors particularly daily temperature and relative humidity are also important in the spread of the disease [ ] . further, the efforts of the academia cutting across multiple disciplines have been working tirelessly to have a better understanding of the prevailing situation. it is in continuation of the same vein that there can be a feasible approach towards understanding the recovery time of the disease. the rationale behind making an effort to approximate the recovery time vis-à-vis the incidence of the pandemic is something that has a bearing on the overall preparations and the mechanism that needs to be put into place at the earliest convenience. in the event of any possibility to determine the recovery time, then the governments will be better placed to make arrangements accordingly and in accordance with the likely number of patients that are to be affected by the disease in the near future. considering the world scenario regarding the spread of covid- , india is also not an exception. the government of india has been working round the clock to make a holistic assessment of the situation. on st may, , the total number of covid- cases in india is maharashtra is the state with the maximum number of recovered patients which is , ( . % of the total cases) followed by tamil nadu with , ( . % of the total cases). the proportion of recovery across india is found to be . % which is greater than the world's proportion of recovery. in case of andaman & nicobar islands and mizoram, though the recovery percentage is , yet it is noticeable that the total numbers of covid- cases in these states are also very low. the percentage of recovery of different states in india till st may, is shown in the map in fig. . understanding the recovery time of disease is very useful information in the fight against the disease. if the incidence of a disease is very high and the recovery time of the disease is also high then the prevalence of the disease in the country is likely to increase which in turn puts extra health, economic and social burden on the country. understanding the recovery time of the disease will help the government to plan proper strategies to counter the disease. with the information on recovery time of a disease in pandemic situation like covid- , the government will be able to plan strategies like requirement of hospitals, doctors, medical staffs, medical equipment's etc. it will also help to make different social and economic policies which will help to fight with the disease. thus in this study, an attempt would be made to study the recovery times of covid- patients of india. the necessary data for the study are collected from a secondary source. information on to evaluate the probability of recovery at different time points kaplan-meier product limit estimator [ ] is used. the average (median) recovery time of covid- patients is estimated by using kaplan-meier survival curve. average recovery time with respect to sex and age of covid- patients are also estimated by using the same method. log-rank [ ] [ ] test is used to compare the average recovery time of covid- patients with respect to sex and age. a random sample of covid- patients is included in the study and status of the the kaplan-meier product limit estimator estimated that the average recovery time of covid- patients is days ( % confidence interval . days to . days). thus from the results it is observed that a covid- patient needs on the average days to recover. log-rank test is used to study the recovery time of covid- patients with respect to sex and age and the results are presented in table . from table , it can be observed that the average recovery time of male patients is days ( % c.i. . days to . days). on the other hand, the average recovery time of female is little higher which is days ( % c.i. . days to . days). the results of the log-rank test shows that there is no significant difference (p-value > . ) in the recovery time of covid- patients with respect to sex i.e., the recovery time of male and female patients is more or less same. the average recovery time of patients of age less than years is estimated to be days ( % c.i. . days to . days) while the average recovery time of covid- patients of age years and above is found to be little bit higher i.e., days ( % c.i. . days to . days). but this difference in recovery time of covid- patients of age less than years and more than years is not significantly different. kaplan has been seen relatively lower in south asian countries including india than many other developed country [ ] . in india the first case of sars-cov- was identified in kerala on th has india met this enemy before? from an eternal optimist's perspective: sars-cov- a review of coronavirus disease- (covid- ) coronavirus update (live): covid- virus outbreak -worldometer. available at phase-adjusted estimation of the number of coronavirus disease revised strategy of covid testing in india covid- pandemic and challenges for socio-economic issues, healthcare and national health programs in india projections for covid- pandemic in india and effect of temperature and humidity statistics, an introductory analysis non parametric estimation from incomplete observations evaluation of survival data and two new rank order statistics arising in its consideration asymptotically efficient rank invariant procedures covid in south asians/asian indians: heterogeneity of data and implications for pathophysiology and research fig: . total covid- cases in india on st may, (data source: www.covid india.org key: cord- -uy s authors: rao, bl; basu, atanu; wairagkar, niteen s; gore, milind m; arankalle, vidya a; thakare, jyotsna p; jadi, ramesh s; rao, ka; mishra, ac title: a large outbreak of acute encephalitis with high fatality rate in children in andhra pradesh, india, in , associated with chandipura virus date: - - journal: lancet doi: . /s - ( ) - sha: doc_id: cord_uid: uy s background: an outbreak of acute encephalitis of unknown origin with high case fatality ( of cases) was reported in children from andhra pradesh state in southern india during . we investigated the causative agent. methods: cell lines and peripheral blood lymphocyte co-cultures were used to isolate the causative agent from clinical samples. identity of the agent was established by electron microscopy and serological and molecular assays. findings: clinical samples tested negative for igm antibodies to japanese encephalitis, west nile, dengue, and measles viruses, and for rna of coronavirus, paramyxovirus, enterovirus, and influenza viruses. virus was isolated from six patients with encephalitis and was identified as chandipura virus by electron microscopy, complement fixation, and neutralisation tests. chandipura virus rna was detected in clinical samples from nine patients. sequencing of five of these rna samples showed · – · % identity with the reference strain of . chandipura viral antigen and rna were detected in brain tissue of a deceased child by immunofluorescent antibody test and pcr. neutralising, igg, and igm antibodies to chandipura virus were present in some patients' serum samples. serum samples obtained after days of illness were more frequently positive for igm to chandipura virus than were those obtained earlier (p< · ). a similar trend was noted for neutralising antibodies. interpretation: our findings suggest that this outbreak of acute encephalitis in andhra pradesh was associated with chandipura virus, adding to the evidence suggesting that this virus should be considered as an important emerging pathogen. viral encephalitis is an important global public-health problem. in india, although many encephalitis outbreaks have been associated with japanese encephalitis virus, several outbreaks have remained undiagnosed. one such outbreak was documented in jamshedpur as early as . a group of patients was characterised by sudden onset of high-grade fever ( - °f), occasional vomiting, rigors, and drowsiness leading to unconsciousness, followed by death in - h. the age of the affected children ranged from · months to years. the case fatality rate was · %, and csf findings were within normal limits. the cause was thought to be viral, but laboratory findings were inconclusive. subsequently, outbreaks of a similar nature were described from nagpur, raipur, bilaspur, and nearby areas of central india in the years , , , , and . similar outbreaks were reported from warangal in andhra pradesh in and . in the absence of a defined cause, these outbreaks were tentatively attributed to reye's syndrome, dengue, chikungunya, japanese encephalitis, measles, and so on. [ ] [ ] [ ] an outbreak of encephalitis was reported between june and september, , in andhra pradesh and adjoining areas in the maharashtra state of india. we report our investigation into the cause of this outbreak. andhra pradesh is a state in southern india situated between - °east and - °north . it is divided into three main regions: telangana (ten districts), rayalseema (four districts), and a coastal region of nine districts. most of the encephalitis cases were reported from the telangana region. the state's general population density is - people per km . there are three distinct seasons: summer (march to july with temperature range of - °c), monsoon (july to december having an average rainfall of · mm), and winter from december to february (temperature range - °c). the state health authorities of andhra pradesh undertook surveillance to detect cases of encephalitis, with a broad case definition of acute fever with cns involvement and negative for other known causes of illness. clinical samples were collected from three groups: an encephalitis group, based on the case definition used by the state government; a fever groupie, fever without cns involvement; and a family-contact group-ie, no fever and no cns involvement. samples obtained were: blood samples, throat swabs, ten csf samples, and one brain aspirate from patients with encephalitis; five blood samples and nine throat swabs from fever cases; and ten blood samples and one throat swab from ten family contacts (including specimens from the brother and mother of a patient who methods cell lines and peripheral blood lymphocyte co-cultures were used to isolate the causative agent from clinical samples. identity of the agent was established by electron microscopy and serological and molecular assays. findings clinical samples tested negative for igm antibodies to japanese encephalitis, west nile, dengue, and measles viruses, and for rna of coronavirus, paramyxovirus, enterovirus, and influenza viruses. virus was isolated from six patients with encephalitis and was identified as chandipura virus by electron microscopy, complement fixation, and neutralisation tests. chandipura virus rna was detected in clinical samples from nine patients. sequencing of five of these rna samples showed · - · % identity with the reference strain of . chandipura viral antigen and rna were detected in brain tissue of a deceased child by immunofluorescent antibody test and pcr. neutralising, igg, and igm antibodies to chandipura virus were present in some patients' serum samples. serum samples obtained after days of illness were more frequently positive for igm to chandipura virus than were those obtained earlier (p< · ). a similar trend was noted for neutralising antibodies. interpretation our findings suggest that this outbreak of acute encephalitis in andhra pradesh was associated with chandipura virus, adding to the evidence suggesting that this virus should be considered as an important emerging pathogen. died from encephalitis). the confirmed chandipura virus encephalitis group consisted of individuals from whose samples we isolated the virus, viral rna, or reactive igm antibodies. the state government did laboratory tests to rule out bacteria and malaria, and to study csf profiles. we tested for japanese encephalitis virus, west nile virus, measles virus, dengue virus, paramyxoviruses, rabies virus, enteroviruses, influenza virus, coronaviruses, and mycoplasma, by use of serological tests, pcr, or both. [ ] [ ] [ ] [ ] all handling of material and tests were done with appropriate biosafety practices. isolation of virus was done by inoculation of clinical specimens ( throat swabs, five csf, and one brain aspirate from a patient who died) into vero, madin-darby canine kidney (mdck), and rhabdomyosarcoma (rd) cell lines, with standard procedures. white blood cells were obtained from ten patients' blood clots by lysing red blood cells, and were co-cultured with phytohaemagglutininstimulated peripheral-blood mononuclear cells from normal donors. all cultures inoculated with the clinical material were frequently checked for cytopathic effects. five csf samples were also inoculated into the brains of -day-old swiss-albino mice to grow virus. tissue culture fluids from cultures showing cytopathic effects were negatively stained with % sodium phosphotungstic acid ph · and examined with the kv mode of a transmission electron microscope (tecnai biotwin, fei, eindhoven, netherlands). complement fixation tests were done with hyperimmune chandipura virus antiserum raised against a prototype strain of the virus ( ). in-vitro virus neutralisation tests were done in vero cells as described previously with tcid ( % tissue culture infective dose) of chandipura virus. the titre of virus-neutralising antibody was assigned as the reciprocal of the antibody dilution capable of neutralising the virus. hyperimmune serum raised in mice against a standard strain of chandipura virus served as a positive control and was used for identification of virus isolate. an immunofluorescence assay was used to test for virus in brain-tissue suspension, which was spread on glass slides, air dried, acetone fixed, and immunolabelled with mouse anti-chandipura-virus hyperimmune serum and anti-mouse fluorescein-isothiocynate-conjugate, by use of standard procedures, along with appropriate controls. rt-pcr for chandipura virus rna was done on the basis of the g gene sequence for an indian chandipura virus isolate (chpi- , genebank accession number j ) the primers shown in the panel were synthesised and used in hemi-nested format for the detection of chandipura viral rna in clinical specimens. pcr products were purified by use of wizard ready reaction kit (applied biosystems, foster city, usa) and an automatic sequencer (abi prism genetic analyser, applied biosystems). both strands were sequenced. we did phylogenetic analysis of the partial g gene sequence ( nt) with mega software. the jukes-cantor algorithm was used with the neighbour-joining method. to assess the reliability of the groupings obtained, we used bootstrap analysis ( bootstraps) available in the software (seqboot: boot strap replications). greater than % bootstrap support was judged to be reliable phylogenetic grouping. igm and igg antibodies against chandipura virus were detected by locally developed capture elisa (patent pending). igm or igg from patient's serum were captured on wells coated with anti-human igm or igg, respectively. chandipura virus extracted from mouse brain by sucroseacetone was the source of antigen. captured antigen was detected with the igg fraction of polyclonal anti-chandipura-virus mouse serum conjugated with biotin (sigma chemicals, st louis, usa) followed by avidin-horseradish peroxidase. o-phenyline-diamine-hydrogen peroxide was added for colour development. negative controls included: age-matched serum from apparently healthy children from an area not affected by the outbreak, and serum and csf from children with flavivirus encephalitis. the cutoff value was determined as mean optical density for negative controls plus sd. for comparison of proportions, fisher's exact test was used. the mann-whitney test was used to compare neutralising antibody titres. the sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. on the basis of the broad case-definition used by the andhra pradesh state government, cases of encephalitis were reported between june and september, , with deaths (case fatality rate · %). most deaths occurred within h of admission to hospital. the distribution of cases was mainly rural, spread over districts of the state, and was spotty without clustering (figure ). age of patients ranged from months to years. the male to female ratio was to · . limited data suggested that csf was usually under pressure; pleocytosis was absent. neurological sequelae were rare in the children who recovered. the typical clinical manifestations in the group with confirmed chandipura virus encephalitis (n= ) included rapid onset of fever ( patients, %), followed by vomiting ( , %), altered sensorium ( , %), convulsions ( , %), diarrhoea (five, %), neurological deficit (four, %), and meningeal irritation (two, %). brain tissue was obtained after death from only one patient: a -year-old, previously healthy girl developed fever, vomiting, and generalised tonic-clonic convulsions, became unconscious, and had severe dehydration. on admission she developed tachycardia, dyspnoea, irregular breathing, bilateral papilloedema, decerebrate posture, and no response to painful stimuli. blood pressure at admission was / mm hg and subsequently dropped to mm hg/not recordable. the girl was put on a mechanical ventilator. she continued with fever ( °f) and developed bradycardia and pupillary dilatation. potassium rose substantially in her serum (to mmol/l). the patient was treated with intravenous fluids, antibiotics, phenytoin, diazepam, and mannitol, and died within h of admission. routine laboratory investigations screening for japanese encephalitis virus, west nile virus, paramyxovirus, coronavirus, measles virus (serum and csf), dengue virus, rabies virus, influenza viruses, and mycoplasma (throat swab and csf) yielded negative results. in the encephalitis group, all ten csf samples were negative for virus isolations. virus was isolated from three of throat swabs (one in mdck; one in rd, vero, and mdck; one in vero and rd), one brain aspirate in rd and vero cell cultures, and two of ten blood clots in peripheral-blood mononuclear cell co-culture. five of the six samples from which virus was isolated had been obtained within days of onset of illness. in the fever group, one of eight throat swabs yielded virus in the rd cell line. assessment of the culture isolates with transmission electron microscopy showed the presence of bulletshaped particles that were - nm long and - nm wide, with distinct surface projections - nm in length and a stain-filled canal at the base of the particle-all features suggestive of rhabdoviruses (figure ). isolates were identified as chandipura virus by complement fixation and neutralisation tests. chandipura viral antigen and rna were detected in brain tissue by immunofluorescence assay ( figure ) and pcr, respectively. four of throat swabs, one of seven csf samples, five of serum samples, and one brain aspirate were positive for chandipura virus rna. one of the five positive serum samples was from the patient (table ) . all isolates were also positive for chandipura viral rna. partial g gene sequences of nt (accession number ay - ) representing clinical specimens from five patients showed - · % identity (mean · %, % ci · - · ; figure ) . these sequences were · - · % ( · , % ci · - · ) identical with the reference sequence. all chandipura virus sequences clustered together with % bootstrap support and were closer to piry virus than to vesicular stomatitis virus (figure ). table shows igm, igg, and neutralising antibody status for patients with confirmed chandipura virus encephalitis, three patients with fever, and two contacts. table shows antibody status in patients with encephalitis, including of the patients with confirmed chandipura virus infection mentioned in table (data were incomplete for the other three patients). since no paired samples of serum from the acute and convalescent phases of illness could be obtained from the patients during this outbreak, the results from testing of singlebleed serum samples were assessed in relation to the time after disease onset at which samples were obtained. a smaller proportion (four of [ %]) of serum samples obtained up to days after onset of illness (early samples) were positive for igm reactive with chandipura virus, compared with samples obtained later than days after onset of illness ( of [ %]; p< · ). a similar trend was also noted for chandipura virus-reactive igg antibodies ( % of early samples positive vs % of late samples) and neutralising antibodies ( % vs %). the geometric mean titres in early versus late samples were significantly different ( · vs · , p< · ) . chandipura virus-reactive igm antibodies were also found in two of five patients with fever but no cns involvement, and in two of ten family contacts. unfortunately, because of the nature of the outbreak response and local resources, we were unable to obtain serum samples from a larger control group. the viruses isolated in different cell lines from clinical samples from patients with encephalitis were confirmed as chandipura virus with various techniques including complement fixation, neutralisation test, and immunofluorescence assay. analysis of partial g gene sequences showed that the genome of the chandipura virus strain associated with this outbreak was distinct from that of the reference strain obtained in . importantly, in one fatal encephalitis case from this outbreak, both chandipura viral antigen and rna were detected in situ in the post-mortem brain tissue. the clinical presentation of this patient was representative of the symptoms seen in most of the other patients reported during the present outbreak. chandipura virus was also subsequently isolated from this tissue. therefore, the presence of the virus in the brain was probably the cause of cns pathology leading to encephalitis in this patient. moreover, the presence of chandipura virus rna in nine patients with encephalitis, all from samples obtained before day after onset of illness, suggests an early viraemic phase of the infection process. that five of six virus isolates were obtained from such early samples further strengthens this observation. further evidence that chandipura virus was the primary causal agent for this outbreak is the pattern of immune response to the virus. substantially higher proportions of positive test results for chandipura virusreactive antibodies were noted among samples obtained more than days after onset of illness, compared with samples obtained earlier, suggesting a seroconversion window period and primary exposure to the virus in the people from whom samples were taken early. of the cases of encephalitis investigated, evidence of recent infection with chandipura virus could be established conclusively in cases ( %) based on either the presence of virus or viral rna, igm antibodies, or both. the absence of evidence of such an infection in some samples could be because samples were obtained very soon after disease onset. a small proportion of the remaining cases might represent encephalitis due to the presence of igm reactive with chandipura virus in two patients with fever and in two family contacts of a patient with encephalitis suggests that infection with the virus may remain asymptomatic or lead to fever without encephalitis; the disease spectrum needs careful study. evidence of igg against chandipura virus detected in adults probably indicates environmental exposure to the virus. several earlier outbreaks of encephalitis recorded in central india from onwards that showed similarities to the present outbreak (clinical features, seasonality, and undetermined aetiology) might perhaps have been due to chandipura virus, which could be endemic in these regions. most of the vesiculoviruses are transmitted by sandflies. interestingly, chandipura virus was detected by pcr in a sandfly pool obtained from the house of an affected patient in the present outbreak (unpublished report). this finding and earlier isolation of the virus from sandflies both in india and africa strongly suggest that sandflies might be the vector of this disease. in india, these insects are more prevalent in the early monsoon period, a season that coincided with the present outbreak. the isolation of chandipura virus from sandflies, , human beings, and vertebrates; the presence of reactive antibodies in human beings and other vertebrate hosts; and the ability of sandflies and mosquitoes to transmit the virus to susceptible hosts; - represents a broad eco-cycle of the virus in nature. the previous isolation of the virus from human beings with febrile and encephalopathy , and association of this virus with the present large encephalitis outbreak, implicates chandipura virus as an emerging pathogen of substantial public-health importance. b l rao isolated and characterised virus, collected and analysed laboratory data, and had substantial intellectual input into manuscript writing. a basu did electron microscopy and laboratory studies related to primary virus identification, analysed data, and had substantial intellectual input into manuscript writing. n s wairagkar did clinico-epidemiological studies of the outbreak, examined patients, obtained and analysed clinical material, compiled data, and had substantial intellectual input into manuscript writing. m m gore did virus isolation studies, planned execution analysis of virus neutralisation data, and had substantial intellectual input into manuscript writing. v a arankalle designed and did molecular virology experiments and had substantial intellectual input into manuscript writing. j p thakare did serology tests, including development of elisas for chandipura virus, igm, and igg, and took part in manuscript preparation. r jadi participated in virus isolation studies and manuscript preparation. a k rao contributed clinical data and took part in patient management, including data analysis. a c mishra was the group leader, substantially contributed to design, interpretation, and data analysis, and had significant intellectual contribution in developing the manuscript. www.thelancet.com vol september , in person and extensive constructive review and suggestions that went into the present manuscript. we also gratefully acknowledge the help and co-operation of the directorate of health services, government of andhra pradesh, india. we would also like to sincerely thank s tikute, s d pawar, g n sapkal, mr hanumaiah, s v gangodkar, v m ayachit, n j shaikh, s p shrotri, and b kundu for their technical support; a walimbe for statistical assistance, mr murlikrishna for photographic help, and m v joshi for providing standard immune serum samples. funds were provided by the indian council of medical research, ministry of health and family welfare, government of india. epidemiology of japanese encephalitis in india: national conference on japanese encephalitis jamshedpur fever etiology of the epidemic of febrile illness in nagpur city, maharashtra state isolation of chandipura virus from the blood in acute encephalopathy syndrome outbreak of killer brain disease in children: mystery or missed diagnosis? laboratory diagnosis of common viral infections of the central nervous system by using a single multiplex pcr screening assay phylogenetic analysis of a highly conserved region of the polymerase gene from coronaviruses and development of a consensus polymerase chain reaction assay nipah virus: a recently emergent deadly paramyxovirus evaluation of a single step multiplex rt-pcr for influenza virus type and subtype detection in respiratory samples application of microtechniques to viral serological investigation ethanethiol sensitive and resistant antibodies to enterovirus in post conjunctivitis neurological syndromes mega · : molecular evolutionary genetics analysis software rapid detection of herpes simplex virus in clinical specimen by use of a capture biotinstreptavidin enzyme linked immunosorbent assay isolation of chandipura virus from sandflies in aurangabad arbovirus surveillance from to in the barkedji area (ferlo) of senegal, a possible natural focus of rift valley fever virus chandipura virus: a new arbovirus isolated in india from patients with febrile illness viruses other than arenaviruses from west african wild mammals: factors affecting transmission to man and domestic animals emerging arboviruses of zoonotic and human importance in india growth and transovarial transmission of chandipura virus (rhabdoviridae:vesiculovirus) in phlebotomus papatasi experimental transmission of chandipura virus by mosquitoes susceptibility of four species of mosquitoes to chandipura virus and its detection by immunofluorescence antibody response to chandipura virus in experimental animals we express our sincere gratitude to stuart nichol (chief, molecular biology laboratory, special pathogens branch, division of viral and rickettsial diseases, centers for disease control and prevention, atlanta, ga, usa) who gave us a unique opportunity to discuss the data key: cord- - ykz raz authors: agarwal, d. k.; de, s.; shukla, o.; checker, a.; mittal, a.; borah, a.; gupta, d. title: alternative approaches for modelling covid- :high-accuracy low-data predictions date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: ykz raz background: numerous models have tried to predict the spread of covid- . many involve myriad assumptions and parameters which cannot be reliably calculated under current conditions. we describe machine-learning and curve-fitting based models using fewer assumptions and readily available data. methods: instead of relying on highly parameterized models, we design and train multiple neural networks with data on a national and state level, from covid- affected countries, including indian and us states and territories. further, we use an array of curve-fitting techniques on government-reported numbers of covid- infections and deaths, separately projecting and collating curves from multiple regions across the globe, at multiple levels of granularity, combining heavily-localized extrapolations to create accurate national predictions. findings: we achieve an r of . on average through the use of curve-fits and fine-tuned statistical learning methods on historical, global data. using neural network implementations, we consistently predict the number of reported cases in geographically- and demographically-varied countries and states with an accuracy of . % for days of forecast and . % for days of forecast. interpretation: we have shown that curve-fitting and machine-learning methods applied on reported covid- data almost perfectly reproduce the results of far more complex and data-intensive epidemiological models. using our methods, several other parameters may be established, such as the average detection rate of covid- . as an example, we find that the detection rate of cases in india (even with our most lenient estimates) is . % - almost a fourth of the world average of %. multiple neural networks with data on a national and state level, from covid- a↵ected countries, including indian and us states and territories. further, we use an array of curve-fitting techniques on government-reported numbers of covid- infections and deaths, separately projecting and collating curves from multiple regions across the globe, at multiple levels of granularity, combining heavily-localized extrapolations to create accurate national predictions. findings: we achieve an r of · on average through the use of curve-fits and fine-tuned statistical learning methods on historical, global data. using neural network implementations, we consistently predict the number of reported cases in geographicallyand demographically-varied countries and states with an accuracy of · % for days of forecast and · % for days of forecast. interpretation: we have shown that curve-fitting and machine-learning methods applied on reported covid- data almost perfectly reproduce the results of far more complex and data-intensive epidemiological models. using our methods, several other parameters may be established, such as the average detection rate of covid- . as an example, we find that the detection rate of cases in india (even with our most lenient estimates) is . % -almost a fourth of the world average of % [ ] . on march , , the world health organization (who) declared covid- a pandemic [ ] , noting that there were "more than , cases in countries, and , people have lost their lives." today, there are over million confirmed cases. however, the availability and reliability of government-reported data remains questionable. we employ a number of curve-fitting and machine-learning techniques to predict government reported numbers of infections in regions around the globe with high accuracy. in india, we note -with surprise -that this accuracy persisted through changes in testing policy, which suggests that these changes were not significant at the ground level. then, we describe a parameterized method of estimating the number of infections (including unreported infections) from the reported number of covid- deaths. this uses demographics adjusted infection fatality ratio (ifr), disease progression, reporting rates, and growth statistics from recent literature and produces a count consistent with other, more complex, epidemiological models (indsci-sim [ ] , mseirs [ ] , etc.). these estimates may be used to compute other epidemiologically-significant variables, such as detection rate, which will hopefully be useful inputs to other models. while our predictions have been successful in predicting government-reported number in may and june ( th may to th june), we note that, with constantly evolving and updating numbers, the accuracy of our predictions can continuously improved by running our methods on the latest data available from reliable sources. we have also applied our methods on current data (updated till th july, ) and report these predictions in appendix f. our data, code, and models are available here: https://github.com/debayanlab/covidpredictions. infection statistics for all countries are collected from the o cial bodies of said countries via ourworldindata.org [ ] . case details and state-level statistics for india (till -may- ) are derived from the ministry of health and family welfare (mohfw) of india via collated datasets [ ]. health and medical data for indian states are aggregated from kaggle [ ] . state-wise case progression for the united states was obtained from the new york times [ ] and the covid tracking project, updated daily. for the reported number of deaths in india, we use daily values provided by mohfw, via ourworldindata.org [ ] . age structuring is derived from the indian census projections [ ] . the pandemic strikes di↵erent regions around the globe at di↵erent times; so, mortality rate, r , doubling time, etc. all vary. therefore, we use curve-fitting and machine-learning models on national-and state-level data to predict government-reported numbers of total infections in multiple countries. we also study and use the case progression in other countries to predict progression in indian states and districts, adjusting for around medical and demographic variables through a multivariate and multi-output neural network. ideally, we would perform projections for each hot-spot, and collate upwards, but that granularity of data is currently unavailable. we note that his method may be applied to any other country as well. we use slope and rate-of-change of slope of the curve for total reported cases in india, the worst hit states in the us, and european countries like france, germany, and the uk; fitting and collating sigmoid curves from the district level for india and state level for the us, and country level for the european countries adjusted for confounding factors. this is surprisingly accurate and is further confirmed by our machine-learning models. india: some data did not identify the district of a reported case. the state, however, was always identified. we assigned districts by weighted random assignment; the weight was the ratio of the cases in a district to that of its state. this was updated every time a case was added. we ignored districts with cases. for all others, we started the day the first case was reported. districts reporting an increase in infections for fewer than five days (across the period we were analyzing) were not subject to predictions using our logistic growth function. instead, the prediction was simply the last reported total. us states: data was taken from the new york times database [ ] . from the date where the total number of reported cases was above to th may was taken as the training data. from th may to th june was taken was testing data. europe: data was taken from the our world in data database [ ] . from the date where the total number of reported cases was above to th may was taken as the training data. from th may to th june was taken was testing data. the gaussian mean (the peak value predicted by the normal distribution) and x (its x-coordinate) were calculated for each district/state/country (appendix a). in case of india, predictions for each district were collated for the national prediction. note that we do not currently account for regional di↵erences in testing rate and migration. we observe that the curves in countries that have a significant number of cases like china and france closely resemble logistic growth. further, similar trends in new york and lombardy . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint are visible as they progress through the pandemic. given these observations, we use machine-learning to fit the curve of italy's covid- case progression (as italy had almost finished its first wave and also had a lockdown) on indian states. the model currently adjusts for around medical and demographic variables; other useful variables were either di cult to represent, reduced model accuracy or unavailable. moreover, we use our global model to observe normalised time series data from china, italy, south korea, france, spain, germany, united states, the united kingdom and all us states and territories to predict a global progression of the pandemic for the next days. for our first model, daily counts were compiled to obtain a list of total cases and the ten indian states with the most cases were listed. similarly, covid- cases in italy were extracted and any missing values were forward-filled. components (see appendix b) from india's census data that could directly a↵ect the spread of cases were collated. all district-data were summed and appended to the state's values. all three datasets were normalized within their respective axes and transformed into one-step-increment long short-term-memory (lstm)-viable data. for the second, global model, country and state-level time-series data was translated to start the day the region crossed cases. this was then o↵set so the time series for all countries ended on the same day and any gap in the beginning was zero-padded. these values were then normalized along respective axes and reshaped to train our lstm. for both models, we employed the default sequential structure with the input layer of long-short term memory (lstm) nodes along with a rectified linear unit (relu) employed to introduce non-linearities, a repeat vector with dimensions of the number of outputs, a lstm nodes which returned sequences activated with relu, time distributed dense nodes with relu activation and, finally, a single time distributed dense node. an lstm [ ] is a gated recurrent unit (gru) which allows an rnn to learn long-term dependencies of sequential input data over extended periods, resulting in better time-series predictions. for state-level predictions, primarily, the optimum input and output dimensions were achieved through loss comparison by sequential search of the variables. the maximum accuracy of correlation was obtained through a time-step input and output. therefore, days of italy's cases along with census variables for each state, were utilized to output the forecasted number of cases for the coming -days in indian states. moreover, the model parameters were hyper-tuned using a random search method for epochs for each of the trails to achieve the the most accurate model without over-fitting data. the hyper-tuned, optimized state-wise model achieved an r-squared score of . for -day forecasts. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . for our global predictions, we use a dense layer with nodes to predict total cases for countries and all us states and territories for the next days. the input uses prior time steps from time-series data from various countries/regions. to determine input length, we performed an empirical analysis of the loss obtained over di↵erent lengths, and chose the best one. to determine the best set of hyper-parameters, we used an automated tuner that optimizes for hyper-parameters in the specified space. the model predicted the progression of cases with a significantly high accuracy -an r-squared value of . on the test set. when predicting active infections we assume that the actual number of infections are correlated more strongly to the reported number of fatalities than it is to the reported number of infections. from the reported number of deaths on a particular day, we back-calculate the expected number of infections on a previous day using disease progression reports and ifr estimates. while we do account for a time lag between the contraction of the virus and reporting of the death, this period is likely to di↵er among people and countries and involves a degree of uncertainty. then, we use curve-fitting methods to extrapolate these numbers and make a prediction for the current day. to account for under-reporting of mortality statistics, we introduce a multiplier. due to the strong dependence of this multiplier on the healthcare infrastructure of the country, it is separately evaluated for every country the method is applied on. for example, in india, the lower bound of this multiplier is , as countries reporting suspected as well as confirmed deaths establish a similar multiplier [ , ] . the million deaths study [ , ] suggests that about % of all deaths are medically recorded in india. accordingly, we assume as a conservative upper bound in india. we apply similar methods for every country to determine these margins. it is reported that the mean incubation period for covid- is around . days ( % ci . - . days) [ ] . estimates of the age-wise mean duration of onset of symptoms to death and delays in reporting of deaths were obtained from cdc [ ] and weighed along the population demographics in the given country. this gives us an approximate period of days from contracting the virus to reporting of death of a covid- fatality in india and similar results on other countries as well. we also conduct several sensitivity analyses using other estimates [ , , ] (see appendix c). there is evidence in literature that the ifr varies significantly with age-structure and quality of healthcare systems of a country. we use age-stratified ifr estimates from china . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . [ ] to calculate an age-weighted ifr estimate for a particular country ( . % for india, based on the census projections). we also consider other popular estimates [ , , , , , , ] in our sensitivity analyses (see appendix c). we do not use any epidemiological models for the growth/spread of covid- . instead, from our original assumption about reported deaths, we back-calculate time-shifted numbers of actual infections and then fit curves to extrapolate these numbers to the present day. in the initial stages of the pandemic, we found an exponential fit to be a closer fit, while with time, logistic curves better approximate these numbers. we fit the following array of exponential and logistic curves and use the best fit among them for further analyses: exponential growth logistic growth richard's curve where d is mean time (in days) between contraction of infection and death, r is growth rate, m is population capacity; ↵, , ⇢ are curve fit parameters. among these, the projections are most sensitive to the estimate of ifr used (see appendix c). this method was applied on data from india, united states of america and certain european countries, both nationally and state-wise (wherever su cient quality of data was available). the total infected number of cases, from th march till th june, were generated from reported deaths using disease parameters and logistic curve-fits. the total number of reported cases for the same time period were taken using ourworldindata.org [ ] . their average daily ratio gave the average present detection rate. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . for each day after th june, the predicted number of reported cases was generated using our models in section . . data from these models were divided by the corresponding predictions made daily by the four functions defined in section . . this gave us the daily predicted detection rate for a ten-day period from th june to th june (see table ). there was no external funding provided for this study and the authors used personal resources to carry out this study. let y i be the ith day prediction including and after th may. let n be the number of valid data points for the district. let us define an x = n+p·i a b·x . then the prediction on the ith day for the district is given as where m is the calculated gaussian mean for each unit (district/state/country) and a, b, c, d, p are curve parameters. the parameters along with their average absolute percentage error between th march and th june for the ten worst hit us states, india, and three european countries have been summarized in we observe that richard's and gompertz' curve gave us the best fit (r > . ) on the data from all the countries we ran our methods on. these include india, usa, united kingdom, france and germany. in general, all logistic curves are better approximates than exponential curves. while richard's curve gives a slightly more accurate fit, gompertz' curve may also be used, as it may prevent overfitting due to the use of fewer parameters (see table ). as an example, we report the prediction for the actual number of infections in india, using both the kinds of curves discussed in figure . results of application of the same methods on us state-wise data was similar and is noted in appendix c. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . considering the neural network approach, our global prediction model utilizes trends from countries that we chose due to the fact that these countries were among the ones with the most cases, and would follow the law of large numbers. we trained our model to predict this pattern on the basis of the growth in each of the selected countries, forecasting for the coming days. we also use state-wise data from the united states and attain an r-squared error of less than % on our test set. this model can be extrapolated to predict the growth of cases for any country, given we have a reasonable amount of data-points.our state-level, curve-scaling, model was unable to provide a national prediction due to the lack of census data in some districts. likewise, we believe that the error of the model could be reduced if we scaled using multiple countries, instead of only one (italy). our simple functions model assumes that the average of the slope from the origin to each point on the curve is reasonably close to the slope of the origin to the gaussian mean for the curve (see appendix a). low case numbers and slow daily increase might skew this average slope so we start training the model after reported cases. nevertheless, the function was able to predict the number of cases with an absolute percentage error of less than % (for days) and less than . % (over a period of days). given better testing statistics for each district or state, a more reliable district-wise or state-wise prediction could be scaled to the national level for multiple countries.thee accuracy of this model . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . suggests that it could be used to predict other parameters (such as active cases, number of deaths and number of cases healed) as well (see appendix d). the prediction presented for these parameters are the number that the government or an authorised agency would report. possible 'second-waves' of covid- in certain countries like the usa can also be indirectly accounted for using our methods. as most european countries are yet to show signs of a second wave, we have avoided any detailed description on the issue. however, while using our curve-scaling methods, the seconds waves may be treated as a superimposition of a sigmoid on an earlier sigmoid. our machine learning based models should not require any further modification as lstms are generally superior at learning such trends in sequential data. if desired, additional 'attention' modules may be appended to the lstms to further improve accuracy. while our methods may be applied on any country with a high number of reported covid- cases, running them on data from india yeilds a detection rate of . % in india, which falls in between the previously reported estimates of the same ( . % [ ] and . % [ ] ). it may be noted that this rate is much lower than the world average of % [ ] and is a genuine cause of concern. recent serological survey results [ ] show that . % of people have been exposed to the virus. this is fairly consistent with our prediction of . % as of th july. other preliminary reports [ ] [ ] of the icmr serological survey, cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . infections in hot-spots (e.g., mumbai, ahmedabad, etc.) are expected to be - times the number of reported cases (i.e detection rates of . - %), which is consistent with our estimates (we calculate an average detection rate of . % for maharashtra). these may serve as validation for our methods, which can safely be used on other countries, as we have demonstrated. the corresponding author confirms that he had full access to all data in this study and had final responsibility for submitting this manuscript for publication. there was no external funding provided for this study and the authors used personal resources to carry out this study. the authors declare no conflict of interest. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted july , . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted july , . . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted july , . . https://doi.org/ . / . . . doi: medrxiv preprint average detection rate of sars-cov- infections is estimated around nine percent indsci-sim a state-level epidemiological model for india modelling and simulation of covid- propagation in a large population with specific reference to india published online at ourworldindata.org indian state census data the new york times. an ongoing repository of data on coronavirus cases and deaths in the u.s. the new york times. available at census of india : provisional population totals. ministry of home a↵airs long short-term memory tracking covid- excess deaths across countries, the economist most countries fail to capture extent of covid- deaths in india, most deaths go unregistered. how reliable is its covid- mortality data? global health: one million deaths the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application case-fatality risk estimates for covid- calculated by using a lag time for fatality estimates of the severity of coronavirus disease : a model-based analysis estimating the number of covid- infections in indian hot-spots using fatality data clinical progression of patients with covid- in shanghai, china a systematic review and meta-analysis of published research data on covid- infection-fatality rates estimation of undetected covid- infections in india the infection fatality rate of covid- inferred from seroprevalence data estimating the infection and case fatality ratio for coronavirus disease (covid- ) using age-adjusted data from the outbreak on the diamond princess cruise ship estimating the global infection fatality rate of covid- covid- : icmr rejects reports that said over % people in hotspots infected, says study not final icmr's sero-surveillance study reveals only . % of the sample population infected with covid- . retrieved from ddnews.gov.in/national/icmr\ot 	extquoterights-sero-surveillance-study-reveals-only- -sample-population-infectedcovid- covid- ) dataset estimating the number of covid- infections in indian hot-spots using fatality data key: cord- -qmcrvufu authors: deepmala,; srivastava, n. k.; kumar, v.; singh, s. k. title: analysis and prediction of covid- spreading through bayesian modelling with a case study of uttar pradesh, india date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: qmcrvufu the pandemic of coronavirus disease (covid- ) started in wuhan, china, and spread worldwide. in india, covid- cases increased rapidly throughout india. various measures like awareness program, social distancing, and contact tracing have been implemented to control the covid- outbreak. in the absence of any vaccine, the prediction of the confirmed, deceased, and recovered cases is required to enhance the health care system's capacity and control the transmission. in this study, the cumulative and the daily confirmed, deceased, and recovered cases in uttar pradesh, india, were analyzed. we used the logistic and gompertz non-linear regression model using a bayesian paradigm. we build the prior distribution of the model using information obtained from some other states of india, which are already reached at the advanced stage of covid- . results from the analysis indicated that the predicted maximum number of confirmed, deceased, and recovered cases will be around , , and . the daily number of confirmed, deceased, and recovered cases will be maximum at th day, rd day, and th day from june . moreover, the covid- will be over probably by early-june, . the analysis did not consider any changes in government control measures. we hope this study can provide some relevant information to the government and health officials. the world is facing the outbreak of the coronavirus which is a highly contagious disease also it is declared as a global public health emergency by the world health organisation (who) [ ] . it is originated in wuhan, hubei, china in december and spread all over the world. the world health organization officially named the disease covid- and classified the covid- outbreak as pandemic on march , [ , ] this virus is highly infectious and transmittable. precautionary measures for covid- contain maintaining social distancing, wearing masks, cleaning hands regularly, avoiding touching the eyes, nose, and mouth (who, ). the first confirmed case of covid- in india was recorded on january . since then, the number of confirmed cases and deceased cases is continuously increasing and most of the states affected by this virus covid- . this disease has recorded millions of cases and thousands of deaths due to rapid pandemic potential. at present, india is the most affected country in asia and has the third-largest number of confirmed cases in the world after the usa and brazil [ ] . it could be soon in the top spot in terms of cases [ , ] . in india, maharastra has the highest number of cases of covid- [ ] . currently, in maharastra, more than four lakhs cases are recorded. tamil nadu, andhra pradesh, karnataka, nct of delhi and uttar pradesh have reported more than one lakh cases [ ] . there is no vaccine until now of this virus. the absence of a vaccine creates the situation worse for the already overstretched health care system. for example, the number of hospital beds per thousand population is less than one [ ] . it is indicating the miserable situation of india's health care system. in india, uttar pradesh (up) is a state that holds a significant value concerning the economy, trade, manufacturing, and services. it has the second-largest economy in india after maharashtra in terms of net state domestic product. as of august in india, confirmed cases had been reported. of these, confirmed cases are from the state of uttar pradesh, india [ ] . uttar pradesh, india's largest democracy with a population of million, will have difficulty controlling the transmission of covid- among its population. in such a grim scenario, many outcomes are potential interest to policymakers; for example: how many confirmed, deceased, and recovered cases will be seen, and by what time? how many will be admitted to icu? how many will need ventilators? when will be started the declining trend of covid- ? the government could take the optimal steps to improve the health system to slow down the transmission rate by knowing even roughly the answer to these questions. multiple strategies would be highly necessary to handle the current outbreak; these include computational modeling, statistical tools, and quantitative analyses to control the spread and the rapid development of a new treatment. it is imperative that the trends and predictions for the state of uttar pradesh must be studied well so that effective strategies can be implemented. we focus on the number of confirmed, deceased, and recovered cases as our target of prediction due to limited available data on the other outcomes. several mathematical and statistical models can be established to study and analyze the transmission process of covid- . so that we can accurately predict the prevalence and explore the situation of the probability of cases and the recovery or deaths. therefore, to reduce the harm of the covid- outbreak, the analysis and research of covid- prediction models have become a hot research topic. the most commonly used models for predicting infectious diseases are internetbased infectious disease prediction models, time series prediction models, and differential equation prediction models based on dynamics. several models have been proposed in literature [ , , , ] . the studies are very less for the india region, and some work has been done by [ , [ ] [ ] [ ] . from an analysis point of view, non-linear models are also important methods to deal with the problem of prediction [ , , ] . as we know, the mechanisms of covid- spreading are not completely understood. therefore bayesian analysis of the epidemic spreading can be interesting. this approach has the advantage that it includes some other prior information in the model other than the data. this study focuses on the analysis and the prediction of the epidemic situation of covid- in the state of uttar pradesh, india, using logistic and gompertz nonlinear regression model, which are accord with the statistical law of epidemiology. the bayesian approach [ ] is used for estimation purposes. here prior information is obtained from other states of india. in this paper, we used the following major databases: ( ) github-covid- in india available from https://github.com/imdevskp/covid- -india-data ( ) covid india is a open source database for india available from: https://www.covid india.org/ the main objective of the study is to make predictions of the cumulative and daily confirmed, deceased, and recovered cases in the state of uttar pradesh, india. respectively. both models have the same meaning of the parameters. here y t represents cumulative cases (confirmed, deceased or recovered cases) of covid- observed at t th time, d is the asymptote that represents the predicted maximum of cumulative cases at the end of the outbreak, b is the slope around the inflection point that represents the growth rate coefficient, e is the time at inflection that represents the time when will occur the maximum daily cases. the difference between these two models is that the logistic model is symmetric around the inflection point while gompertz is not. non-linear regression models were fitted using the drm function of r package drc [ ] of r statistical software. the criteria aic (akaike information criterion) and waic ( watanabe akaike information criterion) are used for comparison of classical and bayesian models, respectively. the regression coefficient (r ) is used to measure the fitting ability of various models. it is defined as where y t is the actual cumulative confirmed, deceased, or recovered covid- cases, y is the average of the actual cumulative confirmed, deceased, or recovered covid- cases. the fitting coefficient is closer to that represents more accurate prediction. by using the results of the non-linear models fitted by least square estimation (lse), we define the prior distribution of the parameters of the bayesian non-linear models for estimating and predicting the cumulative and the daily confirmed, deceased, and recovered cases of uttar pradesh state. from the scatter plot of up states and other states, we found that the parameter d that represents asymptote of the curve has a large number of variations for confirmed, deceased, and recovered cases. but we did not find such variations for the other two parameters b and e. therefore for defining the prior distribution of parameter d, we use least square estimates and standard error of these estimates along with other important factors associated with that considered states, due to which such variations are being found. the considered important factors as additional information are: the total number of tests conducted and the total number of confirmed cases (as of till august ). but for parameters b and e, we use only least square estimates and standard error of these estimates to specify the prior distribution. the prior information on the parameter d can be provided as: for confirmed cases, for recovered and deceased cases, the prior information on the parameters b and e can be provided as: whered i ,b i andê i are least square estimates for i th state. t i and c i be the total number of tests conducted at i-th state and total number of confirmed cases at i-th state respectively. t and c be the total number of tests conducted in up state and total number of cases occured in up state respectively. σ d , σ b and σ e are standard errors of least square estimates of d, b and e. parameter inference was done via the gibbs sampling algorithm. we use watanabe-akaike information criterion (waic) and r to compare models. these bayesian analyses were done using the bmrs [ ] r package. the prediction on daily cases for up state was done by using the results of bayesian non-linear regression model for cumulative cases. in figure , we plotted the bar graphs for daily confirmed cases, daily deceased cases and daily recovered cases, and the scatter plot for the cumulative confirmed cases, cumulative deceased cases, and cumulative recovered cases of covid- for some all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . . states of india. figure shows that there are fluctuations in the daily confirmed cases, daily deceased cases, and the daily recovered cases of covid- for all the considered states. tables , and represent the least square estimates for the parameters of the logistic and gompertz models with respect to considered variables. we used the regression coefficient r to analyze the fitting ability of the models. the value of r closer to one indicates a better prediction. tables and show that the upper asymptote value is found to be greater through the gompertz model as compared to those obtained using the logistic model. from table , we observe that except andhra pradesh (ap), gompertz models provided the greater value of asymptote than the logistic model. we see that there is a difference between the values of time inflection for both the models. the value of r indicates that both the models fit the data well with respect to all the considered variables. from the graphs and tables, we see that delhi is in the controlled stage of the pandemic. delhi crossed the inflection point of the curve and reached it's a plateau, and there are fewer chances of fluctuation in the upper asymptote, which explains the low-value standard error of the estimate of the asymptote. from the covid- updates of india, we observe that in delhi, the death rate is about %, and the recovered percentage is more than %. the possible reasons behind this achievement may be the vast screening of covid- , effective containment, patients treatment, and contact tracing. maharastra has the highest number of cumulative confirmed cases and the cumulative deceased cases (as of till august ). except delhi the covid- pandemic is not in the plateau for other considered states, so there is much uncertainty regarding the asymptote of the curve, which describes the high values of the standard error of the estimate of the asymptote. aic values from tables and showed that the logistic model was the best model for the data of the majority of the states. table showed that the logistic model was the best model only to the data of andhra pradesh and karnataka, and for the rest of the states, the gompertz model was found be best. our aim is not to analyze covid- in all the states which have been considered. the aim of this paper is the analysis and prediction of the cumulative confirmed cases, cumulative deceased cases, and the cumulative recovered cases in uttar pradesh, india. however, we explored the situation of covid- in other states of india to extract the prior information for the bayesian non-linear regression models. figures , and show the cumulative and the daily number of confirmed cases, deceased cases, and recovered cases of covid- in uttar pradesh respectively and the fitted curve by the baysian non-linear regression model using the prior information. in these figures, we see that due to the lack of randomness in cumulative confirmed cases, cumulative deceased cases, and cumulative recovered cases, the sum of the square residual is quite low. tables , , and represent the bayesian estimates, standard error of the estimates, and r for the logistic and gompertz models fitted to the cumulative confirmed cases, cumulative deceased cases and cumulative recovered cases of covid- in up respectively. also, watanabe akaike information criterion (waic) is computed from the fitting of bayesian gompertz and logistic models to the data of the cumulative confirmed cases, cumulative deceased cases, and cumulative recovered cases of covid- in up, india. we used the prior distributions based on the least square estimates from the data of other considered states. based on the waic criterion, we can say that the covid- pandemic curve of up is quite closer to the maharastra curve. this result does not conclude that the prevalence rate of both the state is equal, or they have equal cumulative confirmed cases, cumulative deceased cases, and cumulative recovered cases. the meaning of this all rights reserved. no reuse allowed without permission. perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . . perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . . perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint in figures , and , we plotted the predicted curve by bayesian non-linear regression model using prior information and the best fitted model, i.e., logistic model for up state. the prediction results show that the model can predict the pandemic situation of covid- very well for the considered cumulative and daily variables. prediction is not well for the daily decreased number of cases, the possible explanation for this perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in the copyright holder for this this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint may be that the factors affecting the death rate are different from that of cumulative confirmed cases and cumulative recovered cases and hence, there is uncertainty in the daily number of deceased cases. according to the fitting analysis of the existing data, the logistic model with the maharashtra prior may be the best among the considered models studied in this paper. in tables and , we provided the predicted values of the daily and the cumulative number of confirmed cases, deceased cases and recovered cases of up state. we presented the actual and predicted values up to august , and after that, only predicted values are given up to september . here due to space constraints, we presented only five days interval and recent out of sample values at the daily level. from the tables, we conclude that the model predicts the values well to a great extent. table shows that the predicted daily confirmed cases on september will be , the predicted daily decreased number will be on the same date, and the predicted daily recovered cases will be on the same date. table shows that the predicted cumulative confirmed cases on september will be , the predicted cumulative deceased number will be on the same date, and the predicted cumulative recovered cases will be on the same date. the predicted maximum cumulative number of confirmed cases, deceased cases, and recovered cases by all the considered models will be: - , - , and - respectively as per the current trend. the daily number of confirmed, deceased, and recovered cases will be maximum in between - days, - days and - days from june respectively. in table , we provided the predicted maximum cumulative number of confirmed cases, deceased cases and recovered cases and the predicted date when theses cases reach to the maximum using the best-fitted model in up state. results show that the maximum number of cumulative number of confirmed cases will be on june . the maximum number of cumulative deceased will reach to the on march and the maximum number of recovered cases will be on july . the daily number of confirmed, deceased and recovered cases will be maximum at th day, rd day and th day from june using the best-fitted model. the results of the best fitted model also show that the covid- will be over probably by early-june, . we conclude that the proposed method can be useful, and we believe this study can provide some valuable information to strengthen the implementation of strategies to increase the health system capacity and also help the public health authorities to make the relevant decision. a review of the novel coronavirus (covid- ) based on current evidence advanced bayesian multilevel modeling with the r package brms applied regression analysis bayesian data analysis covid- : forecasting short term hospital needs in france 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( ) india becomes third worst affected country by coronavirus, overtakes russia modeling and forecasting the covid- pandemic in india modelling the epidemiological trends and behavior of covid in italy modeling and forecasting trend of covid- epidemic in iran nonlinear regression modelling nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study package drc. creative commons prediction and analysis of covid- positive cases using deep learning models: a descriptive case study of india seir and regression model based covid- outbreak predictions in india time series analysis and forecast of the covid- pandemic in india using genetic programming coronavirus disease (covid- ) situation report - worldometer-real time world statistics deceased key: cord- -nsj dh authors: chakraborty, chiranjib; agoramoorthy, govindasamy title: india’s cost-effective covid- vaccine development initiatives date: - - journal: vaccine doi: . /j.vaccine. . . sha: doc_id: cord_uid: nsj dh nan the creation of cost effective vaccine is fundamental for the effective mitigation of the deadly covid- pandemic. india is moving to achieve this target to meet the high demand to produce the cheapest vaccine against covid- . india also harbors over . billion people and many cannot afford a costly vaccine. in addition, millions of people who live across over world's poorest countries will also expect the affordable low-cost vaccine. india has a long history of vaccine production and the haffkine institute for example has been recognized by the who as a prequalified vaccines producer before the country got institute of india has long history of producing vaccines against tetanus, influenza, rabies, measles, and mumps. it's currently collaborating with codagenix to develop a vaccine, including live-attenuated vaccine against covid- . besides, it has a partnership with codagenix, a new york based firm specialized on vaccines and the oxford university to produce the covid- vaccine. india also has a tie up with the oxford university to produce the oxford covid- vaccine or chadox ncov- . the serum institute has announced that it will produce the vaccine at low cost and it's registered for phases ii and iii clinical trials (nct , clinicaltrials.gov). india has exported complex vaccines such as the penta-valent rotavirus vaccine before. what's unique about india is that it has the expertise for low-cost per-unit vaccine production of vaccines. due to the low cost vaccine making history, new products against covid- will be of great use in over low-income countries worldwide benefiting millions of people who cannot afford expensive vaccines. india has manufactured the oral polio vaccine and distributed freely across the country as part of the polio eradication initiative by the who. recently, india has requested the world trade organization to waive some provisions in the international agreements that regulate intellectual property rights, to speed up efforts to contain the covid- pandemic and to make sure low-income countries such as india are not left behind. india is currently finalizing the electronic vaccine intelligence network or evin to provide real-time information on the stock and storage details on vaccines nationwide. the government has formed an expert committee to advice on the priorities of vaccine distribution throughout the country. few months ago, the who has praised india's vaccine production capacity in a meeting of covid- . it's time for the developing world to collaborate with india to produce and distribute the cost-effective covid- vaccine as soon as possible. no potential conflict of interest was declared by authors. writing-original draft, c.c; editing, c.c, g.a; all authors have read and approved the final version of this manuscript. madhavi y. vaccine policy in india vaccine development and deployment: opportunities and challenges in india india's vaccine deficit: why more than half of indian children are not fully immunized, and what can and should be done key: cord- - incf e authors: parikh, priyanka a; shah, binoy v; phatak, ajay g; vadnerkar, amruta c; uttekar, shraddha; thacker, naveen; nimbalkar, somashekhar m title: covid- pandemic: knowledge and perceptions of the public and healthcare professionals date: - - journal: cureus doi: . /cureus. sha: doc_id: cord_uid: incf e background and objective the recent pandemic due to the novel severe acute respiratory syndrome coronavirus (sars-cov- ) has become a major concern for the people and governments across the world due to its impact on individuals as well as on public health. the infectiousness and the quick spread across the world make it an important event in everyone’s life, often evoking fear. our study aims at assessing the overall knowledge and perceptions, and identifying the trusted sources of information for both the general public and healthcare personnel. materials and methods this is a questionnaire-based survey taken by a total of , respondents, out of which belonged to the healthcare personnel and were laypersons/general public. there were two different questionnaires for both groups. the questions were framed using information from the world health organization (who), uptodate, indian council of medical research (icmr), center for disease control (cdc), national institute of health (nih), and new england journal of medicine (nejm) website resources. the questions assessed awareness, attitude, and possible practices towards ensuring safety for themselves as well as breaking the chain of transmission. a convenient sampling method was used for data collection. descriptive statistics [mean(sd), frequency(%)] were used to portray the characteristics of the participants as well as their awareness, sources of information, attitudes, and practices related to sars-cov- . results the majority ( . %) of the respondents were indians. about % of the healthcare professionals and % of the general public were worried about being infected. various websites such as icmr, who, cdc, etc., were a major source of information for the healthcare professional while the general public relied on television. almost % of healthcare professionals and % of the general public, respectively, identified ‘difficulty in breathing” as the main symptom. more than % of the respondents in both groups knew and practiced different precautionary measures. a minority of the respondents ( . % of healthcare professionals and . % of the general public) knew that there was no known cure yet. almost all respondents from both the groups agreed on seeking medical help if breathing difficulty is involved and self-quarantine if required. conclusion most healthcare professionals and the general public that we surveyed were well informed about sars-cov- and have been taking adequate measures in preventing the spread of the same. there is a high trust of the public in the government. there are common trusted sources of information and these need to be optimally utilized to spread accurate information. in december , the novel coronavirus disease caused by novel severe acute respiratory syndrome coronavirus (sars-cov- ) emerged in china, followed by a rapid spread all over the world. on march , , the world health organization (who) raised its pandemic alert. as of april , , covid- had caused over , deaths in countries and overseas territories or communities [ ]. in a connected world, fake news and rumor-mongering are common due to a surge in the use of the internet and social media. a confused comprehension in an emerging communicable disease of which even the experts have inadequate knowledge can lead to fear and chaos, even excessive panic, which has the probability to aggravate the disease epidemic [ ] . during the sars epidemic from to , there were misconceptions and hence excessive panic in the general public concerning sars. this led them to be resistant to comply with suggested preventive measures such as avoiding public transportation, going to a hospital when sick, etc. this contributed to the rapid spread of sars and resulted in a more serious epidemic situation [ ] . a similar experience occurred during the ebola outbreak in in africa. these experiences underscore the vital role of engaging with the general public and healthcare professionals and the importance of monitoring their perception of disease epidemic control, which may affect the compliance of community to the precautionary strategies. understanding related factors affecting and influencing people to undertake precautionary behavior may also help decision-makers take appropriate measures to promote individual or community health. hence, it is crucial to understand people's risk perception and identify their trusted sources of information to effectively communicate and frame key messages in response to the emerging disease [ ] . since it is the novel coronavirus, its epidemiological features are not well known and new studies and publications will take anywhere from a month to a year making it important to know and understand the level of knowledge and preparedness of the healthcare personnel in terms of the managing the virus affected patients. today healthcare professionals managing covid- across the world are in an unprecedented situation, having to make tough decisions and working under extreme pressures. decisions include equitable distribution of scant resources among the needy patients, balancing their own physical and mental healthcare needs along with those of the patients, aligning their desire and duty to patients with those to family and friends, and providing care for all unwell patients with constrained or inadequate resources. this may cause some to experience moral distress or mental health problems [ ] . effective communication is a priority in who's covid- roadmap; accurate and salient messages will enhance trust and enable the public to make informed choices based on recommendations [ ] . as the outbreak intensified, social media has taken on new and increased importance with the large-scale implementation of social distancing, quarantine measures, and lockdown of complete cities. social media platforms have become a way to enable homebound people to survive isolation and seek help, co-ordinate donations, entertain, and socialize with each other. social media platforms arguably support the conditions necessary for attitude change by exposing individuals to correct, accurate, health-promoting messages from healthcare professionals in order to investigate community responses to sars-cov- , we conducted this online survey among the general public and healthcare professionals to identify awareness of sars-cov- (perceived burden and risk), trusted sources of information, awareness of preventative measures and support for governmental policies and trust in authority to handle sars-cov- outbreak and put forward policy recommendations in case of similar future conditions. we performed a cross-sectional survey of a convenient sample of respondents. the ethical approval for the study was taken from the institutional ethics committee - , hm patel centre for medical care and education, karamsad via letter iec/ hmpcmce/ / ex. / dated march , . all participants were above years of age conveniently selected from the public at large by reaching out to the general public and healthcare professionals by the authors. the participants were largely from india. the consent of the participants was taken at the beginning of the survey. two different self-administered questionnaires were used. the one for non-medical personnel (general public) is shown in table , while the one for medical and paramedical personnel is shown in table . descriptive statistics [mean (sd), frequency (%)] were used to portray the characteristics of the participants as well as their awareness, sources of information, attitudes, and practices related to sars-cov- . due to large sample sizes in the healthcare professional group as well as the general public group, exploratory visual comparisons were presented without typical statistical tests of significance. a total of health and allied professionals and persons from people at large consented and completed the survey. a majority ( . %) of the participants were indian residents with insignificant responses from outside india. it is presumed that the majority of the respondents are of indian residents but the possibility of a handful of them being non-indians cannot be ruled out because we did not collect demographic data. a comparison of awareness about sars-cov- between the general public and healthcare professionals is shown in table . half of the general public respondents showed eagerness for the sars-cov- test without difficulty in breathing. a similar trend was observed among health professionals. almost all respondents from the general public ( %) and the healthcare professionals ( %) endorsed seeking medical help if the breathing difficulty was involved. slightly more healthcare professionals reported regular influenza vaccination as compared to the general public [ ( . %) vs ( . %)]. almost all the respondents agreed for selfisolation if needed. the majority of the respondents reported that they were washing the hands more frequently and knew the correct way of handwashing. we present here a study of the awareness of sars-cov- among healthcare professionals and the general public with a comparison of many features among them. it is heartening to note that the knowledge with respect to sars-cov- is relatively high among the respondents. there are, however, various limitations of the study and these are inherent due to the circumstances in which this survey was done. the study was begun on march , , one day after janata curfew in india as requested by the prime minister and one day before the lockdown on march , [ ] . the survey was filled during the days of the lockdown when the respondents had a lot of time on their hands and were probably active on social media as well as watching the television news. hence, it is quite relevant that many individuals have their information from these two sources, making it important to ensure that accurate information through verified channels and healthcare professionals are presented and broadcasted to the people. this also points towards the importance of the right people being active on social media so that they can communicate the scientifically validated information to the masses. the curfew and the lockdown ensured that the seriousness of the disease was impressed upon by the highest offices in the country, which is reflected in people taking good precautionary measures to protect themselves from the disease as well as break the chain of transmission. the cases in india have hence not risen to a very high number as rapidly as expected/projected, which also probably indicates that the message was well conveyed and well perceived. as this is a survey that was filled remotely, we need to be cautious in drawing strong conclusions. another limitation of the study is that the questionnaire was in the form of google forms and the language of conduct was english. this implies that the people who did not have access to the internet and were not literate were unable to be a part of this survey. but as the source of information for all the general public remains similar (television is ubiquitous in india), we can infer that they would have a similar response. we base this inference as the main sources of information of the public at large were newspapers, television, and whatsapp despite having access to websites and other online sources. in villages, often the literate readout regional newspapers and news received on mobiles to the rest of the family/friends to ensure dissemination of information. it is now known that the basic reproductive number (r ) of coronavirus is more in healthcare professionals as compared to the lay public and hence the relative indifference or "no worries" approach of healthcare professionals towards getting infected by sars-cov- is a concern. in the scenario where adequate personal protective equipment (ppe) may not be available to the healthcare facilities in india due to increased global demand, it is important that healthcare workers know their risk for being infected. in a recent study in mumbai, % of the healthcare professionals were aware of the various ppe required with only . % of them being aware of isolation procedures needed for sars-cov- infected patients [ ] . the numbers for paramedical staff were also lower. india imports raw materials for ppe production from china and south korea. due to the shortage of materials and low rate of supply, the availability has taken a massive hit resulting in an acute shortage in the market. it is highly likely that many healthcare professionals will not use appropriate ppe, will get infected, and further spread infections to patients [ ] [ ] [ ] . the bhilwara cohort in rajasthan is an example of how a healthcare professional needs to protect against infection since he/she is likely to transmit it to others [ ] . another example in mumbai is saifee hospital, which was shut down due to an infected healthcare professional who continued to work and passed on the infection to many during the asymptomatic phase. the sars-cov- disease presents a unique organism that can be spread for at least five days before developing symptoms and up to days after presentation [ , ] . given its high infectivity, it is a recipe for disaster if healthcare personnel gets it. we have not collected demographic information from the participants and hence it is possible that many of them work in situations where they may not anticipate getting infected. the previous few months have shown how surgeons, orthopedicians, dentists, etc., who typically do not deal with infectious diseases are getting infected by coronavirus [ , ] . in this scenario, it is worrying that only % of healthcare professionals were worried while the public was slightly more worried ( %). the difference in the source of information for healthcare professionals and the general public is stark when we compare information garnered through social media. social media at . % is the second-highest source for the general public, while the healthcare professionals give it a measly %. since social media is prone to fake news, it is heartening that healthcare professionals are not learning from it. however, the reliance of the general public on social media indicates that healthcare professionals, professional organizations, and government officers need to invest a significant proportion of their time and resources to be active on social media to disseminate correct news. the shots heard round the world rapid-response network is an example that needs to be followed [ ] . in another example, we have dr. roberto burioni who has successfully given accurate data on social media. if more healthcare professionals were to enrich social media, it would be a useful platform for the public [ , ] . while many government officials are active on twitter in india, the platform that is commonly used in india is whatsapp, telegram, instagram, and tiktok and these are dynamic and keep changing. whatsapp in the middle of this pandemic reduced the forwarding to just one person for a message that had been forwarded five times from the previous number of forwarding to five people (which was unlimited initially) [ ] . it indicates the importance of this platform across the world for the spreading of messages. the healthcare professionals rated scientific journals at just about . %. it may be due to the low availability of high-quality evidence or poor access that many healthcare professionals in india have to scientific journals, which are mostly published out of developed countries [ ] . in a pandemic situation, this disparity in access can be catastrophic and hence most journals have provided open access to all coronavirus-related publications. healthcare professionals accessed websites such as who, medscape, mohfw, cdc, worldometers, covid .com, icmr, uptodate, and pubmed, for reliable information, which is an indicator of their faith in health organizations across the world. interestingly though at a low . %, much of the general public accessed similar websites such as who, mohfw, cdc, and icmr. at the time that the survey was administered, online webinars via zoom or other applications were just beginning in india to educate clinicians searching for answers. this is not reflected in our current study due to many of the responses being filled before the same or the respondents not being part of these audiences. the study authors have attended many of these meetings conducted by the indian academy of pediatrics, etc., and this information is made available via email or whatsapp messages. in a changing world, both healthcare professionals and the general public need to have reliable and accurate sources of information. the severity of illness was well identified by all who were surveyed as being difficulty in breathing. another heartening aspect was that precautionary measures were well known to both the groups of participants with appropriate hand washing techniques, avoidance of public gatherings, and covering of the mouth while coughing and sneezing as the top three precautionary measures. during the first week of march in india, all the telephone and cellular caller tunes were changed to advisories of how to prevent coronavirus disease and when to seek medical help, which included the above messages apart from appeals on television, etc [ ] . there was less knowledge related to treatment and vaccine among both healthcare professionals and the general public, which was a disappointing finding for healthcare professionals as they were expected to be aware of this. the same could be said of the knowledge of the infectivity period and duration of being asymptomatic after infection. there was a good knowledge of the usage of masks among the general public and healthcare professionals except for the usage of medical masks for healthy people to protect themselves. the icmr and other bodies have issued guidelines on the usage of masks and this seems to have been disseminated widely [ ] . there was also a low insistence on the need for testing those without respiratory difficulty. in a scenario where testing resources are limited, this is an appropriate response but since it is possible to have the infection without respiratory difficulty, especially early on, this disinterest in getting tested, especially in healthcare personnel is worrisome when there is enough evidence of spread from asymptomatic and mildly symptomatic persons. it is also likely that this response may be due to the fact during the time that this questionnaire was administered, the total cases rose from + to about + and the testing strategy of icmr was limited to those with contact or travel to sars-cov- -affected areas [ ] . since writing this manuscript, except for a single source event of a religious gathering in delhi, which caused the doubling of cases to increase from about seven days to . days, it is reasonable to conclude that adequate knowledge exists among the general public. we can only hope that this would be enough to ensure that lockdown to reduce transmission and flatten the curve will be successful [ ] [ ] [ ] [ ] . the covid- pandemic has affected the world in various ways. the deficiency of information, the need for accurate information, and the rapidity of its dissemination are important, as this pandemic requires the cooperation of entire populations. the rapid survey that we conducted had a good response and we show that healthcare professionals and the general public were quite well informed about the coronavirus. they are aware of the measures needed to be taken to reduce the spread of the disease. the knowledge present allows the authors to speculate that the lockdown in india would be effective. the public receives a large amount of information from social media such as whatsapp and the medical fraternity and government need to develop strategies to ensure that accurate information needs to spread in these fora. the public awareness is quite high and it is important that the knowledge of communication channels be known and be kept at the topmost priority throughout the pandemic. the following is part of the text of the approval letter indicating approval for the study. "your research proposal 'response of the public and health care providers to a pandemic of a new virus' was submitted for review and approval by committee members under exempt review. as it involves collection of data using anonymous online questionnaire with maintenance of privacy and confidentiality, it qualified for an exempt from full committee review. the matter was reviewed by committee members and decided to review it under 'exempt from full committee' review. after review and subsequent clarification by you, the project is approved by iec in its present form. as the online form has information and consent section, which needs to be read and accepted by the respondents before answering the study questions, committee waivers the need for any other consent for data collection.". animal subjects: all authors have confirmed that this study did not involve animal subjects or tissue. conflicts of interest: in compliance with the icmje uniform disclosure form, all authors declare the following: payment/services info: all authors have declared that no financial support was received from any organization for the submitted work. financial relationships: all authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. other relationships: all authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work. the public's response to severe acute respiratory syndrome in toronto and the united states monitoring community responses to the sars epidemic in hong kong from day to day epidemiology of severe acute respiratory syndrome (sars): adults and children managing mental health challenges faced by healthcare workers during covid- pandemic who -communicating risk in public health emergencies india will be under complete lockdown for days: narendra modi -economic times covid- awareness among healthcare students and professionals in mumbai metropolitan region: a questionnaire-based survey but no testing kits, from china -the economic times lack of ppe, poor infection control put medical staff at risk of covid- covid- outbreak: protective health gear in short supply -the economic times bhilwara's tale of negligence: infected docs, latest covid- case hint at possible community spread news guidance for discharge and ending isolation in the context of widespread community transmission of covid- clinical course and risk factors for mortality of adult inpatients with covid- in wuhan, china: a retrospective cohort study accessed coronavirus: aiims' doctor tests positive for covid- infection, says sources -deccan herald countering anti-vaccination trends and changing online opinion blasting for science covid fallout: whatsapp changes limit on forwarded messages, users can send only chat at a time -economic times a scientometric analysis of indian research output in medicine during - on every call you make, you will hear a person coughing and that is annoying -indiatoday ministry of health and family welfare -guidelines on use of mask by public strategy of covid testing in india it would've been in . days -economic times how tablighi jamaat event became india's worst coronavirus vector flattening the much-talked covid- curve-how close are we in india? -research matters lockdown may help flatten coronavirus curve in india, says study -business today we are thankful to dr. mili shah for language check of our manuscript. key: cord- -dddf u authors: patil, poorvaprabha; chakraborty, stuti title: where does indian medical education stand amidst a pandemic? date: - - journal: j med educ curric dev doi: . / sha: doc_id: cord_uid: dddf u the recent outbreak of covid- , declared a pandemic, has affected medical education globally. the scenario is no different for medical students in india as they find themselves at a crossroads in their careers, with clinical and elective postings called off. missing out on the opportunity to learn from “first-hand” clinical observation stands to threaten the quality of medical education and learning procured by indian medical students which is extremely essential to deal with the vast patient load that awaits them in their impending future as healthcare professionals. is the indian medical education system being able to cope with the challenges imposed by the increasing burden of covid- ? the authors propose few administrative and on-ground interventions that must seek to work collectively with all government and private medical institutions in order to help students/interns and residents in coping with stress, anxiety or academic losses incurred due to the pandemic. health outcomes are immensely affected by the structure of health systems and policies and also play a pivotal role in determining how various healthcare services are delivered. due to the presence of a federal government in india, shouldering the responsibility of running health care systems' operations and governance have been divided amongst the union (central) and individual state governments. medical education in india is governed by the union and state governments in unison. india's healthcare system consists of a combination of private and public healthcare services and facilities-both providing medical education either under directives of the state/union governments or through private institutional affiliation. the formal training for indian medical education spans a long time and was initiated before india's independence from colonization in . over the years, medical education has evolved significantly to where it stands todaybeing one of the most competitive fields of education to secure a future in, for indian students. a total of medical colleges recognized by the mci (medical council of india) provide approximately seats for more than . million medical aspirants (as per ) who take the national eligibility cum entrance test (neet). once an aspiring student secures a place amidst the grinding competition, she/he is expected to undergo five and a half years of medical training and education, including a period of year of compulsory internship. in addition to studying various clinical subjects, medical students are expected to complete compulsory clinical postings with moderated number of hours in each clinical subject, are subjected to continuous clinical and paper-based evaluation/assessments, need to fulfil clerkships, elective postings-all while dealing with the anxiety and stress that comes with course load completion before final exams. [ ] [ ] [ ] [ ] the recent sars cov- (also known as covid- or novel coronavirus) disease outbreak was declared as a pandemic by the world health organization (who). the rapid spread of the infection has disrupted daily life and put even the best healthcare systems across the world to a test. this has put an insurmountable amount of pressure on all medical services, including medical education. medical students across the world stand at a difficult juncture amidst this unanticipated situation. currently, several governments and medical schools around the world have taken measures to curb electives and clinical teaching in its entirety while some have chosen to maintain a few. nevertheless, medical students find themselves at a painful crossroad of being the future of healthcare in their respective countries and at the same time being unable to provide services during this crisis as a result of not being fullfledged, licensed professionals. [ ] [ ] [ ] [ ] scenario in india covid- has impacted the journey of medical students in proportions far beyond what could possibly be fully mitigated. most medical schools in the country have cancelled face-toface lectures, clinical postings, practical classes, demonstrations, and have moved to online lectures. impact on medical students. in india, students preparing to be medical doctors study anatomy, physiology and biochemistry in the first year of their five and a half years coursework. during the first year, in addition to lectures, students visit the dissection hall almost on a daily basis where they learn about the human anatomy. dissection hall sessions help them in building an understanding of how the intricate structure of the human body functions and lays the foundation for a better understanding of more advanced subjects like orthopedics and surgery. this is further supplemented by practical classes, demonstrations, seminars, small group tutorials and hospital visits. in light of the lockdown, medical students in their first year have been walloped, with most of these lessons now being attempted to be delivered online, which makes it challenging to understand the relationship of different human anatomical structures in the body and eliminates the "learning by doing" component of education by performing dissections. hospital postings/clinical rounds are undoubtedly the most crucial component of medical education that follows after the first year. budding doctors learn how to take a case history, identify signs and symptoms, interact with patients, and observe interesting cases while they also shadow doctors on rounds. everything that they spend hours and days learning from books finally starts to fall into perspective on witnessing findings in patients. a lot of medical students have at least once heard during the course of their education, "what you read, you might forget. what you see (in clinics), you will always remember". covid- has taken away the chance for medical students to learn through clinical rounds; thousands of them are engulfed in uncertainty and fear of how they will be able to make up for this academic loss. with the rapidly evolving nature of the current situation, most medical schools across the country have not been able to decide on how they will make changes to the existing curricula and annual plan to be able to do justice to their students. several colleges have resorted to assigning humongous portions as "self-study" modules failing to take into account familial conditions and the possible disruptive environment in homes while mental health issues and domestic violence are at a steep rise during the nationwide lockdown. this is an even bigger concern, especially for many indian students, residing in joint families, consisting of a large number of family members, where the environment encountered might not always be conducive for academic pursuits. final year students, just a year away from finally being doctors, are anxious about how they will make up for the academic loss and cope with the added burden of an already extremely intense course year. impact on interns and residents. the condition of medical students is not particularly promising but interns and residents undoubtedly have it far more difficult. while residents learn specialty-specific skills during their post-graduation, a -year-long internship is the last component of undergraduate medical education where interns apply and develop their clinical skills, under the guidance of senior doctors. at some health facilities, senior doctors and specialists are not attending to patients, leaving the entire responsibility to interns and resident doctors. several interns and residents have been working extra duty shifts in resource-deprived conditions, with a gross lack of personal protective equipments (ppes)-away from their families and homes. at a few centers, ppes strangely seem to be following a hierarchy-the senior doctors get the best of what is available, residents follow, and interns are left with barely any quality equipment to protect themselves adequately. in a study conducted in may , around % of all respondents also perceived discrimination based on hierarchy (eg, senior doctors vs junior doctors, nurses vs interns) or departments, in the distribution of ppe. a large number of doctors have been reusing masks, gloves, and scrubs. moreover, faced with a shortage of personal protection equipment (ppe), india's healthcare workers have been reduced to using raincoats and garbage bags instead. while stories are surfacing all over social media and internet globally, calling doctors and health professionals covid heroes and sentinels, there have been far too many instances of doctors being assaulted in india over the past weeks. while having put themselves and the lives of their families at risk to protect their communities from the pandemic, there are reports of health professionals facing discrimination and stigmatization, being removed from homes, fighting for proper ppes, being beaten and ill-treated. such incidents doing rounds on social media and news broadcasts could have a long-lasting and indelible impact on aggravating the anxiety and panic of the impending future on the minds of medical students and young doctors. , how this will impact the current generation of budding doctors, in the long run, remains a mystery. amidst the long-standing anarchy that presently shrouds india which has been on lockdown since march th, , the future of medical education for millions of indian medical students is at stake, and the stakes are high. impact on career paths. it is not just the impact of the pandemic on the mindsets of budding doctors that is worrisome; it is also the uncertainty that looms over the future prospects of these medical students. with international licensing exams being called off, admission processes halted within and outside the country, examinations for many postgraduate medical courses postponed, there have been numerous qualms, making the mental impacts of the pandemic on some medical students worse than the others. postponement of national level competitive entrance exams proposes another threat to continuity of the supply of trained doctors and health workforce, which might result in a crunch in trained workforce in a few years. hence, the impact is being experienced not just by existing medical students, but future medical aspirants as well. patil and chakraborty conclusion covid has put healthcare education and health systems around the world to a stress test. the future of healthcare in india, and the world at large, depends on how our institutions collectively mitigate the damage to healthcare education caused as a result of this pandemic. there ought to be administrative interventions into the functioning of medical institutes across the nation to ensure that concrete efforts are made to help students to cope with stress, anxiety and the academic losses they incurred due to the pandemic. examples of which could be: ( ) extension of semesters in institutions across the country to provide adequate time for medical students enabling completion of recommended hours of coursework and hospital rounds at an appropriate pace. ( ) postponement of exams on the horizon enabling students adequate time for preparation. ( ) allowing students with more opportunities to retake/ reappear in written or oral examinations that may have been conducted during the lockdown period which might have warranted for poor performance for students unable to cope with the psychosocial and emotional stressors of dealing with the pandemic (especially students who might have a family member with positive diagnosis). ( ) "self-study/homework" and online lectures are widely being used as a way out, but it is essential to reconsider and reassess the complete reliance and effectiveness of these methods in indian medical education during these times of disquiet; and take into thorough consideration the academic disadvantage a number of future doctors will suffer from, compared to their peers, due to veiled hindrances like distressing familial conditions and unpleasant environments within homes preventing them from reaching their full academic potential. health systems in india ministry of human resource development number of neet aspirants increases by lakh to a record lakh. the times of india depression, anxiety, and stress among final-year medical students covid- and medical education sars and its effect on medical education in hong kong the impact of covid- on medical education medical student involvement in the covid- response competency based undergraduate curriculum for the indian medical graduate risks: the impact of online learning and technology on student physical, mental, emotional, and social health. international technology, education and development conference prevalence and correlates of depression among college going students of district amritsar senior doctors do not attend to us, say covid- patients at victoria. the hindu coronavirus in india: lack of equipment forces doctors to fight covid- with raincoats, helmets. india today india covid- : online survey shows not all is well on ppe availability front. the wire science ppe shortage throws doctors out of gear madhya pradesh: lady doctors hurt in stone pelting in indore. national herald indian doctors fighting coronavirus now face social stigma. quartz india all stages of neet pg counselling postponed due to covid- lockdown. the times of india all authors understand and meet the icmje authorship criteria. both authors contributed to conceptualisation, evidence, literature search, drafting and editing of the manuscript. https://orcid.org/ - - - key: cord- - i zj b authors: khurana, sonal; haleem, abid; luthra, sunil; huisingh, donald; mannan, bisma title: now is the time to press the reset button: helping india’s companies to become more resilient and effective in overcoming the impacts of covid- , climate changes and other crises date: - - journal: j clean prod doi: . /j.jclepro. . sha: doc_id: cord_uid: i zj b covid- is the pandemic caused by one of the coronaviruses. this virus was not known before the outbreak in wuhan, china, in december . by january of it was declared to be a global human health crisis. the deaths and illnesses caused by the virus caused extensive fear and anxiety among people in all societies. the pandemic slowed economic activities nearly to a halt. the challenges of how companies should respond to the disruptions in their supply chains and how they can build more resilient systems, must be systematically addressed. the authors of this paper highlighted essential factors which can help companies to overcome this crisis and other types of crises, by learning from the approaches taken in india, which has a unique and diverse economic system. the analytical hierarchy process (ahp) technique was used to identify the essential factors which can help companies to improve their resilience so they can recover during and after the covid- pandemic era and potentially in other similar complex crises. the results of the ahp evaluation were prioritized by performing a sensitivity analysis to prioritize the essential factors. the “role of governance” was found to be the most important factor that can be used to help in rebuilding industries and societies and in helping them to become more resilient to future severe shocks. the results of this research were used to develop recommendations for company managers, practitioners and policy-makers. the authors hope that this advice will help india to become a stronger nation with more resilient companies, which are better prepared to anticipate and to respond to future crises. we hope people in other nations will also benefit from the finding presented in this paper. it is widely known that the covid- pandemic does not differentiate between nationality, gender, religion, wealth or the economies and markets it affects. dramatic challenges have impacted businesses in every country. in this context, india was not spared. in recent years, j o u r n a l p r e -p r o o f micro, small and medium-scale enterprises (msmes) were recognised by the indian government as the backbone of the economy, as, they provide about % of india's economy (ministry of msme website, ) . the msme sector is a highly dynamic sector of the indian economy. it provides extensive employment opportunities and contributes socially and economically to india's stability. approximately million workers were employed by msmes in india in (ministry of msme website, ). with the importance msmes have in india, revision in the definition of msmes has been needed for a long time. this revision came at the time of the pandemic when the industries were in dire need of the help from the government. the revised categorisation of msmes can help them to grow in size as they derive benefits from being msmes. this is an important step as their survival has been dramatically challenged by the covid- virus that was first detected in wuhan, china in november . it has people in the entire world in the first half of because of which, the covid- virus outbreak was declared a pandemic and a public health emergency of international concern on january (euro surveillance editorial team, ). till july, , there has been . million cases of covid- and more than , people have lost their lives (world health organization, ) . figure depicts the global deaths due to covid- . the data is till nd may, and the graph shown in figure does not constitute deaths from cardiovascular diseases or cancer, which according to world economic forum, are the top causes of deaths in the world. the covid- pandemic hangs over societies' futures, like a spectre. this pandemic has brought economic activity to a standstill, and has resulted in dramatic declines in global trade and growth . the international labour organisation (ilo) described the pandemic as the most serious challenge since second world war; it has forecasted that the pandemic will infect . billion workers, or % of the world's workforce (livemint, a) . the loss of livelihood, social isolation, and fear of contracting the virus have created fear and anxiety among the people which has led to mental illnesses and other types of severe illnesses. even though, covid- was, at first considered to be a physical health crisis, it has given rise to mental health risks as well as it expands globally into a severe pandemic (united nations organisation, ) . the physical and mental health illnesses have caused increased risks of the survival to millions of people. therefore, focus should be on incorporating the approaches which would be able to restore the environment and to improve the health of humans which are vital for sustainable development of society (song et al., ) . the impacts evolving from pandemic are documenting that this pandemic is causing extensive social, psychological and economic damage. (laing et al., ) . the estimation by the ilo stated that in india, more than % of the workers work in the informal sector and they are at risk of moving deep into poverty because of the pandemic, which will adversely affect overall societal development (i.l.o., ). this pandemic has increased the urgency to incorporate all three aspects of sustainability, social, environmental, and economic goals into all dimensions of supply chain management including coordinating inter-organisational business practices to ensure improvement in performances of all of the firms in all supply chains (hussain et al., ; khurana et al., ) . moreover, in the current economic scenario, the success of any firm should be based, not only on profitability, but also on its capacity to contribute to the future of people and planet (bubicz et al., ) . this pandemic has disrupted millions of supply chains, filled hospitals with millions of sick and dying people, closed schools; and highlighted the urgency to consider the social aspects of sustainability along with ways to increase productivity of companies, i.e. to make them covid- resilient (p.i.b., a) . although the "human dimension" is urgent, it must be balanced with the ecological and economic dimensions of all countries. the united nations secretary general antónio guterres made an announcement in mid-march that overcoming covid- would be the main focus of the world and climate change has to take a backseat. many international policymaking conferences on environmental issues have been postponed till . but, unless improvement stimulus support also includes policies focussing on climate change mitigation, there is a high probability that firms will return to their high polluting practices when the pandemic fades (spratt and armistead, ) . adversities bring opportunities for making holistic improvements. thus, this time must be utilized by companies to modify their business models, policies, procedures and practices in the short and long-term so that they become more sustainable, equitable and resilient (ivanov and dolgui, ) . the pressures from stakeholders for equity should act as a catalyst for company leaders to transition their companies to have sustainable performance at all levels. therefore, it is urgent to recognise and bring to the forefront the factors, which can help companies to reduce their losses, incorporate sustainable practices and to increase their resilience to this crisis and to future crises (amankwah-amoah, ). the covid- has given every country many new lessons, which if implemented will help the countries to reduce the negative impact of this crisis and of future pandemics. the lesson to be learnt is that economic development of the country is more important than economic growth of the country. as societal reactions to this pandemic have shown, many businesses have been closed leading to loss of livelihood. many people who have lost their jobs are suffering from mental illnesses and others have developed fear because of uncertainties for their future (nicola et al., ) . therefore, the challenge which needs to be addressed is how to save the lives of people from being killed by the virus or dying due to lack of work, money and food. this can be done by upgrading the healthcare system of the country. for this, one of the obstacles to overcome lies in improving the numerous supply chains of the country (farooque et al., ) . all aspects of supply chains are interlinked. disruption of supply chains cause businesses to close which in return lead to loss of livelihood which affects the mental and physical health of individuals and of society, overall. as people switch to drugs and alcohol, the abuse at home increases. therefore, how companies cope with the problems associated with supply chain disruptions due to this and other pandemics needs to be addressed. previous research on covid- has been performed in the context of medical science. but, a production and operations management perspective of the pandemic is missing (kumar et al., ) . therefore, to proceed on this journey and address these issues, the authors of paper had the objective to identify the factors, which would help to rebuild resilient industries and societies in the post covid- era. consequently, the objectives of the research were: j o u r n a l p r e -p r o o f • to identify the factors which are important in helping india's companies to become more resilient and effective in overcoming the impacts of covid- , climate changes and other crises; • to rank the priorities of the identified factors, which are important in helping companies to recover from such shocks; and • to perform sensitivity, analyses to test the strength of the identified factors under different weighting categories. the main objective of the authors of this paper was to develop a holistic view of sustainable supply chains. because, as this pandemic has made us realise, that a holistic, resilient plan for protection, followed by revival and growth are urgently required otherwise many companies will fail (p.i.b, b). survival of companies in the post pandemic era would depend on their commitment towards the various aspects of sustainability. failure of the company would lead to the loss in the economy of the country. the remaining parts of the paper consist of the following sections: section contains the introduction; section contains the literature review to identify the factors which are important in helping to rebuild companies and societies during and in the post-covid- pandemic era. it depicts the gaps observed in the existing literature; section sketches out the research methodology used in the paper; section outlines the results of the analysis performed by ahp process; section discusses the technique to test the strength of the rank of factors obtained by the above process; section compiles the findings of this research; section highlights implications of the findings of this paper, for company leaders and for researchers; and section summarises the conclusions and highlights urgently needed future research. the authors of this paper hope that the recommendations will help india's and other societies and they will make speedy, equitable, sustainable recoveries during the pandemic and in the post pandemic era. j o u r n a l p r e -p r o o f the st occurrence of covid- in india was documented on january (mohfw, ). like the time when the disease is spreading at a faster rate, it has become essential to save the lives and livelihood of people. therefore, the systematic literature review was performed to review relevant literature that can provide guidance in making urgently needed corporate and societal changes and which can help in building a theoretical foundation for future research on socio-economic vulnerability to pandemics and other crises such as climate changes, which are integral to the pandemic. during the period of january -july, , the covid- pandemic has evolved; it has changed the world, it has dramatically affected human society, which underscores the urgent need to build resilient industries and societies that are able to withstand such shocks in the future. coronavirus has brought the economy to a halt and has changed the lives of societies globally. devastating the operation of businesses, covid- has affected almost all supply chains; be it manufacturing, service, healthcare or agriculture. it will take a long time for the industries to recover the losses incurred by them by supply chain disruptions and societies to recover from the loss of family members who died from the virus due, in part to due weaknesses or fissures in the healthcare supply chains (govindan et al., ) . the prioritisation of economic growth at costs to human health and environmental impacts are among the short and long-term consequences of covid- . however, the main priority in today's scenario has been to save the lives of individuals. this can be accomplished, in-part by creating awareness amongst them to follow social distancing measures and maintaining proper hygiene . but, the pandemic should be used as an opportunity to improve the health care system of the country. improving the health care system would provide benefits now and in the future since the future is dependent on the health of the country which is the new wealth of the country. the present time should be used in investing in cleaner production and sustainable consumption methods and improving in labour intensive sectors which currently often puts the health of workers at risk (song et al., ) . investing in such approaches will help in improving the sustainability of the society which will help to ensure that the needs of the present and future generations are secured. a fiscal stimulus is required to restart the engine of the economy. according to the federation of indian chambers of commerce and industry (ficci) "bharat self sufficiency fund" should be constituted for promoting research and innovation to build a strong and resilient nation and to constitute self-sufficient industry clusters with completely developed value chains inside the country (p.i.b, a). the extensive spread of the pandemic has created psychological suffering and increased frequencies of severe mental illnesses (bao et al., ) . strategies should be formulated that address the food and other needs of the people, and measures for preventing spreading of the disease (rajkumar, ) . a roadmap reassuring the people for meeting the needs of the vulnerable must be prepared because india has a very large informal economy in the workforce. those at the bottom must be at the top in the order of priority. india also stands low in the list of the countries which have the proper equipment in public hospitals (paital et al., ) . therefore, it is difficult for a country like india to contain the spread of the disease. therefore, it becomes more important to work on building a stronger resilient nation and the industries which are capable of withstanding such shocks. reorientation of development models and consumerism driven lifestyles is required in the wake of covid- pandemic so that economic development is attained post covid- pandemic (p.i.b, b). therefore, the measures taken by the government to prevent the spreading of the disease should become a part of life for every individual in order to stay healthy in the post covid world. the silver lining to the crisis for the country like india is that it comes at a time when there is disruption happening in technology. technologies are going through an enormous amount of change. moreover, the survival of the businesses will depend on their digital transformation . adoption of sustainable technologies will become an increasingly important ingredient, among others, to support business recoveries, now and when confronted with future pandemics. company leaders must also be part of the holistic plans to ensure human, ecological and economic health of cities and communities (amankwah-amoah, ). the initial variables which influence the preparedness of companies to recover during the post-covid- pandemic period was identified based upon: a. the literature review, b. obtaining the opinion of academic experts, c. reviewing newspaper articles and reports of reputed organisations, d. obtaining advice from scientists working in eminent organisations, e. building upon information from governmental policy-makers. j o u r n a l p r e -p r o o f that phase was followed by conducting a brainstorming session amongst the experts and the authors via videoconferencing. the experts were selected based on their research expertise in related fields. the experts, who were a part of the brainstorming process, later helped in prioritizing the variables. the details of the expert's responses are included in subsection . . . better recommendations usually come later with the brainstorming sessions (danes et al., ) . the experts' expertise and the second and third author's previous research on related issues under the guidance of the fourth author helped in identifying the appropriate variables and their respective groupings. this was followed by another brainstorming session amongst the experts and the authors to select and group the variables. the brainstorming session helped the authors to finalise the analytical framework. during the process of proposing and discussing the variables, the expertise of the experts and authors practical experience and in-depth understanding of the field of operations and supply chain were very beneficial. a total of forty-two variables were included in the final list. these variables were grouped into nine key factors and related subfactors. table lists identified key factors, which were selected as essential for helping industries to rebuild in the post covid- pandemic period and hopefully contribute to more sustainable societies, globally in the context of the likelihood of more pandemics in the near future due to climate changes. these factors can help business leaders to take concrete solutions that can improve their business' capacity to comply with the 'new norms' that respond to present and future pandemics, in the context of climate changes and other challenges. climate changes are also evidencing the very serious risks to sustainable societal futures, globally. climate changes will not only affect agriculture, fisheries and forestry but also industries such as transportation upon which all societies in developing and developed countries are totally dependent (song et al., ) . roles of governance roles of governance is paramount for the revival of industries in post-covid- • provide economic stimulus packages to provide low-cost money to industries to help them to restart • targeted social security programmes for those below the poverty line • close cooperation of government and industry to improve efficiency and resilience of production and supply chain management issues • measures are to be adopted to ensure demand for locally produced products, i.e. produced in india • strong and quick decision-making and effective implementation of the selected approaches • new norms for personal hygiene and sanitation • new healthcare norms facilitate the barrierfree movements of goods and services so that timely delivery can be accomplished within the country. the focus should be to overcome intracountry barriers. • shift management • flexible production size • workers safety and health to be the paramount agenda • transparency • welfare scheme and its effective implementation . environmental issues drastic reduction in pollution level is observed, i.e. the planet revives with no humans into play • new environmental assessment models and norms • pollution is made from industrial production and mankind consumption level has been reduced. • newer energy sources, renewable sources of energy • energy-efficient devices to be used . capacity building capacity building helps in easy incorporation of the technology • industries must focus on realignment, retraining and re-skilling of their employees • digitisation, automation and artificial intelligence will have to be accelerated in every stream. hands-on training on automation and artificial intelligence is required so that the future of societies is secured. jobs under mgnrega (mahatma gandhi national rural employment guarantee act) should be increased so that the workers who have returned to their home towns can also obtain employment. . change management stakeholders to be prepared mentally and trained to take the new normal • the morale of the workers should be boosted by giving them assurance that their health is the priority of the company; by removing the fear of the disease and by providing them a liveable wage, even when the company is temporarily 'closed.' • training for the "new normal" • psychological issues and management • awareness to be created amongst individuals on the importance of maintaining hygiene • safety of the consumers is to be ensured . organisational change management • organisational should coalesce as a team these factors can be used to challenge us to make dramatic changes in business models, corporate social responsibilities, designs for improved produce-services, improved life-long educational systems, and dramatically improved political systems and health-care systems from the local to the global levels. all of these changes must be envisioned and implemented from holistic, integrative, preventative perspectives. the indian government's priorities are: a. preventing the disease from spreading, b. ensuring provision of food and basic amenities for the poor and c. restarting the engine of the economy. lockdown and social distancing are being used as a means to break the chain of transmission of the disease and simultaneously improve the health infrastructure of the country . the challenge that the government is facing today is of unimaginable magnitude as india has the second-largest population in the world (paital et al., ) . timely, governmental interventions have contained the spread of the disease. nevertheless, the focus should be on rebuilding a more robust, resilient, equitable, sustainable nation which can prevent, anticipate or reduce the impacts of such shocks without affecting the economy (alicke et al., ) . the source of the coronavirus has not been identified as yet, and scientists are in the process of developing a vaccine to cure the same (vieira et al., ) . it is still not known whether this disease will be completely wiped off or it will re-emerge on a seasonal basis, and if it does, will it lead to the same kind of destruction as it has caused during the present time . however, the need of the hour is to help to make industries more resilient, sustainable and equitable so that they are able to face such kind of pandemic in the future. the steps followed in the present study are shown in the research flowchart, as depicted in initial variables have been identified by studying the literature, newspaper articles, the reports of reputed organisations and taking the opinion of the experts. recognition of important factors to rebuild the industry post-covid- was performed using the ahp approach. after the preliminary survey, forty-two variables were selected as highly relevant for seeking to make needed changes in industry and society. this method is built upon four hierarchy decision process levels (see figure ) which are explained below. after developing the hierarchical structure, pair-wise comparisons of the elements of the hierarchy were performed. in all comparisons, the comparative significance of a pair of elements in relation to a higher-level criterion was calculated, considering the decision-making objective. viewpoints from the experts were taken through a scientifically designed questionnaire and specified in terms of clear numeric values. in spite of the carefully designed system, the evaluation scale of ahp was not able to quantify the ambiguity due to human judgement. it is certain that there is a high degree of uncertainty in making decisions on matters related to covid- , and thus was difficult to quantify the suggestions for the company experts and from other stakeholders. but, a solution has to be provided to help the industries in restarting their work and in building resilient societies. even though there are weaknesses with ahp analyses, they are helpful when the objective is to rank the elements and the alternatives. in such cases, ahp is the most reliable method for determining the relative significance of criteria and alternatives. methods involving pair-wise comparisons can be rigid when criteria and alternatives are very closely interrelated (such as in the present case). therefore, it was important to consider all of the relevant elements of the decision problem. on the other side, mcdm methods that depend upon on the direct rating of criteria and alternatives, require less effort on the part of the decision-makers, but determining the weight coefficients for interactions is less precise (calabrese et al., ) . in comparing these methods, ahp is more appropriate to determine weight coefficients as it helps the decision-makers to obtain a better understanding the relative importance of interactive j o u r n a l p r e -p r o o f alternatives and criteria. in the ahp technique, attention is on two elements at a time and therefore, it provides a more accurate evaluation (konidari and mavrakis, ) . since the research for this paper pertained to a complex problem that had the risk of inconsistency, ahp provided the flexibility of its consistency thresholds compared to other methods that require perfect consistency for calculating weights. the threshold of ahp can be reduced or increased based on the decision-makers (ishizaka and siraj, ) . the ( ) calculating eigenvector (λ max ) for every matrix of the order n ( ) cr can be computed with the help of the following formula: ( ) where "n" is the order of the matrix and "ri" is known as the random consistency index. table gives the ri values for matrices of the order - . the experts involved in the ahp survey were selected based on their expertise in the related field. the questionnaire was mailed to the experts to ask about their opinion. a reminder mail was sent to the experts after one week. ten experts of the related field, with a minimum of ten years of experience were chosen for the study. six professionals from the industry, two academic experts and two medical doctors were invited to participate in filling the questionnaire to provide their assessment of the comparative significance of factors and sub-factors. the industrial experts were either managers or owners of msmes who had experience in running their enterprises. one of the experts had experience in managing workers and in taking care of their welfare for more than years. two of the experts were heads of parts supply departments. two experts dealt with managing inventory of parts. the final expert was the owner of an enterprise. two academic leaders who had more than twenty years of experience in research and in teaching supply chain management at their institutes and in providing training to the employees of msmes were also involved in the analytical process. one of the experts from academia was a member of the covid- committee of the government. one medical doctor was heading the cghs dispensary of north delhi and the other medical doctor was a very experienced doctor at the apollo hospital. the questionnaire was mailed to each of the experts. they were asked to make pair-wise evaluations of the critical factors which would help in restarting the businesses and in building resilient industries, which can face future shocks in the indian context. the experts were selected based on their work and experience in the related field. due to the current unprecedented situation of the covid- pandemic, the questionnaire was mailed to the respective experts to obtain their responses safely. table shows a brief description of the experts who participated in the analyses. after scrutinising data obtained from the questionnaires and applying the ahp approach, the key factors were identified. table presents information about ranking the significance of various factors based on the weight obtained by applying the ahp technique. (tables a to a ) depicts the local priority weights of varied factors that were produced to determine the relative significance of these factors and their sub-factors for helping to successfully rebuild the industries in the post covid- pandemic era in india. the rank of specific factors presented in table , depicts that global rank based upon on the value of global weights obtained by using the ahp methodology. global weights are attained by multiplication of the relative weight of factor category values with the relative weights of each specific factor. table suggests that the 'role of governance' has more weightage and thus influences the other factors. govindan et al. ( ) have referred in their paper that slight variations in relative weights leads to significant variations in final rankings. these weights were given from an individual perspective; thus, the sensitivity analysis was used to test the strength of the rankings obtained under the different weight categories. the 'role of governance (rg)' factor received the top priority with the ahp methodology. in order to determine the stability of the priority given to the factor 'role of governance (rg)' this factor's value was changed by . increments from . to . . this helped the researchers to ascertain the robustness of the results obtained by the ahp methodology (thanki et al., ) . table reflects the changes in the relative values of the other categories of factors when the value of the factor, "role of governance" was changed from . to . . figure shows that the changes in the weights of the other factors when the weight of the factor, "role of governance" was incrementally changed from . to . . it can be seen from table and figure that weighting of the other factors were minimally influenced by the changes of the j o u r n a l p r e -p r o o f weight of the "role of governance", thereby indicating robustness of the ranking obtained. this permitted the authors to generalize the results obtained. numbers on the horizontal axis in figure present the factors obtained by the procedure reviewed in section . . values of other factors after changing rg values from . to . table presents the ranking of the sub factors when the weight of the factor "rg" value was changed by . increments from . to . . etc etc etc etc it it it it rg rg rg rg rg rg rg scl scl scl scl ip ip ip ip ip ip cm cm cm oc oc oc oc oc at . of the factors "role of governance", factor scl holds the first rank and ip holds the last rank. from . to . ; rg attains the first rank and the ranks of other critical factors vary. according to the un department of economic and social affairs (desa), the covid- pandemic, has disrupted global supply chains and international trade. this is likely to decrease the economy, globally by almost % in (kumar et al., ) . the current research was designed to identify and to rank the essential factors which would help industries to rebuild in the post-covid- pandemic era in india. the ahp approach removes any unbalanced scale of judgment, doubt, and inaccuracy amongst the pair-wise comparisons performed (borade et al., ; thanki et al., ) . appendix a (a to a ) shows the results obtained by the ahp approach. it has been documented from table for their immediate working capital requirements and to help those who are at the bottom of the value chain. a targeted social security programme for these individuals has to be developed and implemented using a roadmap for helping to make the needed changes while ensuring health and safety of the workers, and others in the reverse and forward supply chains. it may happen that industries put environmental sustainability initiatives behind social sustainability issues in the wake of the pandemic. the pandemic could also cause a reversal in the trend toward more sustainable societies as governments take steps to loosen environmental law enforcement policies to favour the short-term survival of businesses. but the pandemic has given us dramatic, new insights of the significance of delivering a proactive response and of the urgent need to take timely actions. the industries and their competitors will be differentiated in the post covid world by their commitment to implementing sustainability issues and on their willingness and commitment to actualize such holistic, proactive practices (amankwah-amoah, ). the experts in this research predicted that during the post covid- era, much manufacturing will be shifted back from china to india. therefore, the "made in india programme," should be given a push by providing domestic and foreign manufacturers policy and fiscal incentives for manufacturing the products locally. the idea of building back better in terms of living in harmony with nature should be utilized rather than going back to the 'old' normal (the hindustan times, a). have obtained the next highest weight, which underscores the importance of fulfilling the essential needs of the citizens. healthcare equipment has to be supplied on a priority basis so that timely treatment can be provided and the lives of the individuals can be saved. keeping this in mind, specific industries have to be supported to resume operations. however, they will have to follow the mandatory protocols of social distancing and to maintain proper hygiene. the focus should be on the manufacture of products which are important in dealing with the situation. technology giants such as apple and tesla have drawn in their expertise and their supply lines to source supplies and to produce essential products in the usa rather than to depend upon global supply chains. (cankurtaran and beverland, ) . health care systems need an uninterrupted supply of medical equipment, testing equipment and protective equipment. therefore, restructuring of the existing industrial units is required so that they can produce the products which are required to respond to the urgent needs by making changes in their existing plants (elavarasan and pugazhendhi, ) . also, the covid- pandemic has helped to improve the environmental sustainability of the supply chain. but, that is not necessarily helpful enough in addressing the challenges of restarting businesses post covid- . that requires direct emphasis on re-establishing economically, ecologically, socially, sustainable and resilient supply chains (kumar et al., ) . it preparedness obtained the weight of less than half the weight obtained by the factor "role of governance". survival of the businesses post-covid- era will depend on their digital transformation. several useful technologies of industry . and industry . can help to provide the much-needed help to properly control and manage covid- pandemic . technological strategies can provide essential support in dealing with the pandemic state of affairs. technology can aid health care facilities and can help in uniting the society to function as j o u r n a l p r e -p r o o f one (elavarasan and pugazhendhi, ) . it can play crucial roles in every sector of the country. it-enabled services should be used to benefit all during and after this crisis. firms like microsoft and facebook have joined hands with the world health organisation for organising #buildforcovid , a global hackathon for developing a software for addressing issues related to the pandemic (cankurtaran and beverland, ) . additionally, more than million people of india have already downloaded the "aarogya setu" mobile application. this app is one of the most important tools in fighting covid- and one of the lifelines for common people during this global pandemic (p.i.b, c) . it informs the people of their potential risks of infection and the steps to be followed to stay healthy. it-enabled services should also be utilised to provide telemedicine services, especially in rural parts of india. this will bring much-needed relief to people who are finding difficulty in accessing medical services. however, digital transformation requires proper it and security tools to prevent cyber-attacks (pwc report, ). this was followed in priority by "change management". it is a means to transform the company's goals into reality. the main objective is to implement the plan of action for accomplishing change and in helping people to adapt to the changes (alicke et al., ) . stringent public health measures have to be implemented to curtail the spread of covid- (rajkumar, ) . strategies have to be formulated to reduce the fear of the disease. "organisational culture" received the next highest priority. corporate leaders should evaluate the flexibility of their organisation in making decisions for addressing market changes (bernauer and slowey, ) . the covid- pandemic and lockdown lessons should serve as a warning for industries and governments to plan for anticipating, preparing for and in effectively responding to future shocks. emphasis should be given on implementation of industry . technologies. assurance should be provided to the employees that their safety and health are considered to be extremely important to the company . "capacity building" has received the next highest weight. taking cognizance of the situation, it has become necessary to upgrade the skills of the workers. training on industry . technologies should be provided. short term courses and diplomas in such technologies should be provided to prepare the workers to work in companies of the future. industry protocols" in this context, the covid- pandemic has given us the opportunity to envision and hopefully to implement an economic system that focuses on the , un sustainable development goals. firms which operated during the pandemic are perceived in a very positive way; this will help to enhance their reputations among their customers. take for example, the j o u r n a l p r e -p r o o f decision made by brewdog, a firm in uk, to utilize its idle transportation capacity for distributing food to children of lower economic strata, helped to enhance brewdog's reputation among its customers. many firms have taken similar steps in times of crisis to keep their work going (cankurtaran and beverland, ) . this type of altruistic behavior is beneficial for those who receive help and for enhancing the reputation of the company in the post pandemic era. transformation of economic and socio-economic systems should support to help to make them environmentally sustainable and socially equitable, while continuing to be economically sound. the ahp approach was followed by performing sensitivity analysis that was used to analyse the robustness of the results obtained by the ahp methodology. this analysis showed that the "role of governance" factor category influences and impacts many other factor categories. thus, an integrative, holistic, multi-factorial approach is needed to make the needed transitions. covid- is the most severe pandemic that the whole world has encountered recently. recognising essential factors helps in identifying those factors which have received more weight. given the possibility of future pandemics as stated by who chief, and the higher probability of adverse environmental events due to increasingly severe consequences of climate changes, it has become necessary to identify factors which can help to restart the industries so that they are more resilient and also that they can help societies to become more resilient. the objective of the authors of the paper was to integrate this research with earlier related research on design thinking. design thinking was chosen because it focussed upon disruptive thinking and on reframing; therefore, it provides relevant insights pertaining to restarting companies in the context of crises. this term was first used by herbert simon ( ) in reference to the unique mental tools used by researchers in solving problems. the special features of design thinking such as creativity and innovation, capability to visualize, scope of ambiguity and failure, mixing analysis with intuition along with the approach of brainstorming were found to be beneficial for addressing the " wicked problems" associated with the covid- pandemic (head and alford, ) . issues brought up by the pandemic are considered to be "wicked" as they are defined as the problems in which they are not defined properly, there is no proper information, there are no agreements on ideas between the customers and the decision-makers and where the consequences of the decisions taken are not even clear (cankurtaran and beverland, ) . the pandemic has produced a number of wicked problems for industries which, suddenly met with lack of markets and no future for their products. therefore, the 'new normal,' will require deploying decision thinking responses to emerging and multifaceted challenges imposed by the covid- pandemic. the current research can help the government in reviewing its policies formulated for msmes and society as a whole so that they can be benefitted and motivated to rebuild their businesses. it is very important for the government to review the cyber security law so that the policies favouring msmes can be incorporated (alicke et al., ) . the big lesson that the pandemic has taught us is the need for self-reliance and how each village, district, state and the country as a whole needs to become self-sufficient. it can happen if domestic capabilities are given a boost to help in prevention of the disruption of the supply chains in the future. disruption in the supply chains can be prevented by evaluating automotive alternatives to reduce the number of workers on the shop floor. it is also very important to transfer new knowledge across supply chains and training supply chains that must be nurtured, strengthened and supported. it is paramount to communicate about the best practices as the situation evolves and help the suppliers to implement them (pwc report, ). the effects of covid- emphasize the significance of using sustainable, holistic policies, procedures and technologies that will become vital for businesses to sail through the present and future pandemics, as they co-work with governmental leaders to implement the goals related to ecologically sustainable, economic development of cities and communities. the pandemic has highlighted the need of having flexibility in the existing norms, which could improve the ease of the survival of businesses in the short-term. but the survival of businesses in the long-term will depend on their commitment to incorporate an array of aspects of sustainability in their policies, business plans, product-service system designs, as well as how they work with all stakeholders in their supply chains, as well as with their consumers and their neighbours. the authors of this paper underscore the necessity for investing in the health care systems of the country. the most important factor in preventing the spread of the disease is to empower citizens j o u r n a l p r e -p r o o f with the right information and keep social distancing and maintain personal hygiene. social distancing is necessary until the time an effective vaccine is developed to eradicate the disease. also, lessons from past outbreaks revealed that social distancing measures, communication and international cooperation can help in curbing the spread of the disease. many researchers from the past pandemics infer that steps related to social distancing, cancelling public gatherings, isolating the sick, and wearing masks were the most effective measures to slow the spread of pandemics (peeri et al., ; vaka et al., ) . but cushioning the effect of covid- will require the companies to draft innovative ways to ensure the health of workers while simultaneously protecting the environment and their economic viability. though it is tough to sell environmentally friendly policies, incentives by the government and demands from consumers and other stakeholders will help the companies to draft and implement the guidelines ensuring the incorporation of all three aspects of sustainability. the present research is a contribution of the authors towards society as a whole in encountering the pandemic by identifying the essential factors which can be used to help to rebuild the nation, especially the industries in the post lockdown era. guidance from academicians, industry experts and medical doctors was used to identify, evaluate and prioritise the groups of factors which are most likely to be effective in rebuilding the systems by making changes to the 'new normal'. the present paper was designed and prepared to help to re-instil confidence that we, as the citizens of india, should have faith in ourselves in the transition to the future. taking cognizance of the present work can help in understanding that the factors highlighted to help many to become 'corona warrior,' if followed properly. the 'corona warriors' can help in confronting the pandemic and in assisting in creating a restructured society in which there will be a "new normal," as depicted in figure . j o u r n a l p r e -p r o o f global societies are facing multiple challenges in seeking to combat the covid- pandemic, which is 'among the most critical challenges,' we have had to address in a long time. some of the consequences of this pandemic are that many manufacturing organisations were forced to stop their operations and this forced leaders of some firms to explore implementation of sustainable solutions which can help them in building resilient industries and sustainable societies which are able to withstand such shocks in the future. the current study was designed to identify and to prioritise the essential factors that affect in the rebuilding of more robust, resilient, equitable, sustainable industries in the post covid- era. categories of nine major factors with forty-two variables were selected, based on the advice of j o u r n a l p r e -p r o o f the experts. it was followed by using the ahp approach, which was used to develop priorities to the forty-two variables. the ahp approach was used to identify and prioritise the factors which can contribute effectively to make needed changes. based upon the calculations, it was found that the factor 'role of governance' received the highest weight. the "role of governance," is critical in developing and implementing policies to revive the economy by rebuilding the industries. but there are also many other aspects that must be addressed to effectively transit to a more resilient, equitable and sustainable society in the face of disruptions from the current pandemic and to respond effectively in building a society that is fully engaged in seeking to reverse climate changes. although, the authors of the paper have tried to contribute by identifying the factors which can help in building resilient industries, still the paper has limitations which provide opportunities for further research. the findings were primarily based on the review of literature, reports of international organisations and opinion of the experts. the priorities for future action were based upon the opinions of experts obtained with the help of the questionnaire mailed to them. due to the social distancing norms that had to be followed, the entire procedure was conducted via mail. it would have been better to conduct the procedure of getting the questionnaire filled by 'face-to -face' interactions with the experts. additionally, the selection of experts from various sectors of the industries was not uniform; thus increasing the probability that the findings of the study may be somewhat biased towards a particular industrial sector. also, the ahp technique has a limitation of inaccuracy associated with the expert's judgements. thus, the fuzzy ahp, which can provide freedom to experts to express their viewpoints with natural languages, should be addressed in our future research. additional research should be performed on individual companies to obtain more comprehensive insight into the issues they must face due to this pandemic's disruption in their supply chains, their employee's health and their customer's capacity to 'buy' or to rent their products and services. this will help, to obtain a more generalized overview. additionally, the effects of short and long-term governmental and corporate policies on different industrial sectors, needs to be examined. awareness should be created on maintaining personal hygiene. the fight against the covid- pandemic begins with regular hand-washing and wearing masks that are practices which have been found to be useful in slowing the spread of the virus. on these and other levels india has been a leader in addressing the challenges of the covid- pandemic. the objective of the authors of this paper was to provide researchers with a challenge to take these suggestions and help to facilitate their implementation at the local, regional and national levels for the short and long-term future of india and other countries. also, companies that exhibit their dedication towards sustainability issues in the wake of and in the post covid- era will be respected for their holistic responses to the challenges and for their stronger relationships with their key stakeholders. supply-chain recovery in coronavirus times-plan for now and the future stepping up and stepping out of covid- : new challenges for environmental sustainability policies in the global airline industry -ncov epidemic: address mental health care to empower society covid- , extractive industries, and indigenous communities in canada: notes towards a political economy research agenda analytical hierarchy process-based framework for vmi adoption incorporating social aspects in sustainable supply chains: trends and future directions integrating sustainability into strategic decision-making: a fuzzy ahp method for the selection of relevant sustainability issues using design thinking to respond to crises: b b lessons from the covid- pandemic the sequential order and quality of ideas in electronic brainstorming restructured society and environment: a review on potential technological strategies to control the covid- pandemic note from the editors: world health organization declares novel coronavirus ( -ncov) sixth public health emergency of international concern circular supply chain management: a definition and structured literature review barriers analysis for green supply chain management implementation in indian industries using analytic hierarchy process a decision support system for demand management in healthcare supply chains considering the epidemic outbreaks: a case study of coronavirus disease (covid- ) areas of academic research with the impact of covid- wicked problems: implications for public policy and management exploration of social sustainability in healthcare supply chain ilo: as job losses escalate, nearly half of global workforce at risk of losing livelihoods are multi-criteria decision-making tools useful? an experimental comparative study of three methods viability of intertwined supply networks: extending the supply chain resilience angles towards survivability. a position paper motivated by covid- outbreak industry . technologies and their applications in fighting covid- pandemic determinants for integration of sustainability with innovation for indian manufacturing enterprises: empirical evidence in msmes multi-criteria evaluation of climate policy interactions covid- impact on sustainable production and operations management the economic impact of the coronavirus what google tells us about lockdown impact in india's biggest cities? online detail question and answers on covid- for general public the socio-economic implications of the coronavirus and covid- pandemic: a review government working on a separate scheme to address delayed payments issues of msmes¬ shri nitin gadkari b, b. pib' s daily bulletin on covid- shri sanjay dhotre takes stock of the state of it services in the country inter nation social lockdown versus medical care against covid- , a mild environmental insight with special reference to india the sars, mers and novel coronavirus (covid- ) epidemics, the newest and biggest global health threats: what lessons have we learned? considerations for a secure working environment covid- and mental health: a review of the existing literature application of ahp for process parameter selection and consistency verification in secondary steel manufacturing coupled human-environment system amid covid- crisis: a conceptual model to understand the nexus governance, technology and citizen behavior in pandemic: lessons from covid- in east asia the sciences of the artificial ( st ed) improving natural resource management and human health to ensure sustainable societal development based upon insights gained from working within 'big data environments' covid- climate lessons: unprepared for a pandemic, can the world learn how to manage the bigger threat of climate disruption? breakthrough-national centre for climate restoration an investigation on lean-green implementation practices in indian smes using analytical hierarchy process (ahp) approach india looks at china, south korea, and germany for best practices, technology to contain virus once lockdown ends, govt plans make in india boost united nations policy brief: covid- and the need for action on mental health a review on malaysia's solar energy pathway towards carbon-neutral malaysia beyond covid' pandemic covid- : the forgotten priorities of the pandemic world health organization, . who director-general's opening remarks at the media briefing on covid- - the authors look forward, with optimism, that global societies will be able to 'conquer' the pandemic and will emerge with new norms, new lifestyles, and new tools in anticipating and in dealing with future crises. key: cord- -hurpcc e authors: yadava, om prakash title: covid- : are there lessons? date: - - journal: indian j thorac cardiovasc surg doi: . /s - - -w sha: doc_id: cord_uid: hurpcc e nan health is a state subject, and there was a glaring lack of communication and camaraderie between the federal and state structures. even fiscal-federalism was conspicuous in its absence or partisanship. the centre's support to states was lacking or delayed. contradictory orders were flying fast and furious, more inclined to the political ideologies of the incumbent administration, rather than a response to an apolitical disease. morning orders were rescinded by the evening, thereby not only confusing, but demoralizing, the entire workforce, who as such were dealing with the uncertainties of an, yet not well-known, enemy. lesson: too many cooks spoil the broth. there should be well-defined line of leadership, and demarcation of domains of each stakeholder, to avoid chaos and confusion of response, as also for an optimum utilization of scarce resources. 'no' knowledge better than 'some' knowledge as much, if not more, damage from covid- has come from fear psychosis, rather than the virus itself. the root cause of this was the lack of an authentic, transparent, and verifiable single source of information. half-baked knowledge, and at times even gumption, was dished out in the electronic and print media by self-styled 'godmen of medicine' as the 'gospel truth'. in fact, the entire official response to the pandemic was governed by all and sundry including paediatricians, gastroenterologists, dental surgeons and the likes, rather than the public health experts, who were nowhere to be seen, even in the horizon. it is with a view to addressing this gap in knowledge that the indian association of thoracic and cardiovascular surgeons (iacts) has tried to assimilate the scant, and at times confusing and contradictory, knowledge and has issued its guidelines (published later in this issue) to assist our cardiovascular and thoracic surgical fraternity in framing their responses to the challenges of practice in covid times. lesson: let the domain experts lead, take the centre stage and call shots. rest, irrespective of their clout, must for once, take a back stage, sans a mumble. it did not take long for our basic health structure, specially in the government sector, to be exposed and laid bare. professionals have been bemoaning, ever since the independence that our spending on health sector is woefully short and that the intangible benefits of health should not be compared with the tangibles from the manufacturing industry, but should be monetised in terms of disability adjusted life years (daly) saved. we are still lucky that even though the disease is ravaging in the urban areas, it has largely spared the rural hinterland, but i fear it may not be for long, and at which stage, the deficiencies of the primary healthcare infrastructure in terms of primary health centres, community health centres and district hospitals will be exposed further. already, there are signs that the government is waking up to this realisation and the sooner it does, the better it shall be for the future of the country. lesson: government must increase its allocation to health sector to at least % of gdp and focus on strengthening the primary care. as a corollary of the foregoing, the out of pocket spending on health in india is an overwhelming - % and two-thirds to three-fourths of all healthcare is in the private sector. instead of realising this fact and embracing the private sector with an all-encompassing hug, the government has always treated the latter with suspicion, disdain and a 'carrot-stick' policy. successive governments have tried to reign and subjugate it through oppressive legislations and archaic regulations. this attitude needs to be changed and profit, albeit reasonable, should be accepted as ethical, moral and in fact a necessity for a vibrant and effective private healthcare system, to meet the health needs of the society. crushing private sector at the altar of the socio-political agenda of the incumbent political dispensation is going to be to the disadvantage of all stakeholders, and last but not the least the government itself. lesson: create a policy environment for ppp to thrive and flourish regulation is a necessity and that is given. however, it must address the aspirations of the society it serves. therefore, it must factor the ground realities and the resources available, and incorporate the social, economic and cultural confounders to be effective. unfortunately, we seem to be caught in a warp, where we are copying regulations from the developed world and issuing regulatory guidelines as 'one size fits all' solution to the needs of the entire country-a country, as vast and diverse in all dimensions, as india. the recent urgency seen in regulatory bodies in clearing trials and fast tracking of approvals for new drugs is worth appreciating, but even in routine matters, regulatory jigsaw should be simplified and made user-friendly. lesson: we should focus more on standardisation with a view to enabling deregulation. india has neither the ecosystem nor the finances, for basic, molecular level core research. it therefore needs to look at the low-hanging fruits of translational research. we already have enough lab knowledge; we just need to transform it into bed-side knowledge. india is lucky to have an amazing pool of young talent, just suited for this kind of research. this can even subsequently be commercialised and monetised and may help address the economic woes of the country. the information technology (it) and biotechnology companies can team up for developing rapid testing kits for not only coronavirus, but for other diseases rampant in the country, and concentrate on developing point-of-care tests. a start-up culture should be developed with the government providing the handhold by provisioning for the initial seed money, the physical infrastructure, patenting and subsequent commercialisation and marketing of technologies. 'aatam nirbhar bharat' and 'vocal for local' are good initiatives, but need to be transformed from jargon to reality, something which has not happened in the past--'make in india' and 'india shining' initiatives having flustered badly. lesson: 'bench to bedside' innovation is the 'mantra' but we need to 'walk the talk'. healthcare is heading to a new normal. necessity is the mother of invention and a lot of bright minds, either by design or by default, developed new processes and technologies during the covid- outbreak. sure enough some of them will fall by the wayside, but at least some and more meaningful ones will continue to survive even after the covid- pandemic is over, either because of the value they have demonstrated, or maybe even because of necessity. connectivity in india has improved following the global system for mobile communication (gsm) roll-out and indian space research organisation's (isro) support through provisioning of free satellite time for public health initiatives. technologies can now be leveraged, not only for diagnostics but also for healthcare delivery with successful models in south indian states delivering intensive care through tele intensive care units (icus) and ophthalmology services, specially for diabetic retinopathy, being delivered in rural areas through mobile care units. thus, tele-medicine and tele-consultations would, in all likelihood, become a norm in the future. remote sensing and monitoring and point-of-care testing would decongest the bursting at the seams tertiary care hospitals. for a lot of diseases and illnesses, for which we always believed that patient care in a secondary or tertiary care hospital was mandatory, domiciliary care and conservative management have dawned as an effective alternative. the flattening of curve in delhi, and available infrastructure not stretching itself, was achieved entirely with the realisation that 'domiciliary quarantine' was as effective as 'institutional quarantine'. even 'analytics' to change 'big data' into action and value-driven partnership of industry with physicians is the need of the day. lesson: leverage bio technologies and it to deliver healthcare at the door step of the masses. covid- has been a big epidemiological experiment, albeit carried by nature. the universal outcry on a sudden drop in non-covid hospitalisations in all specialities, not only of elective cases but also emergencies, without a proportionate and countervailing increase in non-covid mortalities should sensitise us all-the medical fraternity, public and the government, to the overarching benefits of holistic living and good lifestyle. whether these realisations will stay or be as ephemeral as the virus, only time shall tell. lesson: a stitch in time saves nine. just as we concentrate on our covid- responses, we must not forget that the main health burden of india lies in non-covid illnesses. a recent modelling study in lancet global health showed that the mortality from malaria was expected to increase by % over years as against the pre-covid levels, of tuberculosis by % and hiv by % [ ] . all the routine vaccination programmes have taken a back seat. schools are closed and the midday meal programmes are suspended. this, along with the attendant economic woes of the covid- , compounded further by the natural disasters of floods and typhoons like 'amphan', will have a snowball effect on additional problems of nutritional deficiencies in children and infectious illnesses, besides psychological and mental disorders creeping in. a thought should also be spared both for the physical and mental health of the health task force and the corona warriors in general. let this calamity not go waste and let us treat this as an opportunity, a new dawn in the healthcare landscape of our country. potential impact of the covid- pandemic on hiv, tuberculosis, and malaria in low-income and middle-income countries: a modelling study publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -po zpvw authors: beig, gufran; bano, s.; sahu, s.k.; anand, v.; korhale, n.; rathod, a.; yadav, r.; mangaraj, p.; murthy, b.s.; singh, s.; shinde, r. title: covid- and environmental -weather markers: unfolding baseline levels and veracity of linkages in tropical india date: - - journal: environ res doi: . /j.envres. . sha: doc_id: cord_uid: po zpvw the covid- pandemic, caused by severe acute respiratory syndrome coronavirus (sars-cov- ), is rapidly spreading across the globe due to its contagion nature. we hereby report the baseline permanent levels of two most toxic air pollutants in top ranked mega cities of india. this could be made possible for the first time due to the unprecedented covid- lockdown emission scenario. the study also unfolds the association of covid- with different environmental and weather markers. although there are numerous confounding factors for the pandemic, we find a strong association of covid- mortality with baseline pm( . ) levels ( % correlation) to which the population is chronically exposed and may be considered as one of the critical factors. the covid- morbidity is found to be moderately anti-correlated with maximum temperature during the pandemic period (- %). findings although preliminary but provide a first line of information for epidemiologists and may be useful for the development of effective health risk management policies. this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. the covid- pandemic, caused by severe acute respiratory syndrome coronavirus (sars-cov- ), is rapidly spreading across the globe due to its contagion nature. we hereby report the baseline permanent levels of two most toxic air pollutants in top ranked mega cities of india. this could be made possible for the first time due to the unprecedented covid- lockdown emission scenario. the study also unfolds the association of covid- with different environmental and weather markers. although there are numerous confounding factors for the pandemic, we find a strong association of covid- mortality with baseline pm . levels ( % correlation) to which the population is chronically exposed and may be considered as one of the critical factors. the covid- morbidity is found to be moderately anti-correlated with maximum temperature during the pandemic period (- %). findings although preliminary but provide a first line of information for epidemiologists and may be useful for the development of effective health risk management policies. introduction: the % of people worldwide are exposed to high levels of air pollution as per the world health organisation which estimated that around million mortality every year from exposure to fine particles in polluted air. the foul air penetrates deep into the lungs and cardiovascular system, causing diseases including stroke, heart disease, lung cancer, chronic obstructive pulmonary diseases and respiratory infections, including pneumonia (who, ). on every continent, people suffer the negative health impacts of air pollution. however, in recent times, the outbreak of novel coronavirus (covid- ) has become a global public health challenge and it's ever-increasing in india. the first case of covid- was found in the wuhan city of china during the month of december and has been spread from wuhan to the many countries of the world (i.e. italy, europe, asia) within a few months (bontempi, ; bontempi, et al., ) and turned to be a worldwide epidemic. to control the epidemic conditions, the world wide countries went to the lockdown (muhammad. et al., ) . first covid- case in india was confirmed on january, , which rose to three cases by rd february. later, no significant transmissions were observed in february. however, in the beginning of march, cases were identified. in view work reported here focuses on understanding the association of covid- related mortality and morbidity with various other environmental and weather parameters like temperature and long-term ambient levels of pollution in search of an environmental marker which can be considered closely associated with covid- . present work considers major mega cities reported to be pollution hot spots of india, namely, delhi, mumbai, ahmedabad, pune, kolkata and chennai. material and method • study area: this study focuses on six indian mega cities as shown in figure . delhi is a highly urbanized landlocked city situated at an elevation of m above sea level and covers an area of sq. km. with a population of about million and it is rapidly growing. due to the proximity to the arabian sea mumbai has a humid weather, mumbai is at an elevation of about m above sea level and has a population of million and surrounded on sides by ocean. pune is located in the western ghats of sahyadri mountain range and at m above mean sea level with a population of approximately million. ahmedabad has a tropical semiarid climate located at an elevation of about m above mean sea level having a population of over million. kolkata is located in the eastern part of india. it has spread linearly along the banks of the hooghly river. the city is near sea level, with the average elevation being feet. the whole area in the ganges delta starts within km south of the city. most of the city was originally marshy wetlands, remnants of which can still be found especially towards the eastern parts of the city. kolkata has a subtropical climate with a seasonal regime of monsoons. it is warm year-round, with average high temperatures ranging from about °c in december and january to nearly °c) in april and may. the atmospheric pollution has greatly increased since the early s. factories, motor vehicles, india, chennai is located at . °n . °e on the southeast coast of india. it is located on a flat coastal plain known as the eastern coastal plains. the city has an average elevation of meters. chennai features a tropical wet and dry climate. chennai lies on the thermal equator and near the coast, which prevents extreme variation in seasonal temperature. table . the number of patients tested positive for covid- and fatality counts in different indian cities, considered in this work, are given in table- the basic dataset of pm . in the present study was recorded for hr interval and averaging has been done to derive daily data while no were recorded for min. interval and averaging has been done to derive hr data. the saturation point methodology under fair weather conditions is used in this work to determine the baseline levels of pm . and no using the above-mentioned data. the emission inventory of major pollutants in indian mega cities have results and discussion the data thus obtained from the above study design as per the saturation point methodology is shown in figure s from the mean. the correlation between these two parameters are found to be . ( %) which is found to be significant at % confidence level (p-value< . ) as shown in table shown in the bottom panel as figure c . the highest mortality counts are found in mumbai where the baseline level of pm . is highest. the pm . baseline level and mortality count also indicates significant correlation (r= . with p-value< . ) at % confidence level (table ) . these are two most significant correlations found among all the environmental parameters accounted for in the present study and both are associated with pm . baseline levels. no , respectively with mortality, morbidity, and standardized mortality rate in various cities accounted for in this work. the calculated correlation coefficient is provided in table . although insignificant but relatively higher correlation is noticed between annual mean pm . level and mortality rate ( %), pm . base level and infection counts ( %), and no baseline levels with mortality and infections counts ( %). hence, the current study confirms that the covid- in india at present do not have any significant association with prevailing pollution levels, annual pollution levels as shown in table of later cities are higher than that of delhi (table ) . present work tends to suggest a significant rise in the fatality in people with underlying conditions because of chronic exposure to baseline air pollution levels rather than averaged ambient air pollution levels for pm . and shown in figure to understand the association of covid- with weather and climatological parameters, the correlation study has been done in the present work. figure s shows the correlation plots of covid- related mortality, morbidity, and mortality rate with mean temperature (march- may), minimum temperature. the correlation coefficients of all these parameters are shown in table . in addition to the above, correlation with many other parameters like wind speed and humidity has also been calculated but not shown in figure. the morbidity and maximum temperature of the day during the pandemic period so far (march to may) in different cities of india are found to be anti-correlated with the correlation coefficient of - . (- %) as indicated in table . this result indicates that higher the maximum temperature, probability of infection due to covid- reduces and the population is less susceptible to be infected. however this correlation is not significant even at % confidence level. it can be noticed from table suggested that the respiratory droplets remain suspended for a long time and can make aerosol transmission at low relative humidity. one of the reasons we could not find any significant correlation of covid- with wind speed may be attributed to higher wind speed during summer months in india mega cities as evident from table . j o u r n a l p r e -p r o o f j o u r n a l p r e -p r o o f highlights • covid- affinity with environment and weather marker explored in indian mega cities. • baseline levels of critical air pollutants unfolded from covid- lockdown. • strong correlation of covid- deaths and pm . baseline found ( %) but no linkages with ambient pollution levels. • a moderate but significant correlation with maximum temperature is also revealed. • critical information for epidemiologists for health risk management policies. j o u r n a l p r e -p r o o f ☒ the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐the authors declare the following financial interests/personal relationships which may be considered as potential competing interests: can atmospheric pollution be considered a co- factor in extremely high level of sars-cov- lethality in northern italy? factors determining the diffusion of covid- and suggested strategy to prevent future accelerated viral infectivity similar to covid how high wind speed can reduce negative effects of confirmed cases and total deaths of covid- infection in society roles of meteorological conditions in covid- transmission on a worldwide scale air pollution and its effects on the immune system eosinophilic and neutrophilic sirway inflammation in the phenotyping of mild-to- moderate asthma and chronic obstructive pulmonary disease relationship between global distribution of covid with environmental and demographic factors: an updated three- month study correlation coefficients: appropriate use and interpretation effect of restricted emissions during covid- on air quality in high resolution emission inventory of nox and co for mega city delhi more than % of the world's children breath toxic air every day key: cord- -rfr we authors: singh, j.; ahluwalia, p. k.; kumar, a. title: mathematical model based covid- prediction in india and its different states date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: rfr we by employing the successive approximation method to the real-time data of india and its different states, we have predicted the bounds of the spread of covid- in india and its various states. the calculated lower and upper bound of patients (deaths) till th june comes out to be ( ) and ( ), respectively. states like delhi, gujarat, maharashtra, punjab, rajasthan and tamil nadu are the spike states as suggested by the range of expected covid- patients and deaths. impact of return of stranded pilgrims from nanded (maharashtra) has also been looked into in the case of punjab. it has been found that punjab may see ~ times increase in the lower bound of expected patients till th june due to the return of pilgrims from maharashtra. our study provides an insight into the possible number of expected patients and deaths in near future that may be of importance for the respective governments to be ready with the appropriate preventive measures and logistics to put appropriate infrastructure and medical facilities in place to manage the spread of deadly virus and go down the flattening curve. the whole world is suffering from the covid- pandemic which started from wuhan, china [ ] . so far due to this pandemic, the number of patients have risen to and the death count risen to (mortality rate ~ . %) [ ] . the world health organization (who) declared covid- a pandemic on march by looking at its spread and threat to human life on the earth [ ] . in india, the first case of covid- was recorded on january in kerala, after that the number of cases rose to and death count rose to till th may . it has been confirmed that covid- transmits from person to person through touching, coughing, sneezing [ ] , therefore, social distancing, isolation, and self-quarantine of suspected and infected patients are a must to avoid its spread. to control its transmission, lockdowns and curfews are implemented in various countries. in india the lockdown was implemented by the government of india in the early stages of this pandemic in a country that restricted its fast exponential growth as has happened in china, usa, italy, spain, etc. [ ] [ ] . however, the lockdowns and curfews are not the permanent solution of this pandemic and cannot be implemented for longer periods of time especially for a country like india, because of huge economic cost impacting vulnerable sections of the society, daily wage earners and large migrant labor. beyond lockdowns, every individual has to take his/her responsibility to maintain social distancing, use masks in public, avoid social gatherings, and avoid unnecessary movements to control its spread in the near future until its vaccine is discovered. the main symptoms of this pandemic are high fever, dry cough, and body pain. it has been found recently that some cases are asymptotic [ ] i.e. they do not show any symptoms. such cases are very silent spreaders of the pandemic. it has been found that the virus can survive up to hours in aerosols, hours on copper, hours on cardboard, and hours on plastic and . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint stainless steel [ ] . this is the reason behind the exponential rise in cases of this pandemic worldwide despite the measures that have been taken to prevent its spread on war footing. the forecast of this pandemic based on the real-time data provides a way to help the governments and the concerned authorities to make the policies to minimize the infection of covid- and halt it at the earliest with the participation of public at large. by anticipating the expected growth of patients, it is likely that governments provide required interventions such as covid- health facilities, quarantine centers to screen suspected persons, dedicated covid hospitals for infected cases and chalk out strategies to let the economic activities continue. mathematical models and data analytics are important tools to analyze and forecast the outbreak of infectious disease [ ] [ ] [ ] . in this paper, we have utilized the successive approximation method [ ] for short term forecast of infected and deceased people up to th june . we have calculated the lower and upper bound of patients and deaths till th june for india and its various states. our predictions hopefully can be helpful in social, economic, and health implications of covid- for india at this stage. as india has a highly dense population and combining it with its global health security index (ghs) number ( / ) [ ], india may be at great risk of this infectious disease. data were collected till th may from the official website of covid- (https://www.mygov.in/covid- /) health advisory platform provided by the government of india. data collected for the whole of india and its states, having patients count greater than till th may is analyzed with the help of a successive approximation method as employed in reference [ , ] . we find the spread (death) ratio as the ratio of the number of cases (deaths) . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint on a particular day to the sum of the cases (deaths) on that day and the next day. we use these ratios to find the future number of patients as well as deaths till th june . ܽ are the number of cases at day ݅ than we define the ratio as: for the next day ݅ , the ratio is given by: we use these ratios to find the future state of cases as: where ߟ is the mean ratio given by: by using this technique, we have forecast the spreading of covid- in india and its different states. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint we have plotted the spread and death ratios w. r. t number of days in figure a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint it is pertinent to note that in punjab, the number of cases up to st may were and within one week from this the cases rose to ~ . this sudden rise in the number of positive cases was due large number of pilgrims (~ ) returning to punjab from nanded hazur cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint spread of this pandemic. the rapid and large-scale testing of suspected cases is a must to prevent its spread. isolation of suspected cases, social distancing and quarantine should also be strictly followed in india to prevent the spread of this pandemic. our results may provide insight into the course of spread of covid- in india and its different states, and may be of importance to central government and governments in the states and to take appropriate preventive measures to stop the spread of the covid- till the vaccine is discovered, a scenario which is unlikely to be in immediate future. in summary, india maybe at high risk due to its highly dense population and moderate health facilities (ranks / in global health security index). though we have done well compared to many countries till date, but the future is full of uncertainties. we need to draw appropriate lessons from the predictive nature of studies as has been carried out in this paper with clear indications of the likely spread. also, this study clearly indicates the likely hotspot states where immediate interventions will be needed to break the covid- spread. our results we hope will help the governments to plan their strategies against the spread of covid- . there is lot of implication of increase in testing facilities on the forecast made in this paper we declare no conflict of interest. short-term forecasts of the covid- epidemic in guangdong and zhejiang international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted coronavirus disease (covid- ) situation reports day level forecasting for coronavirus disease (covid- ) spread: analysis, modeling and recommendations a familial cluster of pneumonia associated with the novel coronavirus indicating person-to-person transmission: a study of a family cluster. the lancet fast spread of covid- in europe and the us and its implications: even modest public health goals require comprehensive intervention generalized logistic growth modeling of the covid- outbreak in provinces in china and in the rest of the world the clinical feature of silent infections of novel coronavirus infection (covid ) in wenzhou aerosol and surface stability of sars-cov- as compared with sars-cov- analysis of the worldwide corona virus (covid- ) pandemic trend; a modelling study to predict its spread. medrxiv outbreak analytics: a developing data science for informing the response to emerging pathogens it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://www.grainmart.in/news/a-new-wave-of-coronavirus-spread-seen-in-punjabthrough-nanded-hazur-sahib-pilgrims/ . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint the plots of spread ratio, death ratio, expected patients and deaths in different states of india.. cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review)the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint key: cord- - v nau p authors: aravind, s.r.; saboo, banshi; misra, anoop title: strict glycemic control is needed in times of covid epidemic in india: a call for action for all physicians()()()()() date: - - journal: diabetes metab syndr doi: . /j.dsx. . . sha: doc_id: cord_uid: v nau p nan diabetes india, national diabetes obesity and cholesterol foundation (ndoc), and diabetes expert group* during the current covid - pandemic, there is sufficient data to suggest that diabetes is an important comorbid disease which can increase severity and mortality related to .key pathological factors that contribute to increased mortality in patients with diabetes are; defect in t-cell immunity, baseline high levels cytokines and presence of co-morbidities [ , ] .those with comorbidities ((obesity, coronary heart disease, hypertension, chronic kidney disease chronic obstructive pulmonary disease, immune suppressed conditions etc.) and elderly are particularly at high risk [ , ] . it is possible that indians with diabetes may have lower mortality than seen in western countries because of younger age of contracting covid but this issues remains unproven [ , ] . with this background, in the following sections we discuss the role of patients' glycemic status before they have covid- infection, at the time of admission, and during the hospital stay, vis-à-vis morbidity and mortality, and briefly outline key management issues (table ) . previous studies have shown that a high proportion of patients with diabetes in india have poor glycemic control [ ] [ ] [ ] , and that many already have diabetes-related complications [ ] [ ] [ ] . uncontrolled hyperglycemia could be exacerbated by disordered lifestyle during lockdown and consequent weight gain. such patients with uncontrolled hyperglycemia will obviously have high blood glucose levels during admission and also during hospitalization when they contract covid .this is the first scenario which is quite well known. the second scenario is when a patient not known to have diabetes is develops covid- infection and high blood glucose and even ketoacidosis is detected at admission to the hospital [ ] . high blood glucose levels at the time of hospitalization may be due to undetected diabetes or as a result of recent weight gain during complete and partial lockdown [ ] . weight gain during lockdown may be due to multiple factors; disordered diet, poor exercise, and widespread mental stress, as previously shown [ , ] . in india, unwarranted use of dexamethasone in mild covid infection and other seasonal flu, increases the risk of hyperglycemia. high fasting blood glucose (fbg) at the time of hospitalization in people not known to have diabetes puts them at higher risk (hr . [ % ci . , . ]) for mortality than those who have normoglycemia. the odds ratio for -day in-hospital complications in those with fbg≥ . mmol/l ( mg/dl) and . - . mmol/l ( - mg/dl) vs < . mmol/l was . ( % ci . , . ) or . ( % ci . , . ), respectively [ ] . the third scenario is hyperglycemia in pregnancy. pregnancy in diabetes and gestational diabetes, should be intensively controlled with the help of self-monitoring of blood glucose (smbg) and continuous blood glucose monitoring system (cgms). screening of women with capillary glucose should be done to avoid visiting laboratory [ ] . consultations for antenatal checks, nutritionist, and diabetes educators must be done as appropriate with the use of teleconsultation. the fourth scenario is in-hospital hyperglycemia that needs to be controlled well. however there are a number of factors which pose challenges; triggers for hyperglycemia [surge of cytokines ("cytokine storm"), frequent use of corticosteroids, etc.], ketoacidosis and hyperosmolar states, inability to monitor blood glucose levels frequently because of reduced contact between healthcare worker and patients, and non-inclusion of diabetes expert in the critical care team in many hospitals. data suggesting markedly lower risk of all-cause mortality in the hospitalised patients with well-controlled blood glucose (adjusted hr, . ; % ci, . - . ; p = . ) compared to those from the poorly controlled blood glucose group [ ] should encourage us to go all out for aggressive glycemic control. fifth scenario is new onset of diabetes which is now being reported during covid infection [ ] . besides unmasking of previous hyperglycemic state, beta cell injury is a likely possibility in such cases. in this context, it is important to know that angiotensin converting enzyme- (ace ) receptors, through which sars-cov- attaches to the cells, are present on the cells of endocrine pancreas, at even greater density than in the type and type alveoli in lungs [ ] . it is, therefore, possible (but not proven) that beta cell destruction may occur due to covid attack on pancreatic beta cells, similar to alveolar injury in lungs. indeed, % of patients with severe covid have been shown to have pancreatic injury in one study [ ] . it is possible that injury to beta cells, already under attack from cytokines (cytokine-induced apoptosis) [ ] , could cause acute insulinopenia, and ketoacidosis [ ] . previously, acute-onset diabetes has been shown with sars-cov infection and beta cell injury has been implicated in its pathogenesis [ ] .viral 'sepsis' could induce resistance to action of insulin, posing additional challenges to management (e.g. high insulin requirement). there are a number of other factors which may affect glycemic control in patients with diabetes in india. patients were not able to contact their physicians during lockdown, or do not visit them due to fear that hospitals are hotspots of covid . telemedicine is not acceptable to many patients (especially the elderly) who are not technologically abled [ , ] . economic problems exacerbated by lockdown and covid [ ] may lead to noncompliance to medications and insulin. non-availability of insulin and glucose strips during the period of lockdown was shown to worsen the glycemic control in patients with type diabetes [ ] . we can make efforts to efficiently manage each of these scenarios of uncontrolled glycaemia. all of us must strongly advice and advocate for good glycaemic control in all patients specifically those with covid aiming for low morbidity and mortality [ ] . glycemia must be controlled at all times; when not hospitalized, during pregnancy, during quarantine, at the time of admission, and during hospital stay. practice of smbg should be emphasized. patients with risk for foot lesions/infections should be counselled for proper foot care and self-examination of feet, and treated as much as possible using tele consults [ ] . all patients diagnosed with covid , even if not known to have diabetes, must get screening blood glucose measurement done [ ] . blood glucose monitoring in hospital should be done frequently, by patient or healthcare provider, keeping safety in mind. when available, cgms with real time sensor and virtual reader is a good option. metformin should be continued until it cannot be tolerated, or patient is unable to take it since it may decrease mortality in covid [ ] . insulin must be used to control surge of blood glucose which may also occur due to steroid therapy and/or sepsis. hypoglycemia, which may occur due to nausea, vomiting, aversion to food, mismatched iv fluids or use of hydroxychloroquine, should be looked for and corrected. aggressive fluid and electrolyte therapy for marked hyperglycemia and ketoacidosis must be balanced against possible cardiac and renal compromise. ideally, diabetes expert must be part of the caregiver team in hospital. however, j o u r n a l p r e -p r o o f often a diabetologist/endocrinologist is not there to provide care in hospitalised patients, hence, development of an easy-to-use guidance algorithm for drug and insulin would be useful [ ] . a critical and often neglected point is the advice given to the patient at discharge from hospital. the 'return to normalcy' in severe covid can take a long time and the residual effects of the infection are only now being understood. the job of a physician does not end with the discharge of the patient. proper education and guidance of these patients-for good monitoring and glycemic control at home is imperative. to enable good metabolic and blood pressure control, we must proactively connect with the patients (phone calls, messages) and emphasize (through tele consults, messages, face-to-face consults) that importance of glucose control is more relevant now than ever before [ ] . messages regarding correct diet, exercise (any exercise, indoor exercises), adequate sleep, and adherence to therapy must be re-iterated. patients must be advised unequivocally that weight gain must be avoided, and blood pressure should be maintained as close to normal as possible. elderly must be carefully counselled so that hypoglycemia does not occur. individuals without diabetes should be advised to lose weight if obese, follow correct lifestyle and get blood glucose tested. uninterrupted insulin supply must be ensured for patients with type diabetes. we believe that the available information on covid and diabetes necessitates a call for action for all medical community in general and experts in diabetes in particular, to ensure implementation of previously recommended and evidence-based interventions for the patients, even more aggressively than hitherto been the case. rajput rajesh (rohtak) diabetes in covid- : prevalence, pathophysiology, prognosis and practical considerations diabetes and covid- : evidence, current status and unanswered research questions covid- in people living with diabetes: an international consensus characteristics and outcomes of hospitalized young adults with mild covid- covid in south asians/asian indians: heterogeneity of data and implications for pathophysiology and research glycemic control among individuals with self-reported diabetes in india--the icmr-indiab study current status of management, control, complications and psychosocial aspects of patients with diabetes in india: results from the diabcare india real-world evidence of glycemic control among patients with type diabetes mellitus in india: the tight study diabetes mellitus and its complications in india clinical management of type diabetes in south asia diabetic ketoacidosis precipitated by covid- : a report of two cases and review of literaturediabetes metab syndr effects of nationwide lockdown during covid- epidemic on lifestyle and other medical issues of patients with type diabetes in north india increase in risk for type diabetes due to lockdown for covid pandemic in apparently non-diabetic individuals in india: a cohort analysisdiabetes and met syndr fasting blood glucose at admission is an independent predictor for -day mortality in patients with covid- without previous diagnosis of diabetes: a multi-centre retrospective study the diagnosis and management of gestational diabetes mellitus in the context of the covid- pandemic association of blood glucose control and outcomes in patients with covid- and pre-existing type diabetes new-onset diabetes in covid- binding of sars coronavirus to its receptor damages islets and causes acute diabetes ace expression in pancreas may cause pancreatic damage after sars-cov- infection beta-cell apoptosis and defense mechanisms: lessons from type diabetes roadblock in application of telemedicine for diabetes management in india during covid pandemic acceptability and utilization of newer technologies and effects on glycemic control in type diabetes: lessons learnt from lockdown covid- pandemic and challenges for socio-economic issues, healthcare and national health programs in india impact of lockdown in covid on glycemic control in patients with type diabetes mellitus clinical considerations for patients with diabetes in times of covid- epidemic redefining diabetic foot disease management service during covid- pandemic proposed guidelines for screening of hyperglycemia in patients hospitalized with covid- in low resource settings metformin treatment was associated with decreased mortality in covid- patients with diabetes in a retrospective analysis basal-bolus insulin regimen for hospitalised patients with covid- and diabetes mellitus: a practical approach diabetes during the covid- pandemic: a global call to reconnect with patients and emphasize lifestyle changes and optimize glycemic and blood pressure control key: cord- -a okymx authors: gupta, dipankar title: think “big”: strategizing post-coronial revival in india date: - - journal: indian j labour econ doi: . /s - - - sha: doc_id: cord_uid: a okymx the pandemic has severely disrupted the economy, but this is also an opportunity to change direction. the distress one saw on the streets of workers leaving cities for their rural homes obviously signals the preponderance of informal labour, low-skilled jobs and lack of economic security. the need, therefore, is to move away from small-scale industrial production to high-technology units which demand sophisticated enterprise, skills and knowledge. this would mean the abandoning of threshold limitations in the labour laws as well as urging msmes to grow in size and become competitive enterprises. now, what are the facts that we do not discuss with equal enthusiasm when we deliberate the conditions of the working people? most of these are well known but, for some reason, rarely figure prominently when experts ponder over what our * dipankar gupta dipankargupta@hotmail.com post-covid economy should look like and how to keep it buoyant. the single largest contributor, though, by no means the only, is the premium we have placed on small-scale production units or, rather, the disincentives existing against large-scale enterprises. some might believe that there is no point in going down that road for the state is not in a mood to talk about it. as a result, the moral imperative which valorizes small over big economic units of production remains unchallenged. the general assumption behind this sentiment is that small-scale units exude honesty, authenticity, and indigenous knowledge. sadly, the small-scale sector has not been a growth engine, nor has it helped in adding to knowledge, nor has it provided security or prevented large-scale distress migration. neti, neti, neti, all the way. nor should it be overlooked that these smallscale units are also sites which are generally under-audited, allowing for a number of industrial malpractices to go unchecked. in this connection, one must never forget the searing images of migrants on the highways desperate to get home. they were almost exclusively hired in this sector, which is why they could be calmly fired without the security of any kind. now let's read on. interestingly enough, the government of india's ministry of heavy industry comes to the same conclusion. it says, unambiguously, and with refreshing candour, that the msme sector lags behind because it lacks capital, skill, and the ability required for "compliance with international standards" (ministry of heavy industries and public enterprises : ). yet, so far there has been no determined action from above to correct this state of affairs. this is why we do not find micro units graduating to become small and small to medium. they remain stunted, and uncared for, and survive principally (this applies most to micro units), because their owners ceaselessly self-exploit. at the same time, the msme provisions allow many to take advantage of it because once an enterprise is listed in that category it is easier to get loans, raw material, and access to markets. even when its accounts are not kept well, or there is a violation of pollution norms, nothing much is done about them. they are simply too small to audit. now it is not as if the valorization of the small-scale, or crypto gandhian, enterprises is holding up progress by itself. what lends them crucial support from the outside is the industrial disputes act (ida) which actually disincentivizes largescale units from coming up. this may not have been the intended reason behind the ida, but that does not really matter as nearly all of social science is built on unintended consequences. the ida, as we know it today, found its ideological support among the left in india, as well. the view that promoters and managers of large enterprises are intrinsically more sinful and rapacious than smaller ones has, in general, a certain spontaneous appeal about it. karl marx would have, however, called this a species of "petty bourgeois romanticism" (marx ) but, nevertheless, many left radicals in india pursued this particular line of thought. what was overlooked is that modern industrial enterprises require the coordinated efforts of workers and promoters as knowledge advancement and technical innovation are critical. the truth is that for industrial productivity to rise, innovations are essential, and to put them to work, an enterprise must have in-house skilled labour. all of this requires deep pockets, on the one hand, and workers with skills, on the other. for the latter to happen, labour must be trained so that their skill sets are enhanced and this cannot happen if they are not given a longterm stake in the enterprise. the ida discourages this which is why it is a major impediment to industrial development in our country. the standout feature of the ida is the various thresholds which primarily refer to workforce numbers and days employed. together, they cumulatively disincentivize companies from growing big and prevent workers from achieving their potential. by keeping units below a certain threshold, promoters and managers free themselves from a number of obligations towards workers. these thresholds look attractive to some promoters because they can use them not to pay bonus, or to terminate services without notice or severance pay, but they cause long-term damage (gupta ) . looked at closely, the ida has all the features of a onenight stand: engagement is short, workers stay unskilled, and relationships die before they start. no wonder informal labour has grown so much that it now seeps through every pore of our economy. on account of this, casual workers look up to their labour contractor more than to the owner of the enterprise where they actually work. this is because, in keeping with ida thresholds, most often a labourer's contract with a company is through a contractor and ends before days are over, if not earlier. if it lasts a day longer, then the employee can legitimately demand severance wages from the employer should the contract be terminated. sadly, casual, informal workers can also be used as a bargaining chip to undermine the conditions and pay of regular workers too. a very credible survey reports that over % of workers in regular jobs do not earn the amount they are legally entitled to (anand and thampi ) . this is the primary reason why our enterprises are smaller than those in south korea, malaysia, and the philippines. in india, large firms are about . % of the total; the figures for south korea, philippines, malaysia, and china are . %, . %, . %, and . %, respectively (hasan and jandoc : ). while productivity is low in smaller units (ramaswamy ) , when it comes to large enterprises, productivity per worker in india compares well with other countries (ibid: - ). in the apparel industry, % of units in india have less than five workers, whereas in china about % have above workers (ibid: ). it is hardly surprising then that value added per worker in india is the lowest among all the major asian countries (hasan and jandoc : - ) . the seen hand of the ida is clearly visible here. it has so frightened indian entrepreneurs about trade union action and strikes that they forget all about innovating technology and higher productivity (nathan ). this has resulted in workers lacking permanent status, long-term commitment to the firm as well as the firm's lack of commitment to the workers. it is of a piece then that the management should show little interest in r&d investment as well as in upskilling in-house labour (maira ) . no wonder a contractor is so important in the lives of the working people for a resourceful one could flip them around easily from job to job, without a long hiatus in between. this is yet another reason why ida is such a crippling provision in our law books. in order to revive the msme, the government has expanded its definition rather generously. it has raised the bar on investments and turnover amounts so that more units can be considered as msmes. this has been done without making any changes in the industrial disputes act, without incentivizing r&d, without cutting back on benefits, and without changing the auditing norms of msmes, which are notoriously lax. as a result, have msmes been helped or has the problem been magnified? that is a question whose answer time will tell. msmes cannot be forsaken at one go, and should not, instead efforts should be made, in the interim, to encourage them to grow. the latest government statement on msmes seem to be along these lines. however, a full realization of this policy requires large, high technology industries at the other end of the spectrum, ready to accommodate more sophisticated msmes in their supply chain. as ida encourages indian industry to value education and training poorly, it is to be expected that there would be no enthusiasm for r&d at any level in our economy and society. this aspect is further corroborated by the paltry amount india spends on r&d compared to our neighbours such as south korea, china, or even malaysia. these are countries that encourage large-scale enterprises and, consequently, greater innovation. for india, to nurse ambitions to take on the world, it will have to mend its ways radically, beginning by dismantling the ida. even in the indian it sector, its r&d compares poorly with other countries. ironically, foreign it enterprises invest in india for their r&d, but indian companies do not. the same can be said of pharmaceutical companies as well (nathan ) . this probably explains why the sobriquet "software coolie" is often used to refer to indian it workers. that this characterizes it industry is indicative of the general disinterest we have with regard to upskilling labour and upscaling our industrial production. reliance industries, which is a giant from every angle, spent just . % of its sales revenue on r&d in (yadav ) . nor do we seem to be worried about the fact that for exports to grow continuously a country must first fulfil two basic conditions. it must develop a strong internal market, and its production techniques must be perpetually locked into an r&d upgrading mode (nayyar : - ) . this clearly implies more innovation, greater output, higher skills, better wages, and more audit and compliance. we are still in the thrall of believing that selling cheap labour products is our ticket to worming our way back in as a major exporting country. in conclusion, this article argues that the central feature which needs immediate attention is the dismantling of the current ida. there have been other factors that have gone in tandem, but the ida is the leading factor behind the irrationality and smallness of enterprises in india. it has encouraged the informalization of the economy which has, in turn, spun off a multitude of small units, precariously perched, making for a long supply chain. what then are the issues we should emphasise in the post-"coronial" era for india's economic development? . withdraw the ida as it stands and craft a fresh one which has at least two outstanding features: (a) no thresholds that allow for exceptions to the general rule which should apply to all workers and all promoters. this implies that all workers are entitled to all benefits regardless of the size of the enterprise. (b) there should also be a clear provision for severance pay, and the management should have the right to hire and fire. if these steps are taken, it will provide the foundation for the other steps listed below. . industries should be incentivized to grow big, instead of small. those enterprises that invest significantly in r&d investments ought to be supported and subvented. such measures could be institutionalized through interests at low rates and providing those who undertake r&d, at a significant level, with marketing opportunities. there are examples of such support structures in other parts of the world, and one can learn from them. once the industry begins to feel the need for skilled labour, vocational institutions will become more vibrant. that the poor have shown their eagerness in getting educated needs reciprocity from the side of the employers. . alongside this, msmes should be rewarded, again through interest payment support, if they are able to move up the ladder and graduate upwards from micro to small to medium and then out of the msme bracket altogether. msme's should also have to abide by compliance rules, and this can be enforced by involving the big partners in the supply chain. for example, when ikea or h&m or walmart outsource from indian msmes they are also vigilant about auditing their supply chains. however, their final responsibility is to their parent company and to the sensibilities of their customers, primarily in the western world. india can insist that large indian companies also audit their supply chain along with audit norms that are better suited to our conditions at home. . migration will happen, and should, but, obviously if employment becomes stable with the rescinding of ida, housing projects should be part of an enterprise's csr. csr should begin at home, literally and metaphorically. once migrants get a sense of permanence, they will move in with the family. as it is, we have noticed that there has been an increase in household migration over the years. we also know that "studies" is the second most important reason for male migration which adds to the likelihood of entire households migrating. . further, we should note that only about % of migrants are interstate. we should, therefore, not lose sight of the vulnerability that face short distance migrants, most of them from rural to rural and within the district. it is then not just in metropolitan india where the lockdown has created economic and social havoc. many issues, very similar in character, are being played out, at different levels, across the country: village and town. . in a nutshell, then, industry should get "big" and get smart. all policies for the post-"coronial" phase should concentrate on this twin objective. we do not want the past to return, wobble, stand up, and collapse in a heap when the next destabiliser comes along. if we do not act on these steps now, our economy would have been etherized on the table for nothing. most regular jobs in india don't pay well, plfs. new delhi: livemint against thresholds: raising capacity and formalizing the economy the distribution of firm size in india: what can survey data tell us. adb chicago: charles h. kerr and company indian workforce needs better employers crises, pandemics and reorganization resurgent asia: diversity in development size dependent tax incentive, threshold effects and horizontal subcontracting in indian manufacturing: evidence from factory and field level panel data sets indian corporates need to invest in r&d for make-in-india to succeed acknowledgements i am grateful to professor shubhashis gangopadhyay for his detailed comments on my paper. all shortcomings are, of course, my responsibility, for on many occasions i was unable to rise to his standards. key: cord- -cljfh es authors: chakraborty, parthasarathi; jayachandran, saranya; padalkar, prasad; sitlhou, lamjahao; chakraborty, sucharita; kar, rajarshi; bhaumik, swastika; srivastava, medhavi title: exposure to nitrogen dioxide (no( )) from vehicular emission could increase the covid- pandemic fatality in india: a perspective date: - - journal: bull environ contam toxicol doi: . /s - - - sha: doc_id: cord_uid: cljfh es the corona virus- (covid- ) is ravaging the whole world. scientists have been trying to acquire more knowledge on different aspects of covid- . this study attempts to determine the effects of covid- , on a large population, which has already been persistently exposed to various atmospheric pollutants in different parts of india. atmospheric pollutants and covid- data, obtained from online resources, were used in this study. this study has shown strong positive correlation between the concentration of atmospheric nitrogen dioxide (no( )) and both the absolute number of covid- deaths (r = . , p < . ) and case fatality rate (r = . , p < . ) in india. statistical analysis of the amount of annual fossil fuels consumption in transportation, and the annual average concentration of the atmospheric pm( . ), pm( ), no( ), in the different states of india, suggest that one of the main sources of atmospheric no( ) is from fossil fuels combustion in transportation. it is suggested that homeless, poverty-stricken indians, hawkers, roadside vendors, and many others who are regularly exposed to vehicular exhaust, may be at a higher risk in the covid- pandemic. electronic supplementary material: the online version of this article ( . /s - - - ) contains supplementary material, which is available to authorized users. the threat of severe acute respiratory syndrome coronavirus- (sars-cov- ), or covid- is the toughest challenge thrown at the human race of the present world. the covid- death toll is rapidly mounting worldwide (who ) . the prevalence of the covid- pandemic both in the tropical and temperate countries indicates that this virus is highly tolerant to wide variations in temperature and humidity. the effect of covid- on human health is reported to be more severe in the presence of air pollutants (conticini et al ; ogen ) . the aforementioned information is particularly important for developing countries which are already under the grip of covid- pandemic, and where large sections of the population live in areas with poor ambient air quality. a recent study has shown that atmospheric particulate matter (pm . ) is a potential pollutant which could be responsible for increasing the risk of mortality from covid- (wu et al ; science news by agu ) . however, adverse effects of covid- on the health of individuals who have been exposed to different concentrations of air pollutants have not yet been completely elucidated. in this study, india was selected because of its large population (the second largest population in the world), fastgrowing economy, and poor environmental quality (fifth most-polluted country) (u.s. census bureau ; world bank report ). twenty-one indian cities are ranked among the first thirty most-polluted cities, in the world based on poor air quality (khan and hassan ; cnn ) . therefore, regular exposure to different atmospheric pollutants could put a part of the indian population under severe threat during the covid- pandemic. it is hypothesized that the number of deaths in a particular region by the covid- epidemic could be related to the concentration of different atmospheric pollutants in that region. the aim of this study was to identify the atmospheric pollutants and their sources, whose long-term exposure could increase the severity of the covid- pandemic. it should be noted that our knowledge about the covid- is very limited. the impact of covid- on human health depends on many factors and the mechanism is extremely complex. in this investigation, an attempt was made to establish a link (if any) between, the number of covid- deaths with the concentrations of different atmospheric pollutants in states of india. it is assumed that the deceased subjects resided for the last year in the same state in which they died, and came in contact with the atmospheric pollutants prevalent in that state. the data (used in this study) related to atmospheric pollutants and the covid- pandemic were obtained from online resources (central control room for air quality management-all india and https ://www.covid ind ia.org/ respectively). the details of the data processing and analysis methodologies are presented below. the concentration of surface atmospheric pollutants from stations of cities distributed all over india (as shown in fig. ) were obtained from the website of central control room for air quality management (https ://app.cpcbc cr.com/ccr). the details of averaging of each pollutant are given below. let us assume that atmospheric data is monitored at "n" different stations in "x" different cities (a, b, and c…..x) of a state. if the concentration of a pollutant at "n" different stations in city a are: a , a , a , a ……a n . and, b , b , b ……. b n in city b and c , c , c ……c n in city c, and so on then, the average concentration of the pollutant in the city a will be = in this study, number of cities and n varied from one state to another (based upon the availability of the data). the detailed description of the stations (fig. ) and yearly average concentration of different atmospheric pollutants in different states of india are given in tables sm - . the total number of covid- cases on th june and th june , and total number of deceased on th june in indian states were obtained from https ://www. covid ind ia.org/. the data were used to calculate the case fatality rate (cfr). the cfr describes the proportion of cases who have died from a disease over the course of a disease or pandemic once the pandemic is over. however, during an ongoing pandemic like covid- , the above formula is not applicable. therefore, the correct formula applicable for an ongoing pandemic is the one described by ghani et al ( ) : where, t average time period from case confirmation to death. in this case we assumed t = days to calculate the cfr. total number of covid- cases on th june and total number of deceased on th june were used to calculate the cfr. the cfr values in the indian states are presented in table sm . all the data are presented with % confidence interval. the relationship between the concentration of atmospheric pollutants and the covid- death and cfr in india were evaluated with pearson's correlation coefficient and regression analysis. the average concentration of pollutant in the city b will be the average concentration of pollutant in the city c will be the average concentration of the pollutant in city the x will be the average concentration of the pollutant in the state will be even though the concentrations of atmospheric pollutants (particulate matter with a diameter ≤ . µm (pm . ), particulate matter with a diameter ≤ . µm (pm ), carbon monoxide (co), nitrogen dioxide (no ), nitrogen oxides (no x ), ozone (o ), sulphur dioxide (so )) vary with the changing seasons (fig. sm a-g), atmospheric levels of many of these pollutants remain higher than the recommended limits throughout the year in india (who ). this is likely a major reason that of the top cities of the world in terms of poor air quality are located in india (khan, and hassan ) . the yearly average concentration of many different atmospheric pollutants in the different states across india are presented as supporting material (tables sm - ). pm . is one of the major atmospheric pollutants for many cities in india (ministry of environment, forest and climate change, government of india ; nacp ; louisiana state university ). statistical analysis show that there was a strong positive correlation between the concentration of pm . and pm , indicating that they were probably from same sources. even though there are reports on increasing severity of the covid- pandemic with increasing pm . in the usa, this study however, couldn't find any relationships between pm . and the number of covid- deaths or case fatality rate (cfr) in india (figs. sm and sm ). it is probably due to the fact that the covid- pandemic in india is in stage (clusters of cases) (who ). the atmospheric pm . probably plays an important role in spreading the virus when the epidemic is in stage level (community transfer level) (ma et al ) . therefore, pm . might play a crucial role in spreading the virus in the near future if the pandemic is not controlled soon. the changing concentration of no x and so , showed positive relationships with the number of covid- deaths ( fig. sm ) . however, increasing concentration of atmospheric no , showed a strong positive correlation with the number of covid- deaths and the covid- cfr in different states of india ( fig. a and b) . this indicates that exposure to atmospheric no could exacerbate the morbidity associated with covid- . regression analysis suggests that increasing atmospheric no concentration by . µg m − year − , could increase the number of deaths in india by ~ . increasing atmospheric no concentration by . µg m − year − , in india could increase the cfr by ~ . %. the population living in the indian cities that is regularly exposed to high levels of atmospheric no might be more vulnerable to infection by the covid- virus than the population living in more rural areas. but it is important to remember that the epidemic is progressing rapidly. the death and mortality rate of covid- are increasing and changing everywhere. therefore, the estimated impact of no on the covid- fatality rate (~ . %) in india could be an underestimation. an increase in no concentration by µg m − year − , could further increase the fatality rate in india in the future. human health effects are unlikely to be related to one single pollutant. therefore, in epidemiological research the use of a single pollutant as a surrogates for a complex mixtures of pollutants from certain sources are not correct. since pm . has been identified as a deadly atmospheric pollutant whose exposure can increase the severity of the covid- epidemic (wu et al. ; yongjian et al. ) and this study also identified no as another atmospheric pollutant to affect the cfr of the pandemic, the cfr of covid- in india might change with changes in concentrations of these two atmospheric pollutants. therefore, no /pm . ratio was used as an indicator to understand the contribution of atmospheric pollutants on specific health effects in a particular area in india. the no /pm . ratio has already been used to assess the influence of atmospheric pollutants on human health (hazenkamp-von arx et al ) . this study showed that rise in no /pm . ratio increased the covid- cfr by ~ . % (fig. c) in india. increasing atmospheric no levels or increasing ratio of no /pm . (in the atmosphere) in a city could increase the severity of the covid- pandemic in that city. the concentrations of atmospheric no in indian states were always positively correlated with the covid- cfr (at three different times; on th may, st june and th june) (see fig. a-c) . this indicates that long-term exposure to high levels of atmospheric no could place a large fraction of the indian population under a serious health threat during the covid- pandemic. studies in the literature show that short-term no exposure ( min to h) can cause serious respiratory disorders resulting in increased number of hospital visits and even emergency medical treatment (australian government department of agriculture, water and the environment ; usepa ; rangkuti and musfirah ). exposure to atmospheric no damages the lining of lungs, and weaken the immune system (australian government department of agriculture, water and the environment ). it has been reported that exposure to - ppm no for min may lead to development of bronchiolitis, pulmonary edema and focal pneumonitis, all of which can increase the susceptibility of an individual to covid- manyfold (national research council ). these symptoms however resolve spontaneously on cessation of exposure. however, persistent exposure to no can cause irreversible pathological changes in the lungs like alveolar hyperplasia and increased fibrin in the alveoli. these changes will probably not increase the rate of infection for covid- but will play a major role in prognosis of the patient once infected. furthermore, no induces accumulation of inflammatory cells in the alveoli of lungs. these cells may contribute to development of a 'cytokine storm', which in most cases is responsible for the death of a covid patient (mcgonagle et al ). another indicator of bad prognosis of a covid- patient is a decrease in o saturation of blood. no may further aggravate the situation as it reacts with hemoglobin and converts it to methemoglobin or nitrosohemoglobin which reduces the oxygen carrying capacity of blood (unnikrishnan and rao ) . these mechanisms combined together may explain the increased mortality of covid- patients in regions with high atmospheric levels of no . therefore, the population exposed to atmospheric no could be under serious threat during the covid- pandemic, which could lead to death. a large portion of no comes into the atmosphere due to combustion of fossil fuel from vehicles, power plants, and off-road equipment (usepa a, b) . although it is difficult to pinpoint the origin of atmospheric pollutants in the indian cities, however, a rational analysis of concentrations of different atmospheric pollutants was carried out to identify the sources of atmospheric no in the different states of india. this study found that the annual average concentration of pm . and pm were very highly correlated (r = . , p < . ), indicating that pm . and pm originated from the same source (fig. a) . chaloulakou et al ( ) also used the concentrations of pm . and pm to identify their sources. the pm . /pm ratios were very similar in the different states of india (as shown in table sm ). the aforementioned similar pm . /pm ratio indicates, that the source of the particulate matter (pm and pm . ) were the same in different states of india. since the industries or dust storms or other factors cannot be the same in the different states (because india is a large country, and the geographical locations and growth of industrialization in the states are entirely different), it can be inferred that the source of the particulate matter from motor vehicle emissions, which are similar in different states. this study also showed strong positive correlation (r = . , p < . ), between atmospheric no , and pm . levels (fig. b) . this indicates that fossil fuel combustion in transportation (which is the source of pm . or pm ) is probably one of the major sources of atmospheric no in the indian cities. hazenkamp-von arx et al ( ) have also showed a strong relationship between pm . and no in atmosphere, and concluded that both pollutants are from the same source (transportation). numerous other articles also suggest that transportation is a regular source of no in indian cities throughout the year (nacp , guttikunda et al ) . therefore, it was concluded that traffic emissions were probably the major contributors to the atmospheric concentration of no in the indian cities. the national clean air program was initiated in (nacp ). the target of the program is to curb air pollution. this is a wonderful initiative by the government of india. the nacp aims to reduce pm . and pm air pollution in cities by - % by compared to levels. however, it is not correct to expect a huge improvement in the atmosphere in just year of starting the program. a strong positive correlation (r = . , p < . ), between the annual fossil fuel consumption for transportation (state wise) (see, table sm ) and atmospheric no concentration (fig. c) in the different states of india further reiterates the above mentioned point that a major part of the atmospheric no was derived from vehicle emissions. sheel et al ( ) have shown that fossil fuel consumption in transportation could control atmospheric no concentration in indian cities. therefore, fossil fuel combustion (in transportation) was considered to be the major contributor of atmospheric no in the indian cities of this study. many residents of urban india are regularly exposed to high concentrations of motor vehicle emissions, and consequently may be among the most vulnerable to suffer complications from covid- coronavirus exposure. those who would likely be the most vulnerable are those who spend much of their time near polluted streets in a city. overall, around million people in india regularly get exposed to poor air (li et al ) . homeless people, a part of population living in densely populated slum areas, shanty towers, traffic police, street hawkers, auto-rickshaw drivers, bus drivers, roadside motor mechanics, daily passengers in public transport and, many others who regularly get exposed to vehicular emission could be under threat during this pandemic. cross-sectional studies of chronic exposure to vehicular pollution to the population in many indian cities has reported decreased lung function, increased blood pressure, suppressed immunity, and enhanced lung cancer risk (ray and lahiri ). there are about million homeless people around the world, and they are constantly exposed to various pollutants, which could also put them in grave danger during the covid- epidemic. homeless people can spread contagious disease much faster in society. therefore, immediate necessary action needs to be taken to minimize the health risks of homeless people to control the spreading of covid- pandemic. this is the first report from this region that sought to understand relationships between the concentrations of different atmospheric pollutants and number of deaths and fatality rate in the covid- pandemic. this study couldn't consider many other important covariates (such as confinement measures, clinical practice, number of conducted tests, the capacity of the healthcare system, population density, population demography (e.g. age structure, ethnicity, etc., and socioeconomic status) due to unavailability of online reliable data. therefore, further extensive research is recommended to develop a more comprehensive understanding of the myriad factors involved with the covid- pandemic. ) of the world's cities with the worst air pollution are in india measurements of pm and pm . particle concentration in can atmospheric pollution be considered a co-factor in extremely high level of sars-cov- lethality in northern italy? methods for estimating the case fatality ratio for a novel, emerging infectious disease nature of air pollution, emission sources, and management in the indian cities and no assessment in european study centres of ecrhs ii: annual means and seasonal differences air quality scenario of the world's most polluted city kanpur: a case study. smart cities-opportunities and challenges india is overtaking china as the world's largest emitter of anthropogenic sulfur dioxide source apportionment, health effects and potential reduction of fine particulate matter (pm . ) in india longterm exposure to pm . lowers influenza virus resistance via downregulating pulmonary macrophage kdm a and mediates histones modification in il- and ifn-β promoter regions immune mechanisms of pulmonary intravascular coagulopathy in covid- pneumonia government of india ( ) national air quality index national clean air programme assessment of exposure-response functions for rocket-emission toxicants assessing nitrogen dioxide (no ) levels as a contributing factor to the coronavirus (covid- ) fatality rate atlantis press ray mr, lahiri t ( ) air pollution and its effects on healthcase studies, india. central pollution control board, government of india air pollution can worsen the death rate from covid- comparison of satellite observed tropospheric no over india with model simulations air quality guide for nitrogen dioxide the sources and solutions: fossil fuels nitrogen dioxide (no ) pollution, basic information about no curcumin inhibits nitrogen dioxide induced oxidation of hemoglobin nt-(outdo or)-air-quali ty-and-healt h coronavirus disease (covid- ) pandemic situation report- exposure to air pollution and covid- mortality in the united states association between short-term exposure to air pollution and covid- infection: evidence from china acknowledgements authors are thankful to the director of iit kharagpur, for his encouragement and support. authors acknowledge prof v. vijith for his help during this manuscript preparation. this work is a part of the iit kharagpur supported institutional project (project code fht).funding funding was provided by the sponsored research and industrial consultancy, iit kharagpur, india. key: cord- -ek hct authors: patel, shivani a.; sharma, hanspria; mohan, sailesh; weber, mary beth; jindal, devraj; jarhyan, prashant; gupta, priti; sharma, rakshit; ali, mumtaj; ali, mohammed k.; narayan, k. m. venkat; prabhakaran, dorairaj; gupta, yashdeep; roy, ambuj; tandon, nikhil title: the integrated tracking, referral, and electronic decision support, and care coordination (i-trec) program: scalable strategies for the management of hypertension and diabetes within the government healthcare system of india date: - - journal: bmc health serv res doi: . /s - - -w sha: doc_id: cord_uid: ek hct background: hypertension and diabetes are among the most common and deadly chronic conditions globally. in india, most adults with these conditions remain undiagnosed, untreated, or poorly treated and uncontrolled. innovative and scalable approaches to deliver proven-effective strategies for medical and lifestyle management of these conditions are needed. methods: the overall goal of this implementation science study is to evaluate the integrated tracking, referral, electronic decision support, and care coordination (i-trec) program. i-trec leverages information technology (it) to manage hypertension and diabetes in adults aged ≥ years across the hierarchy of indian public healthcare facilities. the i-trec program combines multiple evidence-based interventions: an electronic case record form (ecrf) to consolidate and track patient information and referrals across the publicly-funded healthcare system; an electronic clinical decision support system (cdss) to assist clinicians to provide tailored guideline-based care to patients; a revised workflow to ensure coordinated care within and across facilities; and enhanced training for physicians and nurses regarding non-communicable disease (ncd) medical content and lifestyle management. the program will be implemented and evaluated in a predominantly rural district of punjab, india. the evaluation will employ a quasi-experimental design with mixed methods data collection. evaluation indicators assess changes in the continuum of care for hypertension and diabetes and are grounded in the reach, effectiveness, adoption implementation, and maintenance (re-aim) framework. data will be triangulated from multiple sources, including community surveys, health facility assessments, stakeholder interviews, and patient-level data from the i-trec program’s electronic database. discussion: i-trec consolidates previously proven strategies for improved management of hypertension and diabetes at single-levels of the healthcare system into a scalable model for coordinated care delivery across all levels of the healthcare system hierarchy. findings have the potential to inform best practices to ultimately deliver quality public-sector hypertension and diabetes care across india. trial registration: the study is registered with clinical trials registry of india (registration number ctri/ / / ). the study was registered prior to the launch of the intervention on january . the current version of protocol is version dated june . the government of india, beholden to its population of . billion, has developed an electronic "ncd portal" that consists of an electronic case record form (ecrf) to manage non-communicable diseases (ncds) within the government sector. the i-trec program builds on the ecrf by integrating a proven-effective clinical decision support system for hypertension and diabetes care, accompanied by clinical training, to assist with patient management. we describe the evaluation protocol for the i-trec multi-component strategy to improve diabetes and hypertensions care at all levels of the four-tier healthcare system in india. lessons learned may inform optimal approaches to improve healthcare processes and health outcomes within the public sector healthcare system in india and in other similar settings. hypertension and diabetes together affect over million indians and their families [ ] . these conditions are rising rapidly in all regions of india, commonly co-occur [ ] [ ] [ ] , and are associated with several adverse health outcomes-such as higher rates of death, myocardial infarction, stroke, blindness, kidney failure. yet, both hypertension and diabetes are treatable such that timely and appropriate therapy mitigates associated morbidity due to complications and premature mortality. while lack of diagnosis is among the major obstacles to seeking appropriate treatment [ , ] , treatment outcomes even after diagnosis are far from ideal. less than half of individuals who have hypertension and diabetes in the community are aware of their condition [ , ] , and only - % achieve adequate blood pressure [ ] or blood glucose control [ ] . under-diagnosis, under-treatment, and poor control for both hypertension and diabetes are disproportionately high in rural settings [ , ] , where the majority of the indian population resides. india's rural healthcare system is currently organized as a hierarchy of facilities that range from relatively lower-skilled personnel supported by simple infrastructure at the village level to relatively higher-skilled personnel supported by sophisticated infrastructure at the district level. this model attempts to maximize geographical coverage by allowing for "up referrals" and "down referrals" across levels of the healthcare system so that the demand of the individual patient can be met by appropriate resources, such as skilled human resources, infrastructure and services. the referral linkages between these institutions, while theoretically in place, are not implemented efficiently or cohesively. in practice, patients access any level of the healthcare system convenient for them, resulting in a mismatch between patient needs and resource availability. challenges to the system are compounded by the heterogeneity of treatment guidelines, diagnostic modalities, and medications [ ] [ ] [ ] [ ] [ ] needed at all levels of health care to appropriately serve the growing population with ncds alongside the large population seeking care for maternal and child health and infectious diseases [ ] [ ] [ ] [ ] . recognizing the growing burden of hypertension and diabetes across all segments of the population, the ministry of health & family welfare, government of india, has taken the initiative to integrate screening and management of these conditions into primary care under its national health mission (nhm) and the national programme for prevention and control of cancer, diabetes, cardiovascular disease, and stroke (npcdcs). a major component of the government strategy is to encourage universal screening for hypertension and diabetes of adults aged ≥ years in the community and subsequent referral of potential cases to higher level facilities. consequently, the expected volume of adults seeking care for hypertension and diabetes at government health facilities is anticipated to surge. building upon the tremendous need and political will to identify optimal and scalable approaches to expand successful care models to manage blood pressure and diabetes within the public healthcare system, we developed the integrated tracking, referral, electronic decision support, and care coordination (i-trec) program. we describe the components of the i-trec program and its evaluation design. setting and target population i-trec was developed as a collaboration between the all india institute of medical sciences, new delhi (aiims), the centre for chronic disease control (ccdc), and emory university. for over a decade, these three institutions have collaboratively developed and tested the combination of information technology (it), enhanced personnel training, and workflow alterations to improve the quality of care for diabetes and hypertension in diverse settings across india [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . most of these prior efforts focused on a single level of the healthcare system and relied on research staff to implement the intervention. in i-trec, however, our goal was to develop and evaluate a coordinated package of tested tools and provider training approaches that catered to functions and personnel available in each type of the tier healthcare system (see table ). we further sought to embed the program within the infrastructural scaffolding provided by the government of india in the interest of future scalability. i-trec was thus designed to be implemented by personnel and using resources (medications, diagnostics) already present within the public healthcare system. the primary implementation partners for the program include the department of health and family welfare, government of punjab (use of it tools and altered work flow to deliver routine care); tata trusts (conduct training of healthcare workers and technical assistance); and dell technologies (development of software and it infrastructure). monitoring and evaluation activities for i-trec will be conducted by aiims, ccdc, and emory university. i-trec will be implemented in mukandpur block of shaheed bhagat singh nagar district, punjab, india, and evaluated through comparison of program indictors with those observed in the neighboring sujjon block in the same district (see fig. ). the program and comparison locations were selected based on consultation with the punjab department of health and family welfare. many barriers to optimal hypertension and diabetes care can be alleviated through it-based quality improvement strategies. clinical decision support software can provide up-to-date guidance to clinicians [ ] to manage hypertension and diabetes following standard treatment protocols. electronic health records can ensure that access to historical patient data and course of illnesses are available to clinicians to guide clinical decisions at whichever facility the patient enters. it tools can also help make referral linkages between the different levels of healthcare more transparent, efficient, and effective by suggesting referral thresholds to clinicians, notifying facilities of referred patients, and maintaining a record of recommendations to refer the patient to. finally, digitized systems to track and monitor case management can incentivize improved health provider performance. motivated by the potential benefits it tools offer clinicians and health systems, the i-trec program includes: an electronic case record form (ecrf) to consolidate clinicians regarding ncd medical content and lifestyle management (see table ). each component of this integrated system is described below. the ecrf is the government of india's digitized health record focused on compiling patient data relevant to chronic diseases. the ecrf allows nurses to enter patient demographic information, medical history, physical examinations, and laboratory investigations into an electronic form through a web-based "ncd portal." patient data are then stored in a cloud server hosted by national informatics centre, government of india. the ecrf ensures that necessary patient medical history will be available seamlessly up and down the healthcare facility hierarchy, reduces redundant data entry when the same patient seeks care at different facilities, and allows clinicians to track patient health information over time across visits. simultaneously, these data serve as inputs for the cdss to provide guidelinebased recommendations to clinicians to optimize medical and lifestyle management and referral of patients. the ecrf itself was developed by a committee of experts across india, including members of the i-trec investigator team (nt and ar). we chose to build upon the government of india's ecrf to align our program with the national effort to incorporate it into the management of ncds in the public sector. the cdss generates customized evidence-based treatment advisories for patients with hypertension and diabetes. the treatment advisories are based on up-to-date national and international guidelines that were further vetted by our expert clinical investigators, and tailored to each level of health facility (primary, secondary or tertiary), for example, by taking into consideration the local availability of medications and diagnostic capability. the cdss algorithms provide the clinician with an instantaneous advisory regarding medication titration based on patient history and current clinical examination as inputted into the ecrf. the attending clinician has the option of rejecting, partially accepting, or fully accepting the advisory to generate a final treatment plan. in addition to the treatment plan, the cdss has in-built prompts to refer patients up or down the healthcare facility hierarchy to direct patients to the most appropriate level of care for ongoing disease management. the treatment plan, referral instructions, and lifestyle advice specific to the patient become a part of the patient's ecrf and are also printed out on paper and given to the patient. healthcare providers employed in both the program and comparison blocks receive refresher content training related to the etiology, behavioral counseling, and medical management of ncds following established npcd cs training manuals. the content training is provided over a full day in separate sessions for auxiliary nurse midwives [anms], staff nurses, and medical officers. the sessions include training on effective techniques for delivering behavioral and lifestyle advice counselling. unlike routine training, this refresher training includes innovative learning methods, such as case studies and role playing to enhance trainee engagement to assure improved comprehension and retention of behavioral and lifestyle counselling approaches. in addition, staff nurses and medical officers in the program block receive it training on the use of the ecrf and cdss, specific to their level of expertise and the level of healthcare facility in which they are employed. patient flow under i-trec figure depicts patient flow within and across facilities in the i-trec program. following nhm and npcdcs recommendations, all adults aged ≥ years are eligible for universal screening of hypertension and diabetes in the community and opportunistic screening in health facilities by government health providers. at the villagelevel sub-centre, the lowest level of the healthcare facility hierarchy, the anm is tasked with screening adults to identify suspected cases of hypertension and diabetes in the community. anms enter screening results into the "anm portal" using a tablet-based application. adults who are suspected to have hypertension and/or diabetes are referred to the nearest primary health centre, the second level of the healthcare hierarchy, for diagnosis and treatment (see table and fig. ). at primary health centres and above-namely community health centres and the district hospital-nurses generate and update the patient ecrf through a webbased application on a computer tablet. at the time the ecrf is first generated, nurses record the patient's clinical history. at future visits, the ecrf is updated with ongoing examination data so that the cdss is responsive to the patient's health status at a given visit. patient data entered into the ecrf are uploaded to a secure cloud-based server once per day, and these data are synced and retrievable at all facilities to inform the cdss and assist with clinical decisions. after the initial ecrf review and update by the nurse, patients with confirmed hypertension or diabetes are instructed to see the medical officer, who is aided by the cdss to manage these conditions. the cdss algorithms are tailored to the expertise, medications, and diagnostic tests available at each level of facility and customized to the clinical history of the patient over all past and present contacts with the health system. medically complex patients, such as those who are resistant to therapy, may be referred further "up" the referral hierarchy. the referral algorithms take into account a patient's full clinical history and current health profile, including the number of medications currently prescribed, treatment response based on laboratory investigations, and comorbidities. for example, if a patient with diabetes under treatment at a phc has uncontrolled hyperglycemia despite being on the maximum tolerated dose of three oral hypoglycaemic agents, the cdss will trigger a referral to a chc. similarly, if a patient with hypertension under treatment at a chc level has uncontrolled blood pressure despite being on the maximum tolerated dose of two antihypertensive drugs, the cdss will trigger a referral to the district hospital. once the patient achieves a stable clinical state, she or he will be referred back "down" to the lowest level of health facility (phc or chc) that is suitable for routine management of stable disease and dispensation of appropriate medication. adults residing in the comparator block will continue to receive the usual care by local physicians and nurses using paper-based record systems and without the assistance of the cdss. we will employ a two-group pre-post quasi-experimental design to conduct a mixed methods evaluation of the i-trec program in punjab, india. while the i-trec program is implemented within the health system by clinicians, we will assess indicators at the levels of facilities, clinicians, patients, and communities. the evaluation protocol was reviewed and approved by the ethics committee at all india institute of medical sciences (aiims), new delhi, india (iec- / . . ). given that the government of punjab will be implementing i-trec, and role of research partners is limited to program design, training, and evaluation, this study was deemed to be observational. the role of researchers at emory university, atlanta was deemed not human subjects research (irb ). participants from whom our research team collects data for evaluation purposes will provide written informed consent following procedures approved by the aiims ethics committee. program indicators are guided by the reach, effectiveness, adoption implementation, and maintenance (re-aim) framework [ ] . the principal endpoints for evaluation are shown in table , and focus on the domains of reach, effectiveness, adoption, and implementation of the program components. reach and effectiveness will be assessed using a combination of community-based data and facility-based data. for example, the proportion of adults ages and older in the community who are screened for hypertension is a measure of reach that will be obtained through a representative community survey. a second measure of reach is the number of patients seeking care for hypertension and diabetes who have an ecrf, which will be measured through health facility data. similarly, effectiveness will be assessed through health outcomes (e.g., reductions in mean blood pressure and/or mean blood glucose) among patients attending figure was developed by the authors program facilities and also among adults with hypertension and/or diabetes in the community. adoption metrics focus on healthcare provider utilization of the ecrf and cdss tools. implementation measures focus on quantifying the proportion of patients who receive care through the ecrf and cdss tools. finally, maintenance will be assessed through qualitative research with stakeholders within the health system to understand views of sustainability. data will be triangulated from multiple sources, including facility and patient assessments, stakeholder interviews, community surveys, and patient-level data from the i-trec electronic database. where appropriate, data will be collected prior to the program launch and again following months of the program. with the exception of the i-trec ecrf-cdss data, evaluation data will be collected by trained research staff. pre-and post-program health facility and patient assessments include ) a health facility form; ) patient flow mapping; and ) patient out-of-pocket cost of care surveys. health facility forms will be completed at all government health facilities ( in program and in control and the common district hospital) to describe the infrastructure, facility personnel and salaries, availability of medications, and availability of diagnostics and laboratory investigations. health facility form completion requires a combination of observational checklists and structured interviews with administrators. patient flow mapping entails identifying and following patients with hypertension and diabetes through typical visits to map the typical workflow, diagnostic and prescription practices, and duration of visits. together, the health facility form and patient flow mapping will provide data to describe the resources (time and costs) associated with typical healthcare visits for patients with hypertension and diabetes with and without the i-trec program. patient cost surveys will be used to obtain data on expenditures related to outpatient and inpatient health care utilization in the last months to understand the cost incurred by patients to manage their disease. administration of the pre-and post-program patient cost surveys will contribute data to understand whether the program has any impact on patient expenditures related to hypertension and diabetes. purposive sampling will be done to recruit patients for the patient flow mapping and cost surveys. qualitative methods will include a combination of focus group discussions of the community members, key informant interviews with healthcare providers and indepth interviews of patients to provide a richer interpretation of quantitative findings and explore the processes underlying the uptake and delivery of the i-trec program. the qualitative research will be conducted before, during, and after program implementation. purposive sampling will be done to recruit information-rich participants for interviews and focus group discussions. for all qualitative data analysis, the textual data (verbatim transcripts created from digital recordings of interviews and focus group discussions) will be reviewed to identify key themes and domains of interest. a code book will then be developed to reflect these domains and include both inductive (derived from the textual data) and deductive (based on literature and theory) codes. inter-coder reliability will be assessed, and the codebook will be finalized and applied to the data. the codebook will include codes specific to each type of data collection and shared codes across participant type. a thematic analysis will be used to describe individual-or community-level views on discussion topics including program barriers and facilitators, community barriers, views of the healthcare system, and acceptability and feasibility of the program. the community-based evaluation component will assess whether the i-trec program has an impact on blood pressure and blood glucose awareness, treatment seeking, and control among adults in the community. this evaluation component is critical to learning the realworld impact of the i-trec program on communitylevel indicators of the care continuum (screening, treatment, control). data collected in the program and comparison blocks prior to the program will be compared with data collected from these same blocks after the program using identical procedures. this design allows us to assess and address several threats to validity, including lack of temporal order, comparability across the two blocks (leading to potential confounding by population composition) and secular changes unrelated to our program that affect study endpoints (leading to potential confounding by external factors). given that we will be sampling separate cross-sections of the population in each group and time point, we do not expect inference to be affected by population aging (maturation threats) over the -year program period. at baseline-prior to intervention-we employed a multi-stage cluster sampling design to obtain a representative sample of adults aged years and older in both blocks under study. within each block, census data were used to select villages proportionate to population size and subsequently we conducted household mapping and listing to generate a sampling frame for households. households were selected using systematic random sampling, and one adult man and woman from each household were randomly selected using the kish method to achieve the desired sample size. at endline, this same procedure will be repeated. the community survey sample size was determined to estimate differences in mean reduction in systolic blood pressure among those with diagnosed hypertension in the community. first, we computed the base sample size required to detect a desired effect size of mmhg given the sbp standard deviation of . , power = . and α = . , based on the mpower heart study [ ] . we estimated that individuals with hypertension would be needed to detect the anticipated effect size. second, we estimated that we would require a sample size of adults in the general population to identify individuals with hypertension, assuming prevalence of diagnosed hypertension of %. third, we determined the optimal sample allocation for a multi-stage sampling design that would be timeefficient for field work and statistical precision. we assumed an intraclass correlation of systolic blood pressure of . based on village-level clustering of sbp in the disha study [ ] (unpublished findings). after applying a % refusal rate based on our prior field studies in the region, we determined that a cluster size of adults per village distributed across villages per block was optimal. this yielded a total sample size of for the community survey to be evenly split between the program and comparison blocks. using patient health data from the ecrf, we will assess processes of care and changes in blood pressure and blood glucose outcomes over time among patients with hypertension or diabetes who seek care at i-trec program facilities in a facility-based evaluation component. because i-trec is being integrated into the routine care in the program block under real-world conditions, we will not be assigning individual patients to treatment nor actively following patients for research visits. rather, all adults residing in the i-trec catchment area (i.e., residents of mukandpur block) will be exposed to the program and patient data will be collected every time a person chooses to receive care at a government health facility. data from all patients visiting facilities in the program block captured in the government of india ecrf will be de-identified and obtained by aiims throughout the program period for monitoring and evaluation purposes. the sample size for the facility-based evaluation is out of our control and contingent on the number of patients who seek care at government facilities. we therefore report the detectable effect size for longitudinal change in systolic blood pressure over time in patients at i-trec facilities after setting power to % and α = . . the program block, mukandpur, has a population of , . we expect that % of the local population will seek care at a government facility, % will be age-eligible ( years and older) per the government guidelines for universal and opportunistic screening of hypertension and diabetes, and % will test positive for hypertension, amounting to an estimated patient pool of adults. assuming that % of all enrolled patients with hypertension and diabetes make repeat visits (enabling us examine changes in outcomes), we will be able to detect a . mmhg difference in sbp. in the program block, we will examine measures of adoption and implementation of the it tools, such as completeness of ecrf forms, acceptance (partial and full) and rejection of the cdss advisories, time stamp of data entry, the initials of the enterer, and average number of new records per day. in both the program and comparison block, data regarding the total number of patients recorded in the out-patient registry at the facility, numbers screened for hypertension and diabetes, numbers receiving medication from the pharmacy, and numbers referred to higher level facilities will be collected through a combination of paper-based registries and routine npcdcs reports. the i-trec evaluation team will obtain these facility-level data using abstraction forms without removing any paper records from premises. in addition, the i-trec evaluation team will periodically conduct random, unannounced visits to directly observe the number of patients seeking care for hypertension and diabetes facilities in both blocks. additional data on intervention fidelity measures (e.g., use of ecrf during health visit, measurement of blood pressure and blood glucose, provision of the i-trec print out to the patient) will also be collected through patient exit interviews and the ecrf backend data. quantitative data analysis will be performed using sas, stata, and r software. descriptive analyses of the community-based data will examine socio-demographic characteristics, health indicators, and healthcare behaviors of the program and comparison block samples at baseline and end-line. the quantitative evaluation of health and healthcare endpoints will focus on assessing changes in the continuum of care indicators and mean blood pressure in the community-based surveys. we will assess changes in baseline to end-line indicators of health outcomes (e.g., blood pressure) and changes in continuum of care indicators (e.g., proportion screened) for both the program and comparison blocks; see table for indicators. a simple difference-in-difference (did) [ ] estimate for each indicator will be computed as did ¼ p g¼i;t¼ -p g¼i;t¼ -p g¼c;t¼ -p g¼c;t¼ where p indicates prevalence or mean of each indicator; g subscripts group (i = program; c = comparison); and t subscripts the time point of data ( = pre-program; = post-program). we will estimate log-binomial models (binary outcomes) or linear models (continuous outcomes, with log-transformation if needed) with robust variance to compute the did after accounting for compositional characteristics of the community and clustering of data within villages. for each outcome indicator separately, the following model will be estimated using individual-level data: outcome indicator program group þpre − post indicator þprogram group x pre − post indicator þ age þ sex þeducation þ religion þmarital status þbelow poverty line þfacility type public versus private ð Þ : the coefficient associated with the interaction term, "program group x pre-post indicator," is the adjusted did estimate accounting for heterogeneity in sociodemographic characteristics. the model will be estimated using generalized estimating equations (gee) to account for clustering of outcomes within the villages (i.e. village is the cluster variable specified for statistical analysis). sub-group analyses will examine differences by gender and socioeconomic status. data points recorded in the i-trec system will be analyzed by month to examine trends over time and seasonality. we will also evaluate change patient outcomes over time (e.g., mean sbp change). while several of the i-trec platform indicators are purely descriptive measures of performance (e.g., mean time for data upload), other indicators of healthcare delivery may be compared between i-trec facilities and comparison group facilities (e.g., patient volume). this is the first study in india evaluating the composite impact of a clinical decision support system integrated with the government of india ecrf, combined with modified patient flow and enhanced healthcare provider training. it is also an important early effort to systematically evaluate a program for integrated management of hypertension and diabetes at all levels of the public healthcare system, starting from the sub-centre up to the district hospital. lessons learned may inform optimal approaches to improve healthcare processes and health outcomes within the public sector healthcare system in india. the i-trec program and its evaluation have several strengths but also some limitations. given the primacy of scalability, the role of research staff is limited to program design, training, monitoring and evaluation. therefore, the context and conditions of implementation are beyond the control of investigators. for example, the availability of drugs, diagnostic investigations, and clinicians are likely to impact the reach, effectiveness, and implementation of i-trec but rest in the hands of the state government. nevertheless, we expect variations in these structural elements to affect both the program and comparison blocks similarly. in order to maintain comparability between the program and comparison block, neighboring blocks within the same district were chosen. however, this means that both blocks share the district hospital, which will have to be taken into account during the analysis. while we will be able to obtain patient data in the program block from the ecrf, no comparable source of data is available to use in the comparison block. moreover, undue monitoring of the comparison block may inadvertently lead to compensation behaviors on the part of clinicians that could undermine our ability to measure performance differences across the two blocks. the community survey, in part, is designed to mitigate these limitations by providing a well-designed comparison of healthcare processes and outcomes as observed in the program and comparison blocks. this implementation research is intended to provide evidence of workable programs to manage chronic diseases in india and inform the evolving npcdcs [ ] . given the similarities in the health system and epidemiologic transition between in india and other low-and middle-income countries, this research has additional scope to potentially inform best practices for management of hypertension and diabetes outside of india. in fact, members of our team (dj, av, dp) have collaborated with the world health organization (who)-southeast asia regional office and the republic of maldives for the development of the "mpen app," which is a cdss tool that draws on similar technologies as what is described here to implement the who prevention of essential ncds package in primary health care in the maldives. we envision that the i-trec program and evaluation will provide opportunities for continued cross-national collaborations and idea exchange to improve hypertension and diabetes care globally. intervention development and pre-testing were completed in august . healthcare providers in both blocks received training in december , and the i-trec program was launched in january . prior to the program launch, pre-program data collection, including facility and patient assessments, qualitative research, and community survey, were completed. since march , both intervention roll-out and research activities have been impacted by the covid- pandemic. specifically, government healthcare system resources have been diverted from ncd care to test and treat patients with sars-cov- , national and local lockdown measures have forced intermittent closures of lower-tier health facilities and prevented field staff from conducting routine monitoring activities. in addition, patient flow through facilities-when open-has generally declined, possibly due to fear of contracting the virus while seeking healthcare. nevertheless, as and when healthcare facilities are operational, the intervention components are being implemented by nurses and physicians in the program facilities and program monitoring activities are underway. we expect intermittent disruptions to intervention implementation and monitoring activities to continue until the covid- pandemic has been fully controlled. this study is supported in part by the national heart, lung, and blood institute (nhlbi) of the national institutes of health (nih), award number u hl under the hypertension outcomes for t research within lower middle-income countries (hy-trec) program. the content is solely the responsibility of the authors and does not necessarily represent the official views of the nih. the sponsor had no role in study design as presented here. sap, kmvn, mka, and mbw were supported in part by funding from niddk (p dk ). pg was supported by funding from the nih fogarty international center (vumc under d tw ). availability of data and materials data generated from this study will be made available to researchers upon request. requests may be made to dr. patel and will be processed through the i-trec data sharing and publications committee. the evaluation protocol was reviewed and approved by the ethics committee at all india institute of medical sciences (aiims), new delhi, india (iec- / . . ). the role of researchers at emory university, atlanta was deemed not human subjects research (irb ) by the emory university institutional review board. participants enrolled in the research study provided written informed consent. uday: a comprehensive diabetes and hypertension prevention and management program in india diabetes and hypertension: is there a common metabolic pathway? the association of hypertension and diabetes: prevalence, cardiovascular risk and protection by blood pressure reduction high rates of co-occurrence of hypertension, elevated low-density lipoprotein cholesterol, and diabetes mellitus in a large managed care population patient and healthcare provider barriers to hypertension awareness, treatment and follow up: a systematic review and meta-analysis of qualitative and quantitative studies prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries cluster randomised controlled trial of a peer-led lifestyle 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diabetes mellitus management package to facilitate evidence-based care delivery in primary healthcare facilities in india: the mpower heart project effectiveness of a multicomponent quality improvement strategy to improve achievement of diabetes care goals: a randomized, controlled trial development of mwellcare: an mhealth intervention for integrated management of hypertension and diabetes in low-resource settings effectiveness of an mhealth-based electronic decision support system for integrated management of chronic conditions in primary care: the mwellcare cluster-randomized controlled trial. circulation the integrating depression and diabetes treatment (independent) study: design and methods to address mental healthcare gaps in india strategies for stakeholder engagement and uptake of new intervention: experience from state-wide implementation of mhealth technology for ncd care in tripura towards better hypertension management in india evaluating the public health impact of health promotion interventions: the re-aim framework task shifting of frontline community health workers for cardiovascular risk reduction: design and rationale of a cluster randomised controlled trial (disha study) in india identification and inference in nonlinear difference-indifferences models diseases-injury-trauma/non-communicable-disease-ii/national-programme-for-prevention-and-controlof-cancer-diabetes-cardiovascular-diseases-and-stroke-npcdcs publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations we would like to acknowledge the contribution of our implementing partners sunita nadhamuni, supriya prabhakar, sruti sridhar and colleagues at dell technologies, bangalore and drs. aman singh and prashant pathak at tata trusts. the authors declare that they have no competing interests. key: cord- -yw ndg authors: ashique, karalikkattil t.; kaliyadan, feroze title: teledermatology in the wake of covid - scenario: an indian perspective date: - - journal: indian dermatol online j doi: . /idoj.idoj_ _ sha: doc_id: cord_uid: yw ndg nan the corona virus disease (covid- ) pandemic has shaken the healthcare delivery system, all over the world. [ ] social distancing is the key to flatten the curve of disease spread and the same applies to healthcare and hospitals. for medical consultations, not involving serious or emergency situations, it would be important to ensure appropriate healthcare delivery, without compromising on social distancing protocols. this has opened up a whole world of opportunity for telemedicine, which was hitherto less used in india, where even a legal framework was lacking for this. the application of telemedicine in the context of dermatology is referred to as "teledermatology." because of the inherently visual nature of the specialty, dermatology can be considered to be especially suitable for telemedicine. there are some important aspects which need to be clarified and standardized for the optimum application of teledermatology in india. in a country where the doctor-to-patient ratio is very small and speciality practice is predominantly urban centric, telemedicine is something that should have come into routine practice long ago. [ ] published information shows that, a doctor, approximately caters to , people and that there is a deficit of nearly , , doctors in the country. [ , ] in india, we have less specialists (dermatologists) per population. indian association of dermatologists venereologists and leprologists (iadvl) has a membership count of , as on th april, (information sourced through personal communication from honorary secretary general of iadvl, dr. feroz. k) to cater to the . million population with a ratio of approximately one dermatologist per , population. the covid- pandemic and the resultant healthcare delivery issues could be a good time to plan and implement an effective and enduring teledermatology system for india. world health organisation (who) has clearly defined telemedicine, [ ] whereas in india, we never had a standard guideline for teleconsultation till the medical council of india (mci) brought the directive to provide healthcare using telemedicine during the covid- pandemic period. [ ] this was to ease the burden and reduce the physical patient load and overcrowding in the outpatient departments across all hospitals in the country. there have been a few interesting publications on this subject which did attempt to throw light on the subject earlier. in a nutshell, the consultant delivers the services from fixed point, without the need for direct contact with the patient or physical examination. this saves a lot of man hours and logistics and resources. documentation can also be done quite easily using a paperless, electronic platform. [ ] [ ] [ ] [ ] [ ] [ ] teledermatology has a definite role when people are restricted or discouraged from visiting hospitals unless there is a dire emergency, as in the covid- crisis. [ ] teledermatology, as in most forms of telemedicine, works best for periodic follow-up of patients unless it is very late review. they are most benefited from this as the doctor can easily decide things being aware of the case and with the data already from the previous personal visit and investigation reports available. immunocompromised patients and organ recipients are best not exposed to crowds and hospitals unless in emergency to reduce chances of receiving cross-infections and hence can opt for teledermatology if the problem is trivial. dermatology patients on prolonged medication and in remission can use teleconsult in between as they may need just a verification from the doctor to continue their medications. india has a lot of expatriates who come home during holidays and they visit indian doctors during this time. they are usually unable to follow-up due to the short time spent here. such people can also make use of the facility to update their progress. drug prescription to people outside the purview of the medical council are not permitted in telemedicine guidelines. bed ridden, pregnant, and debilitated patients who cannot be brought to doctor too often benefit well from the facility. counselling and education sessions where medications do not have much role can be easily and efficiently carried out on teledermatology platforms. [ ] critical care dermatology, like a severe cutaneous drug reaction [eg. sjs/ten], angioedema or acute urticaria, with anaphylaxis, severe vasculitic conditions, or exacerbation of bullous disorders, are best not taken up for teledermatology. teledermatology can still be a tool for triage in such cases and the patient can be advised on the next action to be taken. similarly, conditions involving multisystem complaints are also not suitable for conclusive teledermatology consults. first time consultation even if not an emergency is less amenable for teledermatology, as compared to follow-up consultations. those conditions that mandatorily need a physical examination involving palpation or special tests (e.g. hansen's disease where the power of the limb or sensation over a patch needs to be ascertained, etc.) are best not taken up for teleconsultation to begin with. with broadband services being available throughout the country, telemedicine can be easily practiced even using a patient-initiated model (through mobile applications like whatsapp, zoom , google duo. etc.) these media have the obvious advantage of the patient being familiar in using them. there is no need not wait for a dermatology referral from the health center or a general practitioner. however, patient-initiated consults using mobile apps are limited by lower validity and also the difficulty in linking to a formal electronic medical record and prescription. an ideal system would need the consultation to be linked to a retrievable, secure, electronic medical record (emr), where the patient can login with secure credentials, and after the consultations, the prescribed medications can be procured directly by the patient from linked pharmacists (or delivered at home to the patient). this would also need to be connected to a secure payment gateway. the key technical requirement (other than the high-speed internet) for teledermatology is the quality of the images. most smartphones these days have sufficient image resolution, in terms of megapixels, but it is important that the dermatologist not make conclusions if the images are not clear enough. insist on alternate images in such cases. the ideal format for teledermatology would be a hybrid of the store and forward (saf) and real-time consults (rtc), where the images and basic patient data/history is sent to the dermatologists, who then gives an appointment for a real time consult. the board of governors (bog) of mci has issued telemedicine guidelines by amendment of mci regulations by adding regulation . titled as "consultation by telemedicine" in the said regulations and by adding telemedicine practice guidelines (tpg) as appendix to the said regulation. the directive gives an elaborate description of how to undertake telemedicine practice by the registered medical practitioners in india who is enrolled in the state register or the national register under the imc act . [ ] the council has left the doors for improvement open by stating that the tpg can be amended from time to time in larger public interest with the prior approval of central government (ministry of health and family welfare, government of india). all registered medical professionals are supposed to enrol for an online course which is being formulated for this purpose. the registered medical practitioner (rmp) has all rights to decide to go forward or defer a telemedicine consultation if he thinks it is not going to be of use for the patient. this is one of the most important points in the order. mci has made it mandatory that the following seven points need to be considered vital before any telemedicine consultation; ( ) context, ( ), identification of rmp and patient, ( ) mode of communication consent, ( ) type of consultation, ( ) patient evaluation, ( ) . patient management. the council has categorically mentioned that the medicines listed in schedule x of drug and cosmetic act and rules or any narcotic and psychotropic substance listed in the narcotic drugs and psychotropic substances, act, can not be prescribed via teleconsultations. a sample prescription is also furnished in the directive issued by the mci. we tried to analyze the subsequent guidelines of various state medical councils (karnataka, tamil nadu, punjab, gujarat, kerala, and madhya pradesh) released in the months of march and april, . all of them were in concurrence with the mci guidelines. there is a lack of clarity on certain issues that needs to be sorted out. to cite two examples, there is a mention in some state orders that telemedicine is permitted till lockdown period only and in another order it is mentioned that that telemedicine facility shouldn't cover beyond the purview of that state medical council without a mention if the doctor can cater to patients from other states within the country. [ ] [ ] [ ] [ ] [ ] [ ] iadvl also has come forward with a directive of teledermatology services that can be offered in view of the covid- pandemic. [ ] they have also adopted the guidelines furnished by the mci and stresses the importance of adhering to the norms laid in the said primary order of the mci. the british association of dermatologists (bad) and the american academy of dermatology (aad) also came out with their guidelines on managing teledermatology services during this pandemic time. [ , ] taking into account the mci order which instructs doctors to undergo training in telemedicine prior to undertaking telemedicine facility, telemedicine society of india has come out with an online training module which is offered free for a certain period. [ ] how to run the show? there can be mainly three ways of delivering the services on teledermatology. . patient operated system connecting to the healthcare provider in real time using available modes of texting, imaging, audio, and video facility on smartphone, personal computer, and such devices [figures a, b, a, b, a , b] . trained assistant (located in the remote location) operated system which also works in the same lines the image is clear and the residual wart is well made out and the clinician is able to make a decision seeing the image but the infrastructure is better and there is likely to be a more standardized approach to the procedure. this is also in real time [ figure ] . create, store, and forward system where the images, videos, and information are entered by the patient or the trained assistant in the remote locations and sent to the healthcare system via cloud storage and retrieved and processed at a later time. this is more useful for mass screening and camps, etc., the advantage being, a larger number of patients can be recruited to avail the facility and the quality is also likely to be better than real time as there are scopes for retakes. though legally valid, we are of the opinion that teledermatology in india is still in a test mode and the number of people used to this system are very less be it the patient or the doctor. obviously, hiccups are likely till a flawless system evolves in the coming times. patients who have been used to a traditional face to face consultation may feel less satisfied after an online consultation. the same goes for doctors who have been used to examining patients in person. it would also be frustrating for dermatologists as many a time they may find it difficult to come to a definitive clinical conclusion looking at an image and a brief history. this calls for a statutory disclaimer which is read and understood by the patient or the person handling the teleconsultation, which says that the accuracy may be lesser than a real time personal consultation and teleconsultation cannot be equated to the same. the clinician should make it very clear that he is giving probable differentials and suggesting best treatments with the information available at his disposal. the patient should be advised to come for a face-to-face consultation if the desired response is not seen with the advices given. the need for repeat sessions also has to be kept in mind by both parties in view of the compromised working environment. prescribing procedures or injections via teleconsultation is not recommended in any situations as of now. [ ] one of the major issues in india is the technology illiteracy of the masses and appropriate devices in spite of having access to high speed internet. this calls for adequate training, dedicated telemedicine units in peripheral hospitals or even a telemedicine van (mobile telemedicine unit) with necessary infrastructure and technical manpower that can go to various remote places from where they can coordinate the consultations with the specialist in the parent center. there are several commercially available teleconsultation portals and in the midst of covid- , there is an all the more aggressive marketing in vogue. one of the concerns raised by those who are using such options is that the patient details are retained by the third party and they may even manipulate to divert or decide reviews of the patients. this is at the cost of compromising the rights of the patients which is uncalled for. additionally, patient images and data being left with them is risky and may breach privacy. such matters need to be addressed to. it is always desirable to get a review of such teleconsultation platforms from familiar people and friends before committing to any of them. and the best one would be where data is retained at the clinician's end. people who take consults on whatsapp tend to repeatedly communicate later for even unrelated matters which is intruding into the privacy of the clinicians. a doctor doing a teleconsultation will definitely be expected to get a professional fee for the service rendered. mci had made it very clear in their directive that no additional fee should be charged for a teleconsultation. a receipt if the situation demands has to be handed over to the patient who may be able to present it for reimbursements like the routine consultations. [ ] still, the unaccustomed patient who feels he is getting less than what he is paying for may end up as unhappy after the teleconsultation. this is going to be a mismatch that needs to be addressed and correction will happen only over time once the service becomes widely used and people get used to it. the services are best retained as prepaid and not postpaid to avoid misuse. if it is a unified system in place there can be various ways this can be tackled like a part payment to initiate a consultation and prescription can be generated from the system only upon completion of payment after the consultation standard prescription pattern is the most important requirement for online consultations. this is going to be a tough ask initially as there are multiple software companies coming up with their own approaches. there are plenty of them already available in the market as well. this is the time where the government has to interfere and regularize proceedings or it may go haywire like the emr. although centralizing and streamlining may seem difficult, it is worth the effort. otherwise it may be a bit chaotic as in each hospital or clinic having their own emr software in place which don't sync well. now that it is a legal process, all the laws pertaining to regular consultation are likely to be applied for teleconsultations also. hence all routine steps like consent, identity protection, human rights, professional ethics, etc., should be taken into consideration before venturing into teledermatology services too. all said and done, patients undergoing teledermatology care should be advised to present themselves for a personal consultation when an earliest favorable situation comes up at their disposal to ensure correctness and completeness of healthcare delivery. as mentioned earlier, it would be ideal to incorporate a disclaimer at the beginning of the consult, which would serve as both consent and an understanding of the limitation of teleconsultations. teledermatology has its own limitations. in a study conducted at denmark by vestergaard et al. found that teledermatology has the potential to diagnose suspicious skin lesions faster, limit the number of direct consultations, triage patients directly for surgical procedures, and provide meaningful feedback to the general practitioners but they also observed that the diagnostic accuracy of teledermatology was significantly lower than that of a face-to-face consultations in identifying benign and malignant conditions. [ ] there is always a risk of missing malignant skin conditions and hence this calls for extra caution and suggest that the doctor doing a teledermatology service has to keep this important point in mind. [ ] [ ] [ ] [ ] tips, tricks and techniques • when telephonic dermatology consultations are done, the patient should be asked to send clear images on phone and after the discussion, they can be advised to go to the nearest pharmacy and revert once more. this helps increase correctness as the instructions can be verbally conveyed at ease to the pharmacy and even alternative medications can be suggested at ease • whatsapp business account is one app that can be exploited for teledermatology consultations. [ , ] the advantage is that it can be installed on to the regular phone of the doctor without cluttering the personal whatsapp account. the business account also has the advantage of setting automated replies to messages which can be used to convey information, instructions, and disclaimers about teledermatology consultations to anyone who connects. a tip for doctor using whatsapp is to try the web version (whatsapp web), which allows better visualization of the images, typing and easier attachment of documents, images • while prescribing via whatsapp, the doctor can send across a regular prescription as an image (with official seal and signature), but clearly writing "prescription sent on whatsapp" somewhere on the top so that this is not confused with a regular consultation if something does not work out well later • teleconsultation be it patient delivered, or assistant delivered should be scheduled for a particular day of the week or limited hours in a day only. this should not be at the cost of making oneself less available for face-to-face consults. in organizations with more manpower there can be a teledermatology opd which is managed by consultants on rotation so that there is a system in place. now that the spark has come, telemedicine and teledermatology in india is here to stay and we hope it evolves for better. the covid- pandemic might end up changing our way of life significantly. as in other aspects of life, this will lead to some unexpected positive offshoots in the practice of medicine too, like the increased use of telemedicine, artificial intelligence, and robotics. dermatologists should use the opportunity to adopt the practice of teledermatology and harness its advantages. india is probably a bit late in using the full potential of teledermatology but as the saying goes "better late, than never." this facility if used with caution, within its limitations and exploited to the fullest can definitely help to improve the reach and quality of dermatology care in india. understandably, the present policies made in the context of the pandemic are likely to have loopholes and concerns. it would be important that once the pandemic settles down, the policies are reviewed and revised, special interest groups for teledermatology, under the aegis of organizations like iadvl would need to be instituted. national professional societies like iadvl could itself take the lead in designing and implementing a teledermatology practice platform, with integration of electronic medical records and secure payment gateways. it would also be important to build consensus and bring the whole dermatology community on board. official medical/dermatology associations would need to take inputs and suggestions from practicing dermatologists and devise a detailed, long term, standard operating procedures for teledermatology practice in future. the authors certify that they have obtained all appropriate patient consent forms. in the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. coronavirus disease (covid- ) pandemic. available from nonclinical challenges of indian dermatology-cities vs. villages, poverty, and lack of awareness india has a doctor for every , people, finds who survey a health telematics policy in support of who's health-for-all strategy for global health development: report of the who group consultation on health telematics telemedicine practice guidelines enabling registered medical practitioners to provide healthcare using telemedicine newer insights in teledermatology practice the scope of teledermatology in india telemedicine: a new horizon in public health in india teledermatology and its current perspective teledermatology in india: practical implications teledermatology: its role in dermatosurgery telehealth: helping your patients and practice survive and thrive during the covid- crisis with rapid quality implementation optimizing teledermatology visits for dermatologyresident education during the covid- pandemic advisory on online consultations in view of covid- advisory on online consultations in view of covid- . available from: tnmc advisory on advisory on online consultations in view of covid- advisory on regarding online consultations in view of covid- advisory on online consultations in view of covid- advisory on online consultations in view of covid- online consultation guidelines covid- : teledermatology available from covid- : clinical guidelines for the management of dermatology patients remotely diagnostic accuracy and interobserver concordance: teledermoscopy of suspicious skin lesions in southern denmark accuracy of teledermatology for pigmented neoplasms mobile teledermoscopy-there's an app for that diagnostic agreement and interobserver concordance with teledermoscopy referrals accuracy of teledermatology for nonpigmented neoplasms whatsapp business what's up dermatology? a pilot survey of the use of whatsapp in dermatology practice and case discussion among members of whatsapp dermatology groups key: cord- - dc bqv authors: bardhan, pranab title: the chinese governance system: its strengths and weaknesses in a comparative development perspective date: - - journal: china economic review doi: . /j.chieco. . sha: doc_id: cord_uid: dc bqv abstract this is an overview paper focusing on the organizational aspects of the chinese governance system and their relation to development. compared to other developing countries like india, it has special positive features of career incentives promoting growth at the local level, the ability to take long-term decisions relatively quickly, and a unique blend of political centralization and decentralization of economic power and responsibility, that is conducive to central guidance and local business development. on the other hand, with a lack of sufficient downward (as opposed to upward) accountability and absence of institutionalized systems of scrutiny and challenge from below, mistakes or abuse of power are more difficult to check and correct quickly, political loyalty may often get a premium over performance at the upper levels, and there are insufficient checks on collusion between business and officials. the over-all organizational system is prone to over-reaction in times of crisis and thus only weakly resilient compared to systems where information flows from below are less controlled or choked. the governance system is an essential part of the so-called china development model, and yet somewhat less frequently discussed than the other aspects of this model, and when it is discussed in the general literature on comparative governance, the emphasis outside china has been more on the simplistic authoritarianism-democracy distinction. as briefly discussed in bardhan ( ) , authoritarianism is neither necessary nor sufficient for some of the distinctive features of chinese governance, both positive and negative -and their roots actually go long back in history-just as some of the recently observed dysfunctionality of governance in usa or india is not inherent in their democratic process. in this overview paper i shall focus particularly on the following three aspects of chinese governance, from the point of view of economic development, and occasionally draw comparison with governance features in india, the second largest developing country: i. internal organization of government ii. abuse of governance and corruption. iii. decentralized structures and practices. it is often pointed out that unlike in most authoritarian countries china has a political meritocracy. china's dramatic economic success has now convinced even some western scholars-see for example the book by bell ( )not to speak of the members of the chinese elite, that in terms of performance chinese political meritocracy can achieve as well as (or even better than) a multi-party democracy: an issue of special urgency at a time when there is widespread shakiness of confidence in liberal democracy. not merely are officials in china selected on the basis of an examination system that goes way back in imperial history, their career promotion depends on how well the local economy performs. this works better than in, for example, democratic india's top administrative system, where promotion is based more on seniority than on performance, even though recruitment is on the basis of civil service examinations. an immediate question that arises is: in the political system who defines what is 'meritorious' and what is not? it is possible that what may look like meritorious performance to the chinese party elite and its central organization department, zhongzubu, may not be considered so by many others in the general population, particularly in a large country with inevitable diversities and conflicts of objectives; not to speak of the outlying regions where performance by centrally appointed provincial leaders considered meritorious by the party may not be judged so by many in the ethnic groups like tibetans or uighurs. in general, how do we know what people consider as meritorious without institutions of downward accountability? one of the distinctive features of democracy is that the criteria of meritorious performance arise out of open public discussion. thus how much of a political leadership's performance is meritorious may include considerations of pluralism and inclusiveness in the decision process itself. democratic performance emphasizes the process as much as outcome. in this process citizens in a democracy are not treated as children: what is good for them is not decided by a patrimonial leadership, as is the case much too often in china (or singapore). this is valid even when the latter leadership is very wise and benevolent. also, in a democracy the performance criteria are much more multi-faceted reflecting the pluralist agenda-it is uncommon to reward an official mainly on the basis of the growth rate of the local economy-and thus the incentives get diluted and are less effective. the same thing is happening in china now when other criteria (like environmental goals) enter performance evaluation. the general understanding is that career concerns of top officials act as a key determinant of economic growth at the local level, particularly the county and prefecture levels. and job rotation of officials at that level provides useful on-the-job training at diverse localities. of course such performance incentives sometimes also generate plenty of side income or rent-earning opportunities (for example, from sales of local government land and mining rights), which while helping local revenue also used to enable private illicit income for officials. what about the large numbers of the rank and file of public employees, who mostly remain in one place and for whom career incentives through promotion are not that relevant? they used to help themselves to all kinds of supplemental compensations, perks and benefits making up for low salaries. in other authoritarian countries such systems of supplemental compensation sometimes degenerate into local loot and plunder-the proverbial extreme case is that of zaire under mobutu, where soldiers and bureaucrats were not paid but left to fend for themselves (this tradition largely continues in the democratic republic of congo even today). it is likely that in china this system for the low-level officials was constrained from being excessive by the career concerns of the top local leaders. but a less well-known factor about chinese promotion system is that as one climbs up the political ladder, to the provincial levels and beyond, performance factor seems to diminish in importance in career prospects, and the factor of political connections assumes significance-this is suggested, for example, by landry, lu, and duan ( ) from an analysis of a comprehensive dataset of political appointments at the provincial, prefectural and county levels. they find that the link between economic performance-in terms of gdp and revenue growth-and promotion is the strongest for county officials, significant for municipal officials, and insignificant for provincial officials. similarly, from a comprehensive biographical database of all provincial leaders from until and an analysis of their promotion patterns, su, he, and tao ( ) find no evidence supporting the claim that competence has played much of a role in the central personnel decisions. instead links with the politburo members or family connection with senior party leaders are more important. there are also quid pro quo transactions. using data for over a million land transactions during - chen and kung ( ) have shown o that provincial party secretaries in selling local government land gave firms linked with politburo members nearly % price discounts compared to others (an even more substantial discount to the firms of members of the top standing committee of the politburo) o in return such discount-givers were estimated to be % more likely to be promoted to positions of national leadership (in general the larger the discount the higher was the chance of promotion). the recent crackdowns have somewhat reduced the chances for such promotions. in any case such a general system of promotion has at least one important implication compared to other countries: since performance incentives operate at least at the lower levels, higher-level leaders, even when they are selected on the basis of their loyalty to the current leadership at the top, are likely to have some measure of field-tested competence and experience. this balance of performance and loyalty over an official's career path leads to a major advantage that china enjoys in the quality of its bureaucracy, compared to many other countries (including, say us or india), not to speak of many authoritarian countries where loyalty rules over minimum competence. of course, this also means that competent officials who are not sufficiently well-connected to the top current leadership in china may reach a 'glass ceiling'. some of them may then turn to alternative ways of earning rewards (including some corrupt ways). these corrupt ways have now been substantially curbed in the recent anti-corruption campaigns. there is even some evidence that highperformers connected to previous top leaderships were particularly likely to be investigated, although the campaigns have gone much beyond merely penalizing rival power groups. in india meritocratically recruited bureaucrats are manipulatively transferred. the threat of transfer to unattractive departments or locations acts to ensure loyalty to their political masters. the lure of post-retirement plum jobs for ex-bureaucrats assigned by political leaders also work to keep the former pliant. this often means that junior officers under-invest in acquiring expertise, and one hears about corrupt deals between indian politicians and bureaucrats in the process of 'transfers and postings'. there are also stories about vertical corrupt transactions in buying and selling of positions in the chinese bureaucracy, some of which have been revealed in the recent anti-corruption campaigns-from the data one finds vertical correlation between corruption indictments at higher and lower levels across provinces. in india such corruption may be somewhat more subject to public scrutiny by media, social movements, and investigative agencies, which are usually more open and intense than in china. in uk such manipulative transfers are less common. the system in usa, on the other hand, is characterized by high turnover of senior civil servants (long before firing by twitter under the current president). the political-bureaucratic distinction particularly at higher levels is, of course, blurred in china, as the party is supreme. but even in western democracies the political control over senior appointments and promotions in public service has increased over time. even in the uk, the insulation of career civil service has declined somewhat, and this insulation has always been much weaker in usa than in uk (or denmark or new zealand). the issue of political control pertains not just to the civil service, but also to the various regulatory bodies that any complex economy requires-like the entities that regulate public utilities (e.g. electricity, civil aviation, telecommunication, etc.) and apex bodies regulating monetary or environmental policy or financial markets. decisions in such regulatory bodies need special expertise and some insulation from the day-to-day political pressures and some independence from political interference. such independence is often completely lacking in the chinese system-commitment to independence even when earnestly announced by the political leadership is not ultimately credible. but even in democracies the balance between autonomous experts and the need for periodic public review of their decisions to ensure accountability has been difficult to achieve. in india there are very few genuinely independent regulatory bodies (even apart from the problem of their capture by generalist indian administrative service officers). even the semi-independence of the reserve bank of india has been under some stress. in both china and india the police and bureaucracy are often deliberately incapacitated and made to serve short-term political goals of leaders. in terms of the governance capacity to foster technological innovations, china has advanced much more than most developing countries, particularly in terms of r&d as percentage of gdp (though public r&d support often neglects small and medium enterprises), restructuring and upgrading of elite universities, and measures of progress in science and technology. china, of course, has been very successful in the 'catching-up' process of development, of learning and imitating off-the-shelf technology. in some day-to-day application and enhancement of existing technology (mobile payment, e-commerce, transport, etc.) china is now more advanced than the us. the major technological race between china and the west is currently in areas like artificial intelligence, chip-making, and bio-technology. but in any future advances beyond the existing technological frontier china has a major advantage and a major disadvantage. the advantage follows from the large size of the population and of the domestic market. innovations (like those involving artificial intelligence and machine learning) that thrive on economies of scale, network externalities and big data feedback loops will find hospitable ground in china. the disadvantage for china follows from the lack of an open system that could encourage free spirit, critical thinking, challenging of incumbent organizations and methods, and diversity rather than conformity-these are necessary ingredients of many types of creative innovations. the current system of state promotion and guidance of globally successful large private technological on the basis of city-level panel data jiang ( ) even shows that city leaders with informal ties to incumbent provincial leaders display better performance in terms of growth. also, political loyalty plays an important role in bureaucratic promotion in democracies as well. but in the latter in view of possible electoral consequences, politicians at all levels are a bit more sensitive to the well-being of diverse interest groups. enterprises (alibaba, tencent, etc.) is worth examining from this point of view. on the one hand, the state wants them to be 'national champions', on the other hand, it does not want them to be autonomously powerful enough to be outside the ambit of its control, supervision, and surveillance. will the chinese state allow the full forces of 'creative destruction' that schumpeterians associate with innovations? (in the total no. of annual insolvency cases was smaller in china than even romania, not to speak of the advanced industrial countries). will an autonomously successful firm be considered too 'independent' for the comfort of the party? are today's successful incumbent firms (private or public) 'too big to fail', or in the case of clusters, 'too many to fail'? will the party consider a major commercial failure or a prolonged stock market slump as a sign of lack of confidence in the all-powerful party? what will be the role of venture-capital funds? (there are inherent problems of state-run or -controlled venture-capital funds). it also depends on the nature of future innovations. some innovations are of the 'disruptive' kind that challenge incumbent firms (which the us private innovators in collaboration with venture capitalists are good at and a politically-connected large entrenched organization usually is not). other innovations are of the steady 'incremental' kind that adds up to significant gains (the japanese call it kaizen), in which some large organizations in germany, japan and south korea have excelled. it is likely that the chinese system is more conducive to this incremental kind of innovations. • upward vs. downward accountability even though at the top level between the provincial and the central leadership in china there is some degree of reciprocal accountability, as provincial officials constitute about half of the central committee of the party that elects politburo members, it is probably correct to say that the chinese system is by and large one of upward accountability. downward accountability provides more political legitimacy to democratic governments, but such accountability can sometimes degenerate into pandering to short-run interests and pressure groups, particularly at election time. short-run cyclical official behavior before the party congress is not unknown in china, but in general it is much easier for leaders to take long-run decisions under the chinese governance system. but a severe flaw of the upwardly accountable chinese system is that mistakes in such top-level decisions or outright abuses of power (in collaboration with crony business interests) take longer to detect and to correct (as the flow of information upward is tortuous or choked and the tendency to cover up is often too strong). the recent abolition of term limits for the president and the decline of the collective leadership that deng xiaoping had put in place will make this problem more acute. in multi-party democracies the open adversarial relation between the government and opposition parties and the free media usually uncovers the mistakes and abuses much sooner, and corrections are prompted by public protests, agitations, and ultimately electoral sanctions. this also means that the information problem that even well-meaning bureaucrats in the chinese system face is less severe in multi-party democracies-in china, unlike in many authoritarian countries, the information problem is partly relieved through decentralization (more on this in section iii). one concern about the chinese governance system is about the mechanism through which a system that can go off-equilibrium on account of various kinds of political or economic shocks is restored to equilibrium. in the face of a crisis the chinese state often tends to over-react, suppress information and act heavy-handedly, thereby sometimes magnifying the dimensions of the crisis. this also generates low tolerance for short-run economic volatility and the rush to reckless fiscal policies that exacerbate the staggering problems of capital misallocation that china faces. the institutional mechanisms for structural reform have now become particularly weaker, as the resolution of internal governance conflicts is now more dependent on personalized channels. there also remains the larger institutional issue that china has faced throughout history: how to institutionally guarantee the rule of a 'good emperor', as opposed to a 'bad emperor', or that of a good emperor not turning bad. the recent disruption in the conventions of collective leadership and the acceleration of the cult of personality in leadership can only worsen this problem. as the economy becomes more complex and social relations become more convoluted and intense, the absence of transparent and accountable processes and the attempts by a 'control-freak' leadership to force lockstep conformity and discipline will generate acute tension, conflicts, and informational inefficiency. in india, despite all the recent ominous signs of a democracy sliding into a form of a majoritarian overreach, it is probably still correct to say that the system structurally remains somewhat more resilient than in china. over the last quarter century, there has been a tight, often collusive, relationship between business and politicians in china. this is evident from (a) frequent interchanging of positions between executives in public sector companies and the party's central committee; (b) some of china's richest private businessmen are members of the national people's congress (china's parliament) and the people's political consultative conference, an important advisory body; (c) the average net worth of the richest members of the national people's congress in china is several times that for the richest members of the us congress or the indian lok sabha (lower house of parliament)-there are even accounts of large "donations" made before such businessmen are selected for these bodies in china. all this is apart from the influence of the top political families ("princelings") who have long been in lucrative business. the ownership of many private companies is so murky and intertwined with the public-sector companies that it is often difficult to keep track of the boundaries of the business-politics nexus. there have also been cases of successful private companies "persuaded" to invest billions of dollars' worth in backing state-owned companies. the business-politician nexus is, of course, quite common in india. of the current ruling party members of parliament in india about half are businessmen, the corresponding percentage for mp's of all parties taken together is about a quarter. (there is also evidence that people from other occupations, once elected, often turn to business, particularly of the kind that thrive on political connections and networks). the businessmen bring their own money for election campaigns and other political expenditure, and company donations to party funds for election are large, and now, under the anonymous election bond system, openly non-transparent. both countries have similar patterns of rampant influence-peddling, policy manipulation, politically connected firms getting favors in loans from public banks and access to prize real estate, monopoly mining rights, etc. china being more involved in construction and infrastructure activities, which are usually "rent-thick", there is more scope for corruption, as seems to be suggested by both anecdotal and empirical evidence. fisman and wang ( ) detected corruption in state asset sales by comparing the prices of publicly traded assets to those of non-publicly traded assets. even to take an example from a different area, like public health: drug prices are usually much higher in china than in india, even though the single-payer system in chinese health care should have given the government more bargaining advantage vis-a-vis the drug companies. people attribute this to the more entrenched kickback system between drug companies and doctors, hospitals, and officials in china. it is likely that the business-politician collusion in governance is somewhat more subject to public scrutiny in india than china, and the courts are more independent in india (though clogged and corrupt, particularly at the lower levels). the scrutiny of collusive behavior by indian media is now under some shadow with the concentration of its business ownership. also, it should be mentioned that the relation with the all-powerful party is somewhat precarious for the chinese business tycoons, as political disloyalty or even suspected 'independence' is punished more harshly than in india. indian politicians may be a bit more dependent on businessmen particularly in view of election funding. chinese political centralization (in the imperial authority in the past and in that of the party in recent decades) has been historically tempered by a unique blending of political centralization with economic and administrative decentralization-another distinctive feature of the chinese governance system. xu ( ) has described the system as 'regionally decentralized authoritarianism', in contrast with most authoritarian systems that are highly centralized. india in some sense is the obverse-combining political decentralization (regional power groupings have been quite strong in recent decades) with economic centralization (the vertical fiscal imbalance, for example, is quite severe). china has much better modes of management of infrastructure financing and construction at the local level. for example, urban infrastructure there is constructed, operated, and maintained by separate companies set up by the city government, whereas in india the municipal government itself does it through its own departments. the latter are financially strapped, as they do not have much taxation power and are perpetually dependent on the state government for funds. in general, even after the centralizing reforms since , the fiscal system is much more decentralized in china, where sub-provincial levels of government tend to spend more than half of total government budgetary expenditure, compared to about % in india (this is not including the large off-budget revenue-raising and expenditure of local governments in china). the much worse performance of sub-provincial local bodies in india in the last-mile delivery of public services and facilities is partly attributable to this (even though chinese local governments have also much larger responsibility for infrastructure-building and public services). in india the emphasis has been more on fiscal transfers to local governments than on local tax autonomy. in both china and india decentralization tends to accentuate regional inequality, though in india the constitutional body of the finance commission tends to partially compensate for this by allocating redistributive transfers to poorer regions. in comparison with other developing countries the chinese local government is much more involved in local business development, not just in public services delivery. a few years back when the private automaker, zhejiang geely holding group, bought up the swedish car company volvo in a widely publicized move, much of the money was actually provided by the local municipal government-something unthinkable, for example, in india. jurisdictional competition for mobile resources and business and regional competition in growth rates influencing career promotion of officials have usually played a much more important role in chinese local development. but in recent years the pace of experimentation and trial-and-error pilot projects in local areas, which characterized the early reform period, has slowed down. the current regime's more centralized and personal loyalty-based leadership has made experimentation even more difficult. this is on top of the policy paralysis of a bureaucracy made nervous by the massive anticorruption campaigns. a growing literature in decentralization all over the world has pointed to the problem of capture of local governments by the elite (including officials and intermediaries) and the frequent diversion of benefits and resources to non-target groups. in india there is plenty of evidence of landed interests undermining decentralized welfare programs for the poor, apart from state political administration and legislators hampering devolution of power to the village or municipal authorities. china's more egalitarian land use rights distribution after de-collectivization may have prevented the rise of a landed oligarchy that has often captured local governments in parts of rural india. however, in recent decades chinese decentralization has not been able to avoid the problem of serious local elite capture. chinese local business in collusion with local officials has been at the root of problems of arbitrary land acquisition, toxic pollution, and violation of safety standards in food and in work for factories and mines. such collusion is much more rampant in china than, say, in india, primarily because china has fewer checks from below on abuse of power. on safety standards, for example, chinese coalmine death rates are reported to be times higher than that in india. on the basis of provincial-level panel data on key state coal mines in china from to , jia and nie ( ) provide evidence that decentralization makes collusion between official regulators and firms more likely (in the chinese media such collusion is called guanmei goujie) and is correlated with increases in coal-mine fatality rates. this is also consistent with the general finding of fisman and wang ( ) that politically connected firms in china have higher rates of workplace fatalities, based on firm-level data collected from different industries between and . (while jia and nie focus on the characteristics of regulators, fisman and wang focus on those of firms.) there is also suggestive evidence in the jia and nie paper that media exposure can act as a deterrent against collusion. martinez-bravo, qian, and yao ( ) provide evidence, on the basis of village panel data, that local officials are better controlled by local elections than by central monitoring. there are also fewer checks on debt-fueled over-investment and excess capacity in local government-controlled or politically connected firms (currently a source of major macro-economic problems in china). china's central leadership is now trying to rein in the debt problem of local governments and their dependence on the shadow banking system. thus in this paper we have looked at some positive and negative features of the organizational system of chinese governance and put them in some comparative perspective. such overviews need to be complemented by more in-depth studies at the micro-level of governance, in comparison with micro institutions in other developing countries. decentralization of governance and development awakening giants, feet of clay: assessing the economic rise of china and india busting the "princelings": the campaign against corruption in china's primary land market decentralization, incentives, and tax enforcement decentralization, collusion, and coalmine making bureaucracy work: patronage networks, performance incentives, and economic development in china does performance matter? evaluating political selection along the chinese administrative ladder sponsored human capital: bureaucratic transfer and economic performance. national school of development, peking university meritocracy and patronage in state building: evidence from provincial leaders in china key: cord- -iw sorz authors: gunjawate, dhanshree r.; ravi, rohit; yerraguntla, krishna; rajashekhar, bellur; verma, ashwani title: impact of coronavirus disease on professional practices of audiologists and speech-language pathologists in india: a knowledge, attitude and practices survey date: - - journal: clin epidemiol glob health doi: . /j.cegh. . . sha: doc_id: cord_uid: iw sorz background: coronavirus disease (covid- ) has spread throughout the world and become a global pandemic. this has hampered and led to drastic changes in the functioning of healthcare services, forcing the professionals to adapt and work efficiently. the present study aimed to explore the impact of covid- on the professional practices of audiologists and speech-language pathologists in india using a cross-sectional knowledge, attitude and practices survey. material and methods: the study was conducted in two phases; phase one involved development and validation of the questionnaire, while phase ii involved data collection. a cross-sectional self-reported internet-based study using convenience sampling was carried out. results: two hundred and eleven audiologists and speech-language pathologists responded to the survey. overall, the professionals exhibited good knowledge levels regarding the covid- outbreak. however, there were differences in their attitudes towards service delivery in the midst of the pandemic. further, poor practices towards infection control measures especially in terms of hand washing was noted. conclusion: the findings of the present study are useful in highlighting the need to create better awareness among these professionals about appropriate and standard infection control measures. there is a need to have in place standard operating protocols for hand wash and infection control as well as inclusion in curriculum. a local outbreak of pneumonia of an initially unknown origin was detected in wuhan (hubei, china) . this was determined to be caused by a novel virus, and subsequently named as severe acute respiratory syndrome coronavirus (sars-cov- ) or corona virus disease (covid- ) . in the initial few days, maximum cases were reported from different provinces of mainland china. on th january , the first case of covid- was reported outside china in thailand and by rd january , cases were reported from republic of korea, thailand, japan and singapore. as the cases started increasing, the world health organization (who) declared the outbreak of covid- , a public health emergency of international concern on th january . by th march , the number touched , , . on th march , who made a declaration that the covid- outbreak can be categorized as a pandemic. a pandemic is an epidemic disease that is spread across the world. as of th march , the outbreak was reported from as many as countries with more than , , confirmed cases . in india, the first case of positive covid- was reported on st january , with a recent travel history from china. subsequently, by rd february , a total of positive cases were reported who were treated and discharged. the situation report update dated th february indicated no fresh cases. however, by th march, cases were reported and the number escalated to by nd march . the government issued several orders such as enforcement of social distancing, urging people to stay at home barring essential services, travel restrictions, and importance towards hand hygiene . the sudden increase in the positive covid- cases with changing orders and increasing restrictions led to panic and apprehension among the citizens. however, professionals involved in patient care and rehabilitation services continued to work and provide services. one such professional involved in providing rehabilitation services are audiologists and speech language pathologists. as members of health care, these professionals are expected to extend their services to patients and caregivers/bystanders exhibiting symptoms of covid- . their patient load involves pediatric and geriatric population as well as individuals with speech and hearing disability. most audiological procedures require a direct patient contact while giving instructions, testing (such as placing headphones, probe tips, otoscope specula, electrodes, microphones, impression syringes, earmolds and hearing aids) as well as during counselling. the testing is conducted in a sound treated room or an enclosed chamber with no ventilation. speech therapy requires an emphasis on mouth/lip expressions (such as in articulation therapy) which j o u r n a l p r e -p r o o f would be ineffective wearing a mask. certain procedures such as fiberoptic endoscopic evaluation of swallowing (ffes) and laryngoscopy involve the nose and nasopharynx. procedures such as fees involve using a spray that could aerosolize pathogens on the mucosa. in general, the risk of using instruments and the contact with patients and caregivers/bystanders cannot be overlooked. further, the absence of formal training in infection control measures as a part of these professionals' curriculum could increase the chances of them missing important steps in infection control and leading to contracting the virus. the who , centre for disease control and prevention and government authorities have provided support, guidelines and advisories on the covid- pandemic. the professional bodies for audiologists and speech language pathologists have also made available relevant educational materials and guidelines for professional practices [ ] [ ] [ ] . however, lot of myths and misinformation have been observed. thus, it becomes relevant to know the impact of this outbreak and its associated symptoms on patient care and service delivery among audiologists and speech language pathologists. the present study was conducted with an aim to study the impact of covid- on the professional practices of audiologists and speech language pathologists in india using a cross-sectional knowledge, attitude and practices (kap) survey. the study was in accordance with the helsinki declaration . the institutional ethics committee permitted online surveys on covid- during the lockdown period when this study was conducted. all participants were explained about the purpose of the study. the participation was voluntary. the present study was conducted in two phases; phase i involved the development and validation of the questionnaire, while phase ii, data collection. a score of . was obtained on the content validity index for scale (s-cvi) for the final questionnaire, indicative of excellent content validity (polit & beck, ) . all the questions proposed in the initial version were rated to be of relevance and hence retained in the final questionnaire. the questionnaire comprising of items; demographic details, knowledge and attitudes towards covid- , and practices related to infection control. these questions included a blend of true/false, yes/no, multiple-choice questions, checkboxes and short answer types. a cross-sectional self-reported internet-based study design using convenience sampling was implemented for the present study. the finalized questionnaire was made available using google form, with an email link for the same. five hundred audiologists and speech language pathologists were randomly chosen from the indian speech and hearing association members list. the questionnaire link was shared with these professionals through their personal email ids and messaging service such as whatsapp. no personal information was collected to maintain anonymity. all responses were saved on automatically with access only to the primary author. the data collection was carried out from th to st march . the questionnaire was administered during the second stage of the covid- spread and before the complete shutdown of nonessential/non-emergency services. the google form started with a brief description of the present study followed by a formal consent statement. only those participants who consented to participate could proceed further. the questionnaire was administered in english and took approximately minutes for completion. the data analysis was done using descriptive statistics comprising of mean and sd for continues variables and frequency and percentage for discrete variables. all analysis was done using spss . j o u r n a l p r e -p r o o f india responded to the survey. all the questions were compulsory in order to submit the google form; hence there were no incomplete responses. table depicts the demographic details of the professionals who participated in the study. table demographic details of the participants after the questions on demographic information, the questionnaire comprised of seven questions related to knowledge of symptoms of covid- and its preventive measures. out of the seven, four questions were true-false-not sure statements while the remaining were multiplechoice options. . % of respondents correctly identified the core symptoms of covid- such as fever, tiredness and dry cough, while . %, could not. the correct response for the statement; 'covid- patients also develop aches, pain, nasal congestion, runny nose, sore throat or diarrhoea', should have been true. . % responded as true; remaining . % responded false while . % were not sure. next, 'covid- infection can spread through small droplets from nose or mouth of infected person' was a true statement. a majority ( . %) responded correctly, while . % were incorrect. the fourth statement 'wearing multiple masks, smoking and consuming alcohol are effective against covid- ' was a false statement for which % responded correctly. surprisingly, . % were unsure, and . % reported that these measures are effective. the remaining three questions under the knowledge domain were related to ideal distance to be maintained, incubation period, and recommended composition of the hand sanitizers. the ideal distance to be maintained from a person with covid- infection is feet. this was correct for only % of the respondents ( , . %). the remaining responded incorrectly,viz. - % alcohol was the expected answer. however, less than % ( . %) replied correctly that the composition should include - % alcohol. the remaining responses were distributed across other options; - % alcohol ( . %), - % alcohol ( . %) and % alcohol ( . %). the next five questions were aimed at exploring the attitudes towards covid- infection. the response categories included strongly disagree, disagree, neutral, agree and strongly agree. table displays the frequency and percentages of responses for these statements. table attitudes towards covid- the next four questions were based on the current changes in practices followed by the clinicians in terms of patient care. the respondents were asked to report the measures they would incorporate if they were to develop any symptoms related to covid- . more than % ( . %) expressed that they would get screened or tested. the remaining responses included waiting for some time for symptoms to resolve ( . %) and taking home remedies ( . %). the same positive practices were also applicable for any of their patients exhibiting symptoms related to covid- . % responded that they would recommend medical advice immediately while . % would recommend their patient to discontinue therapy and return when symptoms j o u r n a l p r e -p r o o f resolved. only . % responded that they would discharge their patient to ensure their own safety while . % to suggest remedies on their own. based on the responses, most of the participants would practice preventive measures related to travel as noted in table . table preventive measures related to travel maximum number of participants were using hand wash procedures ( . %) while . % were not following it. among the ones who used hand-washing procedures, only . % used standard protocols for hand wash. the participants were asked to elaborate upon the infection control procedures being followed while working with patients, depicted in figure . when asked whether the professionals would like to shift to tele-mode for imparting audiological and speech therapy services, . % responded in affirmative, . % were not sure while remaining . % responded in negation. the different sources of information preferred by the participants have been depicted in covid- has become a matter of serious concern across the globe where the entire healthcare sector is fighting hard against this pandemic. audiologists and speech language pathologists as health care workers are involved in providing services, involving direct contact with patients. this outbreak of covid- has raised concerns as these patients and/or their j o u r n a l p r e -p r o o f caregivers might be exhibiting symptoms of the disease or may be carriers themselves. these challenges are further compounded by the absence of formal training in infection control measures as a part of the professionals' curriculum. as a result, most of the knowledge, attitudes and practices are based on their experience or word of mouth information. in the present outbreak, both audiological and speech therapy services were available until the closure of nonessential/emergency medical services. it is hence considered crucial to assess the knowledge levels regarding covid- , changing attitudes and impact on their practices among these professionals. to the authors' knowledge, this is the first published survey on the knowledge, attitudes, practices towards covid- and sources of information among these professionals. the professionals who participated in the present study were well distributed across the age range of to years with to years of experience. the gender distribution was skewed towards females, with almost % being females. however, this is not surprising as this gender variation in this profession is well established . bachelors is the minimum qualification required for practicing in india as an audiologist and speech language pathologist. majority of the participants hold a master's degree followed by bachelors and a few were with doctoral degrees. the distribution across the work setting was balanced between clinical, hospital-based as well as academic and clinical settings. more than % professionals correctly identified the core symptoms associated with covid- as well as it being transmitted through droplets from nose or mouth. however, the other symptoms such as aches, pain, nasal congestion, running nose, sore throat or diarrhea were less commonly known. this difference could be the result of the emphasis being given towards the core symptoms and mode of transmission across all the awareness drives. as per the guidelines, a distance of feet has been recommended from a person who is coughing or sneezing . however, only % professionals were able to correctly answer this question. the recommended composition of a hand rub or a hand sanitizer is - % alcohol ; however, this was correctly answered by less than % professionals. at the time of this survey, the government advisory included only screening of individuals with an international travel history . however, despite a government advisory and good knowledge levels, these professionals exhibited changes in attitudes towards service delivery for patients. further, almost - % of the professionals were reluctant to provide services even to those individuals who were asymptomatic and not confirmed cases. when asked j o u r n a l p r e -p r o o f 'i feel covid- will be successfully controlled', half of the participants replied in affirmation, % in negation while % choose to be neutral. these varied responses could be attributed to the partial lockdown of services at the time of the survey. further, the stress associated with the outbreak and the feeling of being at risk of contracting it might have impacted their attitude towards their service delivery . the professionals were asked to choose the type of preventive measures they would use while imparting clinical services. more than % used sanitizers, hand wash, masks and however, in the present survey, although a large majority of respondents ( . %) followed hand wash procedures, only some ( . %) used standard procedures. this attracts attention towards the absence of awareness towards the standard hand washing procedures which has also been observed in other healthcare providers . standard infection control precautions emphasize on hand hygiene, isolation, sterilization of reusable instruments, needle safety, wearing personal protective equipment, disposal and waste management . based on the responses, it can be noted that most of the respondents followed the precautions at personal level as well as at place of work. social distancing is the most recommended precautionary measure for preventing covid- ; however, this was followed by only % of the professionals. surprisingly, % respondents were not following any infection control measures. maximum respondents preferred reliable sources of information on covid- such as world health organization website. nevertheless, a considerable number also reported the use of internet and social media. the validity of information from internet and social media is questionable. the present survey was conducted using a self-rated questionnaire and hence assessing the real practices was beyond the scope of this study. presently, india is slowly lifting the lockdown and restrictions, the audiologists and speech language pathologists are resuming their j o u r n a l p r e -p r o o f j o u r n a l p r e -p r o o f an interactive web-based dashboard to track covid- in real time world health organization. coronavirus disease (covid- ) advice for the public world health organization. coronavirus disease (covid- ) india situation report ministry of health and family welfare government of india. advisory on social distancing measure in view of spread of covid- disease world health organization. coronavirus disease (covid- ) outbreak: rights,roles and responsibilities of health workers, including key considerations for occupational safety and health centers for disease control and prevention. coronavirus (covid- ): information for healthcare professionals ministry of health and family welfare government of india. detail question and answers on covid- for public academy of doctors of audiology. covid- resources infection control resources for audiologists and speech-language pathologists world medical association declaration of helsinki: ethical principles for medical research involving human subjects why the scarcity of male slps-and what can be done world health organization. who guidelines on hand hygiene in health care world health organization. novel coronavirus disease (covid- ) india situation handwashing liaison group. hand washing j o u r n a l p r e -p r o o f services. the findings of the study are important as they help to highlight the areas that need more awareness among these professionals about appropriate and standard infection control measures. there is a need to have in place standard operating protocols and curriculum that includes importance of hand wash and infection control in indian context. the findings might differ if obtained professionals from different countries, due to the differences in guidelines and outcomes of the pandemic. similar studies among the same professionals from other countries could help in understanding the global perspective towards this outbreak and serve as a ready reckoner for future course of action. there is no conflict of interest to disclose acknowledgement: the authors thanks all the fellow professionals for participating in this study. we thank the indian speech and hearing association for their support. key: cord- -gkzfqmfv authors: chang, lennon y. c.; mukherjee, souvik; coppel, nicholas title: we are all victims: questionable content and collective victimisation in the digital age date: - - journal: asian j criminol doi: . /s - - - sha: doc_id: cord_uid: gkzfqmfv traditionally, the idea of being a victim is associated with a crime, accident, trickery or being duped. with the advent of globalisation and rapid growth in the information technology sector, the world has opened itself to numerous vulnerabilities. these vulnerabilities range from individual-centric privacy issues to collective interests in the form of a nation’s political and economic interests. while we have victims who can identify themselves as victims, there are also victims who can barely identify themselves as victims, and there are those who do not realise that they have become victims. misinformation, disinformation, fake news and other methods of spreading questionable content can be regarded as a new and increasingly widespread type of collective victimisation. this paper, drawing on recent examples from india, examines and analyses the rationale and modus operandi—both methods and types—that lead us to regard questionable content as a new form of collective victimisation. web . is a participatory platform whereby information and the dissemination of information are no longer in the hands of a few. this indiscriminate liberty regarding dissemination of information has led to the circulation of a plethora of content which is authentic, but has also opened the door to 'questionable content' such as fake news, misinformation and disinformation. over the past few years, there has been a significant rise in the circulation of misinformation, disinformation, fake news and other problematic content through the meteoric rise in social media platforms. web . not only saw the rise of social media, but also of blogs, online news portals and media sharing applications, and it coincided with the widespread availability of cheap sim cards and low-cost smartphones. this led to a paradigm shift in an individual's role in information dissemination. individuals, who traditionally primarily played a passive role as consumers of information and not as active producers or circulators of content, can now also play an active role creating and circulating information. with the paradigm shift, the risk of abuse increased many fold. the indiscriminate access and power brought a significant rise in misinformation, disinformation, propaganda and other problematic content. the compact oxford english dictionary defines misinformation as false or inaccurate information given by someone. disinformation is defined as "information intended to mislead". propaganda is defined as "information that is often biased or misleading, used to promote a political cause or point of view", while satire is defined as "use of humour, irony, or exaggeration as a form of mockery or criticism". in this article, all the above-mentioned kinds of information are clubbed together under the umbrella term 'questionable information' or 'questionable content'. the abuse of technology to create and disseminate questionable information is producing a new form of "collective violence" and "collective victimisation." the world health organisation has defined collective violence as "the instrumental use of violence by people who identify themselves as members of a group-whether this group is transitory or has a more permanent identity-against another group or set of individuals, in order to achieve political, economic or social objectives" (zwi et al. , p. ) and the group suffering from the collective violence are collective victims (vollhardt ) . current research on collective violence/victimisation is concerned with the experience, denial/recognition of victimisation, victim identity, collective memories and includes violence caused by war, terrorism, state-perpetrated violence and organised violent crime (e.g. bagci et al. ; littman and paluck ; vollhardt ) . while research has shown that people see fake news as a bigger threat than violent crime, illegal immigration and even terrorism (mitchell et al. ) , there is still no research that discusses how the abuse of technology in the form of questionable information is causing a new form of collective victimisation. although questionable information might seem relatively harmless at the individual level, it can play a significant role in shaping the thought process of a large segment of society and influence decision making. when it comes to political content or sensitive issues, it could cause serious harm to society and then everyone becomes a victim. this article will focus on the significance of information in a democratic system and the scope and nature of questionable content. this paper proposes that to address successfully questionable information and collective victimisation, we need to consider its rationale and modus operandi (both the methods and types). this paper will also describe approaches undertaken by countries to meet the challenge of questionable information and their efficacy from the perspective of collective victimisation. not only ensures that the people are aware of their democratic rights but also are correctly informed about the obligations and duties which democracy entails (kuklinski et al. ) . only when individuals have the tool of information, can they judiciously and appropriately exercise their democratic rights including but not limited to voting rights. in the nineteenth century and into the twentieth century, citizens consumed political news primarily through newspapers. politicians and other political actors relied on newspapers to be their medium to propagate their ideologies or defend their actions. with the development of electronic media in the form of radio and television, political news found a faster and more attractive medium to reach most members of society (lazer et al. ) . while society was grappling with the challenges televised journalism was posing, the internet age dawned upon us and this was further enhanced by the introduction of the web . platform upon which social media thrived. online news consumption is reaching new heights due to the analytics and algorithms of social media to the extent that this form of media is well on track to eventually replace television in general (nguyen and western ) . social media is playing a significant role in the personal, social, economic and political transformation of individuals and can influence the mental health and decision-making capacity of people. in the recent past, several existing forms of crime have been facilitated through social media, and new forms of crime have been created which are dependent upon technology such as tampering with computer source documents, identity theft, phishing, online lottery scams, illegal access, data interference and child pornography. many of these crimes are a technological extension of existing crimes such as stealing computer resources, cheating by impersonation, terrorism and sexual crimes (broadhurst and chang ; chang ) . the theory of victimisation which was developed to address the concerns and issues of victims of crimes has remained static in terms of its scope as it limited itself to individuals and dominantly victims of conventional crimes. questionable content appearing on web-based platforms differs from content in traditional media in two primary ways: (a) traceability of the source of information and (b) the limit and extension of circulation. for instance, a news piece which is incorrect and falsified, when circulated through traditional media such as a newspaper or telecast, is easily traced and suitable action can be taken directly against the perpetrators. but in the case of similar misinformation on social media, who is the original source of the story often remains unknown. this added protection shields perpetrators and creates a more favourable environment for those wishing to circulate questionable content. secondly, the reach of content distributed on social media is less certain than the reach of content distributed through traditional media where tv ratings and print circulation are approximately known. content on social media has the potential to "go viral" and reach many more people than traditional media. thus, even though the consumption of questionable content on social media is predominantly individualistic, the ultimate impact is on society as a whole and can cause collective victimisation. questionable content in this context can be crystallised as content that is politically or ideologically motivated online disinformation, fake news, hate speech, online misinformation and foreign encroachment in the domestic affairs of the state, misreporting and misconstrued satire (shin et al. ; tenove et al. ) . such content has the potential to impact individuals and the population collectively by changing the attitude of consumers, creating scepticism towards the electoral process, blocking educated political decision-making, causing political unrest, communal riots, and violence, sabotaging free and fair electoral processes, altering the political landscape, marginalising certain classes or communities and damaging the economy (brown ) . the threats to the collective are not theoretical, as the world has already witnessed events such as the pizzagate incident (persily ) , russian interference with the u.s. presidential election (marvel ) and a wave of disinformation originating in china fed onto taiwanese internet domains, seeking to interfere in local and national elections (wong and wen ) . india, although a country with relatively limited internet penetration, has a significant number of people using social media and the spread of misinformation is extensive. the dissemination of questionable content has caused communal violence, lynching and innumerable incidents of violence against particular groups of people in india, as well as influencing the election (arun ; roozenbeek and van der linden ). fake news, online misinformation and disinformation regarding covid- (see below) occurred to such an extent that it moved the issue from being just a health pandemic to also being about communal tensions and religious conflict (ellis-petersen and rahman ). some of the questionable content was, on the face of it, absurd and yet many people believed it (sengupta ) . the nature of the platform makes it extremely difficult to curb. these forms of victimisation viewed through the prism of standard principles, embodied in constitutional law, human rights law, criminal law, the basic tenets of democracy, the un charter and international law, constitute a violation of india's domestic law as well as international law. in the space of a few months in early in india, there were a number of cases of questionable content regarding covid- , targeting different political parties and religions and which had an impact over the collective even though they were accessed individually : (a) an audio clip claimed that a vendor with a certain religious background was spreading covid- . the perpetrator produced a min and s audio clip, within which he suggested that a vendor was selling vegetables at a low price with the ulterior objective of spreading covid- . the audio clip was examined by the fact-checking organisation 'boom' and was found to be fake (alphonso ). it is apparent the perpetrator intended to use the audio clip to create communal hatred in the time of the pandemic. individuals received the message in their personal space, but the insecurity it created within the victims potentially could have given birth to a collective distrust in vendors based on their religious background and even violence if not tackled in time. many would not be aware of the follow-up fact-checking and would continue to live with the misinformation and the prejudice it fuelled. (b) during the time of covid- , a photo of switzerland's matterhorn mountain lit with the indian flag was tweeted, claiming that it was lit in the name of hope after the leader of the government supplied hydroxychloroquine tablets (hcq-a drug for the treatment of rheumatoid arthritis and believed by some scientists to lessen the symptoms of covid- ). the tweet went viral and was shared widely via twitter and facebook. a factchecking organisation in india, altnews.in, found that, although the image of the indian national flag had been projected on the matterhorn, the claim shared along with the image that this happened after india supplied hcq tablets to the country was false. the projection on that day was to express solidarity with indians in the fight against covid- and was one of a series of flag projections intended to be a sign of hope as the world battled the novel corona virus (kinjal a, b) . while the tweet in itself seems harmless, it had the intended effect of encouraging indians to feel an 'exclusive' and positive emotion about the nation and the performance of the political party in government. (c) over twitter, a picture demonstrating social distance practice during covid- at mizoram, a state in northeastern india, received many likes. however, boom (india) & boom myanmar ran verification of the picture, and it was found that the picture was not of mizoram but of kalaw, a hill town in myanmar's shan state (nabodita ) . while some would argue that by encouraging social distancing, its accuracy was unimportant as it had a positive influence over people. however, it was fake news and it might have had the perverse effect of causing additional covid- cases due to a false sense of security based on a belief that safe practices were protecting the community. (d) the impact of questionable content is strongly felt when popular individuals, political personalities or individuals circulate and share the information. for example, a video from bijnor, a district in the indian state of uttar pradesh, depicted an elderly fruit seller belonging to a minority faith, accused of sprinkling urine over bananas to be sold. eminent political figures and media personnel fuelled the circulation by circulating the video. it did not take much longer for the video to get viral. it was later found, and verified by bijnor police, that the elderly fruit seller had only washed his hands with water from the bottle and did not sprinkle urine as claimed in the video (jha ). the above incidents are illustrative of the power of questionable content and the damage it can cause to individuals and societal harmony. this damage can be brought on very quickly by the participation of entertainment or sport celebrities and political leaders as potential 'super spreaders'. the rationale for targeting such individuals is simple, as their re-posting is understood by their supporters as an endorsement and this will give a significant boost to the circulated content, even if it is questionable content. gossip and rumours have undoubtedly existed since the invention of languages; however, the invention of the gutenberg printing press in enabled precise and rapid reproduction of books, dramatically reducing their cost and increasing their availability, and thereby also increasing the scope for the circulation of misinformation and disinformation (posetti and matthews ) . the advent of the participatory web interface with its indiscriminate access to information has again significantly increased the opportunity for misinformation and disinformation and the speed at which it circulates. to access social media, all that an individual needs is a workable network and a device supporting the social media applications or website and then the individual is good to go. this indiscriminate access has been far more widespread than the understanding amongst the population about the nature of the technology. with no qualification necessary to use and access social media, the perpetrators and victims of questionable content are separated by no more than a click (chang ) . the industry of misinformation and ancillary activities we argue can be regarded as a new type of collective violence and is generating a new form of collective victimisation where individuals are not even aware that they are victimised. we consider here the rationale and motivation behind questionable content, and then the characteristics of questionable content. while any individual with a device which supports social media platforms potentially can be a perpetrator, perpetrators tend to be certain entities with particular objectives such as political entities, extra-political entities, extremists (ben-david and matamoros fernández ) and individuals or a group of individuals with nefarious motives. there are websites and portals which are entirely dedicated to the production of fabricated and manipulated information that operate under a name which is deceptively similar to that of a legitimate news organisation (allcott and gentzkow ). india is periodically a victim of such websites, as was evidenced by the website "viralinindia", which was shut down on account of abusing information prior to the general election. however, such entities are hard to shut down permanently as it is easy to re-emerge in some other form (usha ) . while perpetrators capitalise on the insecurities, prejudices and limited education of the victims and on the channel algorithms, the victims are unaware of and are not alert to the motives of the perpetrators. unwittingly, they aid and assist the perpetrators to (i) polarise the population for or against a particular cause, (ii) evoke emotions among the population and cloud independent and rational judgement, (iii) spread conspiracy theories and infuse distrust in the existing knowledge base, (iv) troll and infuse an existential crisis in an individual or even a group, (v) deflect blame and target another, create a parallel narrative and (vi) impersonate (roozenbeek and van der linden ). the perpetrators engage in all the above-mentioned strategies either for a pecuniary benefit or ideological validation (allcott and gentzkow ; silverman and singer-vine ). most media attention has focused on the use of these strategies by foreign agencies interested in domestic politics. during the taiwanese presidential election, questionable content was put into circulation. the questionable content did not stop with fake news and sought to manipulate public opinion by spreading misinformation (kuo ; lee and blanchard ). having regard to china's claim that taiwan is a part of china, the interference by an international entity must be viewed as potentially threatening taiwan's security and the coveted principle of self-determination. the modus operandi along with the content of questionable content helps us to determine and identify the actor, the rationale and also the intended target. various forms of questionable content are crafted to attain different objectives and impact individual behaviours or attitudes differently. collectively, they are often termed as a semantic attack, as the questionable content tends to adversely impact the semantics of information (kumar and geethakumari ) . the factors which differentiate between legitimate information and questionable information are certainty, accurateness, comprehensiveness and deceptiveness. a semantic attack is directed towards individual users of social media and is crafted in such manner which awakens the insecurities of individuals or reaffirms their existing belief (allcott and gentzkow ). in a nation with a heterogeneous and diverse population, the impact of miscommunication and like events could be tremendous. a nation-state with diverse religious practices, cultural heritage, socio-economic standards and educational disparity, and with the substantial reach of social network-enabled devices in the hands of such a diverse population, is prone to be a victim of insecurities. social media is a platform which provides an insight into the lives of others and individuals who previously had limited knowledge about the lives or thoughts of others can now access them with the click of a button. social media has led to a significant detrimental effect in the psychological condition due to comparison of self over social media with other participants (vogel et al. ) . the comparisons which stem out of insecurities are not limited to lifestyle comparisons but also intellectual comparisons. people engage to influence others by showcasing their intellectual abilities and ideological bent, which often is guided by intolerance and rigidity to accept a diverse outlook leading to extremism and polarisation (jost et al. ) . the propagation of questionable content is further aided by the speed of its circulation and uncertain geographical location of the source. styling and the text of questionable content are crafted in a particular manner depending on the type of questionable content such as satire, fake news, disinformation, propaganda and misinformation and on its audience. the style of questionable content differs from real news on several counts. fake news is often crafted with a longer and striking title, or heading, which attracts immediate attention, the vocabulary used is simpler, with limited use of technical words so that even a reader with limited education or intellectual abilities is not discouraged from reading it. furthermore, the presentation of the content is colourful, capitalised and dramatised to grab the attention of the potential target (horne and adali ) . when it comes to content, articles are shorter in length compared with real news and there are fewer punctuation marks and quotes which lowers the possibility of tracing the content back to an authoritative figure. there is greater use of adverbs, pronouns and redundancies. the content also prefers using self-referential terms such as 'i', 'we', 'you' and 'us' (horne and adali ). such self-referential terminology behaves as if the content directly speaks to the reader or on behalf of the reader; consequently, the reader feels connected with the message and messenger. satirical websites are producing content some of which can cause similar damage as fake news and misinformation when its reception is without a context. the wide range of actors also includes websites engaging in the production of a mixed format of news, with a certain portion being true and other portion fabricated thereby creating a cloud in the judgement of people at large (allcott and gentzkow ). india has been a victim of delivery of content from a website which engages in the dissemination of satire from eminent political figures leading to a grant of authenticity to the satire, at least in the mind of some. for example, a leading politician resorted to quoting from "fakingnews", a portal which declares itself as a satire and humour website, and he was subsequently re-tweeted by the official political handle of the political party forming government. (chaudhuri ) . the device of questionable content is equally exploited by the opposition in the indian parliament as they use this mechanism to question the credibility of the governing political party. opposition parties in the indian parliament have often attempted to malign the image of the prime minister by questioning his lifestyle and using visuals which are either wrongly dated or wrongly contextualised (kinjal a, b) . questionable content in india frequently has elements such as religious intolerance, people with a certain political affiliation violating the law, photos and news related to celebrities, outrageous claims regarding the performance of government and international accolades received by india. most of the content is supported with photographs from unconnected events (see examples from boomlive, https://www.boomlive.in/fake-news). the questionable content capitalises on the strong religious sentiments of the majority, or political sentiment, which itself is connected to religious affinity, or with a little description and an image, which aids people with limited education to interpret or celebrities, who are often revered as a god by a large section of india's population. it is not that every individual who is accessing social media is bound to fall in the trap laid by questionable content. the most vulnerable are individuals with limited education or awareness about the medium and scope of the medium, those who lack an objective outlook or have had experiences which have had an impact on their psychological condition making them either insecure or prone to seeking validation of existing prejudiced ideology (allcott and gentzkow ; silverman and singer-vine ). having an education does not guarantee protection from questionable content. however, it can be argued that a limited education (including digital literacy) plays a significant role in the victimisation of individuals as it enables them to access social media but does not enable them to discern or make rationale choices in favour of real information. a lack of awareness and skills to identify fake news from real news enhances the circulation of questionable material. the insecurities upon which the questionable content capitalises were also in evidence in taiwan during the elections in and , as well as during the covid- pandemic. to socialise, individuals do not need to leave their homes anymore, they can reach out to anyone and everyone through the algorithms of social networking. an individual sitting in the comfort of their home can spend hours over a social network, reading, watching, writing, contributing content. however, the significant change is that they now also are engaged in sharing the content they consume. while the individual presumes that they are acting on their own in their private domain and are not involving others, the moment their activities involve sharing, the impact goes beyond them individually. with the act of sharing, an individual actively enters the realm of algorithms of the social network, and the shared content has the potential to have an impact beyond the individual, extending to the individual's social network and then beyond to the social networks of the individual's social network growing exponentially until it eventually impacts society collectively, or at least a certain portion of it. when the information circulating is real and genuine, the impact is not necessarily adverse; however, unchecked questionable content undoubtedly has an adverse impact on people collectively. except for the perpetrators, who introduced the questionable material, all the other individuals who consumed it and actively shared it without verification could be considered collective victims of questionable content. often, when questionable content comes from someone in their contact list or from friends and family, the propensity is to believe in the content and it is often misconstrued as authentic and genuine as opposed to content received from an unknown person. recipients of questionable content often do not undertake a fact-finding exercise or analyse the information from an objective standpoint to ascertain its reliability; they are prone to trust their friends and family over social media unless there exists an ideological difference with the actor. with this trust reposed upon the contact and network, the recipient turns into actor and feels the need to share and inform others in their contact group thus becoming a victim as the recipient and also inflicting injury to others. the individual sharing questionable content has an impact on the collective by virtue of changing the attitude of consumers towards a particular issue or by creating general indifference towards an election by generating a certain amount of scepticism and distrust (persily ) . irrespective of the end goal-pecuniary benefit or ideological reach-questionable content creates a "blanket of fog" which conceals and cloaks authentic information and creates confusion over what to believe or to fall prey to the content circulated. the idea of "educated political decision" is subsequently lost leading to a situation where voters have been exposed to incorrect information influencing how they cast their votes or whether they vote at all. when this results in the election of individuals who would not otherwise have been elected, it can be regarded as collective victimisation as it engulfs the majority of the population (persily ) . the experience of the usa in suggests that social media can play a vital but not decisive role in communicating electoral news and that the average american voter did not just believe any fake news; however, they were likely to believe stories that favoured their preferred candidate (allcott and gentzkow ). india, the world's largest democracy, has also fallen victim to questionable content circulated over web-based social media platforms. oxford internet institute ( ) suggested that "the proportion of polarizing political news and information in circulation over social media in india is worse than all of the other country case studies we have analysed, except the us presidential election in ". and according to oxford internet institute ( ), a data collected in february to april , months right before the general election, showed that both bharatiya janta party (bjp) and indian national congress (ins) shared a substantial amount of news on facebook that they classified as "divisive and conspirational content", i.e., junk news and information. the potential of the questionable content impacting a collective is not only limited to political events as was seen during the covid- pandemic. crimes and forms of crimes have been ever-evolving and the internet age has created both new opportunities for crime and new crimes. the big question that lies before the government of each state is how to regulate information systems, and specifically questionable content. government-imposed regulations can be a double-edged sword as regulations can eliminate or restrict the flow of questionable content, while at the same time can potentially act as a legally sanctioned mechanism to gag real news and ultimately violate media independence, freedom of information and the right to free speech. it is a difficult issue to balance as india saw when the indian government was about to enforce a rigorous law suspending the accreditation of journalists propagating questionable content but soon froze it owing to protests from the media. in india, questionable material (rumours) circulated deliberately over whatsapp, a popular platform for text and media exchange over a smartphone, has resulted in several incidents of lynching (arun ) . the indian government felt that the onus was on whatsapp to stop the acts of lynching. through notices to whatsapp, the government put pressure on the company to address the problem by preventing the messages from spreading. whatsapp responded by installing a "forwarded" label to tell the reader that the individual sharing the content did not create it. while web-based platforms such as whatsapp are undoubtedly being used to amplify and target hate speech, if the aim is to limit the incitement to violence, then other factors that contribute to the production and promotion of questionable content such as the context, and the roles of leaders and local police, need to be addressed (arun ) . a holistic approach is needed for regulation including the identification and application of penal laws against the perpetrators. equally, those vulnerable to spreading questionable content need to be made cyber security aware to protect themselves from the content and from spreading the content (chang and coppel ) . in april , the us law library of congress published a report on initiatives taken by a few countries from different regions to counter the menace of fake news. the uniform issue in the study was the role and impact of questionable content in the fair and free election process (the law library of congress ). a similar study was done by www.poynter.org, with selected countries representing various regions (see https://www.poynter.org/ifcn/antimisinformation-actions/). both studies reveal that countries have undertaken three approaches: (a) steps by government to monitor, assess and assist in the reduction of questionable material over social networking sites; (b) steps closely resembling the sanctions and strict measures against questionable content and (c) steps involving elements of awareness to control collective victimisation. however, there is not a uniform approach by the nation states. countries are attempting to address the growing challenge of questionable content through different measures including monitoring, imposing a sanction, conducting awareness programs and demanding accountability. however, regulation is not a simple answer as was seen in malaysia where legislation in faced heavy criticism for its broad definition of 'fake news' and was also examined for potentially being oppressive and regressive (the law library of congress ). a similar stance was taken in israel where there has been growing apprehension within the political opposition about excessive governmental control over information systems that could lead to violations of the essential right to information and freedom of speech (the law library of congress ). in both india and myanmar, the internet in parts of the country was shut down to stop the dissemination of information, ostensibly for security reasons but also to limit awareness of the situation on the ground. this can be seen as the gagging of the right to speech and an excessive imposition that violates not only human rights but also adversely impacts the economy (aung and moon ; kiran ). in , the indian government proposed to penalise journalists for publishing and propagating fake news; however, the proposal was withdrawn amid protest and claims of interference by the prime minister's office (dutta ; khalid ) . rather than impose a repressive regulatory approach, the taiwanese government has adopted a "humour over rumour" strategy to counter questionable content. in order to provide timely and correct information, the government uses humourous memes to provide information. by mocking government officials themselves (e.g. the meme with the premier showing his rear saying "we only have one butt" (see image ) to encourage people not to panic buy toilet paper during the covid- pandemic) or using a "spokesdog" (rather than a spokesperson) to communicate its public messages (see image ). these messages successfully attract people's attention in a timely manner and effectively cut back the dissemination of questionable content. in another alternative to government regulation, fact checking organisations, such as altnews.in (india). boomlive.in (india) and mygopen.com (taiwan), investigate and identify questionable content. however, they are not always perceived as being independent. furthermore, social media platforms and applications that curb questionable content not only assist governments but also run the risk of becoming-or appearing to be-unaccountable agents of the government in determining what is acceptable content. in addition to the abovementioned, certain other innovative measures have been developed by the participants of the dotcom world (chang and grabosky ) . one such innovation involves an online game which enables the individual players to play the role of questionable content producer, and through this role-playing, the player gets psychological training to identify techniques used to produce such content (roozenbeek and van der linden ). regulation will never be enough to protect the population from questionable content and there needs to be a focus also on "hardening" the target. cybersecurity awareness training programs equip an individual with the ability to discriminate between real news and questionable content form part of the armoury. one example of such effort is cyberbaykin (see https://www. facebook.com/cyberbaykin/), which was created to raise awareness about cyber safety and risk in myanmar (chang and coppel ) . it is evident that questionable content over social media in the form of fake news, misinformation, disinformation, propaganda and misconstrued satire have become a menace to reckon with. it is also acknowledged that human rights relating to freedom of speech and the right to information are threatened. effective regulation of the world of questionable content will not be possible unless all measures such as monitoring and sanction are aided by awareness and accountability measures. one of the key barriers in need of resolution to successfully regulate questionable content in the information system is the lack of an acknowledgment that questionable content is collectively victimising the nation's population. the primary challenge to such an acknowledgement is due to the limited construct of the identification of 'victim'. traditionally, the subject of a criminal offence is considered to be the victim, and barring a few circumstances like war, genocide and similar acts, it is an 'individual' who forms the subject matter of victimisation. often, psychological damage is not considered as victimisation as evidencing the criminal act is difficult. the challenge of extending the idea of victimisation to a collective is a notch higher, in terms of difficulty. a question may arise, even after acknowledging that questionable content is playing an adverse role in the electoral process, why this is not categorised as collective victimisation of the nation's population? the answer might lie in the lack of scope to provide compensatory privilege to a collective, which is the essence in the study of victimology. besides, there exists another significant rationale for not categorising a nation's population as a collective victim: the authority or the political force shouldering the responsibility of regulating and addressing the collective victimisation may have taken advantage of the menace of questionable content. however, that remains a subject for later study. nonetheless, to make progress, we as a community need to appreciate and accept at the outset the concept of collective victimisation of a nation's population resulting from questionable content, before we try to make inroads to resolve and address the problem. viral audio clip claiming muslim vendors in surat are spreading coronavirus is false on whatsapp, rumours, and lynchings myanmar reimposes internet shutdown in conflict-torn rakhine, chin states: telco operator collective victimhood beliefs among majority and minority groups: links to ingroup and outgroup attitudes and attribution of responsibility for conflict hate speech and covert discrimination on social media: monitoring the facebook pages of extreme-right political parties in spain cybercrime in asia: trends and challenges propaganda, misinformation, and the epistemic value of democracy cybercrime in the greater china region: regulatory responses and crime prevention across the taiwan strait cybercrime and cyber security in asean building cyber security awareness in a developing country: lessons from myanmar the governance of cyberspace pm modi quotes 'faking news' in parliament to target former j&k cm omar abdullah govt to crack down on fake news, cancel accreditation of journalists publishing it. the print. retrieved coronavirus conspiracy theories targeting muslims spread in india. the guardian. retrieved this just in: fake news packs a lot in title, uses simpler, repetitive content in text body video from bijnor viral with false allegation that elderly muslim vendor sprinkled urine on fruits how social media facilitates political protest: information, motivation, and social networks modi government withdraws controversial order on fake news was switzerland's matterhorn mountain lit up in tricolour after india supplied hcq tablets? congress leaders falsely share photo of luxurious aircraft as pm modi's boeing plane internet shutdown: india suffers $ . billion economic loss misinformation and the currency of democratic citizenship detecting misinformation in online social networks using cognitive psychology taiwan's citizens battle pro-china fake news campaigns as election nears. the guardian the science of fake news chinese 'rumors' and 'cyber armies' -taiwan fights election 'fake news'. reuters. retrieved the cycle of violence: understanding individual participation in collective violence protecting the states from electoral invasions. the william and mary bill of many americans say made up news is a critical problem that needs to be fixed image of myanmar market's social distancing shared as mizoram the complementary relationship between the internet and traditional mass media: the case of online news and information junk news and misinformation prevalent in indian election campaign can democracy survive the internet a short guide to the history of 'fake news' and disinformation fake news game confers psychological resistance against online misinformation is government spraying coronavirus vaccine using airplanes? no, it's fake news the diffusion of misinformation on social media: temporal pattern, message, and source most americans who see fake news believe it, new survey says digital threats to democratic elections: how foreign actors use digital techniques to undermine democracy initiatives to counter fake news the rise and fall of fake news site 'viral in india': an interview with founder abhishek mishra social comparison, social media, and self-esteem collective victimization the social psychology of collective victimhood taiwan turns to facebook and viral memes to counter china's disinformation collective violence key: cord- - c h of authors: beena, v.; saikumar, g. title: emerging horizon for bat borne viral zoonoses date: - - journal: virusdisease doi: . /s - - -z sha: doc_id: cord_uid: c h of bats are the only flying placental mammals that constitute the second largest order of mammals and present all around the world except in arctic, antarctica and a few oceanic islands. sixty percent of emerging infectious diseases originating from animals are zoonotic and more than two-thirds of them originate in wildlife. bats were evolved as a super-mammal for harboring many of the newly identified deadly diseases without any signs and lesions. their unique ability to fly, particular diet, roosting behavior, long life span, ability to echolocate and critical susceptibility to pathogens make them suitable host to harbor numerous zoonotic pathogens like virus, bacteria and parasite. many factors are responsible for the emergence of bat borne zoonoses but the most precipitating factor is human intrusions. deforestation declined the natural habitat and forced the bats and other wild life to move out of their niche. these stressed bats, having lost foraging and behavioral pattern invade in proximity of human habitation. either directly or indirectly they transmit the viruses to humans and animals. development of fast detection modern techniques for viruses from the diseased and environmental samples and the lessons learned in the past helped in preventing the severity during the latest outbreaks. bats are the only flying placental mammals that present all around the world except in arctic, antarctica and a few oceanic islands. they are the second largest order of mammals that evolved from one of the oldest fossil, icaronycteris, during eocene period ( million years ago) and diverged into known species which constitute % of [ mammalian species [ ] . although the bats attribute advantages in the diverse ecosystem as pest controller (insectivorous bats) and pollinators (frugivorous bats); the worrisome fact is they act as natural reservoirs for a large number of emerging as well as re-emerging pathogens that other animals and humans can contract. moreover they gained a bad reputation in classical literatures, in which bats are associated with evils-lucifer, darkness, dracula-blood fed vampires and as omens and in modern scientific society they were obligatorily dangerous, as evolved as a super-mammal for harboring many of the newly identified deadly diseases without any signs and lesions. recent database on bat viruses from countries worldwide comprises more than bat-associated animal viruses belonging to viridae detected in bat species [ ] . recently reported % of the emerging and reemerging pathogens included in bioterrorism list as category a, b, c were recognized in different bat species. the emergence of bat borne zoonotic viruses significantly arise a global public health impact. many of the emerging and reemerging viruses are formidable foes for the physicians putting them into confusion due to their mutagenic nature. best example is the recent report of zika virus in india, which doesn't cause any developmental mutagenicity in children compared to the outbreak in brazil in . in asia and pacific regions, bats were demonstrated as natural reservoirs for a large number of this types of emerging as well as re-emerging pathogens such as sars, ebola, marburg, nipha, hendra, tioman, menangle, australian bat lyssa virus, rabies and many encephalitis causing viruses in humans and animals [ ] . sub saharan africa, where people hunt bats as bush meat is the biggest hot spot for viral spill over from bats to humans and other mammals. southeast asia is also been considered as another danger zone. a change in agent, host and environment is responsible for the emergence and re emergence of various diseases. from bats the pathogen get transmitted to humans via intermediate hosts like horses(hendra) and pigs(nipah) and different species of animals get infected by consumption of partially eaten fruits of bats and the chewed out materials of bats after extracting the juice. studies suggest bats can travel a long distance ( - km) which also develops issues of introducing new disease to the place unknown earlier. phylogenetic analysis suggests a co evolutionary relationship between viruses and the existing bats [ ] . all these facts arose international scientific attention for the study on bats and bat associated viruses and it suggests that a series of events happened to precipitate the emergence of the viruses which were ancient and circulating in the bats for a long time. recent applications of conventional pcr/rt pcr, metagenomics and next-generation sequencing (ngs) technologies revealed the complexity of the bat virome, which may impact upon its reservoir capacity and consequently affect vector-reservoir host interactions. several studies showed bats as an important reservoirs for a number of rna viruses (including, lyssa, corona, paramyxo, filo and astro viruses) and dna viruses (including, parvo, circo, herpes and adeno) [ ] . variation in the incidence and diversity of viruses in bats suggests that some species of bats are reservoir host and some others are incidental hosts [ ] . the bat virome in frugivorous bats are less compared to the insectivorous bats [ ] . more than viruses were reported in bats wherein most are rna viruses. out of viruses found to be associated with bats, were rna viruses due to high degree of mutations and recombination [ , ] . the first report of a transmission of a viral disease from bats to humans was a rabies virus (rabv) belonging to the lyssa virus genus [ ] . rio bravo virus was the first non rabies virus to be recognized as originating from bats in s [ ] . majority of viruses identified in bats were belonging to flavi virus group including west nile virus and kyasanur forest disease virus [ ] and the application of metagenomics helped to identify picorna viruses in bats. since a large number of different types of virus were identified in bats it is better to understand the spectrum and characteristics of viruses that bats carry. it may help to prevent and control potential emerging bat-borne diseases. further as bats are acknowledged for emerging zoonoses, identification and characterization of novel viruses from bats is needed. unlike other animals the detailed information regarding bat anatomy, ecology, importance in ecosystem and their ability to act as reservoirs for a large number of viruses which are potentially harmful for humans and animals have to be studied. moreover, knowledge regarding the antibody and cytokine synthesis in bats, pathogenicity and the pathology associated with infections are lagging. some of important pathogenic rna viruses identified in bats so far with emphasis on nipha virus transmission and few more bat borne viruses are discussed below. the oldest and most eloborately studied viruses in bat was the bat lyssa virus of family rabdoviridae. rabies virus was detected in both haematophagus and non haematophagus bats [ ] . in australia, in , a new lyssa virus from pteropid bats was characterized by sequencing, electron microscopy and by mouse model study [ ] . australian bat lyssa virus produces non suppurative meningo-encephalomyelitis and negri bodies were detected in brain of some bats with lesions similar as in rabies [ ] . in western europe, when rabies incidence was found declining among terrestrial mammals, new cases in cats were reported. later it was discovered as european bat lyssa virus (eblv ) circulating among european bats got transmitted to cats [ ] . the virus is also being reported in sheep, stone marten and in humans presuming cross transmission from bats to other terrestrial mammals [ ] . in straw-colored fruit bats rabies virus was injected intracerebrally and it was found to be suffered with diffuse, mild to moderate meningoencephalitis with two to three cell layer thick perivascular cuffing [ ] . earlier rabies bat virus (rabv) and eblv was restricted to america and europe respectively. but now many reports are there about the presence of lyssa viruses in bats of other countries including india. in asia, only few reports of rabies virus isolates; one from india and in thailand but were not confirmed by further studies. recently in india, bats sampled from nagaland hills were tested positive for rabies antibodies, but the epidemiology, prevalence distribution and pathogenicity is still incomplete. all these evidences of rabies virus antibodies in different places give a room for speculation for the presence of lyssa virus in free ranging bats in india. india reported the first bat parainfluenza virus of paramyxoviridae from a rousettus leschenaulti bat in [ ] . hendra, henipa and nipha viruses of paramyxovirus group attain recognition as the twenty-first century emerging diseases [ ] . hendra and nipah viruses have regular spill over from pteropus bats to humans and domestic animals. the first outbreak of hendra virus was reported in , in brisbane, australia killing horses and humans. in addition to the affected target species, the seropositivity was reported from flying foxes which serve as the major reservoir host of the virus [ ] . nipha virus disease is a heart breaking disaster in which more than one million pigs were culled. it's a newly emerged deadly infection characterized by fever, respiratory distress and encephalitis and was reported in from pigs and humans in the south east and south asian region. later a series of outbreaks were reported in various countries like bangladesh, malaysia, singapore and in india at different time points [ ] . direct contacts with infected pigs were main source and a case fatality rate of - % was noticed during the outbreak. the case fatality rate in outbreak in siliguri, india was found to be % [ ] . during initial outbreak in , neutralizing antibodies for nipha virus were detected in bats present throughout peninsular malaysia residing around the infected pig farms [ ] . nipha virus was first isolated from urine of pteropus hypomelanus and pteropus vampyrus [ ] . two strains of the virus were isolated from the pteropus lylei in cambodia and from different species of bats in indonesia, thailand and philippines [ ] . all these reports suggest that the henipa virus is distributed throughout the pteropid bats in the world. an encephalitis outbreak that occurred in people of southern phillipines in is considered mostly due to horse meat consumption and to horses the virus get transmitted by eating the fruits partly eaten by bat [ ] . therefore the bats are proved to be the global reservoir hosts for the paramyxo viruses. diagrammatic representation of bat transmitted nipha viral zoonoses is depicted in fig. . in india a survey on bats of different species for the pathogenic nipha, ebola and marburg using enzyme linked immunosorbant assay showed nipha virus specific igg from serum sample of a bat [ ] . the amino acid and nucleotide sequences derived from pteropus showed % homology to the nipha virus reported in and outbreak in india and bangladesh. seropositivity for nipha virus in pteropus giganteus in the northern region of india was tested using indirect elisa method and recorded % sensitivity and % specificity when compared with cnt [ ] . bats were again proved to be the source for the recent nipha outbreak in kerala, india [ ] . during the survey on bats for nipha virus in malaysia in , researchers isolated a novel virus and named as tioman virus. later tioman virus was isolated from the bat tissue specimen (pteropus giganteus) in the north east region of india. yaiw et al. [ ] experimentally proved that the tioman virus capable of infecting and replicating in lymphocytes of lymphnodes, payers patches, spleen, thymic epithelioreticular cells and tonsillar tissue of pigs. philbey et al. [ ] and wong et al. [ ] separately infected pigs oronasally with tioman virus and postulated as this could be the possible source of paramyxovirus transmission from bats to pigs. from three species of fruit bats, three new henipa virus and two new rubula viruses were detected from indonesia [ ] . identification and complete genome analysis of three tuhoko viruses (the university of hong kong) thkpm , thkpm and thkpm in roseuttues leschnaulti was studied in china [ ] . these three viruses have a common origin and in phylogenetic analysis they were found closely related to menangle and tioman viruses. hendra, nipha and menangle virus are the only three virus of the paramyxoviridae affect humans recovered from bats so far. in china, a novel toti virus like virus was identified and isolated from the bat guano and its cytopathic effects were studied in sf , hz and c / cell lines [ ] . since these are bsl agents, their incidence prevalence study and pathology reports are limited in most of the asian countries. filo viruses are the most lethal haemorrhagic fever causing pathogen in human and non human primates. the filoviridae family includes ebola virus (zaire, sudan, reston, tai forest and bundybugai), marburgh and recent cueva virus. in philippian, during an outbreak in reston ebola is found circulating in pigs and among nonsymptomatic human cases [ ] . these suggest that there are multiple hosts involved in filovirus. in bangladesh, rousettus leschenaultii bats were found seropositive against ebola zaire and reston viruses [ ] . in china, r. leschenaultii was found seropositive for reston and zaire ebola viruses along with other insectivorous bat species (yuan et al. [ ] ). detection of filoviruses in pigs in philippines, fruit bats in china and bangladesh and orangutans from indonesia reveal the extent of spread of the filoviruses among different species in asia [ ] . a panviral microarray study reported the presence of reston ebolavirus co-infected with porcine reproductive and respiratory syndrome in pigs in philippines. towner et al. [ ] using immunoperoxidase method demonstrated the peri mebranous localization of marburg virus antigen in the liver of infected roseuttues aegyptius bats and presence of small collections of mononuclear inflammatory cells and hepatocyte necrosis. the epidemiological role of bats in transmission of flavi viruses is not yet clear. in bangladesh while screening for nipha virus a novel gb like virus was identified from sera of a single colony of pteropus giganteus [ ] . novel gb virus d, belongs to a new group in flaviviridae, pegi group. serosurveillance of around bats from different countries using unbiased high throughput sequencing method revealed the presence of sequences showing - % similarity to viruses in hepaci and pegi group. this study concluded that bats are the natural reservoir for the entire hepaci and pegi groups [ ] . in southern china, seroprevalance study against je, detected the presence of antibodies in % ( / ) of bats by micro-seroneutralization test and bats out of this were have neutralizing antibodies [ ] . during the period from to , four isolates of je virus such as b from roseuttues leschnaulti and gb from murina aurata were reported in china and these isolates were similar to human liyujie and mosquito bn isolates [ ] . as a part of investigation on bat borne je in japan, a virus different to je was accessed in serological study and named as yokosu virus [ ] . international scientific community gained interest to do research on bats after the discovery of sars in horseshoe bats. in addition to sars-cov, five human coronaviruses (hcovs), including two alpha named as - e, -nl , and beta corona virus like oc , -hku and a mers cov were identified [ ] . bats are considered as the ancestor for sars cov, mers cov, human cov e and nl [ , ] . sars cov like virus antibody prevalence was found to be % in chinese horse shoe bats and roseuttues sp. but pathology associated with these viruses in bats was not noticed. large diversity of corona virus was noticed in south east asian countries like china, philippines, japan and thailand. majority of corona viruses were discovered from tissues, blood samples and faeces, indicate an enteric tropism of this virus in bats. detection of corona viral genome fragments in spleen and brain of indonesian bats suggests that the virus is not restricted to the respiratory and enteric epithelium [ ] . search for the herpes viruses in bats dated back in when a cytomegala virus particle was demonstrated in the acinar cells of submandibular gland of two myotis lucifugus bats [ ] . a novel beta herpes virus was detected from the lung, kidney, spleen, liver and blood of a number of insectivorous bats by blast search of the complete gb sequence and phylogeny base studies [ ] . by targeting glycoprotein b (gb) and dna-directed dna polymerase (dpol) genes of hvs, two gamma and two beta herpes virus were identified in bats in china [ ] . out of faecal sample from different species of bats in southern china, samples were positive for herpes virus ( gamma herpes virus and were beta herpes virus). detection of herpes virus in the digestive tract and anal swabs of bats suggests oral faecal route as main mode of transmission for herpes virus in bats [ ] . in philippines during , bats belonging to megabat species were examined and a novel gamma herpes virus was identified from % of the intestine ( / ) and % of the lung ( / ) and serum samples ( / ) [ ] . bat adenovirus was first isolated in japan from a fruit bat (pteropus dasymallus yayeyamae) and named as ryukyu virus -rv [ ] . kohl et al. [ ] carried out genome pyrosequencing of bat adenovirus and found there was an interspecies transmission during evolution of canine adenovirus and from vespertilionid bat adenovirus. also, the adenovirus infected bats showed virus tropism in intestine, liver and kidneys but the lesions were noticed in spleen and lungs like follicular hyperplasia and non suppurative interstitial pneumonia respectively. later the adenovirus was isolated during the surveillance programme for nipha, ebola and sars in - periods in china from myotis bats and grouped the novel bat adeno virus tjm (bt-adv-tjm) in mast adenovirus genus [ , ] . this report also demonstrates the epidemiology of bats adenovirus is prevalent in myotis species and scotophilus kuhlii out of the bat species surveyed in china. the fourth mastadenovirus was isolated from r. leschenaultii bat in india and it showed approximately % divergent at the nucleotide level from its closest known relative, japanese batadv [ ] . the average prevalence of adeno associated virus was found to be . % from provinces in china [ , ] . tan et al. [ ] performed next generation sequencing for three adenovirus isolates from rhinolophus sinicus bats in china and reported an unusually large e genome present in these isolates. the bat hepadna can infect human hepatocyte and are antigenically related with the hepatitis b virus. even though an effective hepatitis b vaccine is available, the virus is not globally eradicated. recent studies suggest hepatitis b virus is present in a number of free ranging bats [ ] . in asia, america and africa during the period from to , individual bats ( liver and sera) from different bat species were collected and screened using nested pcr for hepadna virus. the result shows that there was a low prevalence rate ( . %). also the histological studies reveals like in all other host, only few inflammatory cells mainly lymphocytes were seen in the portal triad of the infected bats without any symptom and have high viremic form [ ] . in myanmar, out of individual bats of species, bat hepatitis virus (bthv) was detected in the pooled liver tissue of long fingered bats (miniopterus fuliginosus) by electron microscopy and also the full genome of bthv [ ] . in china, a novel bat hepatitis virus was identified by full genome sequencing of the identified virus in pomona roundleaf bats [ ] . recently in china out of bat liver screened by rt-pcr with degenerate primers followed by sequencing and phylogentic analysis, one hepaci virus and novel hepadna viruses were identified [ ] . some of the less significant viruses identified in different bat species are shown in table . viral diseases are rising up day by day and majority are zoonotic and about - % are where the bats as host. sometimes the viruses disappear and remain passive for long time and re emerge with increased virulence. researchers trying to develop vaccines against many viruses, but in a developing country with huge population like india, it is not advisable. for the last few decades bats are found as plethora for many numbers of viruses, but the exact role in maintenance and transmission of these viruses to terrestrial animals has not been studied yet clearly. besides, there doesn't exist a proper pathogen database for indian bats. by making the public aware about the major yang et al. [ ] emerging horizon for bat borne viral zoonoses factors associated with bat borne zoonotic disease transmission such as magnitude and frequency of bat human interaction and public reminders like not to touch bats, it is easy to control and prevent the bat borne diseases to a large extent. after ebola outbreak in west africa, peoples in different communities were advised about the safety measures to be taken while the bush meat consumption, bat hunting and during frequent cave visits. handling bat guano also arise health risk because in brazil while screening of fruit eating bats it was found bats have high concentration of influenza a subtype (hl nl ) in their intestines and faeces [ ] . in addition to viral zoonoses, non viral zoonotic pathogens like histoplasma capsulatum causing histoplasmosis (fungal infection) and countless number of zoonotic bacteria were reported in bat faeces. high prevalence and diversity of these viruses and its low pathogenicity in bats raises questions like whether virus was coevolved along with bats. along with detection and characterization of bat born viruses, the pathology associated with these viruses in the host and the environmental factors which trigger these virus spills over will be found helpful in preventing epidemic. so as to counteract the future outbreak we have to conduct active pre emergence research such as surveillance, identification of the potent pathogens, susceptible hosts, pathogenicity on the natural hosts and the various factors triggering cross species transmission. deforestation and urbanization are the major factors for all these deadly outbreaks. the human encouragement to forest areas and close contact with wild animals, increased breeding of mosquitoes in congested areas and change in climate and ecology become precipitating factors for the bat borne zoonotic viral outbreaks. all the bats borne disgusting outbreaks became a lesson for future and after the deadly viral outbreaks in different parts of the world, our country become alert to begin a fight against the viruses and it found useful in preventing a huge outbreak in recent years, nipha and zika outbreaks in india. modern molecular diagnostics, the potential and biology of the agent, host immune response studies and vaccine developments helped to prevent further outbreaks to great extend. control and management measures such as campaining the public regarding the issues, and practice personal hygiene, washing hands properly before food esp in rainy seasons and avoid eating fallen fruits and vegetables without proper washing should be followed. detection of coronavirus genomes in moluccan naked-backed fruit bats in indonesia viral zoonoses that fly with bats: a review bats: important reservoir hosts of emerging viruses bat influenza a (hl nl ) virus in fruit bats sur une grande épizootie de rage dbatvir: the database of batassociated viruses outbreak of henipavirus infection a previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans endogenous hepadnaviruses in the genome of the budgerigar (melopsittacus undulatus) and the evolution of avian hepadnaviruses european bat lyssavirus transmission among cats phylogeography, population dynamics, and molecular evolution of european bat lyssaviruses bats carry pathogenic hepadnaviruses antigenically related to hepatitis b virus and capable of infecting human hepatocytes genomic characterization of severe acute respiratory syndrome-related coronavirus in european bats and classification of coronaviruses based on partial rna-dependent rna polymerase gene sequences henipavirus infection in fruit bats (pteropus giganteus) discovery of an endogenous deltaretrovirus in the genome of long-fingered bats (chiroptera: miniopteridae) natural hendra virus infection in flying-foxes-tissue tropism and risk factors characterisation of a novel lyssavirus isolated from pteropid bats in australia phylogeny and origins of hantaviruses harbored by bats, insectivores, and rodents hepatitis virus in long-fingered bats identification of a novel orthohepadnavirus in pomona roundleaf bats in china bat parainfluenza virus. immunological, chemical and physical properties histopathology and immunohistochemistry of bats infected by australian bat lyssavirus close relative of human middle east respiratory syndrome coronavirus in bat vampire bat rabies: ecology, epidemiology and control genome analysis of bat adenovirus : indications of interspecies transmission deadly nipah outbreak in kerala: lessons learned for the future phylogeny of the genus flavivirus severe acute respiratory syndrome coronavirus-like virus in chinese horseshoe bats identification and complete genome analysis of three novel paramyxoviruses, tuhoko virus , and , in fruit bats from china prevalence and genetic diversity of adeno-associated viruses in bats from china bat guano virome: predominance of dietary viruses from insects and plants plus novel mammalian viruses origin and evolution of nipah virus isolation of novel adenovirus from fruit bat (pteropus dasymallus yayeyamae) ebola reston virus infection of pigs: clinical significance and transmission potential bats and zoonotic viruses: can we confidently link bats with emerging deadly viruses? novel paramyxoviruses in bats from sub-saharan africa filoviruses in bats: current knowledge and future directions ebola virus antibodies in fruit bats kysanuar forest disease virus infection in the frugiviorous bats, cynopterus sphinx an apparently new virus (family paramyxoviridae) infectious for pigs, humans, and fruit bats bats are a major natural reservoir for hepaciviruses and pegiviruses isolation of a novel adenovirus from rousettus leschenaultii bats from india detection of a novel herpesvirus from bats in the philippines molecular detection of a novel paramyxovirus in fruit bats from indonesia lagos bat virus infection dynamics in free ranging straw coloured fruit bats (eidolon helvum) novel bat adenoviruses with an extremely large e gene cytomegalovirus in the principal submandibular gland of the little brown bat, myotis lucifugus isolation of genetically diverse marburg viruses from egyptian fruit bats identification of a novel bat papillomavirus by metagenomics duplex nested rt-pcr for detection of nipah virus rna from urine specimens of bats molecular characterization of nipah virus from pteropus hypomelanus in southern thailand nipah virus: an emergent deadly paramyxovirus infection in bangladesh japanese encephalitis viruses from bats in yunnan detection and genome characterization of four novel bat hepadnaviruses and a hepevirus in china bat coronaviruses and experimental infection of bats, the philippines nipah virus infection: pathology and pathogenesis of an emerging paramyxoviral zoonosis virome analysis for identification of novel mammalian viruses in bat species from chinese provinces the complete genome sequence of a g p[ ] chinese bat rotavirus suggests multiple bat rotavirus inter-host species transmission events emerging horizon for bat borne viral zoonoses detection of nipah virus rna in fruit bat (pteropus giganteus) from india tioman virus, a paramyxovirus of bat origin, causes mild disease in pigs and has a predilection for lymphoid tissues isolation and characterisation of novel bat corona virus closely related to the direct progenitor of severe acute respiratory syndromecorona virus a novel totivirus-like virus isolated from bat guano nipah virus infection in bats (order chiroptera) in peninsular malaysia serological evidence of ebolavirus infection in bats, china isolation of a novel coronavirus from a man with pneumonia in saudi arabia emerging paramyxoviruses: receptor tropism and zoonotic potential high prevalence and diversity of viruses of the subfamily gammaherpesvirinae, family herpesviridae, in fecal specimens from bats of different species in southern china publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- - kxj s authors: imdad, kashif; sahana, mehebub; rana, md juel; haque, ismail; patel, priyank pravin; pramanik, malay title: a district-level susceptibility and vulnerability assessment of the covid- pandemic's footprint in india date: - - journal: spat spatiotemporal epidemiol doi: . /j.sste. . sha: doc_id: cord_uid: kxj s in this study, we trace the covid- pandemic's footprint across india's districts. we identify its primary epicentres and the outbreak's imprint in india's hinterlands in four separate time-steps, signifying the different lockdown stages. we also identify hotspots and predict areas where the pandemic may spread next. significant clusters in the country's western and northern parts pose risk, along with the threat of rising numbers in the east. we also perform epidemiological and socioeconomic susceptibility and vulnerability analyses, identifying resident populations that may be physiologically weaker, leading to a high incidence of cases and pinpoint regions that may report high fatalities due to ambient poor demographic and health-related factors. districts with a high share of urban population and high population density face elevated covid- risks. aspirational districts have a higher magnitude of transmission and fatality. discerning such locations can allow targeted resource allocation to combat the pandemic's next phase in india. the emergence of the covid- pandemic from wuhan, china (columbus et al. ; lupia et al. ; torales et al. ) , in december and its rapid dispersion across the globe (bonilla-aldana et al. ; cruz et al. ) , caught most countries and healthcare systems off-guard. ameliorative measures ranged from initially quarantining patients to progressively containing entire provinces (harapan et al. ) , as the virus' ambit grew beyond political and geographic boundaries. however, with the virus' spread continuing unabated and being supplanted by transmissions from pre-symptomatic and asymptomatic individuals (who b), partial and complete lockdown of regions and entire countries were quickly adopted. nations like india, where the outbreak became potentially threatening after its initial rampage in east asia and western europe, were somewhat quicker to impose such lockdown measures (the lancet ). yet, despite such restrictions being imposed, many countries, india included, have experience sharp jumps in cases due to existing gaps in their healthcare systems and vulnerabilities in their socioeconomic and politicaladministrative setups (mcaleer ), which exacerbate contamination risk and dampen recovery rates. furthermore, the closure of offices and factories has already cast a lasting effect on the global economic landscape (ajami ; gong et al. ; mckibbin and fernando ) . large numbers of low-income migrant workers, who mostly live on-site at their workplaces or are heavily dependent on daily incomes/wages for sustenance, have perforce been uprooted. this has, in all probability, further reduced their ability to withstand a viral outbreak due to impaired health from malnutrition/hunger and the need to travel long distances to return to their original homes. such a situation has especially emerged in india, where thousands of migrant workers mostly from the southern and western zones of the country, have thronged bus terminals and railway stations or have even attempted to travel across states on foot (lal ; singh ) , raising the spectre of further widespread community transmission and the incursion of the virus into especially socioeconomically vulnerable areas (and more importantly into rural hinterlands) that are ill-equipped in terms of healthcare (both at the individual and community level for resident populations and returning migrants- nacoti et al. ) and economic resources to deal with a surge in infections. we therefore seek to examine a number of aspects in this paper. firstly, we delve into the pattern of covid- outbreak in india, relating this with air-travel from abroad (as the covid- is essentially an 'imported' virus-who b) and those availing the same within the country. secondly, we track the contagion's spread through the nation during the successive lockdown phases by mapping its geographic trajectories and its potential outreach zones, i.e. the areas where the virus is most likely to spread into. for doing this, we have had to perforce use slightly older data than that which reflects the current situation, due to the intervening lag time for computation, analysis and writing up of the results. some research accounts have noted that the contagion's virulent nature is dampened and hindered by higher temperatures (briz-redon and serrano-aroca ; prata et al. ; xie and zhu ) and that it reacts to raised humidity levels (ahmadi et al. ; luo et al. ; qi et al. ), conditions which mostly persist across india. along with this, some studies have reported that hydroxychloroquine or chloroquine-based drugs may be useful in combating this virus (colson et al. ; gao et al. ; , though this finding is disputed as well (boulware et al. ; hernandez et al. ) . india has had a history of chloroquine use and vaccination due to its historical struggles with malaria (das et al. ; anvikar et al. ) , and it may thus be seemingly possible that her citizens are likely more resistant to the covid- threat. based on the above two aspects, we first estimate the epidemiological susceptibility of a particular location (since this is a medical/health issue foremost), identifying those areas where the disease is most likely to affect people. subsequent to this, we examine the overall susceptibility of a region to a covid- outbreak, factoring in the socioeconomic and health conditions of its residents, which makes them more prone to succumbing to the virus. finally, we look at the overall socioeconomic vulnerability of the districts (i.e. where deaths are most likely to occur) and its variation across the country. susceptibility analyses are important to ascertain the likely incidence of a disease and the populations it can affect (lohmueller et al. ) . this also helps health-care providers perceive the risks involved for certain groups in order to better influence their health-related behaviour (bmj ; brewer et al. ) . in relation to the virus, a range of susceptibility studies have been performed to understand how the physiological attributes of patients condition their response to the virus (rothan and byrareddy ; shi et al. ; zhao et al. ) , and its links with the disease's spread in different areas (fanelli and piazza ; karako et al. ) . other studies have compared habits like smoking or ambient environmental conditions (coccia ; with the virus' threat and examined how co-morbidities can occur due to underlying health issues yang et al. ). attempts to estimate this coronavirus' spread have however been comparatively less in the overall indian context (e.g. biswas and sen ; dhanwant and ramanathan ; pandey et al. ) , with some regression models being employed to predict virus outbreaks across the country (tomar and gupta ; singh and adhikari ) . others have tried to estimate the covid- 's prevalence within smaller regions (e.g. simha et al. ( ) for the southern indian state of karnataka and kumar ( ) for the western state of maharashtra), measures of controlling its rampage across the country (mandal et al. ) and the debilitating effects it can engender on the nation's overall healthcare system/setup (chatterjee et al. ) . the other aspect examined in the indian context has been the efficacy of the implemented lockdown measures (e.g. paital et al. ) , following similar studies that were undertaken elsewhere (e.g. ibarra-vega ; tobias ). sardar et al. ( ) in examining the effects of the initial lockdown measures have opined that it would have little effect in the western indian states that are the most affected by the virus but can prove to be somewhat beneficial in other areas, while das et al. ( ) have provided guidelines on the critical community size required to make lockdowns effective. however, it has been demonstrated that there exists a great deal of heterogeneity in how people and regions respond to and are affected by this pandemic (sominsky et al. ) , with an urgent need for further science-based assessments of the virus' spread (bedford et al. ) . with india being an extremely diverse country, in geographic as well as socio-demographic aspects, it is very much feasible that the virus' impact and spread will vary markedly across regions. furthermore, due to the large variations in economic and healthcare attributes across the nation, the physiological response and case-fatalities will also differ significantly across areas. therefore, we seek to examine the covid- 's footprint across the nation and link it intricately with the situational realities in different locales, something which is sorely required but has received scarce attention in the current context. the entire analysis has been based on the district-level administrative zones ( figure ) denoted in the indian population census of , which lists districts nationwide, in order to keep parity with the census datasets used. the number of district-level covid- cases as reported by the ministry of health and family welfare (mohfw), government of india (goi) was the principal secondary dataset utilized. this data was also used for the identification of covid- hotspots and analysis of its possible outreach. on th march , the government of india (goi) ordered a nationwide lockdown for days (phase-i), from march - april , further extending this in phase-ii ( april - may) and then to phase-iii (may to may ). therefore, when this study was commenced in april, , the district-wise numbers of covid- cases were collected on four dates from the mohfw, goi, database to understand the patterns of the virus' spread in each timeslot and feasibly represent each of the lockdown phases. these dates were-a) pre-lockdown phase (on rd march); b) early lockdown phase ( th march); c) mid-lockdown phase ( th april) and d) late lockdown phase ( th april). subsequently, the lockdown was extended till may (phase-iv, though with significant allowances for transport and industries/commercial establishments). to show this evolving situation, we have subsequently also mapped the nationwide situation on june and again on july (see section . ). two sets of indicators were used for the ensuing susceptibility and vulnerability analyses. for selecting these, we considered all the relevant information at the district level that could feasibly be associated with the covid- outbreak (these datasets were collated from information made available by office of the registrar general of india ( ), mohfw ( ), iips and icf ( ) and similar other sources-see table and table ) . the district-level susceptibility is related to the viral transmission, while the vulnerability denotes the risk of fatality after infection. we identified the various potential indicators based on an extensive literature review (e.g. coudhry and avindandan ; dowd et al. ; frança et al. ; rocklov and sjodin ; sajadi et al. ; who a; zhong et al. ) and the parameters finally selected for both the susceptibility and vulnerability analyses basically encapsulate the district-wise overall socioeconomic, demographic, climatic, health and hygiene conditions. their descriptions and references are listed in table and table , respectively, while the conceptual framework devised for the entire workflow is depicted in figure . since the dispersion of the covid- virus from its source region and its subsequent entry into other locales was mostly via returning air-travellers, the initial spreading centres were most likely to develop around cities that handled large volumes of air traffic. the annual air passenger data for - was collected from the airports authority of india (https://www.aai.aero/en) for international airports across the country. the number of covid- cases within a district was used as an attribute of its centroid, and a spatial buffer analysis was done to understand the relation between the distance from the airport and the number of covid- cases. the inverse distance weighting interpolation method was used to represent the ratio between the number of covid- cases and the number of air passengers for each international airport, with higher ratios obviously indicating the greater likelihood of a large number of covid- cases emanating from or being transmitted by passengers who have passed through that particular airport. the district-level numbers of coivd- cases in the different time periods were visualised through a series of maps. similarly, changes in the virus hotspots and its potential outreach were identified for each time step using the getis-ord gi* statistic (getis and ord ; ord and getis ) . in contrast, the moran's i values (moran ) were used to distinguish between statistically significant covid- clusters and their relations with other such proximate clusters (cf. ). the covid- 's potential outreach was assessed using the vector-based double and vector-based integer assessment through python coding. the euclidean distance was computed from each district's centroid and the number of covid- cases for that district was used as its mass (cf. dong et al. ; klobucnik and malikova ) . as such, the higher the number of covid- cases in a district, the higher would be its outreach potentiality towards the surrounding districts -with this following a distance-decay function (e.g. frolov ; pueyo et al. ). the estimated covid- potential value was normalized (cf. choi et al. ) in the range of - for weighting each conditioning parameter. subsequently, the derived normalized district potential outreach values were also scaled between to and the natural breaks classification scheme was used to group the districts on the basis of their respective values. the term susceptibility and vulnerability are often used interchangeably for individuals and communities with excessive health burdens or issues. more specifically, the vulnerability component indicates the external factors (i.e. exposure to a disease), while the susceptibility aspect refers to the inherent (mostly physiological) characteristics/capabilities of individuals and communities of coping with the diseases (kovats et al. ) . in this study, the covid- susceptibility indicates the efficiency of the disease's spread into regions/communities, whereas the vulnerability implies the degree to which these regions/communities may be unable to cope with the adverse effects of covid- infection and thereby suffer grave health consequences and possible death (kovats et al. ) . so, higher values of susceptibility indicate an enhanced risk of the spread of this infection, while higher values of the vulnerability index imply a greater threat of death from the covid- infection. the epidemiological susceptibility analysis dataset, therefore, includes the actual number of covid- cases in the country along with other relevant socioeconomic, demographic and climatic factors. the socioeconomic susceptibility analysis dataset, on the other hand, excludes the variable denoting the number of covid- cases in a district. we sought to undertake such a dual analysis in order to represent both, the actual situation which has emerged (keeping in mind data limitations and lags) as well as the situation that can arise (i.e. if all areas are eventually targeted or intruded into by the virus, which ones may succumb more easily). while constructing the epidemiological susceptibility index, the maximum weightage was given to the variable denoting the district-wise number of covid- cases, as the virus' mere presence in a district endangers that area the most and makes it more liable to become a spreading centre than any other ambient socioeconomic, demographic or climatic factor. for the socioeconomic susceptibility index, all variables were given almost equal weights (see table ). with the widespread transmission of covid- already underway, it is tricky to conduct any susceptibility analysis using real-time information due to the obvious time-lag between information gathering and analysis. in this paper, we have used the then most recent available data for the districts as released by the mohfw, goi, when we commenced our analysis in the latter half of april . similar to the weightage pattern accorded for the socioeconomic susceptibility computation, the index for ascertaining the socioeconomic vulnerability was also developed by assigning equal weightage to all variables ( table ) . the above computed socio-economic susceptibility and vulnerability indices have some indicators that are common to both and some that are exclusive to each. the justification for each indicator has been mentioned in the relevant tables. for example, some of the indicators which are not related to the spread of infection (and thereby the computation of the susceptibility index) but are associated with fatality (such as old age population and health infrastructure) were considered only while computing the vulnerability index (see table ). the susceptibility or vulnerability index is the normalised value of the un-normalised index. for computing the susceptibility and vulnerability indices, an un-normalised index (i.e. the summation of all the weighted indicators) was first computed (eq. ). after this, a normalised index was prepared, which ranged between to (eq. ). before beginning the statistical enumeration, all the variables were converted to positive directions (i.e. a higher value would show a greater risk of susceptibility or vulnerability). the index construction procedure can be specified as follows: where, w stands for the weight assigned to each ith indicator. the expresses the scale free indicator obtained by dividing the original value (x) by the mean value ( ̅ ) for the variables (eq. ). the rationale of this scale free indicators has been previously analysed in the literature (kundu , c.f. haque . (eq. ) eventually, the normalised index was computed as follows: the final output value obtained ranged between and (normalised index), with a higher value representing a greater risk of susceptibility or vulnerability to covid- . the assessment of spatial heterogeneity in the relationship between two variables may be useful if the presence/numbers of covid- cases is available for all districts. due to the unavailability of this data, we have only focussed on eliciting linear and non-linear relationships of the district-wise number of covid- cases with the ambient socioeconomic, demographic and climatic variables. in computing the linear relationship, we obtained the pearson's correlation plot using the 'corrplot' package in r (wei and simko ) . for the multivariate analysis, the non-linear relationship of covid- cases and its correlates were computed using the generalized additive model (gam), via the 'gam' package in r (hastie ). covid- cases were first diagnosed in india in late january, and crossed , cases by the end of the second week of may (with present numbers in early-august, being more than lakhs). with this highly contagious disease transmitting primarily through international tourists and returning travellers from aboard, the initially affected sites in india were mostly cities that have international airports (or regions adjoining such places) or are major tourist destinations. this is made apparent by the district-wise spread pattern of the covid- virus ( figure ). in the first phase ( figure a ), cases were reported from western india (around mumbai and ahmedabadtwo of the main commercial hubs of the country), from around new delhi (the national capital) and ladakh (popular tourist destination and a prominent indian army base) and from the southern states of kerala (from where many residents migrate/travel for work to the gulf region), tamil nadu, andhra pradesh and karnataka (all of which have major metropolitan centres and commercial hubs-chennai, hyderabad and bengaluru). further intensification of the above pattern in the next time step of th march was apparent, with the adjoining regions reporting substantial case numbers ( figure b ). broad swathes of the eastern part of the country still remained mostly unaffected, except for kolkata (the major regional metropolitan centre) and its surroundings. in the next time step ( th april ), two large contiguous zones in northern india and western-central-south india april ( figure d ), showed the merging of the two entities described above, with infilling of their intervening districts (i.e. reporting of cases from previously unaffected areas) and a rise in cases in districts already afflicted. this resulted in a near-continuous stretch, from kashmir to kanyakumari, along the central and western corridors and down the eastern and western coastal belts, reporting covid- cases. by now the eastern zone had noted a rise in cases (with its epicentre at kolkata). this manifested as a narrow line of districts along the densely populated ganga plains in uttar pradesh and bihar, which merged into the larger/more contiguous zone further west. the above trends highlighted that, as expected, the distance from an international airport and the numbers of covid- cases were characterised by distance-decay [i.e. were inversely correlated and with increasing distance from the airport, case numbers decreased (figure ) ]. during the successive lockdown phases, the percentage of cases within km of an airport had decreased slightly, but numbers rose gradually for locations within - km of an airport. thus, districts situated within this distance buffer ( - km) seemingly had a higher probability of being affected by covid- and thereby swelling the overall case numbers. this indicated that the virus had spread out from its initial centres during the latter part of the lockdown and that its footprint was becoming much more apparent across the hinterland. of the international airports examined, the ratio of air passengers to covid- cases were far higher for the mumbai, delhi, bengaluru and hyderabad airports ( similarly, hyderabad and bengaluru (the main information technology hubs of india) are also entwined with global markets while new delhi (the national capital) is connected by flights worldwide for diplomatic, administrative and tourism purposes. thus, the initial outbreaks occurred mostly through these four airports. as mentioned before, many residents of kerala work in the gulf countries and this state is also a major tourist destination, with numerous flights routed to it through the mumbai and bengaluru airports. therefore, it was also an initial hub of covid- cases. the getis-ord gi* method was used to identify the spatial distribution of potential hot spots (statistically the location of the cold spots remained almost similar to that discerned from the pre-lockdown phase data of rd march , with clustering mainly around west bengal. the mid-lockdown phase data of th april ( figure c ) indicated intense clustering of high values around maharashtra and gujarat. however, the initial high values clustering around kerala started diminishing in this mid-lockdown phase, possibly due to the pre-emptive actions regarding testing and quarantine taken by the kerala state government and the union government's policies. in fact, kerala was initially considered as the first indian state likely to 'beat the curve' when it showed a continuous downtrend/decrease in its number of active covid- cases from th april till th may (this situation has subsequently changed markedly for the worse and the patterns/trends as of st june and th july for the whole country have also been discussed in section . ). the cold spot intensity had declined in the eastern part, almost throughout west bengal. the th april dataset ( figure d ) revealed a much more concentrated hot spot with a z-score of . in maharashtra and gujarat. by then, the entirety of kerala and andhra pradesh had ceased to be part of any hot spot region. however, the area and intensity of the cold spot region located in the eastern part of the country had also declined significantly, indicating that the next phase of the virus' spread could target this zone. again, subsequent events and updated news reports about the covid- spread has validated just this, with the eastern region around kolkata presently emerging as one of the most affected by the pandemic. while the getis-ord gi* analysis of the district-level covid- cases identified the clustering of low and high index values, it only delineated large clusters through neighbourhood analysis and ignored those districts that had high numbers of cases but were surrounded by low-value neighbours or vice versa. thus, the mo n's i (jackson et al. ) was computed to obtain additional insights into the statistically significant high-high, high-low, low-high and low-low clusters derived previously for each of the four datasets (figure ) . orissa are easily visually correlated as districts with high epidemic susceptibility. the potential gravity of the covid- spread was assessed for the four different time steps to ascertain its likely outreach areas (figure ). the possible potential outreach on rd march ( figure a ) was mostly around the delhi ncr (national capital region). some small outreach pockets were seen in kerala and maharashtra (e.g. mumbai and pune). from the th march dataset ( figure b ), potential outreach epicentres were found in three significant locations-delhi-centric, mumbai-centric and kerala-centric (due to reasons outlined in section . ). in the th april dataset, kerala displayed a marked improvement in controlling the outbreak, as discussed previously ( figure c ). however, rapid growth was observed for mumbai and its surrounding areas and this scenario continued into the next phase as well ( figure d ). we thus predicted that based on the potential outreach analysis, the gravity of the covid- outbreak was likely to be very high in western india, especially in maharashtra. the current situation reflects this, as this state ranks highest within india in covid- incidence with over . million reported cases, numbers of active cases as well as deaths (india covid- tracker at https://www.covid india.org/ as on st october ). maharashtra is overwhelmingly afflicted in mumbai and its nearby areas of thane and pune. neighbouring gujarat has also been hardest hit in ahmedabad, surat and vadodara. as per the performed potential outreach analysis, the north-eastern states (except assam) and the himalayan states are relatively less affected by the covid- outbreak. however, the eastern districts of bihar, jharkhand and west bengal are seen to gradually come under the pandemic's grasp, over the different times-steps, pointing towards this zone possibly carrying forward the rising patient numbers in the near future, as the spread in western/northern india may start to peak or gradually decline. most of the covid- afflicted residents in eastern india have a travel history from either mumbai, kerala or delhi. initially, only a few cases were observed in this region due to its lower volume of international air traffic (as denoted by the lower air passenger to covid- case ratio) but case numbers have risen during the latter lockdown phases and beyond it due to inter-state in-migration from the western and southern parts of the country, particularly as a result of large numbers of returning migrant workers (mullick ) . overall, the potential outreach analyses denoted that the virus' epicentres have been mostly concentrated in and around mumbai in maharashtra. as kerala and also karnataka initially recovered quite quickly, the earlier epicentre in southern india was reduced during the subsequent lockdown phases (however, infections have again risen sharply in karnataka and tamil nadu towards the end of the final lockdown phases in may as restrictions have relaxed and presently, these two states along with andhra pradesh occupy the second to fourth positions in the country in terms of covid- incidence). the eastern part of the country now faces the imminent threat of becoming an epicentre if further transmissions into the region occurs from the ongoing return of many currently unemployed migrant labourers from other parts of the country and consequent community transmissions. the comparative outlooks of the undertaken hotspot and the potential outreach analyses differed slightly in perspective. while the hot spot enumeration discerned covid- affected zones based on the actual ground situation/data as ascertained for that point in time, the potential outreach maps denoted the gravity factors for the four different time periods and depicted how conditions may worsen in the major epicentres or have eased off in other areas (based on the then available data). the outreach analysis thus gauges the outbreak's potential across india and denotes zones likely to be affected next. using the indicators listed in table and table , we had developed the area-based composite covid- susceptibility and vulnerability indices at the district level-for india, with a view towards providing policy makers with some indication on which districts are likely to be most susceptible or vulnerable to a covid- outbreak and specifically where should the government target its resources and accordingly plan a data-driven intervention strategy. the elicited results from these indices are presented below. a five-pronged classification scheme (ranging from very high to very low) was used to visualise the enumerated district-level epidemic susceptibility values (derived using quintile class- table ). there are significant regional clusters in the northern, eastern, southern and parts of the north-eastern states of india (figure ). large swathes of south-western and northern india, covering most districts of kerala, tamil nadu, telangana, andhra pradesh, karnataka, maharashtra, gujarat, rajasthan, delhi, haryana and punjab are highly susceptible to this pandemic. primarily, these were the areas where the initial outbreak occurred and the subsequent transmission of has been phenomenal, with people therein being seemingly less able to cope with the covid- virus (i.e. their physiology is more easily affected by it). possibly, the prevalence of urbanization (which creates congestion), an existing burden of non-communicable diseases (hyper tension, diabetes and obesity) and a greater proportion of the elderly population in these regions may have heightened the overall epidemic susceptibility. ironically, most of the highly urbanized and economically well-off states seem to have reported higher covid- susceptibility, since the initial epicentres of the virus outbreak were in their large cities. contrarily, almost all districts in the seven north- susceptible to the pandemic. it is interesting that despite being economically poorer and having low indicators with respect to almost every socioeconomic and health related parameter than the rest of india, these areas are less susceptible to the pandemic, suggesting that the covid- outbreak might be an erratic phenomenon that cannot be explained solely by traditional socioeconomic theories and which might require further investigation. as many districts in the moderate susceptibility to covid- class lie in economically poorer zones, this can have important connotations in terms of impaired health-care services and facilities, thereby deteriorating immune response and patient recovery. furthermore, as discerned in previous sections, india's eastern region is likely to become a secondary virus epicentre. thus, even though this zone is denoted in the moderate susceptibility category, its lower socioeconomic standing and existing poorer healthcare assets and availability/accessibility accord it high priority for pre-emptive future resource allocation in order that the likely forthcoming challenges can be met adequately. figure visualizes the socio-economic susceptibility index for india's districts, following a similar classification to that adopted for figure (see table ). the underlying assumption of this particular index is that if all districts are evenly infected by the covid- outbreak, then what would be the magnitude or susceptibility of further transmission in a certain area, with this being dependant on its socioeconomic status. results reveal that large portions of eastern, north and north-western india are high to very highly socioeconomically susceptible to this pandemic. these areas are particularly characterized by high population densities, chronic malnutrition, poor health infrastructure, larger family sizes, poor hygiene practices, poverty concentration and marginalization including lower health-related knowledge and awareness, thereby precipitating such outcomes. on the contrary, most districts in the north-eastern, southern and extreme northern regions (e.g. in the northern part of rajasthan and in punjab, himachal pradesh, jammu and kashmir and uttarakhand), and are found to be socioeconomically less susceptible in terms of covid- transmission. interestingly, some areas that initially had higher numbers of covid- cases have emerged in the low susceptible category (e.g. kerala) and this merits further explanation. in kerala, after the initial outbreak was reported, effective state government measures temporarily lowered further transmissions by facilitating mass testing, awareness creation at the community level and though stringent physical distancing and lockdown norms. alongside this, most importantly, there has been efficient management of both international and inter-state migrants in the state. however, conditions have progressively worsened as restrictions have eased, and large numbers of expats have returned from the gulf region and from other parts of the country (nidheesh ) . the state has also seen a very high jump in the number of reported cases in the aftermath of the annual onam festival (held from august to september) (the hindu ), with numbers rising from about , before it to above , presently by the end of september (india covid- tracker at https://www.covid india.org/ as on st october ). with the autumn festival season approaching fast, there are thus grave fears that there could be a significant rise in case numbers across the country (cna ), while fears over such a rise have also affected local economies further (sharma ) . aspirational districts (ads) are more susceptible to covid- outbreaks due to their already limited coping-up capacities, as they are some of the socio-economically poorest/most backward regions of india. the overall health infrastructure and particularly the numbers of primary and community health centres in such locales are also less, with limited staff and bare minimum facilities further compounding the issue. however, the incidence of covid- cases in these areas was initially fairly low, being less than % (a total of cases as of th may ) of the total cases nationwide. of the ads affected by the virus on the above date, the worst-hit have been ranchi ( cases), baramulla ( ), ysr ( ), nuh ( ), jaisalmer ( ) and kupwara ( ), which are all located in the red zone (the locales that faced the most stringent lockdown norms) as per the indian government's classification. considering their susceptibilities, the goi (through the niti aayog) has taken steps to ensure appropriate and timely action for resolving supply shortages in test kits, personal protective equipment (ppe) and in providing masks to the respective empowered populations/groups in these districts. we were also able to identify these districts based on their respective susceptibility indicators, e.g. percentage of poor population, household size, impaired child health (i.e. suffering from anaemia, underweight or stunted development), and poor female health (anaemia and underweight). apart from these ads, we further identified some other districts that are also quite susceptible due to their socioeconomic background and these areas (most districts of madhya pradesh, orissa, andhra pradesh, bihar, jharkhand, west bengal and uttar pradesh) need support similar to that being provided to the ads (i.e. urgent supply of testing kits, ppe and masks). based on the selected set of indicators, the discerned socioeconomic vulnerability to the covid- 's impact ( figure ) is likely to be higher in many districts of madhya pradesh, orissa, telangana, andhra pradesh, bihar, jharkhand, west bengal and uttar pradesh and these areas are likely to report higher fatalities. there is a % overlap of the places most at risk in these states with those demarcated under the union government's aspirational districts programme, i.e. of the discerned highly to very highly vulnerable districts are also ads. the scarcity of healthcare facilities and personnel in these districts remains a major issue and such areas also have a large number of inter and intra state migrants, who have steadily returned home during the lockdown. therefore, it is quite possible that cases of covid- infection shall sharply rise in these locations and that the poorer medical infrastructure shall increase the infection rate and incidence of deaths, if adequate measures are not taken. contrastingly, this impact shall be markedly lower in the states of kerala, punjab, haryana, himachal pradesh and in most of the north-eastern states and the rann of kachch (in gujarat). some districts of tamil nadu, gujarat, rajasthan and maharashtra are moderately vulnerable. the enumerated index values are higher in some districts due to these housing a greater proportion of those that are more vulnerable to this contagion (i.e. more number of children and women who are anaemic and/or underweight, lower female education levels and a higher prevalence of diabetic patients). therefore, these districts are likely to find it difficult to cope with the covid- threat and its related morbidity aspect. on the other hand, the lesser vulnerable districts seemingly do have sufficient capability to deal with the threat, as observed in the districts of kerala, from where very few morbidity cases were initially reported, compared to the other parts of india, despite this state being an early epicentre of covid- . figure shows the correlations derived between the covid- cases (i.e. the number of cases per district) and its socioeconomic, demographic and climatic factors. this pandemic is positively associated with the percentage of urban population and the population density of a district. it is also positively associated with the percentage of women having attained th or lower standard of schooling. furthermore, districts with a higher share of poorer households ( %) had lower viral transmissions. in the second half of april , although the virus had spread across districts, the gravity of the outbreak was mostly concentrated in districts that were major urban agglomerations, such as mumbai, delhi and hyderabad. people in urban areas are relatively more mobile (with the resultant greater public transport congestion and crowds) than ruralites. they may also be forced to maintain lower residential and social distances due to the higher densities of built-up zones as well as population, especially within slums areas where housing shortages are quite severe (haque et al. ) . these factors together with the inherent economic deprivation faced by slum residents would likely enable a more widespread outbreak in such congested locales (ahmed et al. ) , as has been evidenced by the large numbers of cases reported from the dharavi slum area of mumbai, which is one of the largest such entities in asia. this is also the likely cause for the extremely high number of infections being subsequently reported from delhi and its surrounding urban agglomeration and from chennai and its neighbourhoods. as urbanites generally attain a higher level of education, the pandemic's outbreak is also positively associated with the educational status, more so because this 'imported' virus mainly came into the country via air-travel (i.e. from the movement of economically well-off sections of the population, who can be expected to have also attained higher education levels). the above bivariate linear relationships do not provide the non-linear associations between variables. for this, the multivariate non-linear association was evaluated via the gam. the outcome variable for this model was the cumulative number of covid- cases in the district, i.e. the total tested/confirmed positive cases. the obtained findings predict a flexible relationship between the enumerated variables ( figure ). districts with a population density between - people/km specifically have a higher risk of this virus spreading amidst them. of the districts affected by the virus (as per the last date on which the data for this paper was collected), apart from a few situated in urban metropolitan cities, all others contain medium to large towns which have a moderate level of population density. the highly urban districts face a greater threat of a covid- outbreak, particularly when the urban population share crosses %. in the urban agglomerations of india, a significant proportion ( . %) of residents live in slums (e.g. about half the population of greater mumbai lives in such locales). while they play a vital role in the city's functioning, these slum areas are poorly planned and obviously very densely populated, as a result of the ever-accelerating urbanization trend in india. such sites thus become potential hotspots for infectious diseases like covid- . this unplanned urban growth also poses considerable risk in terms of impaired preparedness and ready response to any infectious disease outbreak, with mass quarantining at such close quarters, while maintaining social distancing, being almost impossible. hence, the responses of healthcare officials, governments and communities to this ongoing pandemic can be devised towards generating a paradigm shift in how urban spaces and residences are planned and designed, with possible ramifications for future peri-urban transformations, inner-city renewal and slum rehabilitation (jha ; regmi ; van den berg ). the findings also suggest that although districts with a higher prevalence of children suffering from anaemia and/or being underweight face an elevated risk of this viral transmission, the relationship slope is not very significant. thus, these health indicators are not strongly correlated with covid- cases in the indian context. a possible reason for this seemingly discordant finding is that may be the goi and/or state governments had till the last date of the initial data collection for this paper (i.e. th april ) not conducted an adequate number/proportion of population-level tests, rather testing only those who had already developed covid- related symptoms. therefore, a similar analysis performed on a bigger and possibly more representative sample obtained via large-scale population-level testing may yield better explanations. several studies have found that climatic parameters such as mean annual temperature and relative humidity have a crucial role in spreading the covid- virus (sajadi et al. ; , with evidence suggesting that a mean temperature of °c and a medium to high ( % to %) relative humidity range is most suitable for its transmission. the greater majority of india's districts have a higher daily mean temperature than °c in april and except for a few districts in the himalayan and coastal belts, all districts have an average relative humidity less than the suitable level. therefore, unlike as discerned in other studies, we could not find any significant relationship between the currently prevalent climatic parameters and this viral outbreak. the lockdown measures in india were extended to may (phase-iv, though there were significant allowances in terms of movement and industries/commercial establishments gradually during this period), with the period from june till june being denoted as unlock- and again as unlock- (from july to july), as the nation reopened and eased off restrictions further. each of the three attributes-the spread of covid- cases, the clustering of cases and the hot/cold spots have thus evolved further since this study was commenced with the initial database of the first few lockdown phases in mid-april, . this section has thus been prepared to show the changed conditions as on st june , and on th july , in the above aspects, thereby denoting the complete scenario at the end of all the lockdown phases, that effectively ended on st may , and the continued evolution of the disease in india during the unlock- ( - june) and unlock- ( - july) phases. it was apparent that the spread of covid- in india could not be wholly attained simply by the various lockdown measures. this was evidenced by the overall continued rise in case numbers throughout the country [ figure in the central portion of the country overall cases were still relatively on the lower side. hotspots were clustered mostly in a broad swathe along the western and southern region [ figure (b)]. cases in the western part of the country were more intensely concentrated in certain districts, as was evident from the low-low and low-high clustering patterns [ figure (c)]. the covid- crisis' impact on society and the global economy has been profound and likely to be long-lasting. possibly, governments either underestimated its threat or did not have robust enough socio-political systems and healthcare infrastructure to combat transmissions. instead, while helpful, the lockdown measures have engendered economic instability and developing nations have been the worst affected, trying to contain the pandemic while addressing rising unemployment and at-stake livelihoods of a vulnerable population. thus, it is paramount that correct and sustainable economic/socio-political decisions are taken. for this, proper predictions of the pandemic's path, with pinpointing of areas that it can affect the most, are pertinent, for prudent and targeted resource allocation. our analysis has highlighted the initial centres of the covid- pandemic in india and its spread. by identifying its hotspots and significant clusters, we pinpointed locales where possible community transmissions have occurred. our computations were based on the data garnered during the initial lockdown phases implemented in india. however, subsequent reports of the pandemic's spread have largely validated our earlier estimates of the areas that were most likely to be affected (i.e. the virus gaining a foothold and then spreading in various clusters of eastern india, around kolkata). our analysis thus lays the groundwork for identifying future hot spot zones so that communities and local governments can anticipate and allocate critical resources accordingly. mass testing of covid- in such hotspots can curb the disease's spread into adjoining areas. by also designating locales that are relatively safer and less susceptible/vulnerable to the pandemic (i.e. cold spots), we also provide a framework for earmarking places where economic activities can be carried out more safely, to boost flagging economies. we have also identified districts that are more vulnerable to the virus. these locations can, if possible, strive to build food stocks to avoid any food-security related issue in case sudden lockdowns are again required if a second wave of the virus arises. in the most vulnerable cities and the suburban areas located within - km around them, crowds in market places must be stringently restricted, with continued social distancing norms and masks being mandatory. districts that have high epidemiological susceptibility need enhanced vigilance (possibly through specially constituted rapid-action teams and through detailed co-morbidity surveys) to avoid transmissions and a higher incidence of death. areas that are socioeconomically susceptible face the greatest threat as they house substantial numbers of people who may not be physiologically capable of coping with the covid- virus. overall, our demarcated hot and cold spot areas and those that are epidemiologically susceptible or socioeconomically vulnerable tallies quite well with the red-orange-green containment zones delineated by the goi (ndma ), providing further validation of the performed analyses. there are still some parts of india where the covid- has not been able to intrude significantly, especially in physiographically rugged and isolated tracts and in some rural hinterlands. it is paramount that these locations be guarded against community transmissions while more afflicted areas are dealt with adequately. though the quickly enforced lockdown no doubt caused much misery, especially for migrant workers 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. world health organisation exposure to air pollution and covid- mortality in the united states. medrixv (preprint) effects of temperate and humidity on the daily new cases and new deaths of covid- in countries association between ambient temperature and covid- infection in cities from china prevalence of comorbidities and its effects in patients infected with sars-cov- : a systematic review and meta-analysis relationship between the abo blood group and the covid- susceptibility. medrxiv preprint knowledge, attitudes, and practices towards covid- among chinese residents during the rapid rise period of the covid- outbreak: a quick online cross-sectional survey the authors are grateful to their respective institutions for providing the infrastructure required to conduct this research. the assistance of ms. sayoni mondal, research scholar at the department of geography, presidency university, kolkata, india in arranging the article references is gratefully acknowledged. none percentage of the total population living in urban areas urban areas are particularly most vulnerable as they are the initial centres of the outbreak. the prevalence of slums within cities especially raises the risk of this viral transmission (coudhry and avindandan ) .office of the registrar general of india ( ) percentage of women having th standard education and aboveproxy parameter for the awareness about the covid- spreading. it is assumed that if an area has a higher proportion of women or more years of schooling, then overall household awareness will be higher and this can lower transmission (zhong et al. ). ( ) percentage of households exposed to smokingsmoking or being exposed to smoking in any form can elevate the risk of infection from covid- (who ). wealth status the economically wealthier section can make better arrangements for rigid interventions such as lockdown while poor people may be forced to go out to arrange food supplies. accessing meals from community kitchens, receiving food items from donations, buying essentials items from the government fair shops, may elevate the probability of the less economically well-off sections to catch the infection. percentage of households exposed to smokingsmoking may not only increase the risk of viral transmission but also raise the probability of dying, as the covid- primarily afflicts the pulmonary system. key: cord- -zriofqez authors: marbaniang, ivan; sangle, shashikala; nimkar, smita; zarekar, kanta; salvi, sonali; chavan, amol; gupta, amita; suryavanshi, nishi; mave, vidya title: the burden of anxiety during the covid- pandemic among people living with hiv (plhiv) in pune, india date: - - journal: res sq doi: . /rs. .rs- /v sha: doc_id: cord_uid: zriofqez introduction : there is a dearth of data on anxiety related to the covid- pandemic from people living with hiv (plhiv). this is a cause of concern as anxiety is associated with antiretroviral therapy (art) nonadherence. globally, india has the third largest population of plhiv and third highest number of covid- cases which are rapidly increasing. therefore, it is crucial to understand the burden of anxiety and its sources among asian indian plhiv during this pandemic. methods: we used data from a telephonically delivered assessment among plhiv engaged in care at a tertiary healthcare associated antiretroviral therapy (art) center in pune, india. assessments were conducted between april and may , , one month into the government mandated lockdown. gad- was used to assess for anxiety over two-preceding weeks. significant sociodemographic and clinical differences between groups (gad- < and gad- ≥ ) were assessed using fisher’s exact and wilcoxson rank sum tests, for categorical and continuous variables, respectively. thematic analysis was employed to analyze an open-ended question that asked about the most pressing cause(s) of concern. results : of plhiv contacted, median age was years (iqr: – ), % (n= ) were cisgender women and % (n= ) had a monthly family income< usd. thirty-eight percent (n= ) had prior history of tuberculosis and % (n= ) were living with another comorbidity. a fourth ( %, n= ) had gad- scores indicative of generalized anxiety. plhiv who had fewer remaining doses of art had significantly higher gad- scores compared to those that had more doses (p= . ). thematic analysis indicated that concerns were both health related and unrelated, and stated temporally. present concerns were often also projected as future concerns. conclusions : in a group of socioeconomically disadvantaged plhiv, a fourth were found to have anxiety, that appeared to be influenced by concerns about art availability. furthermore, the persistence of sources of anxiety and therefore an increase in anxiety for these plhiv is anticipated as the pandemic worsens in india. we recommend the regular utilization of short screening tools for anxiety to monitor and triage plhiv as an extension of current hiv-services. across the world, the covid- pandemic and subsequent lockdowns authorized by governments as containment measures have had a profound impact on mental health. studies from diverse settings have consistently reported an increase in the burden of mental health conditions during this period [ ] [ ] [ ] . it is however recognized that the differential power structures which shape social hierarchies, could also be instrumental in making certain groups more prone to worse mental health [ ] . this includes people living with hiv (plhiv) who already have a disproportionately higher burden of mental health conditions [ ] . presently, there is a dearth of data for plhiv, obfuscating our understanding of the pandemic's effect on mental health among them. from a public health standpoint, an important aspect of understanding mental health among plhiv is the association it has with hiv treatment outcomes and transmission dynamics. depression is associated with treatment failure [ , ] , lower cd count and risky sexual behavior [ , ] , and anxiety with disengagement from care [ , ] . the importance of generating data on mental health among plhiv, in the setting of the pandemic, where reported mental health is worsened, can thus be inferred. india has the third largest population of plhiv [ ] and as of july , the third highest number of con rmed covid- cases globally [ ] . in a recently published meta-analysis of studies from india, anxiety or depression were identi ed as risk factors for art nonadherence [ ] . in yet another meta-analysis, that included data from india, anxiety was found to be associated with % higher odds of nonadherence [ ] . therefore, the pandemic through declining mental health, could have a crippling effect on india's hiv response that functions within an overburdened health system [ ] , that is further being paralyzed by rapidly increasing covid- cases [ ] following the easing of lockdown restrictions on june , [ ] . taking into consideration the ndings of the two aforementioned recent meta-analyses; assuming that in a crisis like the covid- pandemic, anxiety precedes depression; and recognizing that the two conditions co-occur frequently [ ] , we sought to assess the burden of anxiety symptoms and their sources among plhiv in pune, india. we used data from participants (≥ years) enrolled in a -month prospective cohort study that is seeking to understand the development of non-communicable diseases among plhiv. the details of this study have been reported elsewhere [ ] . participants in the cohort are registered for care at the antiretroviral therapy (art) center a liated to byramjee jeejeebhoy government medical college and sassoon general hospitals (bjgmc -sgh), a publicly funded tertiary healthcare center in pune, india. the art center functions under the aegis of the national aids control organization (naco): india's premier hiv governmental agency, and currently caters to approximately plhiv from lower and lower-middle socioeconomic backgrounds. pune, a city in western india, has consistently reported a high prevalence of hiv, compared to the national average ( . % versus . %) [ , ] . it is also located in maharashtra, a state that is worst affected by the pandemic, contributing to a third of all con rmed covid- cases in the country [ ] . the city announced a second lockdown on july , following a surge of covid- cases [ ] . in order to reschedule planned th year study visits, in view of the government mandated lockdown, participants were telephonically contacted by two study counsellors, on a phone number that had been previously consented upon. contacted participants were additionally verbally consented for a single time point general anxiety disorder- (gad- ) assessment in marathi (the locally spoken language) which is freely available online [ ] , a covid- symptoms screening based on the us cdc checklist [ ] , and history of exposure to covid- . the gad- assesses anxiety symptoms using a series of questions within a timeframe of weeks. an open-ended question followed these assessments, "in the present situation, what is/are the most important thing(s) that you are worried about?" for this analysis, we used data collected between april , and may , . the ethics committee of bjgmc-sgh approved this project. participants were rst divided into two groups based on their gad- scores. those with gad- scores < were assigned to one group and those with scores ≥ to another. the cut-off of gad- ≥ has been shown to be % sensitive and % speci c for generalized anxiety disorder [ , ] . the distributions of participants' sociodemographic and clinical characteristics were described over these two groups. wilcoxon rank sum and fisher's exact tests were used to evaluate signi cant differences for continuous and categorical variables, respectively. as sensitivity analyses, the cut-offs for gad- were also speci ed at scores of , and . a two-tailed p-value of . was used to infer statistical signi cance. all analysis was performed using stata . . responses to the open-ended question as noted by the counsellors, were rst translated verbatim from marathi into english, by a translator pro cient in both languages. thematic analysis was utilized to analyze the responses. data was coded independently by two authors (im and sn) employing an inductive approach. codes and themes were identi ed directly from the responses. the results we present are situated within a broadly essentialist framework, where the material and experiential reality of participants was taken at face value [ ] . codes and themes were organized in nvivo . of participants scheduled to be contacted, % (n = ) were contactable. three attempts on two separate days were made to contact all participants. the most common reasons for participants not being contactable were: i) participants choosing not to receive phone calls ( %, n = ); ii) participants being out of cellular coverage area ( %, n = ); iii) the phone number provided no longer being in use ( %, n = ). none of those contacted refused the gad- assessment, and the scale had high internal consistency for the study population (cronbach's alpha . ) study population characteristics and ndings from statistical analysis median age of the participants contacted was years (iqr: - ), most were cisgender women ( %, n = ) and % (n = ) had a monthly household income of < usd. prior to the lockdown, a majority ( %, n = ) had been employed in the informal sector. thirty-eight percent (n = ) had history of tuberculosis and % (n = ) were living with another comorbid illness. a signi cant proportion were not aware of their latest cd counts ( %, n = ) or viral loads ( %, n = ) ( table ) . two participants reported exposure to symptomatic sars-cov- individuals though none of the participants reported positive symptomatology. median gad- score for the study population was (iqr: - ), range - † informal sector employment for women mainly included working as house maids or domestic help ( %), for men this was mainly as daily wage laborers ( %) ‡ living with a spouse: no includes plhiv who are single, widowed, separated or divorced § comorbidity includes having any of the following: copd, asthma, cvd, hypertension, diabetes, renal disease, cancer. approximately % (n = ) had gad- scores ≥ . when dichotomized by gad- scores, plhiv with fewer median days of remaining art appeared to have higher scores compared to those who had more days of art (p = . ) ( table ). this remained signi cant even when the gad- cut-off was raised to (p = . ). there were no signi cant differences observed for the other variables (table ). this remained true even when gad- cut-offs were changed. when strati ed by gender, cisgender men living without a spouse appeared to have higher gad- scores as compared to cisgender men living with a spouse (p = . ). gad- scores were independent of living with a spouse for women (supplementary le). similarly, we observed minimally signi cant higher gad- scores among men whose monthly family income was < usd compared to those who had higher monthly family income (p = . ). however, these ndings were no longer signi cant when the gad- cut-off was changed to , or , indicating signi cance to be a function of the cut-off used and hence unreliable. the open-ended question was added after participants had been contacted. a further participants declined to answer the question, so thematic analysis was conducted on a subset of participant responses. relative to cause(s) for concern, assessed through the open-ended question, four themes were identi ed. these were a) concerns related to the immediate present; b) concerns related to the imminent future; c) lack of social and nancial support; and d) indifference to circumstances secondary to covid- . themes a) and b), were further classi ed as health-related or health unrelated. cognizant of the qualitative framework of thematic analysis, we do not quantify the exact number of participants that expressed each theme. however, themes a) and b) were expressed by approximately two-thirds; c) by roughly half and d) by a third of the participants. a) concerns associated with the immediate present health-related: these were articulated as perceptions of increased susceptibility to covid- or beliefs of being infected with covid- in the absence of symptoms. these appeared to directly stem from participants' selfawareness of hiv-resultant immunode ciency. "i have low cd counts and i am also taking medicines for tuberculosis. i am scared that i will get infected with coronavirus." (age range: - , cisgender man, gad- score: ) "i have low immunity because of hiv, i am worried of getting covid- infection. i feel that even a common cold could be coronavirus." (age range: - years, cisgender woman, gad- score: ) health unrelated: financial insecurity resulting from unemployment and a lack of savings, predominantly drove apprehensions about food security, eviction and the ability to provide for the family. "i am a construction worker. i am at home with my two children. my wife is dead. currently i am worried about how the house will run as there is no money and no work." (age range: - , cisgender man, gad- score: ) "as the only earning member of my family, i am worried. my children are young. we are doing whatever it takes to get by, but because of the lockdown i am unemployed now. the house is rented. i cannot return to my village either." (age range: - , cisgender man, gad- score: ) "there is no food at home currently and i cannot feed my children. i am a housewife and i have no income or savings. the children used to earn by washing cars." (age range: - years, cisgender woman, gad- score: ) b) concerns associated with the imminent future health-related: these were articulated as apprehensions about covid- persistence continuing to endanger personal health, following reopening. "i work as a care counsellor in the art centre. there are no coronavirus patients at this time point, but i am worried what will happen if they visit the centre in the future?" (age range: - years, cisgender man, gad- score: ) "i am scared to return to get my medicines at the art centre after the lockdown, if coronavirus does not end. coronavirus must end." (age range: - years, cisgender woman, gad- score: ) health unrelated: fears about shortages of opportunities for gainful employment or dismissal from current employment fed into anxieties about an uncertain future that such eventualities would ensue. such fears also often co-existed with an anticipation for "normality". "i am going to lose my job because of this lockdown. i am eager to know when will covid- end, when will we go back to normal life?" (age range: - years, cisgender woman, gad- score: ) "i stay with my mother and sold fruits for a living. now that has closed, and i don't know when i will be able to start again. when will covid- end? when can we start normal life?" (age range: - years, cisgender woman, gad- score: ) c) lack of social and nancial support: isolation from family members and friends accompanied feelings of loneliness and helplessness, and the lack of nancial buffers perpetuated these feelings. "i stay alone. i used to run a beauty salon that i rented, which is now closed. i have no money to pay the owner who is asking for rent. i have no savings and no one to talk to. i have a lot of tension and i feel lonely." (age range: - years, cisgender woman, gad- score: ) "i stay alone. my daughter is recently married. i worked in a company but it has closed. i have no salary and i stay in a rented house. i receive no help from my in-laws who stay in the same neighborhood." (age range: - years, cisgender woman, gad- score: ) this theme was also common among migrant workers from outside or within the state. "my family is in bihar (a state miles to the east). i want to go home, but i can't. there is a lot of tension and i worry a lot. i have no work and no money now." (age range: - years, cisgender male, gad- score: ) d) indifference to circumstances secondary to covid- : some remained unperturbed by the pandemic and its control measures. however, this indifference appeared to be closely linked to a sense of security, by virtue of a profession, continuing employment or location. "i work in the elds. there is no coronavirus there. everything is ne." (age range: - years, cisgender man, gad- score: ) "now, i have work on the sewing machine and i am not worried at all." (age range - years, cisgender woman, gad- score: ) "i do not get out of the house and i am not worried at all." (age range: - years, cisgender woman, gad- score: ) discussion a fourth of the participants had scores indicative of generalized anxiety disorder, which were not differential by age, gender, or socioeconomic background, underscoring the pervasiveness of anxiety symptoms in the current pandemic. additionally, a range of health-related and health unrelated factors directly linked to the pandemic, affected participants' perceptions, and shaped their present beliefs and future expectations. compared to a hong kong study conducted during the early phases of the pandemic among hiv-uninfected individuals, that utilized the same scale and had comparable age and gender distributions [ ] , our results are marginally higher. however, in comparison to estimates from the largest study to report on anxiety symptoms among asian indians plhiv [ ] , our estimates are notably lower. we attribute this incongruency primarily to differences in scales and classi cations used in both studies but acknowledge that perceptions of diminished vulnerability to covid- among some, as evidenced in our qualitative ndings, could also play a role. it is therefore imperative that our results are not interpreted in isolation, but in the context of the evolving pandemic in india. as mentioned earlier, nonadherence to art is one of many adverse effects of anxiety [ , ] . while our study population is appreciably small, potential nonadherence in a fourth of it, could have far reaching consequences on viral suppression, hiv-transmission and antiviral resistance for the community [ ] . further, mental health services are not integrated within the indian hiv-care delivery framework [ ] . accordingly, linkage of participants to these services falls outside the realm of hiv-programmatic capabilities. given india's severe shortage of trained mental health professionals [ ] , such linkages are not always feasible. in the current pandemic when mental health conditions are on the increase [ ] , linkages become even more challenging. since anxiety, de ciency of mental health services and art nonadherence are interdependent [ ] , it is not di cult to surmise the negative effect that the pandemic could have on india's - - goals. for our participants' that had gad- scores ≥ , we intend to follow-up with them and repeat the assessment after two months. in the event that they have persistently high gad- scores, we will link them to a mental health professional at bjgmc-sgh. we identi ed three themes that broadly encapsulated our participants' cause(s) for concern, which extended across a wide range of gad- scores. as exhibited in their remarks, while one theme could be a predominant cause of concern, more often than not themes were interconnected. thus, a present cause of concern could also be a recurring future concern. it is not untenable to extrapolate from our participants' statements that the chronicity of a particular concern is directly dependent to the rapidity with which their nancial, social or apprehensions about personal health are addressed. we have represented this as a conceptual framework in fig. . although the themes we identi ed may not seem speci c to plhiv, they must rst be contextualized to our participants existing socioeconomic backgrounds and the manner in which the pandemic will potentially affect their vertical social mobility. secondly, they need to be understood from the aspect of how low socioeconomic status and restriction in social mobility will in turn affect hiv treatment outcomes. more than half of our participants have a) less than the - estimated monthly per-capita income for india [ ] ; b) less than years of education, and c) were employed in the informal sector or didn't have employment prior to the lockdown. the response of the indian government to address the nancial crisis being faced by the poor as a consequence of the lockdown has been in the form of two programs, namely the pradhan mantri garib kalyan yojana (pmgky) and the second tranche of the atmanirbhar bharat [ ] . these stimulus programs have been criticized as being lower than those offered by other governments [ , ] . analysis of the pmgky also indicates that it has not mobilized additional funding but reallocated funding across existing budgets or allowed individuals to make advance withdrawals, raising concerns about the utility of these measures for the poor in the long run [ , ] . furthermore, the world bank estimates that the covid- pandemic could push a substantial section of individuals in socioeconomic positions similar to our participants into extreme poverty [ ] . as the association between socioeconomic deprivation and poor mental health is well-established [ ] , the worsening of mental health for most of our study population is foreseeable. this would in turn affect hiv-treatment outcomes (through reduced adherence, increased antiviral resistance, etc.) for a group of disadvantaged individuals within an already vulnerable population. interestingly, while none of the participants expressed concern about the remaining doses of art directly, we found plhiv with fewer remaining doses to have signi cantly higher gad- scores compared to those with more doses. our nding suggests that though the concern about art availability may not be at the forefront of our participants' concerns, it could be instrumental in affecting anxiety levels among plhiv. the deputy director general of naco has assured that contrary to ndings from a recent survey done by the world health organization (who) which showed several countries to be at risk for art stock-out [ ], india will not face such a crisis [ ] . this is encouraging news for asian indian plhiv, which will probably go a long way to allay fears about art availability. however, indian policy makers need to consider if access to art is as uncompromised as art stocks in this pandemic. there are a few limitations to our ndings. firstly, our results cannot be extrapolated to all plhiv in pune, based on our small sample size. however, since the socioeconomic backgrounds of plhiv registered for care at the art center are largely homogenous, the reported prevalence of anxiety symptoms and consequences secondary to these anxiety levels could be generalizable to them. secondly, as we do not have gad- scores prior to the lockdown, we cannot conclude with absolute certainty that the present levels we observed are entirely attributable to the pandemic. but given that a) our participant's expressed concerns were almost exclusively related to the pandemic; b) the gad- assessment timeframe being two preceding weeks and; c) our study being carried out one month into the lockdown in india, we ascribe our observed anxiety levels for the most part to the pandemic. it is also di cult to determine whether we have underestimated or overestimated the prevalence of anxiety symptoms even within our cohort, especially given the high non-response rate. participants with higher levels of anxiety undoubtedly could choose not to receive our calls more, but it is equally plausible that those who responded were more anxious. we also used only a single question to conduct a thematic analysis, which limits a more nuanced understanding of the issue at hand. however, using thematic analysis as a guiding framework allowed us to more concretely consolidate the wealth of information provided by our participants into de nitive themes. lastly, although we did not observe differences in gad- scores by comorbidity or prior tuberculosis status, we are unable to comment on how mental health in such individuals will change over time given their higher risk for covid- infection [ , ] and what that will mean in terms of disengagement from care or hiv treatment outcomes for them. however, we are instituting longitudinal follow-ups for all our study participants and we will better understand these associations by the end of . despite our limitations, our ndings provide important insights into the burden and sources of anxiety symptoms in a small group of asian indian plhiv. to our knowledge, these ndings are the rst to be reported from india during this pandemic for plhiv. our ndings also come with the sobering implication that the covid- pandemic will have devastating effects on the mental health of asian indian plhiv and downstream hiv-related treatment outcomes, especially as the pandemic continues to grow in india. this is more likely to happen for plhiv who are socioeconomically disenfranchised. while sweeping nancial assistance, along with extensive social and health support mechanisms would indeed be a panacea for covid-related anxiety symptoms for plhiv, we do not believe that these are practicable. instead, we recommend that whenever possible hiv care providers make regular use of short screening tools available, to identify and prioritize plhiv at risk for anxiety and other mental health conditions. this strategy will not redress the deleterious effects of the pandemic on hiv care, but at the minimum reduce their impact. the bjgmc-sgh ethics committee approved this study and all study participants provided verbal consent that are in accordance with the indian council of medical research (icmr) guidelines. not applicable as no individual data has been used. availability of data and materials: the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. the authors declare that they have no competing interests. the author(s) disclosed receipt of the following nancial support for the research, authorship, and/or publication of this article: this study was supported through a grant from amfar, the foundation for aids research with support from the national institute of health's national institute of allergy and infectious diseases, eunice kennedy shriver national institute of child health and human development, national cancer institute, national institute of mental health, national institute on drug abuse, the national heart, lung, and blood institute, the national institute on alcohol abuse and alcoholism, the national institute of diabetes and digestive and kidney diseases, and the fogarty international centre, as part of the international epidemiology databases to evaluate aids (iedea; u ai ) and the nih-funded johns hopkins baltimore-washington-india clinical trials unit for niaid networks [um ai ]. the content and views expressed are those of the authors and does not necessarily represent the o cial views of any of the governments or institutions mentioned above. im conceived the idea, conducted the thematic analysis and authored the rst draft. shs and sos provided intellectual input and helped to contextualize the analytical ndings to the existing health program. sn conducted the study on the ground and coded for thematic analysis. kz collected all the data that was used. ac cleaned the data and performed statistical analysis. ag, ns provided inputs to the manuscript and helped with its nal form. vm provided technical expertise and helped with manuscript drafting. all authors reviewed the manuscript and provided inputs. three themes (black boxes) were identi ed in thematic analysis as causes of concern. as indicated by dotted lines, the themes were not always mutually exclusive. however, one theme could be a predominat cause of concern. causes of concern also appeared to recur and their persisience implicated in the absence of mitigating measures. as an example, participants were concerned in the immediate present about not having any money to be able to provide for the family. in the absence of nancial buffers such as savings, this concern was also projected into the imminent future. this is a list of supplementary les associated with this preprint. click to download. supplementarytable.docx a nationwide survey of psychological distress among italian people during the covid- pandemic: immediate psychological responses and associated factors mental health consequences during the initial stage of the coronavirus pandemic (covid- ) in spain anxiety and depression among general population in china at the peak of the covid- epidemic multidisciplinary research priorities for the covid- pandemic: a call for action for mental health science mental health and hiv/aids: the need for an integrated response depression, adherence and attrition from care in hiv infected adults receiving antiretroviral therapy early warning indicators for rst-line virologic failure independent of adherence measures in a south african urban clinic effect of depressive symptoms and social support on weight and cd count increase at hiv clinic in ethiopia depression in the pathway of hiv antiretroviral effects on sexual risk behavior among patients in uganda the interaction of mindful-based attention and awareness and disengagement coping with hiv/aids-related stigma in regard to concurrent anxiety and depressive symptoms among adults with hiv/aids mental health and retention in hiv care: a systematic review and meta-analysis adherence to antiretroviral therapy among hiv patients in india: a systematic review and meta-analysis associations between anxiety and adherence to antiretroviral medications in low-and middle-income countries: a systematic review and meta-analysis covid- pandemic and challenges for socio-economic issues, healthcare and national health programs in india how covid- response disrupted health services in rural india livemint its coronavirus caseload soaring, india is reopening anyway: the new york times kaplan & sadock's synopsis of psychiatry: behavioral sciences/clinical psychiatry: wolters kluwer health high prevalence of insulin resistance and occurrence prior to hyperinsulinemia threshold among people living with hiv in pune determinants of consistently high hiv prevalence in indian districts: a multi-level analysis covid- state tally: maharashtra closer to lakh-mark; states have more than , cases hindustan times pune: nd phase of lockdown from symptoms of coronavirus: centres for disease control and prevention psychometric properties of the generalized anxiety disorder scale- (gad- ) in outpatients with anxiety and mood disorders a brief measure for assessing generalized anxiety disorder: the gad- using thematic analysis in psychology depression and anxiety in hong kong during covid- level of suboptimal adherence to rst line antiretroviral treatment & its determinants among hiv positive people in india prevention of hiv- infection with early antiretroviral therapy rethinking india's psychiatric care as india's lockdown ends, a mental health crisis is just beginning: world economic forum india's per-capita income rises . % to rs , a month in fy business today india's policy response to covid- . the center for policy impact in global health government bailouts are beginning: we're keeping track shreya. india's covid financial package: rehashed existing programmes, little new spending available from here's what we can do about it world bank blogs: world bank the wiley blackwell encyclopedia of health, illness, behavior, and society: chapter: socioeconomic status and mental illness india won't face stock-outs of antiretroviral medicine as result of covid- : naco the indian express q&a: tuberculosis and covid- : world health organization who is at higher risk?: johns hopkins university page / the authors express their profound gratitude to all the participants who took time to respond to our telephone calls and provide us with the wealth of information they have, in this time of crisis. we would also like to thank rohini kamble who helped with data entry. our gratitude also extends to suhasini surwase who helped collect some of the data that was used for this analysis. key: cord- -hb bsb q authors: khader, mohammed abdul; jabeen, talha; namoju, ramanachary title: a cross sectional study reveals severe disruption in glycemic control in people with diabetes during and after lockdown in india date: - - journal: diabetes metab syndr doi: . /j.dsx. . . sha: doc_id: cord_uid: hb bsb q background and aims: uncontrolled diabetes has been associated with poorer clinical outcomes in covid- . we aimed to evaluate and assess the impact of covid- pandemic on management of diabetes and challenges faced by people with diabetes in india during and after the lockdown phase. methods: a cross-sectional study based on an online questionnaire survey was designed. the questions collected socio-demographic details, medical and social history, and impact of the pandemic on medical and social life from participants. linear regression was employed to evaluate association of different parameters with the change in glycemic levels. results: the frequency of clinical visits during the covid- pandemic were reduced in . % of participants. . % of participants were able to monitor their blood glucose levels (bgls) in which . % ( . %, . %, and . %) participants experienced an increase in bgl (mild, moderate, and severe respectively). only . % of participants possessed the digital glucometer at home. . % of participants reported a decrease in physical activity while . % reported an increase in food intake. . % of participants were able to buy all medicines and . % were gone for virtual consultations while . % reported that they didn't have access to healthcare services. overall, . % participants experienced disruption in therapy. a highly significant correlation (r = . , p = . ) was found between increasing age and reporting of higher bgls. conclusion: this study provides a firsthand evidence of major disruption in diabetes care activities during and after the lockdown phase in india and increased risk of poorer clinical outcomes, if infected by sars-cov- . the coronavirus disease (covid- ) , a pandemic originated from china as a cluster of unknown pneumonia cases is continuing to wreak havoc globally [ ] . as of july , the world health organization (who) has documented , , positive covid- cases and the death toll stood at , . india, with no exception, is ringing high alarm bells to the outbreak. currently, india has a load of , , covid- cases, making it the worst-hit nation of asia and third worst-hit nation in the world after the united states and brazil [ ] . the outbreak is frequently testing the preparedness of health services and their ability to cope with a pandemic response [ ] . the first confirmed case of sars-cov- positive in india was reported on th january. following the drastic growth in daily case counts, the government had drawn up plans to deal with a worsening of the pandemic in the country. a series of lockdowns starting from th march were imposed on people in the country to break the chain of virus transmission [ ] . further, united nations and who have praised india's response to the pandemic as 'comprehensive' and 'robust'. however, since the start of "unlocking" and easing of restrictions from june st , india is witnessing an exponential rise in covid- cases indicating the possibility of 'community transmission' [ ] . accumulating evidence suggests a high risk of becoming severely ill with the coronavirus in people with increasing age and pre-existing comorbidities [ , ] . the mortality rate due to covid- in india is very low (i.e. . %) and interestingly majority (nearly %) of deaths are being observed in those having comorbidities [ ] . among all, diabetes found to pose a particular adverse risk for covid- infection [ ] . uncontrolled diabetes compromises innate immunity, the first line of defense against sars-cov- [ ] . this results in disruption of cell-mediated immunity, diminished lymphocyte transformation, impaired leukocyte function, greater viral replication in pulmonary epithelial cells, and consequent pneumonitis [ ] . since people with diabetes are at increased risk of morbidity and mortality associated with sars-cov- infection, their routine care, and monitoring are highly important [ ] . apart from the risk of covid- infection, a poorly controlled diabetes has the potential to root life-threatening complications like macrovascular diseases (angina pectoris, myocardial infarction, stroke, peripheral artery disease), microvascular diseases (retinopathy, nephropathy, and neuropathy), and immune dysfunction (more susceptible to bacterial and fungal infections) [ ] . with medical focus largely centered on covid- , the clinical support needed by patients living with non-communicable diseases (ncds) is getting severely affected [ , ] . treatment delays, discontinuation of routine care, services, and uncertainty around medicine availability have left them more at risk than ever. a survey of countries by the who reported dramatic curtailment of health services for patients living with ncds during the covid- pandemic. it was reported that diabetes treatment has been partially or completely disrupted in % of the countries surveyed. the lower-income countries and countries moving in to transition towards the community transmission are being majorly affected [ ] . a recent study in the brazilian population revealed the impact of covid- on diabetics [ ] . india harbors million diabetes patients, which makes it the second most affected nation in the world, after china. the number is projected to grow million by as per the international diabetes federation [ ] . on the other hand, only a few papers have discussed the association between the covid- outbreak and its impact on diabetes care in india. however, these studies had a relatively smaller sample size and were primarily conducted during the period of nation-wide lockdown [ ] [ ] [ ] [ ] . by virtue of being with a higher prevalence of diabetes and a hasty upsurge in covid- cases during the unlocking phase, and with their overlapping on morbidity and mortality of people, it is essential to study the impact of covid- on diabetic care in india and helps improvise the preparedness for current and future thereat imposed by covid- . keeping the above points in view, this study was designed to evaluate the impact of covid- pandemic on medical treatment, routine care services, and challenges faced by people living with diabetes in india. a cross-sectional study based on an online questionnaire survey was designed to assess the impact of covid- on the medical treatment of diabetes people. the study was conducted in between : ist, june th , , and : ist, july th , . people with diabetes were invited for the study through social networking platforms including facebook, whatsapp, linkedin, text message, through their affiliated institutions, and diabetes social media groups. the questionnaire consisted of multiple choice questions in english and telugu. the survey initiation clearly stated the right of the individuals to participate or not to participate in the survey. all the participants enrolling must have to fill the informed consent form. inclusion criteria -people who are diagnosed with diabetes -any gender -age more than years exclusion criteria -not able to provide informed consent for the study the questionnaire consisted of mainly domains: a) socio-demographic details, e.g., subject's age, gender, state, city, town, educational qualification, financial income; b) medical and social history, e.g., type of diabetes, comorbidities, smoking, and drinking habits; c) impact of covid- outbreak on their medical and social life, e.g., frequency of clinic visits, changes in glycemic levels, digital glucometer at home, access to health care services, changes in the eating habits and physical activity, changes in drinking and smoking habits, online consultations, the reason for cancellation or postponement. in the end, a blank j o u r n a l p r e -p r o o f space was given to leave a comment. the questions were designated to relate the current situation of participants "during" the pandemic, to "before" the pandemic. descriptive analysis was computed in terms of mean value ± (standard deviation) for continuous variables and frequency (percentage) for categorical variables. student's t-test was used to examine the association between continuous variables. multivariable logistic regression analysis was used to adjust for the effect of cofounders when appropriate to determine the association of binary outcomes. linear regression was employed to evaluate the association of different parameters with the change in glycemic levels. a p-value of < . was considered statistically significant. all statistical analyses were done using the spss statistic . (ibm spss statistics, new york, united states) database. bar diagrams, tables and charts were created using microsoft excel version to depict percentages, and averages. a total of responses obtained in the study duration and responses excluded due to the incomplete information. a total of responses then assessed for the study. the majority of participants were male ( . %) and belonged to the age group of - ( . %). the mean age was . years. the participants were from different states in india -telangana, andhra pradesh, tamil nadu, maharashtra, karnataka, kerala, delhi, punjab, and rajasthan., of which, . % comprised from telangana state (hyderabad= . %). a significantly higher number of participants lived in urban localities ( . %). the highest levels of education for most of the participants were graduation ( . %) and secondary ( . %). % of participants had a monthly income ₹ > , and . % had a monthly income in the range of ₹ , - , . people with type- diabetes were predominant in the study ( . %). comorbidities were present in . % of the participants. the most common comorbidities were hypertension and dyslipidemia. . % and . % of participants had smoking and drinking habits respectively. the complete socio-demographic profile of the participants is shown in table . impact of epidemic on medical treatment and social life of people with diabetes: the frequency of clinical visits of participants significantly decreased as compared to prepandemic period (fig. . a) : ( . %) participants didn't visit the clinic till now i.e., from march nd to june th ; ( . %) participants visited once in three months; ( . %) visited once in two months; and ( . %) visited once monthly. ( . %) participants monitored their blood glucose level (bgl), either with digital glucometer in-home or through blood samples in a lab or a clinic (fig. . b) in which . % ( . %, . %, and . %) participants experienced an increase in bgl (mild, moderate, and severe respectively) (fig. . a) . ( . %) possessed blood glucose measuring device (digital glucometer) at home (fig. . c) . the covid- pandemic disrupted physical activity and food intake. ( . %), ( . %) and ( . %) participants showed a decrease, no change, and increase in physical activity respectively than before the pandemic ( fig. . d) . ( . %), ( . %), and ( . %) participants showed an increase, no change, and a decrease in food intake respectively than before (fig. . e) . the epidemic increased virtual consultations. ( . %) participants used the virtual platform to follow up with doctors during the study period, while ( . %) expressed that they used the virtual platform before the pandemic also (fig. . b) . further, the covid- pandemic disrupted the purchase of medicines. ( . %) participants purchased all the medicine. ( . %) did not buy due to unavailability of medicines, ( . %) did not buy due to financial constraints and ( . %) felt purchase of medicines difficult due to fear of corona ( fig. . f) . participants allowed to choose more than one reason in case of multiple answers applied. among participants, a total of ( . %) didn't have access to healthcare services as before the pandemic (fig. . g) . the major reasons for cancellation and postponement of appointments with doctors were a) fear of getting infected with covid- - ( . %), b) absence of physician from the clinic - ( . %), c) lack of communication with clinics - ( . %), and d) financial constraints - ( . %). participants were asked to choose more than one reason in case of multiple answers applied (fig. . h) . a total of ( . %) expressed that the covid- pandemic disrupted their therapy [majorly - ( . %) and slightly - ( . %)] (fig. . c) . further, logistic regression analysis showed a significant correlation with regard to increasing age and reporting of an increase in bgls (r= . , p= . ), (fig. . c) . this study provides the firsthand evidence of major disruption in diabetes care activities during and after the lockdown phase in india. with india witnessing exponential growth in covid- cases since the start of unlocking [ ] , the challenged healthcare resources laid down falling short to meet the needs of the entire population, including individuals with diabetes. in our survey, we found the majority of people irrespective of being in urban or rural localities, were not able to follow up with doctors. however, people living in rural areas were found to have an additional level of difficulties through traveling, making it more inconvenient for them to see a doctor. with global priorities set to contain the spread of the virus, the absence of physicians for people having ncds and fear of getting infected with covid- are playing key roles in the disruption of diabetes care. other major factors identified were financial constraints and altered work-timings of clinics due to pandemic. the majority of participants monitoring their bgl either at home/laboratory/clinic said that they observed a spike in their bgl. our data mainly consisted of people having type- diabetes ( . %). recent literature has mainly focused on disrupted glycemic control among type- diabetes people [ , ] . therefore, irrespective of the type of diabetes, there is a need to monitor bgls in this population. diabetes people infected with sars-cov- had a more than triple mortality rate of % in comparison to % in those without diabetes [ ] . uncontrolled diabetes has the potential to results in long-term complications, if not addressed at the earliest [ ] . % of participants had digital glucometer at home while % didn't have. this was not studied previously. in the times of covid- , the use of such devices are a must for diabetes people and they should be educated about its importance. pharmacists working in clinical settings and dispensing areas can play a great role in patient education about such devices. concerning authorities should make sure that no shortage of such devices happens. regardless of the existence of pandemic, such devices help diabetics for selfmonitoring and self-care [ ] . with no doubts, lockdown measures and mobility restrictions were found effective to control the spread of covid- [ ] , but, at the same time, showing their harmful consequences on prevention and control of diabetes and other ncds [ ] . barone et al, reported that stricter measures against the pandemic may lead to present and future severe impact on diabetes care in south and central america [ ] . though mobility restrictions are eased during the postlockdown phase in india, fear of getting infected with covid- and "work from home" scenario is keeping people confined to their homes only. . % of participants experienced a decrease in their physical activity and . % had an increase in their food intake than before. a decrease in physical activity of diabetes people ( . %) was also reported by barone et al. the study also reported an increase in food intake ( . %) among diabetics. in line with recommendations suggested by barone et al, internet and television broadcasting can be used as an effective medium to create awareness among people of habits and behaviors, such as regular physical activity [ ] . however, the use of television by participants was not investigated in the current study. the proportion of people using virtual consultation platforms with doctors has significantly increased. only . % of participants said of using virtual consultation before while it got increased to . % during the pandemic. a pilot study from government medical university reported teleconsultations were given by ophthalmologists during covid- lockdown in india [ ] . overall, . % of participants said not having access to overall healthcare services as before and . % said pandemic has disrupted their therapy. increased age people were found to have the worst glycemic control (p= . ). the presence of comorbidities and behavioral habits predicted increase bgls, but did not reach statistical significance. many participants in the comment section provided at the end said that they are more stressed about uncertainty prevailing due to pandemic and waiting for normalcy to return. le joesnen et al, reported an increase in covid- specific worry among diabetics in denmark [ ] . the results from our survey revealed flaws in government measures, healthcare policies to protect this vulnerable group of people from public health emergency due to the covid- pandemic. though a lot of plans are being made by the government and states [ ] , they did not cover most of this population. we found people with old age are those having a major disruption in the bgls. since the risk of becoming severely ill with sars-cov- appears to be high in people with increased age and poorly controlled diabetes, disturbed diabetes care is paying the way for the consequences that might be worse than the pandemic itself. this may also result in the diabetes population in india projected to grow million by much sooner than predicted earlier. as india has entered into the "unlock" phase, an increase in covid- caseload is resulting in an additional disruption in care for diabetes people. since many other countries have also entered into the "unlocking phase", an immediate call to look for people having diabetes seems eminently appropriate. self-monitoring of bgls through devices like digital glucometer is essential. availability of medicines, diagnostic tools shouldn't get under stocked. diabetes people should be educated about the symptoms of hyperglycemia, essentially in times when their visit to doctor's in-person appears risky and difficult. though the use of telemedicine platforms is growing with much attention in india since the beginning of the pandemic, many milestones are still needed for its acceptance among people [ ] . since many people in the survey said fear of getting infected with covid- and the absence of physicians from clinics were the main reasons for therapy disturbance, clear knowledge and understanding of people about telemedicine will provide greater convenience while not having to expose themselves to infection in an in-person clinic. broader strategies to protect people's jobs and economic crises arising from pandemic are essential. the main limitations of our study includes a) our sample is not reflective of the diabetic population of india. we had more than two-third participants from southern india ( . %) therefore the geographical distribution could lead to varying responses. b) all responses have been collected through online-mode without having access to objective data to validate the subjective responses and c) only people having internet facilities were able to participate in survey while india has . % of people who don't have access to the internet. our study revealed a severe disruption in diabetes care activities during and after the lockdown phase in india. the covid- pandemic has created additional challenges for the healthcare sector and people with diabetes are not spared from this. though the lockdown measures are eased, the ongoing pandemic continues to devastate the healthcare services for ncds. considering more severe symptoms and complications of sars-cov- in diabetics; disrupted glycemic control, physical inactivity and altered food consumption are paying the way for consequences that may be worse than the epidemic itself. india is having the second largest diabetes population globally and need an additional set of measures to be implemented soon. teleconsultation, use of digital devices, minimizing sedentary behavior, and home delivery of medicines should be encouraged among people with diabetes and ncds. the authors received no specific funding for this work. the authors reports no conflict of interest. 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estimation of effects of nationwide lockdown for containing coronavirus infection on worsening of glycosylated haemoglobin and increase in diabetes-related complications: a simulation model using multivariate regression analysis covid- impact on people with diabetes in south and central america (saca region) teleconsultation at a tertiary care government medical university during covid- lockdown in india -a pilot study diabetes and covid- : psychosocial consequences of the covid- pandemic in people with diabetes in denmark-what characterizes people with high levels of covid- -related worries telemedicine for diabetes care in india during covid pandemic and national lockdown period: guidelines for physicians table : socio-demographic profile and health status of the participants (n= ) we are immensely grateful to all the participants who took part in the survey. we thank our colleagues who greatly assisted the research. we thank dr. laeeq ur rehman who helped to distribute the anonymous survey to all diabetic groups and target physicians. we thank our friends across the states in helping us to distribute the survey platform to diabetics. all authors (akm, tj and rn) contributed equally to the designing of study, acquisition and analysis of data, preparation, revision and final version of approval of the manuscript. all authors have read and consented to the manuscript. j o u r n a l p r e -p r o o f a cross sectional study reveals severe disruption in glycemic control in people with diabetes during and after lockdown in india.abdul khader mohammed , pharmd, talha jabeen * , pharmd and ramanachary namoju , ms.affiliations: key: cord- -g h y on authors: patrikar, s.; kotwal, a.; bhatti, v.; banerjee, a.; chatterjee, k.; kunte, r.; tambe, m. title: incubation period and reproduction number for novel coronavirus (covid- ) infections in india date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: g h y on novel coronavirus (covid ) rapidly spread from china to other parts of the world. knowledge of incubation period and reproduction number is important in controlling any epidemic. the distribution of these parameters helps estimate the epidemic size and transmission potential of the disease. we estimated incubation period and reproduction number of covid for india utilizing data reported by ministry of health and family welfare (mohfw), government of india (goi) and data in public domain. the mean incubation period seems to be larger at . (sd= . , % ci: . , . ). and th percentile estimate for best fit normal distribution is . days. weibull distribution, the best fit for the reproduction number estimated pre lockdown reproduction number as . ( % ci= . , . ) and post lockdown reduced to . ( % ci= . , . ) implying effectiveness of the epidemic response strategies. the herd immunity is estimated between to % for r of . and . respectively. while the novel coronavirus (covid- ) spread rapidly from china to other developed countries, india saw a steady flow of patients mod early march and by may , it had gripped the country with , confirmed cases and deaths [ ] [ ] . the novel coronavirus (sars-cov- ) though related is distinct from severe acute respiratory syndrome (sars) coronavirus and middle east respiratory syndrome (mers) coronavirus . many researchers struggled to estimate the magnitude of the epidemic wherein the epidemiological parameters remained uncertain. knowledge of key epidemiological parameters including incubation period and reproduction number is important in controlling any epidemic. the distribution of these parameters helps estimate the epidemic size and transmission potential - of the disease. the incubation period is defined as the time from infection to the onset of illness and is crucial for epidemiological modelling in predicting the transmission dynamics, infectiousness and quarantine period . it is also important for several important public health activities like length of active monitoring, surveillance and control. the reproduction number (r ) is the most fundamental parameter in infectious disease dynamics describing the contagiousness or transmissibility of infectious agents and is defined as the average number of secondary cases caused by a single infectious individual in a entirely susceptible population . an outbreak is expected to continue if r has a value > and to end if r is < . r fluctuates if the rate of human-to-human or human and vector interactions varies over time or space. there exists scant evidence which supports the applicability of r outside the region for which the value was calculated . estimation of changes in transmission over time can provide insights into the epidemiological situation and identify whether outbreak control measures are adequate and are having the desired measurable effect, and help in undertaking midcourse corrections. herd immunity is defined as the resistance to the spread of a contagious disease within a population that results if a sufficiently high proportion of individuals are immune to the disease, especially through vaccination or immunity post natural infection . when a high proportion of the population is immune, it is difficult for all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint infectious diseases to spread, because there are not many people who can be infected and the transmission chain gets broken. our current understanding of these epidemiological parameters for india is limited. hence this study was undertaken to address above issue and estimate incubation period and reproduction number of covid- for india utilizing data reported by ministry of health and family welfare (mohfw), government of india (goi) and the data available in public domain. the analysis is based on publicly available data. data were retrieved from the official website of the mohfw, goi . since the analysis is based on publicly available data ethics approval was not required. the incubation period data post adjustment of delay-time in test results was subjected to best fit model. besides normal distribution four other commonly used incubation period distribution (weibull, log normal, gamma and erlang) were fitted. estimation of the median incubation period, mean (sd), and quantiles ( th , th , th , th and th ) was also done. for reproduction number, the best fit model (weibull distribution) was used. besides the best, fit three more distributions based on review of literature for distribution of reproduction number (lognormal, gamma and exponential) were considered. the values of r were estimated for pre and post lockdown period to evaluate the impact all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint of the epidemic control measures instituted by the government of india. the herd immunity (hi) estimate was based on r value . (hi= (r - ) or r = − /r ) the statistical software used were ibm spss statistics for windows version . (spss inc., chicago, ill., usa) and easy-fit, a software system for data fitting in dynamical systems. data on lab confirmed cases were extracted, the range of age was from . years to years with a mean age of . years (sd=± . ). ratio of male to female was . : with . % males and . % females. using date of exposure and date of confirmation of disease status/illness onset, the estimates of incubation period were determined. table gives the incubation period estimates for various distributions. we fitted five distributions to the data: normal, weibull, log normal, gamma and erlang. the normal distribution provided best fit for data with median and mean incubation period of . (sd=± . , % confidence interval ci: . - . ). the incubation period ranged from to . days ( th percentile to th percentile) for this best fit. the weibull distribution was the best next fit with mean incubation period to be higher than normal distribution with mean of . (sd= . ). figure show cumulative distribution functions for best fit. the median incubation period for other distributions ranged . to . . the probability and cumulative distribution functions for various distributions in order of best fit is provided in the supplementary. the reproduction number was estimated for days before lockdown and post lockdown to assess the impact of various control measures to include social distancing adopted by india. weibull distribution was the best fit for the reproduction number followed by log normal and gamma distribution. we estimated the initial reproduction number before lockdown by goi to be . ( % ci= . - . ) and post lockdown the reproduction number reduced to . ( % ci= . - . ). the herd immunity is estimated in the range of - %. table gives the descriptive statistics of reproduction number before and post lock down. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. this data driven paper to the best of our knowledge presents the estimates of incubation period and reproduction number of covid- in india for the first time. we characterised the distribution of incubation period and reproduction number for covid- for india. we estimated that the incubation period follows the best fit of normal distribution with around days ranging from to day with th percentile of the distribution at . days. the incubation period seems to be longer for india as compared to to days by who and - days by ecdc weibull distribution seems to be the best fit for reproduction number distribution in india. the reproduction number for india is estimated to be . in pre lock down phase and reduced to around . post lockdown phase with a herd immunity threshold of . %. though the value of r has reduced from . in pre lock down period to . in post lock down period. i.e. . % reduction it is still greater than . covid- epidemic will increase as long as r is greater than and control efforts to bring r below needs to be implemented aggressively. a report based on the impact of the interventions across european countries estimated a posterior mean of . [ . - . ] for norway and . [ . - . ] for sweden, with an average of . across the country posterior means, a % reduction compared to the pre-intervention values . a study from wuhan, hubei all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. ( % ci: · - · ). the wide range of r from different studies indicates the challenges in estimating r . additionally, r is dynamic in the sense that any factor having the potential to influence the contact rate, including population density, social distancing, and seasonality will ultimately affect r . our estimate of herd immunity threshold as % (with r = . ) is staggering as , , people need to be infected to achieve herd immunity in india which may result in high death rate. many countries have implemented aggressive lock downs however some countries like sweden had a different approach to tackle covid- by taking individual responsibility for social distancing and keeping society functioning with no official lock down by the sweden government and still successful in keeping the reproduction number in control . long term lockdowns are not sustainable as its ill effects impacts many other health programmes. as per who the weekly detection of new tuberculosis cases in india has gone down by nearly per cent during the covid- lockdown. the malaria modelling analysis by the global malaria programme at who and the hiv modelling study, convened by the who and unaid , predicts the collateral damage of covid will be as devastating as pandemic, with millions succumbing to preventable, treatable illness and disease. however, in absence of vaccine and other uncertainties regarding the virus, herd immunity is debatable issue as a preventive measure and achieving herd immunity is likely to be a long-drawn process. limitations of the study: the data on complete information for estimating incubation period as well reproduction number could be extracted for limited number of cases. also, the time delay of test results, with varying turn around time among states, for estimating incubation period was averaged for india based on the public domain information and media reports. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. this study provides the estimates for key epidemiological charachteristics of covid- in india. the mean incubation period seems to be larger at . and th percentile estimate for best fit normal distribution to be . days. best fit for reproduction number follows weibull distribution. our estimates for pre lockdown reproduction number was . . and post lockdown the reproduction number reduced to . . this implies and shows that the epidemic response strategies adopted by india are effective. however the herd immunity is estimated in the range of - % for r of . and . respectively. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint home | ministry of health and family welfare | goi a novel coronavirus from patients with pneumonia in china report : estimating the potential total number of novel coronavirus cases in wuhan city nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study the extent of transmission of novel coronavirus in wuhan, china, the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application who coronavirus disease (covid- ) pandemic centers of disease control and prevention novel coronavirus ( -ncov) situation report- -world health organization (who) stockholm: ecdc; early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia incubation period and other epidemiological characteristics of novel coronavirus infections with right truncation: a statistical analysis of publicly available case data no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application report -estimating the number of infections and the impact of non-pharmaceutical interventions on covid- in european countries, imperial college covid- response team estimation of the reproductive number of novel coronavirus (covid- ) and the probable outbreak size on the diamond princess cruise ship: a data-driven analysis real-time modeling and projections of the covid- nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study johns hopkins university and usaid.the potential impact of the covid- response on tuberculosis in high-burden countries:a modelling analysis global malaria programme all rights reserved. no reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity.the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint all rights reserved. no reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity.the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint figure : cumulative distribution function for best fit normal distribution for incubation period for india all rights reserved. no reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity.the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint all rights reserved. no reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity.the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint key: cord- - blzw oy authors: malavika, b.; marimuthu, s.; joy, melvin; nadaraj, ambily; asirvatham, edwin sam; jeyaseelan, l. title: forecasting covid- epidemic in india and high incidence states using sir and logistic growth models date: - - journal: clin epidemiol glob health doi: . /j.cegh. . . sha: doc_id: cord_uid: blzw oy background: ever since the coronavirus disease (covid- ) outbreak emerged in china, there has been several attempts to predict the epidemic across the world with varying degrees of accuracy and reliability. this paper aims to carry out a short-term projection of new cases; forecast the maximum number of active cases for india and select high-incidence states; and evaluate the impact of three weeks lock down period using different models. methods: we used logistic growth curve model for short term prediction; sir models to forecast the cumulative, maximum number of active cases and peak time; and time interrupted regression model to evaluate the impact of lockdown and other interventions. results: the predicted cumulative number of cases for india was , ( % ci: , , , ) by may , and the observed number of cases was , . the model predicts a cumulative number of , , ( % ci: , , , , , ) cases by may , as per sir model, the maximum number of active cases is projected to be , on may , . the time interrupted regression model indicates a decrease of daily new cases after the lock down period which is statistically not significant. conclusion: the logistic growth curve model predicts accurately the short-term scenario for india and high incidence states. the prediction through sir model may be used for planning and prepare the health systems. the study also suggests that there is no evidence to conclude that there is a positive impact of lockdown in terms of reduction in new cases. title of the article: forecasting covid- epidemic in india and high incidence states using sir and logistic growth models. since the beginning of the covid- epidemic, there has been several mathematical and statistical modelling that have predicted the global and national epidemic with varying degrees of accuracy and reliability. , the accuracy of prediction and its uncertainty depend on the assumptions, availability and quality of data. the results can vary significantly if there is difference in the assumptions, and values of input parameters. during a pandemic like covid- , the availability and quality of data keep improving as the epidemic progress, which make predictions uncertain in the early stages and expected to improve in the later stages. moreover, an epidemic may not always behave in the same manner as pathogens are likely to behave differently over time. in terms of covid- , different models are used to estimate the key features of the disease such as the incubation period, transmissibility, asymptomaticity, severity, and the likely impact of different public health interventions. among the models, susceptible, exposed, infection and recover (seir), susceptible, infection and recover (sir) models, agent-based models and curve-fitting, logistic growth models due to the exponential nature of growth of the epidemic or extrapolation models, are commonly adopted using different biological and social processes. , [ ] [ ] [ ] [ ] [ ] [ ] in this scenario, the logistic growth models are better preferred option. choudhary ( ) has predicted the estimated cases very early till april , , using time series models. however, it was found to be a gross underestimation. in spite of the limitations, considering the unprecedented nature of the pandemic, uncertainties about the disease and the need for urgent but appropriate social, economic and public health responses; accurate forecasting of the size, severity and duration of the epidemic is critical to inform policies, programme and strategies. this paper aims to carry out short-term projection of new cases using the logistic growth curve model; forecast the maximum number of active cases for india and selected highburden states using the sir model with correction factor based on china, italy and south korea; and evaluate the impact of lockdown and other interventions on the incidence of daily cases. logistic growth is characterized by an increasing growth in the beginning, but a decreasing growth at a later stage, as it approaches the maximum. in covid- , the maximum limit will be the total population and the growth will necessarily come down when a greater proportion of the population is sick. the reason for using logistic growth for modelling the coronavirus outbreak is based on the evidence that the epidemic follows an exponential growth in the early stages and expected to come down during the later stages of the epidemic. the modified logistic growth model , is presented as follows, where, y(t) is the number of cases at any given time t c is the limiting value, the maximum capacity for y a = (c / y ) - b is the rate of change. • the number of cases at the beginning, also called initial value is: c / ( + a) • the maximum growth rate is at t = ln(a) / b when y is equal to c (that is, the population is at maximum size), y/c will be . therefore, the ( -(y/c)) will be and hence the growth will be . β is a transmission parameter, which is the average number of individuals that one infected individual will infect per time unit. it is determined by the chance of contact and the probability of disease transmission. γ is the rate of recovery in a specific period. d, the average time period during which an infected individual remains infectious which is derived from γ. = . the ratio = , is the basic reproduction number. r is the average number of people infected by an infected individual over the disease infectivity period, in a totally susceptible population. in order to fit a sir model, the parameters were obtained by minimizing the residual sum of squares between the observed cumulative active cases and the predicted cumulative infected cases. we have fixed r and as . and days respectively. , therefore, is . and the is . . the data for india was taken from the crowd sourced invariably, the sir model overestimates the active number of cases. in order to compute the overestimation, the actual number of reported cases from china was obtained up to april , and used to estimate the maximum number of active cases in china. subsequently, the ratio of maximum (peak) active cases projected by the model to the observed peak active cases was computed. the similar estimation was done for italy and south korea as well. in order to choose the best correction factor that is appropriate for india, we compared the age and gender distribution of population of these three countries with the age and gender distribution of population in india. china correction factor was applied to states such as maharashtra, rajasthan and tamil nadu. as the population size in delhi is small which is about four to five times lower than the other states, sir model was not done for delhi. data that were used in the modelling is presented in appendix. time interrupted regression analysis was done to assess the impact of weeks' lockdown on the incidence of new cases. dummy variable was introduced at april , . the hypothesis was that there will be a decline in the incidence of new cases after the lock down period, that is after april , . that is, the regression coefficient will be significant and negative in direction. as there were only cases reported from jan to march , , we excluded these time points from the analysis. table is presented in figure a & b. the rajasthan and tamil nadu, it will be , , , and , respectively. the corresponding peak time was expected to be june , , june , and june , respectively. the diagrammatic representation of the trend is presented in figure . the results of the interrupted time regression analyses are presented in table . the model indicates a decrease of daily new cases after april , , weeks after the lockdown which is not statistically significant. there have been several studies forecasting the incident cases of covid- in various countries. however, there are a little peer reviewed articles about india. forecasting covid- through appropriate models can help us to understand the possible spread across the population so that appropriate measures can be taken to prevent further transmission and prepare the health systems for medical management of the disease. it is also essential to evaluate the effectiveness of interventions so that appropriate and timely programmatic changes can be made to mitigate the epidemic. we forecasted the number of cumulative cases for india and four other high incidence states using logistic growth model which has projected the cumulative cases very closely to the observed cases. this model is based on the current trends of the cumulative cases in india and specific states. we have used the logistic growth model due to the exponential nature of growth of the epidemic which eventually get stabilised as against pure exponential model. , - end of may, . however, the total number of cases had already crossed , by april , , which was a gross underestimation. the sir model with correction factor predicted , cases which will be the maximum number of active cases by may , . however, the peak time gets pushed to june in other states. when we performed the sir model using the reported cases from china, south korea and italy, we found that the model predicted more number of active cases than what they observed up to a time point for which the data was analysed. in order to address the overestimation, we formulated a correction factor which is essential to predict the epidemic accurately. besides, as suggested by ranjan ( ) , the sir model depends heavily on the population who are susceptible. therefore, it may overestimate the maximum cases when the epidemic is not generalized in the population. therefore, this could be considered as a warning signal for preparing the health systems in terms of planning treatment facilities and other interventions. in covid- epidemic, assessing the effectiveness of lockdown is one of the key interest areas. india had a head start in imposing the lockdown relatively early, in addition to strong public health measures to mitigate the spread of the epidemic. it also raises an interesting question whether this lockdown has really impacted the incidence cases. several studies have assessed the effectiveness of interventions with varying level of results. , we carried out interrupted time series analyses that suggested no significant decline in the number of daily cases immediately after the lock down. ironically, there is an increase in the number of daily cases immediately after the weeks of lockdown period. it indicates that the lockdown and other interventions did not have any impact on reducing the number of daily cases after a certain period. this may be due to the fact that the number of tests done over a period of time has increased significantly. however, we need to revise the model every week as and when the data gets accumulated. limitations: as in any other projection using models, the limitation is that each model would behave differently, not merely due to differences in underlying assumptions but differences in population density, existing capacity of the health systems, current level of interventions and socio-demographic and economic situation across and within the states and districts. therefore, district level projections may be required, which would account the variations between the states and within the states. in covid- , there has been a higher level of uncertainly about the number of reported confirmed cases due to the issues in varying testing strategies, the proportion of asymptomatic cases and the effective transmission rate. because of this, we may be missing a significant number of reported confirmed cases which may affect the accuracy of any models. in conclusion, the short term projection predicts exactly well with the observed number of cases in india and in other states through the logistic growth model. the findings from sir model may be used for planning the interventions and prepare the health systems for better clinical management of the infected in the country and respective states. none of the authors have conflicts of interest to report. this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. not required early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia geneva: world health organization mass testing, school 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disease transmission in india: a mathematical model-based approach epidemic situation and forecasting of covid- in and outside china covid- in india: predictions, reproduction number and public health preparedness forecasting covid- cases in india. towards data science analysis of a modified logistic model for describing the growth of durable customer goods in china modeling logistic growth covid- growth modeling and forecasting with prophet an introduction to compartmental modeling for the budding infectious disease modeler application of the susceptible-infected-recovered deterministic model in a gii.p emergent norovirus strain outbreak in romania in the reproductive number of covid- is higher compared to sars coronavirus pattern of early human-to-human transmission of wuhan segmented regression analysis of interrupted time series studies in medication use research predictions for covid- outbreak in india using epidemiological models predictions, role of interventions and effects of a historic national lockdown in india's response to the covid- pandemic: data science call to arms covid- : mathematical modelling and predictions -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- -feb- - feb- -feb- -mar- -mar- -mar- -mar- -mar- -mar- -mar- -mar- -mar- - mar- -mar- -mar- -mar- -mar- the authors whose names are listed immediately below certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.author names: ________________________________________________________________________________________ ______________________________________________________________________________________________________ ______________________________________________________________________________________________________ the authors whose names are listed immediately below report the following details of affiliation or involvement in an organization or entity with a financial or non-financial interest in the subject matter or materials discussed in this manuscript. please specify the nature of the conflict on a separate sheet of paper if the space below is inadequate. key: cord- - xx noxq authors: mali reddy, b. r.; singh, a.; srivastava, p. title: covid- transmission dynamics in india with extended seir model date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: xx noxq india is one of the most harshly affected countries due to covid epidemic. early implementation of lockdown protocols were useful to control certain parameters of transmission dynamics, but the numbers are consistently increasing in later months. india population is divided into different clusters on the basis of population density and population mobility, even varying resource availability and since the recent cases are coming from throughout the country, it allows us to model an overall average of the country. in this study, we try to prove the efficiency of using the seir epidemiological model for different rate study analysis for covid epidemic in india. along with it we derived newer components for better forecast of the pandemic in india. we found that there is a decrease in r value, but still the epidemic is not under control. the percentage of infected patients being admitted into icu for critical care is around . %, while the chances of recovery of critical patients being admitted to the icu seem to be slim at . % of the admitted being dead. originating in china during the end of , covid- is being called the world's major problem. everything from public health to the global economy is badly affected. the disease is caused by a novel virus called sarscov- (severe acute respiratory syndrome coronavirus ). the first case was officially reported on st december and later after one month, it has declared as the world's major health hazard by the world's health organisation [ ] . till the date of august , the disease has spread and affected countries or territories around the world [ ] . during early , china was the first country to record the covid- infectious number up to , followed by france, italy and other european countries [ ] . they had their peak during march and april but somehow, they managed to lower down the number of active cases and the average of the new number of cases in a day dropped to less than (for the period of may, june and july) [ ] . in the case of india, the numbers are initially lower (during the period of march april) because of lockdown implementation and inadequate testing facility in india. but in later months, india has recorded big numbers in covid tally and because of higher population density, cities like mumbai, delhi, chennai and ahmedabad contributed most of the numbers in the country's total [ , ] . the indian population is divided among different clusters and therefore, there is a difference in a pandemic in different states. recently, some of the states have seen flood issues (assam and bihar) which created a sudden disturbance in social distancing measures and ultimately there is an increase in the number of cases from those states [ ] . for india, during the first phase of coronavirus pandemic, the numbers were added by few major cities but now, a small number is added by every district in india and therefore, india has an average of more than , cases in the last days (from august rd to august th ) whereas it was an average of less than , in earlier months [ ] . since the covid has spread across the country, so it is better to model it through an epidemiological method. there are several studies or models in epidemiology, where they try to understand the behaviour of disease spread [ , , ] . these existing models are a general epidemic model to get an idea of transmission dynamics of a pandemic, stages of the pandemic and what shape it would take with time. some of the very popular epidemiology models are sir, sis and seir [ , ] . pandemic and infection spread is always dependent on the type of disease. in the case of covid- , it is an airborne disease and the virus directly targets the lungs. therefore, its spread rate is quite higher than other infectious diseases. secondly, the infected person gets to know about the infection in about days on an average (in the case of non-asymptotic infection). symptoms take to days on an average to show up and till then the individual could have spread the infection to other populations. there are the two most dominating factors for exponential growth in the total number of new cases day by day. for our current paper, we tried to understand the pandemic behaviour in india on the basis of the seir model. huo hf et. al. studied the dynamics of the sexually transmitted disease using seir epidemiological model [ ] . there are four main elements in the seir model viz. susceptible (s), exposed (e), infectious (i) and recovered (r). apart from its limitations in applying to real scenarios, it is mostly used to analyse the covid- pandemic by countries across the world [ , , ] . in the seir model, the transition from one compartment to another depends on the rate, probability and population. the rate describes how long a change takes, the population is the group of individuals that this change applies to and probability is the possibility of transmission taking place for an individual. infectious diseases tend to spread from one group of population to another. thus it is necessary to gain insights on their rate of spread, what proportion of a population is susceptible, what proportion is infected, etc. a compartmental model helps us separate the population into several components. a basic seir model resembling the scale of covid- transmission dynamics is divided into population compartments: • susceptible (s) (healthy population, vulnerable to be infected) . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted august , . . this is a seir model where there are four possible transitions between defined compartments. here are all the parameters our model needs (that's just all the variables in the equations plus the variables in the functions for r₀(t) and beds(t): is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint the following differential equations show the transitions from one compartment to other (mathematical expression for seir extended model): the proportion of infected recoveries per day the total number of people an infected person infects length of the incubation period fatality rate rate at which infected people die. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint parameter in r (t) in the case of covid- , the disease can have an incubation period before getting infected. the period when the infected individual has not spread the virus to other individuals is called the exposed compartment in the seir epidemiological model. there is a transition sequence, as shown in figure , which is the key to the seir model. the susceptible population can come in contact with infected ones and then they are in the exposed compartment. this is a transition from susceptible to exposed i.e. s → e. the transition s → i will have almost the same probability because exposition can happen immediately and the total population remains the same. mathematically, an infected person can spread the disease and every individual exposes new ones per day. in our case, every exposure becomes infected and the rate becomes . for coronavirus disease, a dead compartment is significant and crucial because of the non-availability of known treatment. there is quite a higher number of deaths in a day in india for the last few weeks. while adding a transition from infectious to death i.e. i → d, we define a new parameter . can be defined as the rate of the deceased case (for example, when an infected individual takes five days to die, the will be / ). apart from the rate of the deceased case, there would be no change in the recovery rate. the death rate will be -recovery rate. in other words, recovery rate can be referred to as the probability of transition from infectious to recovered i.e. i → r. similarly, the death rate can be referred to the probability of transition i → d. the sum of both the probability is always . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint r tends to remain the same in the ideal case if there is no change in regulations like social distancing. it varies when there is a change in social distancing regulations or with variation in higher-order population mobility as in india's case. due to the implementation of a nationwide lockdown, the country has seen a labour migration from states to states. it was a huge migration and affected the social distancing parameters. therefore, implementing lockdown and then unlocking resulted in a variation in r₀ value . the following equation shows the time dependency of r₀ value : • r start and r end are the first and the last day values of r • x is the value of x at the inflection point (the day recording steepest decline in the value of r ) • k allows us to vary how quickly r declines the fatality rate α depends on a number of parameters such as health infrastructures in a state. for this study, we only consider the dependency on health resources and the average age of the infected population. here, s is some arbitrary but fixed (that means we choose it freely once for a model and then it stays constant over time) scaling factor that controls how big of an influence the proportion of infected should have; α opt is the optimal fatality rate. for example, if s= and half the population is infected on one day, then s ⋅ i(t) / n = / , so the fatality rate α(t) on that day is % + α opt . or maybe most people barely have any symptoms and thus many people being infected does not clog the hospitals. then a scaling factor of . might be appropriate (in the same scenario, the fatality rate would only be % + α opt ). due to limited resources available, governments are adapting to triage especially in india and other highly impacted places. doctors are differentiating between critical and normal patients in the wake of limited icu beds. this needs to be incorporated into the seir model for better prediction. if a country with b, icu beds suitable to treat critical covid- patients. if the amount c i.e. the number of critical patients more than b. this means that all the critical patients being admitted after filling up b icu beds cannot be treated properly and thus might end up dead due to shortages. thus we expanded our transition: from c, there are two populations we have to look at: max( , c-b) people die because of shortages, and the rest get treated like we . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted august , . . discussed above. well, if c<b (enough beds), then c people get treated. if c>b (not enough beds), then b people get treated. that means that the remaining amount of people getting treatment is min(b, c) (again if c<b, then min(b, c)=c people get treatment; if c>b, then min(b, c)=b people get treatment; the math checks out). revising the model, with deaths happening immediately for all those above the number of beds available (one could change this to taking several days, dying with a probability of %, etc.). instead of one(r₀(t)), two time-dependent variables: r₀(t) and beds(t) are integrated into the model. for r₀(t), the older logistic function will be used. while for beds(t), the idea is that, as the virus spreads, countries react and start building hospitals, freeing up beds, etc. thus, the number of beds available increases over time. where beds₀ is the total number of icu beds available and s is some scaling factor. in this formula, the number of beds increases by s times the initial number of beds per day (e.g. if s= . , then on day t= , beds(t) = ⋅ beds₀) δ and γ are fixed to δ= / and γ= / estimates based on acquired from [ ] . concerning β(t) , we're calculating beta through r₀(t) and γ, so there's no need to find any separate parameters for the beta. the beds scaling factor s can be fitted; admittedly, it does not play a big role in the outcome as, until now, the number of people not receiving treatment due to shortages was small compared to the total amount of deaths. we collected two estimates for the probabilities p(i→c) and p(c→d) , split up by age group. this helped us calculate the probabilities, weighted by the proportion of the population per age group. we needed a simple and flexible approach to modelling the data and curve fitting. it should allow the value of parameters to be constrained by an algebraic expression or vary over a range. lmfit provides a high-level interface to non-linear optimization and curve-fitting problems for python [ ] . it seemed the best fit for the extended seir model. data was integrated into and the known parameters' boundary conditions were with initial guess value. to validate the use of the lmfit module in the above model, data of newly infected cases per day were compared to check if it was the best fit. and the model was perfectly valid. we applied the lm-fit algorithm for parameter estimation in python and the code is available at https://github.com/brahmatheja /extended-seir-model-. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint the forecast for fatality rate is expected to be constant in the near future, proper handling of resources and instant availability of beds to the needed might keep the fatality rate at bay. currently, the fatality rate is at . %. value of r had a steady decline since the start of complete lockdown in india and seems to pursue a similar value since the gradual opening of lockdown too. the forecast towards coping with this disease. but actual values may hinder the actual prediction in the near future if safety norms are not followed properly. currently, the r value is at . for the overall country. this value is very high at places with high population density (like delhi, mumbai etc.) **citation for r_ value of cities . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted august , . . https://doi.org/ . / . . . doi: medrxiv preprint due to the limited availability of resources, they will exhaust themselves after a certain time. as we can see a gradual spike in deaths per day from november onwards, with the daily count being at around . through study, we are able to construct a general understanding of transmission dynamics and what numbers we could expect in future considering the present scenarios. if the above forecast is right, india has not been through its worst yet. though a decrease in r value, it does not mean covid epidemic is under control. the percentage of infected patients being admitted into icu for critical care is around . %, while the chances of recovery of critical patients being admitted to the icu seem to be slim at . % of the admitted being dead. they need to prepare for more medical equipment, increasing icu beds requirement and better physical distancing norms to keep the deaths per day at bay. the goal was to forecast and prepare accordingly, at the same time understanding the seriousness of the situation to estimate and plan for hospital equipment and protective gear. statement on the second meeting of the international health regulations ( ) emergency committee regarding the outbreak of novel coronavirus ( -ncov) coronavirus disease (covid- ): a literature review age-structured impact of social distancing on the covid- epidemic in india predictions for covid- outbreak in india using epidemiological models seir modelling of the covid- and its dynamics a hybrid multi-scale model of covid- transmission dynamics to assess the potential of non-pharmaceutical interventions why lockdown? why national unity? why global solidarity? simplified arithmetic tools for decision-makers, health professionals, journalists and the general public to explore containment options for the novel coronavirus floods in the time of coronavirus: doubly whammy as assam battles deluge, pandemic; times now digital updated lmfit: non-linear least-square minimization and curve-fitting for python the effectiveness of quarantine of wuhan city against the corona virus disease (covid- ): a well-mixed seir model analysis the dynamics of a seir-sirc antigenic drift influenza model dynamics of an edge-based seir model for sexually transmitted diseases forecasting covid- -associated hospitalizations under different levels of social distancing in lombardy covid- outbreak on the diamond princess cruise ship: estimating the epidemic potential and effectiveness of public health countermeasures key: cord- -m vc p authors: kaushik, ashlesha; gupta, sandeep; sood, mangla title: covid- pandemic in india: what lies ahead-letter to the editor: mitra p, misra s, sharma p. covid- pandemic in india: what lies ahead [published online ahead of print, apr ]. indian j clin biochem. ; – . doi: https://doi.org/ . /s - - - date: - - journal: indian j clin biochem doi: . /s - - - sha: doc_id: cord_uid: m vc p nan being the worst affected states [ ] . older adults are most severely affected as noted by the authors; however, novel pediatric manifestations resembling kawasaki disease have been recently recognized, marked by elevated biochemical markers of inflammation including ferritin and d-dimers [ ] , labeled recently as multisystem inflammatory syndrome by the world health organization. while several studies are underway for vaccines and therapies for covid- worldwide, a recent report showed remdesivir, a nucleoside analog that causes premature viral rna (ribonucleic acid) chain termination thereby inhibiting viral replication, to be effective in adult patients [ ] . interleukin- inhibitors like tocilizumab are also being used as therapeutic agents, given the associated cytokine storm with covid- [ ] . therapy with convalescent plasma has shown promise and a phase ii, open label, randomized controlled trial to assess the safety and efficacy of convalescent plasma to limit covid- associated complications in moderate disease (placid trial) has been initiated by indian council of medical research (icmr) in hospitals within india [ ] . the authors have raised several important issues for the pandemic in india. with the largest national lockdown to contain the spread of virus in the country with a population of . billion (imposed on march th, and later extended in four stages till may st ), we could say that from theoretically being at the highest risk of becoming the epicentre for covid- , india has thus far been saved from becoming the global hotspot. until now, the case rate in india is relatively low at per million, fatality rate is . per number of cases, and recovery rate is % [ ] . for some time) [ ] ; and segregating healthcare facilities across the country as non-covid and covid facilities. three types of dedicated covid facilities include covid care centers (for mild or suspected cases), covid health centers (for moderate cases with basic life support facilities) and covid hospitals (with fully equipped intensive care units with ventilators and oxygen support for sick patients). thus far, a total of , , patient-samples have been tested for covid- in india [ ] . icmr testing protocol recommends reverse transcription polymerase chain reaction as the confirmatory diagnostic test, however, we agree with the authors that antibody testing would be valuable for population-wide use for delineating people at risk for disease transmission as well as acquisition. presently, however, antibody testing is neither widespread nor utilized except for pooled sampling. till now, covid- in india has been addressed predominantly by containment measures (quarantine, isolation of infected individuals, contact-tracing and reducing movement of people in areas with high case-loads). however, with the recent rise in number of infected cases, it is now time to shift focus from containment to community mitigation, also known as 'flattening the curve' in epidemiological terms. potential interventions include social distancing, minimizing unnecessary exposure of vulnerable population (individuals aged over years, those with cardiovascular disease, diabetes, chronic respiratory disease and cancer) by helping them stay at home, and education of the masses. with planned relaxation of lockdown in the coming days, implementing guidelines to prevent covid- infection at workplace and containment zones would be paramount, including travel advisories, increased use of tools like arogya setu app for contact tracing and encouraging tele-consultations [ ] . we concur with the authors that an increase in the capacity for testing and treatment, isolating confirmed cases, and tracing new cases is needed to disrupt the transmission chain, and seems to be the way forward in tackling this infection, till an effective vaccine or cure becomes available. covid- pandemic in india: what lies ahead world health organization novel coronavirus ministry of health and family welfare, government of india. covid- cases in india an outbreak of severe kawasaki-like disease at the italian epicentre of the sars-cov- epidemic: an observational cohort study compassionate use of remdesivir for patients with severe covid- effective treatment of severe covid- patients with tocilizumab indian council of medical research. covid- disease updates author contributions all authors contributed to the study conception and design. material preparation, data collection and analysis were performed by ashlesha kaushik, sandeep gupta, mangla sood. the first draft of the manuscript was written by ashlesha kaushik and all authors commented on previous versions of the manuscript. all authors have read and approved the final manuscript. ak: contributed to the concept, design, definition of intellectual content, literature search, manuscript preparation, manuscript editing and manuscript review. sg: contributed to the definition of intellectual content, literature search, manuscript preparation, manuscript editing and manuscript review. ms: contributed to the definition of intellectual content, literature search, manuscript preparation, manuscript editing and manuscript review.funding none. conflict of interest the authors declare that there is no conflict of interests/competing interests. key: cord- - uvta authors: singh, brijesh p. title: modeling and forecasting the spread of covid- pandemic in india and significance of lockdown: a mathematical outlook date: - - journal: nan doi: . /bs.host. . . sha: doc_id: cord_uid: uvta a very special type of pneumonic disease that generated the covid- was first identified in wuhan, china in december and is spreading all over the world. the ongoing outbreak presents a challenge for data scientists to model covid- , when the epidemiological characteristics of the covid- are yet to be fully explained. the uncertainty around the covid- with no vaccine and effective medicine available till today create additional pressure on the epidemiologists and policy makers. in such a crucial situation, it is very important to predict infected cases to support prevention of the disease and aid in the preparation of healthcare service. india is fighting efficiently against covid- and facing greater challenges because of its large population and high population density. though the government of india is taking all needful steps to prevent its spread but it is not enough to control and stop spread of the disease so far, perhaps due to defiant nature of people living in india. effective measure to control this disease, medical professionals needs to know the estimated size of this pandemic and pace. in this study, an attempt has been made to understand the spreading capability of covid- in india through some simple models. findings suggest that the lockdown strategies implemented in india are not successfully reducing the pace of the pandemic significantly after first lockdown. a novel corona virus is responsible for epidemic popularly known as covid- is a new strain that has not been identified previously in humans. world health organization (who) declared covid- a pandemic on march , . the virus that caused the incidence of severe acute respiratory syndrome (sars) in in china, middle east respiratory syndrome (mers) in in saudi arabia and the virus that causes covid- are genetically related to each other, but the diseases they caused are quite different (who). these viruses, in general, are a family of viruses that target and affect mammal's respiratory systems. the sars corona virus spread to humans via civet cats, while the mers virus spread via dromedaries. in case of the novel corona virus, typically happens via contact with an infected animal, perhaps the common carriers are bats initial reports from seafood market in central wuhan, china. the novel corona virus (covid- ) started from wuhan, china and thus, initially known as the wuhan virus, expanded its circle in south korea, japan, italy, iran, usa, france, spain and finally spreading in india. it is named as novel because it is never seen before mutation of animal corona virus but certain source of this pandemic is still unidentified. it is said that the virus might be connected with a wet market (with seafood and live animals) from wuhan that was not complying with health and safety rules and regulations. as of july , , with the continuously increasing global risk more than million confirm positive cases and more than . million of deaths have occurred in the world. as number of cases growing day by day, in most of the countries of the world, some most populous countries like china, india, brazil, usa, etc., are badly affected by it. in this context, the crucial role of modeling, transmission dynamics and estimating development of covid- are expected. the population based mathematical model especially growth model in this scenario are the most preferable techniques to understand the epidemic future trajectory. epidemiological characteristics like propagating dynamics, severity, susceptibility, and the effects of control measures, for covid- has produced a greater concern for researchers (cowling and leung, ; lipsitch et al., ) . since preventive measures like lockdown and social distancing have immense pressure on economy of the country, quantitative estimates and predictions are necessary to learn the impact of spread that will help in plan the strategies against covid- . given the paucity of such quantitative measures, the predictions on the basis of different idea given in this paper become critical and to know when the covid- stops. in recent past a number of studies with various technique and tools have been carry out to understand the dynamics of propagation of disease and future course of action. for covid- , various models which are capable of providing worth insights for health care policy making are being continuously developed and used to explain this pandemic retrospectively as well as to project the events (batista, ; koo et al., ; kucharski et al., ; tuite and fisman, ; wu et al., ) . wu et al. ( ) has been done to analyzing the pace of virus transmissibility through estimating the value of r with the help of stochastic markov chain monte carlo method. another analysis with mathematical incidence decay and exponential adjustment is performed. further to explain growth behavior of covid- a statistical exponential growth model adopting the serial interval from severe acute respiratory syndrome is applied by zhao et al. ( ) . a three-parameter logistic growth function is applied and predicted for china as well as some other countries is found very satisfying (shen, ) . in the context of india, an early study of covid- (when it started spreading in india) done by singh and adhikari ( ) rightly believed that countrywide lockdown on march for days may be insufficient for controlling the covid- pandemic. malhotra and kashyap ( ) tried to forecast the endpoints to explain the progression of covid- in indian states, using sir and logistic growth models and found the endpoint of covid- in india is in july , . india with a huge population about . billion, among majority of the people are living in poor hygienic condition and the medical facilities like number of doctors and hospitals are less in india as compared to developed countries indicates that the situation of india will become very critical but comparatively better public health system and political control in india than the above developed countries. the picture of india is not so good and has more than million confirm positive cases and more than thousand of deaths. although the death rate of this pandemic is low in comparison of other pandemics and diseases but its high rate of spread and no proper cure available so far is the major concern in the present time. right now in india only districts out of districts have covid- case more than . these districts are mainly metropolitans; if we implement preventive measures properly then spread can be under control at desired level, but due to defiant nature of people living in india, political desire and rivalry, still we india society are facing problem made by covid- . the first case of covid- is reported in india on january , when a student returned from wuhan, china (covid india.org). the government of india was quick to launch various levels of travel advisories beginning from february , , with restrictions on travel to china and nonessential travel restrictions to singapore, south korea, iran and italy. the efforts to control by the hon'ble prime minister narendra modi ji through janata curfew (public curfew) on march , , can be seen as the beginning of wide-scale public preventive measures. india has launched several social distancing measures and personal hygiene measures during the second week of march. symptoms of covid- are reported as cough, acute onset of fever and difficulty in breathing. out of all the cases that have been confirmed, up to % have been deemed to be severe. cases vary from mild forms to severe ones that can lead to serious medical conditions or even death. it is believed that symptoms may appear in - days, as the incubation period for the has not yet been confirmed. however, in india days minimum quarantine period is declared by government for suspected cases. since it is a new type of virus, there is a lot of research being carried out across the world to understand the nature of the virus, origins of its spreads to humans, the structure of it, possible cure/vaccine to treat covid- . india also became a part of these research efforts after the first two confirmed cases were reported here on january , . then in india screening of traveler at airport migrant was started, immediate chinese visas was canceled, and who was found affected from covid- kept in quarantine centers (ministry of home affaires government of india, advisory). for the spread of covid- , when disease dynamics are still unclear, mathematical modeling helps us to estimate the cumulative number of positive cases in the present scenarios. now india is interring in the mid stages of the epidemic. it is important to predict how the virus is likely to grow among the population. the covid- pandemic presents a challenge for data scientists to model it; however, the epidemiological characteristics of the covid- are yet to be fully explained. the uncertainty around the covid- with no vaccine and effective medicine available until today create additional pressure on the epidemiologists and policy makers. in such a crucial situation, it is very important to predict infected cases to support prevention of the disease and support in the preparation of healthcare service. a mathematical modeling approach is a suitable tool to understand the dynamics of epidemic. in the study some mathematical approach to understand the dynamics of novel covid- in india has been discuss. in absence of a definite treatment modality like vaccine, physical distancing has been accepted globally as the most efficient strategy for reducing the severity of disease and gaining control over it (ferguson et al., ) . also in india it is reported that the country is well short of the who's recommendations of minimum threshold of . skilled health professionals per population (anand and fan, ) . therefore, on march , , the government of india under prime minister narendra modi ji ordered a nationwide lockdown for days, limiting movement of the entire . billion population of india as a preventive measure against the covid- pandemic in india. it was ordered after a -h voluntary public curfew on march. the lockdown was placed when the number of confirmed covid- cases in india was approximately . on april, prime minister of india extended the nationwide lockdown until may, with a conditional relaxation after april for some regions. on may, the government of india again extended the nationwide lockdown further by weeks until may. also, the government has divided the entire nation into three zones viz. green, red and orange with relaxations applied accordingly. there are already various measures such as social distancing, lockdown masking and washing hand regularly has been implemented to prevent the spread of covid- , but in absence of particular medicine and vaccine it is very important to predict how the infection is likely to develop among the population that support prevention of the disease and aid in the preparation of healthcare service. this will also be helpful in estimating the health care requirements and sanction a measured allocation of resources. it is well known fact that covid- has spread differently in different countries, any planning for increasing a fresh response has to be adaptable and situationspecific. data obtained on covid- outbreak have been studied by various researchers using different mathematical models srinivasa rao arni et al., ) . many other studies (anastassopoulou et al., ; corman et al., ; gamero et al., ; huang et al., ; hui et al., ; rothe et al., ) on this recent epidemic have been reported so many meaningful modeling results based on the different principles of mathematics. most of pandemics follow an exponential curve during the initial spread and eventually flatten out ( junling et al., ) . sir model is one of the best suited models for projecting the spread of infectious diseases like covid- where a person once recovered is not likely to become susceptible to the infection again (kermack and mckendrick, ) . susceptible-infectious-recovered (sir) compartment model (herbert, ) is used to include considerations for susceptible, infectious, and recovered or deceased individuals. these models have shown a significant predictive ability for the growth of covid- in india on a day to day basis so far. a time dependent sir models have been defined to observe the undetectable infected persons with covid- (chen et al., ) . a recent study by mandal et al. ( ) has shown that social distancing can reduce cases by up to %. further, time series models have been employed for predicting the incidence of covid- disease. as compared to other prediction models, for instance support vector machine (svm) and wavelet neural network (wnn), arima model is more capable in the prediction of natural adversities (zhang et al., ) . chatterjee et al. ( ) studied a stochastic mathematical model of the covid- epidemic in india. the logistic growth regression model is used for the estimation of the final size and its peak time of the covid- pandemic in many countries of the world and found similar result obtained by sir model (batista, ) . it is well known that the effects of social distancing become visible only after a few days from the lockdown. this is because the symptoms of the covid- normally take some time to come out after getting infected from the covid- . an estimates indicates that, with hard lockdown and continued social distancing, the peak total infections in india will be million and the number of infective by september is likely to be over million (schueller et al., ) . the study of infectious diseases is called epidemiology. a disease is called endemic if it persists in a population and pandemic when it occurs worldwide. the spread of an infectious disease involves not only disease related factors such as the infectious agent, mode of transmission, latent period, infectious period, susceptibility and resistance, but also social, cultural, demographic, economic and geographic factors. mainly there are three types of models for infectious diseases that are spreading directly through person to person contact in a population. some simple models are formulated and analyzed mathematically considering differential equations. parameters are estimated for infectious diseases and also used to compare the vaccination levels necessary for herd immunity. the three models considered here are the simple epidemiological models and suitable for diseases which are transmitted directly from person to person. more complicated models must be used when there is transmission by insects called vectors or a reservoir of nonhuman infective. epidemiological models are widely used to understand the pattern and policy development. even though vaccines are available for many infectious diseases, these diseases still cause suffering and mortality in the world, especially in developing countries. in developed countries chronic diseases such as cancer and heart disease have received more attention than infectious diseases, but infectious diseases are still a more common cause of death in the world. the transmission mechanism from an infective to susceptible is understood or nearly all infectious diseases and the spread of diseases through a chain of infections is known. however, the transmission interactions in a population are very complex so that it is difficult to comprehend the large scale dynamics of disease spread without the formal structure of a mathematical model. an epidemiological model uses a microscopic description (the role of an infectious individual) to predict the macroscopic behavior of disease spread through a population. in many sciences it is possible to conduct experiments to obtain information and test hypotheses. experiments with infectious disease spread in human populations are often impossible, unethical or expensive. data is sometimes available from naturally occurring epidemics or from the natural incidence of endemic; however, the data is often incomplete due to underreporting. this lack of reliable data makes accurate parameter estimation difficult so that it may only be possible to estimate a range of values for some parameters. since repeatable experiments and accurate data are usually not available in epidemiology, mathematical models and computer simulations can be used to perform needed theoretical experiments. mathematical models have both limitations and capabilities that must recognized. sometimes questions cannot be answered by using epidemiological models, but sometimes the modeler is able to find the right combination of available data, an interesting question and a mathematical model which can lead to the answer. comparisons can lead to a better understanding of the processes of disease spread. modeling can often be used to compare different diseases in the same population, the same disease in different populations, or the same disease at different times. comparisons of diseases such as measles, rubella, mumps, chickenpox, whooping cough, poliomyelitis and others are made (hethcote, ; yorke and london, ; yorke et al., ) and in the article on rubella in this volume by hethcote ( ) . quantitative predictions of epidemiological models are always subject to some uncertainty since the models are idealized and the parameter values can only be estimated. however, predictions of the relative merits of several control methods are often robust in the sense that the same conclusions hold over a broad range of parameter values and a variety of models. optimal strategies for vaccination can be found theoretically by using modeling. longini et al. ( ) use an epidemic model to decide which age groups should be vaccinated first to minimize cost or deaths in an influenza epidemic. hethcote ( ) uses a modeling approach to estimate the optimal age of vaccination for measles. within a short period of time, covid- has traumatized the world with a greater magnitude and coercion than older pandemics. its eventuality is grabbed by the fact that it has infected millions and killed thousands across the globe. global markets, accessible transportation, large scale production have largely contributed to make this pandemic spread faster. this has drastically affected the social life and health mental as well as physical of human beings worldwide. the already burdened health infrastructure across the globe is virtually exposed up to an irreparable point. the who declared - corona virus outbreak a public health emergency of international concern (pheic) on january th, and a pandemic days later on february th, . with its outbreak in wuhan, china, the pandemic seems to occupy and include all the vitals of the world thereby affecting the mechanistic processes of any nation. the countries are trying hard to combat and contain this outbreak by following suitable set of protocols that tend to alter the transmission rate effectively. in the initial phase of spread of covid- ; italy, spain, france and some other european countries are one of the worst sufferers of the pandemic and the coercive measures have resulted in the disruption of all the necessary services. on the other hand, the case is virtually less severe in south asia. india is less affected by the covid- , however, china is its neighboring country having border through buffer states like nepal and bhutan. being the second most populous country of the world, india is fighting hard to minimize the damage of covid- . as on th april, the total number of infected cases in india was , with deaths and most recoveries (covid india.org). india reported its first case on th january and entered the countrywide lockdown on march th, with constantly increase in number of covid- cases. indian government as well as states government has issued early guidelines and travel advisories to limit the further damage of disease. also, the timely precautions taken by the government have contributed greatly toward combating this pandemic. the paper attempts to devise a model that would conveniently help in assessing the predictability of pandemic covid- in future time period. this can be achieved by evaluating the different parameters that directly or indirectly affect the ongoing rate of pandemic. moreover, theoretical explanation, quantitative analysis and other parameters are highly required to predict the peak and size of any pandemic. we obtained information on cumulative number of covid- confirmed cases in india from covid india.org. all cases are laboratory confirmed following the case definition by the government of india. some studies modeled the epidemic curve obeying the exponential growth (de silva et al., ). the nonlinear least square framework is adopted for data fitting and parameter estimation for covid- at this early stage. first exponential and then logistic growth curve is used to model the covid- pandemic, since epidemics grow exponentially not linearly. but it is surprising that exponential growth curve always provide increasing number of daily new cases. there is no saturation point. another deterministic model used for understanding the dynamics of epidemic is the susceptible-infectious-recovered (sir) model, which has been used to accurately predict incidence like sars. in the sir model, we need to know the input parameters first the stats we feed into the model (chatterjee et al., ; mandal et al., ; singh and adhikari, ) . the first one is r called the basic reproduction number. it is essentially the number of new cases a single infected person will cause during their infectious period. it is one of the most important parameters for assessing any epidemic. corona virus has an r $ . . in contrast, the swine flu virus had an r $ . in the swine flu epidemic (gupta, ) . the r will inform us about how many people will get infected with one infected person. other one is the case fatality rate (cfr), which is the percentage of infected people that will die due to the infection. the cfr for corona virus has been reported between . % and %. the lower values are more appropriate in resource better settings of medical facility. but sir model assumes that every person is moving and has equal chance of contact with each and every other person among the population irrespective of the space or distance between different people. it is assumed that the transmission rate remains constant throughout the period of pandemic. also this model considered to have the same transmission rate for who have been diagnosed and are in quarantine or those who have not been quarantined. the harmonic analysis methods and dynamic model (rao srinivasa arni et al., ) estimates show that the number of covid- infected would be (if there were infected individuals as of march , , who was not taking any precautions to spread), , (if there were ) and , (if there were ). sir model is a theoretical epidemiological model, in which, the population is categories into three component such as: susceptible (s), which is the group of people who are vulnerable to exposure with infectious people, infected (i), are those with the disease and can transmit it to the susceptible and the third component is the individuals who have recovered from the infectious disease and developed immunity and not susceptible to the same illness anymore (r). this framework enables us to understand the dynamics of any epidemic. thus sir model is a compartmental model in which individuals are separated into different compartments based on their status and follow the corresponding population sizes over the time. the diagrammatical representation of threecompartment model (kermack and mckendrick, ) is given as where, s(t) ¼ proportion of individual susceptible to covid- at time t, i(t) ¼ proportion of individual who have been infected by covid- and are capable of infecting others at time t, and r(t) ¼ proportion of individual who have been infected by covid- and recovered at time t, such that s(t) + i(t) + r(t) ¼ . hereβ is the transmission parameter controlling how much the disease can be transmitted. this is the average number of individuals that one infected individual will infect per unit time. it is determined by the chance of contact and the probability of disease transmission. while γ is the parameter representing the rate of recovery in a particular period. the model allows us to describe the number or proportions of persons in each compartment by solving the following ordinary differential equations, several assumptions have been discussed with respect to the sir model (brauer and castillo-chavez, ; daley and gani, ) . based on the sir model, the basic reproduction number is defined as, here, r is the average number of new covid- cases produced by a single covid- infected case over the time. in order to fit a sir model, the parameters were obtained by minimizing the residual sum of squares between the observed active cases and the predicted active cases. the utilization of the seir model lies in the fact that it focuses on the basic processes that are directly related to this growing pandemic. in the preparation of this model, there is a need that the population is to be divided into some subdivisions which are susceptible subdivision s(t), that denotes the population which is susceptible to catch the virus; exposed subdivision e(t), that denotes the population which is infected but the symptoms are not visible yet; infected subdivision i(t), that denotes the population which has been infected by the virus and are showing the symptoms; recovered subdivision r(t), that denotes the population which has immunity to the infection. the basic assumption to formulate this model is that the recovered patients acquired permanent active immunity. it can be justified by the strong reason that none of the patients were re-infected by the covid- . there have been numerous cases where patients died after being discharged from the hospital but it was found that the patients were either discharged for having mild symptoms or the testing machine reported wrongly. now we have normalized these components as s + e + i + r ¼ . furthermore, suppose that there are equal birth and death rates, i.e., μ and α is the mean latent period for the disease. γ is the mean infectious period and recovered individuals are permanently immune. the contact rate β may or may not be a function of time. thus the seir model is defined as the variable r is determined from the other variables according to equation s + e + i + r ¼ . a growth curve is an empirical model of the evolution of a quantity over time. growth curves are widely used in biology for quantities such as population size in population ecology and demography for population growth analysis, individual body height in physiology for growth analysis of individuals. growth is also a key property of many systems such as an economic expansion, spread of an epidemic, the formation of a crystal, an adolescent's growth and the condensation of a stellar mass. this is the simplest growth model, in which population grows at a constant rate over time. linear growth is described by the equation where p t represents the numbers or size of the system at time t, p t+ represents the system's numbers or size of the system one time unit later, and a is the system's (linear) growth rate. many times this model fails to explain natural phenomenon. another simple model describes exponential growth, in which population grows at a constant proportional rate over time. the relation may be expressed in either of two forms, depending on whether reproduction is assumed to be continuous or periodic (shryock and siegel, ) . exponential growth results in a continuous curve of increase or decrease, whose slope varies in direct relation to the size of the population. where r is the constant rate of growth, p o is the initial population size, and the variables t and p t respectively represent time and the population at time t (method ). another form of exponential curve is as follows where k ¼ p n p = n and that therefore the growth rate in eq. ( ) with the current incidence of the covid- going on, we hear about exponential growth. in this study, an attempt has been made to understand and analyze the data through exponential growth curve. the reason for using exponential growth curve for studying the pattern of covid- incidence is that epidemiologists have studied these types of happenings and it is well known that the first period of an epidemic follows exponential growth. the exponential growth function is not necessarily the perfect representation of the epidemic. i have tried to fit exponential curve first, and at the next point to study the logistic growth curve because exponential curve is only fit the epidemic at the beginning. at some point, recovered people will not spread the virus anymore and when someone is or has been infected, the growth will stop. logistic growth is characterized by increasing growth in the beginning period, but a decreasing growth after point of inflection. for example, in the corona virus case, the maximum limit would be the total number of exposed people in india because when everybody is infected, the growth will be stopped. after that the increasing rate of curve starts to decline and reach to the minimum. the logistic model reveals that the growth rate of the population is determined by its biotic potential and the size of the population as modified by the natural resistance, or, in other words, by all the various effects of inherent characteristics, that are density dependence pearl and reed, . natural resistance increases as population size gets closer to the carrying capacity. logistic growth is similar to exponential growth except that it assumes an essential sustainable maximum point. in exponential growth curve, the rate of growth of y per unit of time is directly proportional to y but in practice the rate of growth cannot be in the same proportion always. the logistic curve will continue up to certain level, called the level of saturation, sometimes called the carrying capacity, after reaching carrying capacity it starts declining. a system far below its carrying capacity will at first grow almost exponentially, however, this growth gradually slows as the system expands, finally bringing it to a halt specifically at the carrying capacity (pearl and reed, ; shryock and siegel, ) . the logistic relationship can be expressed as where a, b and k are constant and y t is that value of the time series at the time t. the reciprocal of y t follows modified exponential law. hence, the given time series observation y t will follow logistic law if their reciprocal /y t follows modified exponential law. thus in general, we may take the factor y is called the momentum factor which increases with time t and the factor (k À y) is known as the retarding factor which decreases with time. when the process of growth approaches the saturation levelk, the rate of growth tends to zero. now we have dy y kÀy ð integrating, we get log y kÀy ¼ αkt + γ, where γ is the constant of integration. k y ¼ + e Àαkt :e Àγ ) y ¼ k + e À γ+αkt ð Þ , this equation is same as eq. ( ) where a ¼ Àγ and b ¼ Àαk. logistic curve has a point of inflection at half of the carrying capacity k. this point is the critical point from where the increasing rate of curve starts to decline. the time of point of inflection can be estimate as Àa b . for the estimation of parameter of logistic curve, method of three selected point given by pearl and reed ( ) has been used. the estimate of the parameters can be obtained with equation given as: k ¼ y y + y ð ÞÀ y y y y À y y where y , y and y are the cumulative number of covid- cases at a given time t , t and t respectively provided that t À t ¼ t À t . you may also estimate the parameter a and b by method of least square after fixing k. to predict confirmed corona cases on different day, logistic growth curve has been also used and found very exciting results. the truncated information (means not from the beginning to the present date) on confirmed cases in india has been taken from march to april , . the estimated value of the parameters are as follows k ¼ , . , a ¼ . and b ¼ À . , with these estimates predicted values has been obtained and found considerably lower values than what we observed. on april and , the number of confirmed corona cases are drastically increasing in some part of india due to some unavoidable circumstances thus there is an earnest need to increase carrying capacity of the model, thus it is increased and considered as , and the other parameters a and b are estimated again which are a ¼ . and b ¼ À . . the predicted cumulative number of cases is very close to the observed cumulative number of cases till date. the time of point of inflection is obtained as . , i.e., days after beginning. we have taken data from march , so that the time of point of inflection should be april , and by may , there will be no new cases found in the country. exponential growth model and model given swanson provided natural estimate of the total infected cases by june , is all most all people in india. this estimate is obtained when no preventive measure would be taken by the government of india. the testing rate is lower in india than many western countries in the month of march and april, so our absolute numbers was low, when government initiate faster testing process then we have observed more number of cases and found this logistic model fail to provide cumulative number of corona confirm cases after april , thus there is a need to modify this model (fig. ) . in order to the modification, i have taken natural log of cumulative number of corona confirm cases instead of cumulative number of corona confirm cases as taken in the previous model. this model provides the carrying capacity is about , cases and time of point of inflection is april , . the present model provides reasonable estimate of the cumulative number of confirmed cases and by the end of july there will be no new cases found in the country. further, the number of covid- cases increases and the model estimate does not match to the observed number of case, therefore we need to change the data period, since the logistic curve is data-driven model that provide new estimate of point of inflection and maximum number of corona positive cases by date when disease will disappear, that helps us to plan our strategies. finally in this study we changed the data period, i.e., we have taken data from april th to july th . this provides the carrying capacity is about lakh cases and time of point of inflection is august th, with a maximum number of new cases on a day is about , per day. the model based on this data (from april th to july th ) provides reasonable estimate of the cumulative number of confirmed cases, and predicted value along with % confidence interval provided up to august th, (see table ) and by the end of march we expect there will be no new cases in the country in absence of any effective medicine of vaccine (fig. ) . to know the significance of lockdown we define the covid- case transmission is as , where x t is the number of confirm cases on t th day. we have calculated c t and the doubling time of the corona case transmission in india. the doubling time is calculate as ln c t ¼ : c t . we have calculated covid- case transmission c t on the basis of days moving average of daily confirm cases (in the beginning the data in india is very fluctuating) and it is found gradually decreasing in india. this indicates the good sign of government attempts to combat this pandemic through implementing lockdown. these findings indicate that in future the burden of corona will be expectedly lowering down if the current status remains same. in table given below, an attempt has been made to show the summary statistics of corona case transmission c t during various lockdown periods in india. it is observed that average covid- case transmission was maximum ( . with standard deviation . ) in the period prior to the lockdown. during the first lockdown period the average covid- case transmission was . with standard deviation . , however, in lockdown it was . with standard deviation . and in lockdown covid- case transmission was . with standard deviation . , however, in the period of fourth lockdown the average case transmission was . with standard deviation . , thus it is clear that both average transmission load and standard deviation are decreasing. table reveals the result of anova for average c t during various lockdown periods which is significant means that the average corona case transmission is significantly different is various lockdown periods considered. a group wise comparison of the average covid- case transmission c t during various lockdown periods is shown in table which reveals that first lockdown is significantly affects the spread of corona case transmission than others but second lockdown period is not significantly different than third and fourth. same result is observed for third and fourth lockdown period. this indicates that the covid- transmission is not under control now. fig. shows corona case transmission and doubling time in india. the corona case propagation in decreasing and doubling time is increasing day by day. let us define a function called tempo of disease that is the first differences in natural logarithms of the cumulative corona positive cases on a day, which is as: where p t and p tÀ are the number of cumulative corona positive cases for period t and t À , respectively. when p t and p tÀ are equal then r t will become zero. if this value of r t , i.e., zero will continue a week then we can assume no new corona cases will appear further. in the initial face of the disease spread, the tempo of disease increases but after sometime when some preventive measures is being taken then it decreases. since r t is a function of time then the first differential is defined as where r t denotes the tempo that is the first differences in natural logarithms of the cumulative corona positive cases on a day, r t is the desired level of tempo, i.e., zero in this study, t denotes the time and k is a constant of proportionality. eq. ( ) is an example of an ordinary differential equation that can be solved by the method of separating variables. the eq. ( ) can be written as dr t r t ¼ kdt integrating eq. ( ), we get where c is an arbitrary constant. taking the antilogarithms of both sides of eq. ( ) we have r t ¼ e kt+c ) e kt e c ) r t ¼ ae kt where a ¼ e c . this eq. ( ) is the general solution of eq. ( ). if k is less than zero, eq. ( ) tells us how the covid- cases will decreases over the time until it reaches zero. value of a and k is estimated by least square estimation procedure using the data sets. the government of india implemented lockdown on march th, and expected that the tempo of disease is decreasing. government suggested and implemented social distancing and lockdown to control the spread of covid- in the society. in table , the predicted value of covid- cases obtained with this method is given along with % confidence interval. about . lakh cases are expected by august th, . with this model it is expected that about lakh peoples will be infected in india by the end of october and after that no cases will happen since the tempo of disease r t will become zero (fig. ) . in table an attempt has been made to show the summary statistics of tempo of covid- r t during various lockdown periods in india. it is observed that average tempo is maximum ( . with standard deviation . ) in the period prior to the lockdown. during the first lockdown period the average tempo is . with standard deviation . and after that it is found decreasing in the various lockdowns. table various lockdown periods is shown in table which reveals that first lockdown is significantly different than others. consecutive mean difference shows that the decrease in disease spread has been observed but insignificant, means there is no impact of lockdown on controlling the disease spread. to analyze the temporal trends and to identify important changes in the trends of the covid- outbreak joinpoint regression is used in china (al hasan et al., ) ; here in this study we performed a joinpoint regression analysis in india to understand the pattern of covid- . joinpoint regression analysis, enable us to identify time at a meaningful change in the slope of a trend is observed over the study period. the best fitting points known as joinpoints, that are chosen when the slope changes significantly in the models. to tackle the above problem joinpoint regression analysis (kim et al., ) has been employed in this study to present trend analysis. the goal of the joinpoint regression analysis is not only to provide the statistical model that best fits the time series data but also, the purpose is to provide that model which best summarizes the trend in the data (marrot, ) . let y i denotes the reported covid- positive cases on day t i such that t < t < … < t n . then the joinpoint regression model is defined as ln y i ¼ α + β t + δ u + δ u + :…+ δ j u j + ε i ( ) & and k < k … < k j are joinpoints. the details of joinpoint regression analysis are given elsewhere (kim et al., ) . joinpoint regression analysis is used when the temporal trend of an amount, like incidence, prevalence and mortality is of interest (doucet et al., ) . however, this method has generally been applied with the calendar year as the time scale (akinyede and soyemi, ; chatenoud et al., ; missikpode et al., ; mogos et al., ) . the joinpoint regression analysis can also be applied in epidemiological studies in which the starting date can be easily established such as the day when the disease is detected for the first time as is the case in the present analysis (rea et al., ) . estimated regression coefficients (β) were calculated for the trends extracted from the joinpoint regression. additionally, the average daily percent change (adpc), calculated as a geometric weighted average of the daily percent changes (clegg et al., ) . the joinpoints are selected based on the data-driven bayesian information criterion (bic) method (zhang and siegmund, ) . the equation for computing the bic for a k-joinpoints regression is: where sse is the sum of squared errors of the k-joinpoints regression model and n is the number of observations. the model which has the minimum value of bic(k) is selected as the final model. there are other methods also for identifying the joinpoints such as permutation test method and the weighted bic methods. relative merits and demerits of different methods of identifying the joinpoints are discussed elsewhere (national institute cancer, ) . the permutation test method is regarded as the best method but it is computationally very intensive. it controls the error probability of selecting the wrong model at a certain level (i.e., . ). the bic method, on the other hand, is less complex computationally. in the present case, data on the reported confirmed cases of covid- are available on a daily, thus the daily percent change (dpc) from day t to day (t + ) is defined as if the trend in the daily reported confirmed cases of covid- is modeled as then, it can be shown that the dpc is equal to it is worthwhile to discuss here is that the positive value of dpc indicates an increasing trend while the negative value of dpc suggests a declining trend. the dpc reflects the trend in the reported covid- positive cases in different time segments of the reference period observed through joinpoint regression techniques. for the entire study period, it is possible to estimate average daily percent change (adpc) that is the weighted average of dpc of different time segments of the study period with weights equal to the length of different time segments. however, when the trend changes frequently, adpc has little meaning. it assumes that the random errors are heteroscedastic (have nonconstant variance). heteroscedasticity is handled by joinpoint regression using weighted least squares (wls). the weights in wls are the reciprocal of the variance and can be specified in several ways. thus standard error is used to control heteroscedastic in the analysis during the entire period. to observe the trend of reported cases, the moving average method has been used in this study. the daily percent change (dpc) in the daily reported confirmed cases of covid- during the period march th, through july th, is used for forecasting the daily reported confirmed cases of covid- in the immediate future under the assumption that the trend in the daily reported confirmed cases of covid- remains unchanged. the number of cases increased by the rate of . % per day in india; however, the rate is different in the different segment. also table reveals that the growth rate is positive and significant (about %) from th march to rd april and after that the growth rate is decreasing in comparison of first segment, i.e., for days (from rd april to th april). the possible reason may be lockdown imposed in india. in the third segment, i.e., from th april to th may a high increase has been observed but it is insignificant. from th april to th may the rate is although the positive but dramatically lower than the previous segments growth rate. in the next segment, i.e., th segment which is of days, we observe a significant increase of . % in covid- cases. in the last and th segment from th may to th july, i.e., for days, the growth rate is found again positive and significant ( . % per day) in the covid- cases. fig. shows that the trend increases in india still sharply and there is no hope of decline in covid- cases. fig. shows the forecasted value of covid- daily cases in india. the covid- cases will increase further if the same trend prevailing. table presents the forecast of the predicted cases of covid- in india along with % confidence intervals. this exercise suggests that by august th, , the confirmed cases of covid- in india is likely to be , , with a % confidence interval of , , - , , and daily reported cases will be , with % confidence interval of , - , . this daily reported covid- positive cases may change only when an appropriate set of new interventions are introduced to fight covid- pandemic. it is observed that analysis indicates that in the month of august, india faces more than thousand cases per day (fig. ). india is in the comfortable zone with a lower growth rate than other countries. logistic model shows that, the epidemic is likely to stabilize with lakh cases by the end of march and peak will come in middle of the august, however, propagation model provide estimate of maximum covid- case as lakh but the timing is different (by end october) than the logistic model. logistic model need to monitor the data time to time for good long term prediction. the projections produced by the model and after their validation can be used to determine the scope and scale of measures that government need to initiate. joinpoint regression is based on the daily reported confirmed cases of covid- , asserts that there has virtually been little impact of the nationwide lockdown as well as relaxations in restrictions on the progress of the covid- pandemic in india. the joinpoint regression analysis provides better estimate up to th august for the confirmed covid- cases than the other two methods. to know the better understanding of the progress of the epidemic in the country may be obtained by analyzing the progress of the epidemic at the regional level. in conclusion, if the current mathematical model results can be validated within the range provided here, then the social distancing and other prevention, treatment policies that the central and various state governments and people are currently implementing should continue until new cases are not seen. the spread from urban to rural and rich to poor populations should be monitor and control is an important point of consideration. mathematical models have certain limitations that there are many assumptions about homogeneity of population in terms of urban/rural or rich/poor that does not capture variations in population density. if several protective measures will not be taken effectively, then this rate may be changed. however, the government of india under the leadership of modi ji has already taken various protective measures such as lockdown in several areas, make possible quarantine facility to reduce the rate of increase of covid- , thus we may hopefully conclude that, country will 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services on the rate of growth of the population of the united states since and its mathematical representation joinpoint regression analysis with time-on-study as time-scale. application to three italian population-based cohort studies transmission of -ncov infection from an asymptomatic contact in germany covid- in india: potential impact of the lockdown and other longer term policies a logistic growth model for covid- proliferation: experiences from china and international implications in infectious diseases age-structured impact of social distancing on the covid- epidemic in india model-based retrospective estimates for covid- or coronavirus in india: continued efforts required to contain the virus spread reporting, epidemic growth, and reproduction numbers for the novel coronavirus ( -ncov) epidemic nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study recurrent outbreaks of measles, chickenpox and mumps ii seasonality and the requirements for perpetuation and eradication of viruses in populations a modified bayes information criterion with applications to the analysis of comparative genomic hybridization data comparison of the ability of arima, wnn and svm models for drought forecasting in the sanjiang plain preliminary estimation of the basic reproduction number of novel coronavirus ( -ncov) in china, from to : a data-driven analysis in the early phase of the outbreak further reading covid- key: cord- - auhkxce authors: kumar, pramod; pandey, rajesh; sharma, pooja; dhar, mahesh s.; a., vivekanand; uppili, bharathram; vashisht, himanshu; wadhwa, saruchi; tyagi, nishu; fatihi, saman; sharma, uma; singh, priyanka; lall, hemlata; datta, meena; gupta, poonam; saini, nidhi; tewari, aarti; nandi, bibhash; kumar, dhirendra; bag, satyabrata; gahlot, deepanshi; rathore, surabhi; jatana, nidhi; jaiswal, varun; gogia, hema; madan, preeti; singh, simrita; singh, prateek; dash, debasis; bala, manju; kabra, sandhya; singh, sujeet; mukerji, mitali; thukral, lipi; faruq, mohammed; agrawal, anurag; rakshit, partha title: integrated genomic view of sars-cov- in india date: - - journal: wellcome open res doi: . /wellcomeopenres. . sha: doc_id: cord_uid: auhkxce background: india first detected sars-cov- , causal agent of covid- in late january , imported from wuhan, china. from march onwards, the importation of cases from countries in the rest of the world followed by seeding of local transmission triggered further outbreaks in india. methods: we used artic protocol-based tiling amplicon sequencing of sars-cov- (n= ) from different states of india using a combination of minion and minit sequencing from oxford nanopore technology to understand how introduction and local transmission occurred. results: the analyses revealed multiple introductions of sars-cov- genomes, including the a a cluster from europe and the usa, a cluster from middle east and a cluster (haplotype redefined) from southeast asia (indonesia, thailand and malaysia) and central asia (kyrgyzstan). the local transmission and persistence of genomes a , a a and a was also observed in the studied locations. the most prevalent genomes with patterns of variance (confined in a cluster) remain unclassified, and are here proposed as a -clade based on its divergence within the a cluster. conclusions: the viral haplotypes may link their persistence to geo-climatic conditions and host response. multipronged strategies including molecular surveillance based on real-time viral genomic data is of paramount importance for a timely management of the pandemic. the ongoing pandemic of covid- caused by sars-cov- following its first appearance in china has pressed the global community to take measures to flatten its transmission (chan et al., ; zhu et al., ) . the severe symptoms of infection can include pneumonia, severe acute respiratory syndrome, kidney failure and even death with a coalescence of factors (young et al., ; zhu et al., ) . many covid- cases have been reported to be asymptomatic and may serve as carrier of sars-cov- (he et al., ; xu et al., ) . genome sequences of sars-cov- suggest its origin and transmission patterns after it enters a new population is proving to be an important step towards formulating strategies for management of this pandemic (andersen et al., ; chen & li, ) . the first three cases in india were reported in late january and early february, in individuals with a travel history of wuhan, china. india took drastic steps to contain the further spread of the virus including imposition of travel restrictions to and from the affected countries. there were no new cases of covid- for almost a month. however, while the global focus was on china and other eastern countries like south korea and japan; european countries, the middle east and the usa reported a surge in cases of covid- . march onwards, india also witnessed a surge of imported cases from countries other than china which has been further assisted with local transmission. in march, imposition of nationwide lockdown checked the epidemic curve. despite these measurements, india is at the verge of a large outbreak as the transmission is rapidly increasing with more than , reported cases of covid- by the fourth week of june . we carried out whole genome sequencing of sars-cov- (n= ) from pan-india through surveillance program of the national center for disease control (ncdc), delhi. here, we combine genetic and epidemiological data to understand the genetic diversity, evolution, and epidemiology of sars-cov- across india. the spectrum of variations would be an important tool towards contact tracing, effective diagnostics and backbone for drug and vaccine development. the study was conducted jointly by the ncdc and csir-institute of genomics and integrative biology (csir-igib). institutional ethical clearance was obtained at both institutes prior to initiation of research; the need for consent from the patients was waived by the committee. a total of laboratory-confirmed cases of covid- from targeted testing and available samples at ncdc which represent different geographic locations or states and travel history from different countries during the early phase of the outbreak (table and extended data, supplementary figure s [kumar et al., b] ). were included in the study for genomic analyses. targeted testing involved suspected cases; having symptoms (fever, cough and breathlessness) with recent travel history to high-risk countries (china, south asia, middle east, european countries such as italy, spain, uk, france and usa) or positive contacts of covid- cases. the nasopharyngeal and oropharyngeal swabs (in viral transport medium) were received at ncdc, delhi through the integrated disease surveillance programme were subjected to viral inactivation followed by rna extraction using qiaamp viral rna mini kit (cat. no. , qiagen) . total rna content in the elute was quantified using nanodrop (thermo fisher scientific). the / ratio ranged between . - . for the majority of the samples. to ensure that sub-optimal rna samples are also included in the study, we made use of superscript iv (cat. no. , thermo fisher scientific, waltham, ma, usa) , for superior first strand cdna synthesis and included them for sequencing. a quantitative reverse transcription (rt)-pcr assay was used on purified rna for detection of sars-cov- in the samples. quantitative rt-pcr was carried out using taqman assay chemistry on abi platform. the primer/probe concentrations and reaction conditions for diagnostics were as per the who protocols (corman et al., ) . two target genes were used for diagnosis of sars-cov- , envelope (e) gene for screening and rna dependent rna polymerase (rdrp gene) for confirmation. the positive samples were analyzed based on the country of origin (traveller), contact with positive case, geographical location (community), gender and age. samples from each group were selected and further processed for wgs of the sars-cov- . whole genome sequencing of sars-cov- cdna synthesis: total rna from sars-cov- positive samples were quantified using nanodrop and ng of the rna was taken for double-stranded cdna synthesis. briefly, first strand cdna was made using . μl of random hexamer ( ng/μl), . μl of dntps ( nm) and . μl of total rna with volume adjusted with nuclease-free water (nfw), followed by incubation at °c for mins and cooling on ice. to this, . μl of x ssrt iv buffer, . μl of mm dtt, . μl of ribonuclease inhibitor and . μl of ssrt iv enzyme ( u/μl) was added (cat. no. , thermo fisher scientific, waltham, ma, usa) with incubation at °c for minutes, °c for minutes and °c for minutes. . μl of rnase h was added to this and incubated at °c for mins. next, . μl of first strand cdna was heated at °c for minutes after addition of pmol of random primers, μm dntps and x klenow buffer, followed by immediate cooling on ice. soon after, . μl of klenow fragment (cat. no. m s, new england biolabs) was added with incubation at °c for mins, °c for mins and °c for mins. this was followed by ampure beads purification (cat. no. a , beckman coulter) and quantification using qubit dsdna hs assay kit (cat. no. q , invitrogen) . nanopore library preparation and sequencing: a total of ng of double stranded cdna was taken for next generation sequencing (ngs) using a highly multiplexed pcr amplicon approach for sequencing on the oxford nanopore technologies (ont) (oxford, united kingdom) minion using v primer england biolabs). after adaptor ligation, it was purified using a combination of short fragment buffer and ampure beads resulting in a sequencing ready library. library quantification was conducted using the qubit dsdna hs assay kit (cat. no. q , invitrogen) and ng of the library was used for sequencing. barcoding, adaptor ligation, and sequencing were performed on samples with ct values between - . a 'no template control' was created at the cdna synthesis step and amplicon generation step to detect cross-contamination between samples. controls were barcoded and sequenced with both the high-and low-titer sample groups. the sequencing flowcell was primed and used for sequencing using minion mk b. a common pool of cdna was used for making both illumina and nanopore sequencing libraries and subsequent sequencing. cdna ( ng) was used to construct the illumina library using thenextera xt protocol, as per manufacturer's instructions ( v , illumina inc). briefly, tagmentation of cdna was done which tagged and fragmented the cdna by addition of amplicon tagment mix (atm) and tagment dna buffer, as per manufacturer's protocol, illumina inc with incubation at °c for mins with heated lid option. tagmentation was stopped by addition of neutralization tagment buffer. this was followed by the addition of unique index adapters (i and i adapters) to the samples. index adapters are then used for pcr amplification at °c for mins, °c for secs and -cycles of °c for secs, °c for secs, °c for secs; and °c for mins. the pcr product was purified using agencourtampure xp beads. the quantity of the sequencing ready library was measured using qubit dsdna hs assay kit (cat. no. q , invitrogen) and quality by agilent dna hs kit (cat. no. - , agilent). illumina's miseq platform was used for sequencing. analysis pipeline for nanopore sequencing data the raw fast files were base-called and demultiplexed using the guppy basecaller (version . . ). the fastq files were normalized by read length, thereby eliminating possible chimeric reads. pre-alignment quality control was carried out to assess the read quality using nanopack tools (version . . ) (de coster et al., ) . minimap (version . ) has been used to align the raw reads with the reference (mn . ) (li, ) . nanopolish were used for accurate variant calling from the aligned output (loman, ) with options, minimum flanking sequence - , ploidy - and minimum candidate frequency - . . the possible heterozygous variants are filtered out as a separate group after the variants have been called. post-alignment qc was then performed with nanopack tools as well as the seaborn (version . . ) package in python to create the distribution of amplicon quality and ct-value vs coverage and depth. finally, a consensus fasta was created, wherein genomic regions with low coverage and low quality were masked using bcftools (version . ). the raw reads from the miseq were quality-checked by fastqc (version . . ). trimgalore was used to trim the reads containing bad quality and the minimum length of base pairs was kept as a threshold for the reads. hisat is used to map the reads to the human genome (grch ) to remove potential the human rrna reads for the contamination with default parameters [kim et al., ] . the unmapped reads from the human are converted from bam to fastq using bam fastq (version . ) to align to the sars-cov- . hisat was used to align unmapped reads with the sars-cov- reference genome (mn . build). using both samtools (version . ) and bcftools from the sars-cov- aligned bam files the consensus fasta was generated. the variants in the samples were called using bcftools and varscan. the fasta sequences were aligned using mafft (version . ) considering the mn . version as the reference sequence. phylogenetic trees were constructed using the neighbour joining algorithm as statistical method and maximum composite likelihood as model in mega x software. figtree (version . . ) was used for the graphical visualisation of phylogenetic analysis. pheatmap (version . . ) and complexheatmap (version . . ) packages from r . . were used to plot the heatmaps. haplotype network analysis was conducted using popart (version . ) [leigh & bryant, ] . in order to categorize the specific amino acid change and the proteins containing the variants, they were annotated with snpeff (version . ) [cingolani et al., ] . the annotation was performed according to the known reference genome of sars-cov- (i.e. nc_ ) in the ncbi database [wang et al., ] . sars-cov- polypeptide orf ab encodes non-structural proteins (nsp) as a result of proteolytic processing. hence, for better mapping of the variants present in orf ab, we annotated the variants according to the respective nsp residue number. further, conservation analysis of the full-length sequences of proteins harbouring these mutations was done on the basis of the six other coronaviruses. the multiple sequence alignment of seven protein sequences was performed with clustal omega [madeira et al., ] . the conservation score of orf a and orf were calculated with low confidence due to introduced gaps at these positions during alignment. the amino acid type was defined as hydrophobic (g, a, v, l, i, m, p, f, w), polar (s, t, n, q) or charged (h, k, r, d, e). with this definition, the type of change of residues was calculated. to map the high frequency mutations on proteins, we took protein structure models of sars-cov- from the swiss model repository (https://swissmodel.expasy.org/repository/ species/ ) [waterhouse et al., ] and models were generated through comparative modeling and by using robetta prediction server [kim et al., ] . in total three structural models were obtained from swiss model repository and the nsp structure was obtained from rcsb [pdb id m ] [gao et al., ] . the details of missing residues or structural domains of each protein is described below. the spike protein exists as a homotrimer consisting of residues in each chain with a total of amino acids. while electron microscopy structures are available for different conformations of spike protein, in particular s region, many residues within the s and s stalks are missing [walls et al., ; wrapp et al., ] . therefore, to map the mutations onto the structure we obtained the s stalk model of the spike protein (residues - ). similarly, nsp also known as pl-pro (papain-like proteinase) is a large multi-domain transmembrane protein. for mapping the nsp mutations, we considered the model for the nucleic acid binding domain (residue - ), which is conserved in betacoronaviruses [angelini et al., ] . the nucleocapsid protein comprise of n-terminal and c-terminal domains connected by linker region. however, structural information for the linker region is unknown. the majority of the sas-cov- -positive samples were obtained from new delhi, covering the national capital region of delhi, india and a few clusters identified by the surveillance team (covering the states of delhi, tamil nadu, maharashtra, uttar pradesh, andhra pradesh, west bengal, bihar, orissa, rajasthan, haryana, punjab, assam and union territory of ladakh). the mean (standard deviation) age of the total subjects was . ± . years with age range . - years and median of years. the male-to-female gender ratio of in the age group < years was : , while the remaining subjects > years had the ratio of : . exposure to covid- was suggestive of travel history of subjects to europe, west asia and east asia. a minority of subjects were from foreign countries: indonesia (n= ), thailand (n= ) and kyrgyzstan (n= ). the identified localities of the subjects will further help in molecular surveillance of sars-cov- in respective geographical regions. the average amplicon coverage for the v artic primers used in the study was more than x coverage across the majority of the samples (extended data, supplementary figure s [kumar et al., b] ). we also looked into whether lower ct values are a good indicator of genome coverage using a minimal set of virus mapping reads. we plotted genome coverage and average sequencing depth across ct value of both the genes (e and rdrp). it was observed that higher ct values ( onwards) have increased possibility of lower genome coverage (extended data, supplementary figure s [kumar et al., b] ), although some lower ct value samples also had incomplete genome coverage. we sequenced a subset of samples on orthogonal platforms and sequencing methods (shotgun and amplicon) using ont and illumina platform. significantly, we observed that the genetic variants were common between both the platforms. a total of samples passed the quality threshold for mapping full genome coverage threshold for sars-cov- genome < . n content with median coverage ~ × (see underlying data for each accession number [kumar et al., a] . a total of samples that did not qualify the threshold criteria were excluded from strain identification. the phylogenetic analysis of high quality sequences reveal all the strains to be grouped into two major clades, a sub-clade and other clades (figure and being called n), c t (s-protein), n= (other being low depth/n bases). the variant c a (nsp ); n= being observed as another frequent alteration ( figure b) . we also observed few novel variants, g t (nsp ); n= and tc t (nsp ); n= , t c (orf a/b); n= , a t (s protein); n= , g a (nsp /rdrp); n= , a g (nsp /helicase); n= and g t (nsp /exonuclease); n= in this cluster. the majority of the key cluster variants , , , , are also shared in sequences submitted from singapore and brunei; additionally, similar clade sequences were observed in india submitted by national institute of mental health and neuro-sciences (nimhans) and gujarat biotechnology research centre (gbrc) cohort (see underlying data for details of all accession numbers [kumar et al., a] . based on the geographical location of the subjects of this cluster, a considerable number of indonesians (n= ) and two each from thailand and kyrgyzstan were part of this cluster from our study site. this probably suggests introduction of this particularly from east asian countries into india. redefining cluster with neighbourhood re-joining with over represented variants in cluster for variants / / / / , we defined this cluster with a clade. this has similarity with sequences submitted from singapore, brunei and other indian sequences submitted. the haplotype network analysis suggests that these sequences are having a common origin from east asia/south-east asia ( figure c and figure ). this a clade has multiple variants in important region of viral genome, rdrp (a v), n-capsid (p l), nsp (t k), nsp (l f) and nsp (s r) variants. in our cohort of samples, the majority of subjects were from tamil nadu, delhi and indonesia and others were from various other states (figure ). to provide quantitative insights into the mutant proteins, we characterized amino acid substitutions across the viral genomes. of the point mutations identified, were missense that resulted in amino acid substitutions. extended data, supplementary figure s [kumar et al., b] plots the occurrence of these mutations as a function of each viral protein. the frequency of amino acid variations was highest in nsp (l f), present in genomes, followed by nsp (a v) in , nsp (t k) in and nucleocapsid (p l) in genomes. interestingly, the d g mutation in spike protein, which is considered as a prevalent global mutation [bhattacharyya et al., ; korber et al., ] , was present in only of the sequenced genomes. the analysis of occurrence of each mutation with the type of amino acid change have shown that ~ % of these are synonymous changes (extended data, supplementary figure s [kumar et al., b] ). within frequently occurring mutations, p l, l f, a v also showed no major residue alterations. however, t k in nsp involve acquisition of a charged group along with the key s protein mutation (d g) also involves loss of the charged group. these mutations that lead to positively charged groups may cause more severe structural and functional effects. we also compared sars-cov- mutation sites with other six coronavirus sequences (extended data, supplementary figure s b [kumar et al., b] ). most of the mutations were present in variable locations. out of mutations, are present on highly conserved residue locations. interestingly, a higher frequency of mutations are at positions that evolve faster/are variable across the coronaviruses, except for a l and l f, which are present on conserved locations. the structural analysis of different viral proteins, nucleocapsid, nsp , nsp , and spike protein was conducted and analysis of nucleocapsid protein [kang et al., ] showed its variants were present in the linker region ( figure a ). the observed mutations in nsp (a highly conserved protein) are overlaying onto the interface (p l) and niran (a l) region. the latter is critical as it contains a zn+ binding site; however, little is known about the exact functional output. in contrast, the p l mutation is present on protein interaction junctions where a hydrophobic cleft is known to bind to inhibitors ( figure b ). the amino acid change from proline to leucine may result in significant backbone changes, due to the absence of unique proline-induced distortions in the protein backbone. next, we mapped mutations within nsp protein ( figure c ). in particular, the mutations were present on the nab domain of nsp , which is a nucleic acid binding domain and also interacts with nsp [jian et al., ] . this mutation may impact rna synthesis machinery; however, little is known about its exact mechanism of action. lastly, the d g mutation in spike protein is an interesting substitution and has been reported with increased tally ( figure d ) [bhattacharyya et al., ; korber et al., ] . structurally, this mutation is located in the s subunit that also contains the rbd domain. although present outside the functional region, the proximity of d g around s cleavage site implicates an important change in the local environment. this is the first comprehensive genomic picture of the sars-cov- prevalent in the indian population during the early phase of outbreaks. the understanding is important keeping in view the vast geographical expanse and population density of india. there were three major waves of viral entry in india associated with multiple outbreaks (extended data, supplementary figure s [kumar et al., b] ). the first wave includes importation of sars-cov- (a a cluster) through travelers from europe (italy, uk, france, etc.) and the usa. second wave of sars-cov- (a cluster) was linked with the middle east (iran and iraq). the third wave comprises combined viral (haplotype redefined as a ) entries from southeast asia (indonesia, thailand and malaysia) and central asia (kyrgyzstan). the study, taken together with those of other reported genomes (potdar et al., ) , revealed that the a cluster (previously unclassified) is the most prevalent in the available genome sequences from india. the observed distinct a genome lineage of sars-cov in the indian subcontinent, which is present in east asian countries like singapore and indonesia, may allow further research and investigation to understand the evolution of sars-cov- genomes in southeast asian countries. many novel mutations identified may be specific to indian conditions, but more genomic data is needed to strengthen the assumption to rule out sampling bias and other factors (lu et al., ) . however, a more detailed analysis of these genomes might provide information whether these variations need to be considered during design of diagnostic primers as the need for testing shoots up. it may allow for creation of cost-effective panels to trace the movement of lineage specific strains across geographical regions more rapidly and effectively. lots of efforts are ongoing to identify suitable vaccine candidates through docking studies. these observations are important to consider the variants that map to the indian genomes during such prioritization studies, since these strains would now form a major fraction of the genomes that are likely to become more prevalent in india after lockdown. mapping of these variant genomes in conjunction with the clinical history in terms of recovery, hospitalization and co-morbidity might allow identification of variants that should be actionable and would also have relevance for prognosis. it is imperative that robust genomic data based on large sample size, including rural populations with even distribution can bring out the real scenario once correlated with epidemiological data eventually helping in drafting of further management policies. [kumar et al., a] . this project contains all gisaid accession numbers generated and analysed in this study. figshare: supplementary figures s -s . https://doi.org/ . / m .figshare. .v [kumar et al., b] . this file contains the following extended data: • supplementary figure s : a schematic diagram showing numbers of samples with their geographical affiliations with respect to states of india. • supplementary figure s : sequencing data quality parameters and orthogonal platform validation. the proximal origin of sars-cov- pubmed abstract | publisher full text | free full text severe acute respiratory syndrome coronavirus nonstructural proteins , , and induce doublemembrane vesicles pubmed abstract | publisher full text | free full text global spread of sars-cov- subtype with spike protein mutation d g is shaped by human genomic variations that regulate expression of tmprss and mx genes a familial cluster of pneumonia associated with the novel coronavirus indicating person-to-person transmission, a study of a family cluster sars-cov- , virus dynamics and host response supplementary figures s -s . figshare. dataset. b popart: full-feature software for haplotype network construction minimap , pairwise alignment for nucleotide sequences acknowledgements ncdc greatly acknowledge the support of prof. dr. christian drosten, charite -universitatsmedizin, berlin for promptly providing the positive controls for qpcr. the authors do acknowledge gisaid for sharing the genomic sequences in public domain and other contributors sars-cov- genomic data (detailed acknowledgement mentioned in the supplementary material). we would like to gratefully acknowledge the efforts of officials involved in idsp network and associated hospitals in sample collection and timely data sharing. we would like to thank the financial aid provided by ministry of health and family welfare, government of india. csir-igib would like to acknowledge genotypic technologies pvt. ltd., bangalore, india for its role in facilitating ont sequencing. authors also acknowledge the role of all the technical and support staff of ncdc involved in covid- testing and subhash gurjar (csir-igib) for facilitating reagents procurement amidst lockdown and for providing other assistance in the laboratory work. icmr fellowship - - (isrm/ ( )/ ) for vivekanand a is acknowledged. reviewer report september https://doi.org/ . /wellcomeopenres. .r © yadav s. this is an open access peer review report distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. department of biological regulation, weizmann institute of science, rehovot, israelthe study entitled 'integrated genomic view of sars-cov- in india' explores the comprehensive genomic analysis of the sars-cov- early outbreaks in india. the study is highly relevant to the current epidemic and may add important information for further research and strain evolution of sars-cov- , especially in india. along with other clades previously known (named a a, a and a ….), the authors reported that a (previously unclassified) is the most prevalent in the available genome sequences from india. the authors discussed that several novel mutations identified may be exclusive to the indian population/conditions. it can also be helpful to trace the movement of lineage-specific strains across geographical regions more efficiently. the study is well designed, executed and concluded, and has significant merit to be published. the authors may address the following minor comments before indexing:the authors should mention what was the positive and negative control for the qpcr. .abstract -methods: sentence may be refreshed into two small sentences. .methods: subheading 'sample collection and molecular investigations' line seven -may be as 'absorbance ratio ( / nm) was ranged between . - . for most of the samples indicating its good quality . yes are all the source data underlying the results available to ensure full reproducibility? yes are the conclusions drawn adequately supported by the results? yes competing interests: no competing interests were disclosed.reviewer expertise: molecular biology, cell signalling, epigenetics reviewer report august https://doi.org/ . /wellcomeopenres. .r © nema v. this is an open access peer review report distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. this manuscript is well designed and executed to explore importation of sars-cov- genome with respect to major clade depicting a a, a and a wave to india however, sars-cov- cluster b as well as a a though minor is not mentioned for its entry in india and the indian subcontinent.the following amino acid substitutions are reported predominantly in orf ab region of the sars-cov- genome and its occurrence is in the following order l f > a v > t k > d g > p l > s r, however only d g from spike region seems to be showing more infectivity and transmission efficiency in europe while rest of the amino acid substitutions need to be explored for their infectivity and transmission efficiency. this will provide significant association between different mutation patterns and transmission profile with respect to india and the indian subcontinent. if applicable, is the statistical analysis and its interpretation appropriate? i cannot comment. a qualified statistician is required. are the conclusions drawn adequately supported by the results? yes competing interests: no competing interests were disclosed.reviewer expertise: molecular biology, metagenomics, tuberculosis drug discovery i confirm that i have read this submission and believe that i have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. key: cord- -y rqdy authors: tiwari, sunita; kumar, sushil; guleria, kalpna title: outbreak trends of coronavirus disease– in india: a prediction date: - - journal: disaster medicine and public health preparedness doi: . /dmp. . sha: doc_id: cord_uid: y rqdy objective: the objective of this paper is to prepare the government and citizens of india to take or implement the control measures proactively to reduce the impact of coronavirus disease (covid- ). method: in this work, the covid- outbreak in india has been predicted based on the pattern of china using a machine learning approach. the model is built to predict the number of confirmed cases, recovered cases, and death cases based on the data available between january , , and april , . the time series forecasting method is used for prediction models. results: the covid- effects are predicted to be at peak between the third and fourth weeks of april in india. this outbreak is predicted to be controlled around the end of may . the total number of predicted confirmed cases of covid- might reach around , and the number of deaths due to covid- are predicted to be around april , , in india. if this outbreak is not controlled by the end of may , then india will face a severe shortage of hospitals, and it will make this outbreak even worse. conclusion: the covid- pandemic may be controlled if the government of india takes proactive steps to aggressively implement a lockdown in the country and extend it further. this presented epidemiological model is an effort to predict the future forecast of covid- spread, based on the present scenario, so that the government can frame policy decisions, and necessary actions can be initiated. t he world health organization (who) office of china received information on the first case of pneumonia of unknown etiology on december , , in wuhan city of china. in the next days (december , -january , ), another cases of similar type were reported in china; however, the reason was still unidentified. further, on january , , china declared that they had identified an advanced type of coronavirus. the virus is called severe acute respiratory syndrome coronavirus- (sars-cov- ), and the who named the disease, coronavirus disease (covid- ). covid- originated in china; however, since the last months, it has become a public health threat and has spread almost all over the world. on march , , the who declared the virus outbreak a pandemic. as of april , , the total number of confirmed cases reached in countries and territories, which has resulted in deaths. there is no vaccine or specific drug combination available to control the effect of covid- . therefore, to control the loss of lives, governments of most of the countries are imposing several restrictions on their citizens. the first confirmed case of covid- in india was reported on january , , and on april , , a total of cases were confirmed. it took days for the number of novel coronavirus cases in india to go from to , whereas, in turkey, it took only days. the indian government imposed a complete lockdown for days, that started from march , , to april , , to control the outbreak. it is urgent to study the covid- cases of china to prepare a situation report of india for the coming days so that the government, authorities, and citizens can take or implement the control measures proactively. this study is focused on predicting the outbreak trends in india based on the pattern of the outbreak in china, considering that the population density of both countries is very high. the prediction model is built from the publicly available dataset of covid- . this dataset includes the daily numbers of cumulative confirmed cases, recovered cases, and death cases from january , , to april , . this prediction model predicts the daily number of cumulative confirmed cases, recovered cases, and death cases from april , , to april , . this section covers the details of methods used for predicting covid- cases in india. the dataset of covid- has been downloaded from kaggle. the dataset is contributed by the center for systems science and engineering (csse) at johns hopkins university (jhu). this dataset includes nationwide details of confirmed cases, recovered cases, and death cases. the presented work uses the data of china from january , , to april , , to predict the outcome in india in the next days. a predictive model is built using weka to predict the day-wise number of confirmed cases, recovered cases, and death cases. time series forecasting is performed on the data collected, and a model is prepared. the daily numbers of confirmed cases and their corresponding days are given as input to obtain the relationship between both variables. the predictive models are derived from the data available from china on the assumption that the covid- epidemic trend in india is similar to that in china with a time lag. this assumption is based on the high population density of both countries. figure shows the model overview. each stage is detailed with the following information. data of confirmed cases by date, recovered cases, and death cases of china are filtered from the dataset. additionally, the available data for india are also filtered for validation. data are transformed for processing and stored in.csv files for further processing. the database of china is divided into training data and test data; % of the data is used for training the predictive model, and the remaining % is used for testing. the aim of the training model is to fit the model using the training data. the model is trained using the time series forecasting methods. after training the model, prediction models are tested to evaluate the performance in testing datasets. in the validation step, the accuracy of results is verified, comparing the test data with predictions. the predictive model is built for predicting the daily number of confirmed cases of covid- in india. we obtained the predictive model to predict the number of confirmed covid- cases. the confirmed cases in india and china are shown from january , , to april , , in figure . from this figure, it is concluded that the number of cumulative confirmed cases in india is likely to increase at a swift pace after april , . as per this prediction model, india may have nearly a million confirmed cases by the end of may . this may be controlled if the climatic conditions and government of india policies become favorable to control the virus. similarly, the predictive model is built for predicting the daily number of covid- deaths due to the pandemic in india. the results for this are shown in figure . the number of death cases from covid- is predicted to increase around april , . around april , , the number of death cases in india is expected to be around . this number may further increase after april , . the overall mortality rate in india is expected to be lower as compared to the rest of the world. the demographic characteristics of india differ from other countries. in , approximately . % of the indian population are age years and older, whereas this number is more than % in italy. [ ] [ ] covid- is fatal in older patients, and therefore the fatality rate of india is lower as compared with that of other countries as of april , . along the same lines as above, the model is built for predicting the daily number of recovered cases of covid- in india, as shown in figure . this number is expected to increase after april , . as discussed previously, by the end of may , india may have around million confirmed cases, and there could be a severe shortage of hospital beds by june . this may lead to an increase in case fatality. evaluation is performed on confirmed cases, death cases, and recovered cases. the popular metrics for evaluation are mean absolute error (mae) and root mean square error (rmse). the mae and rmse values of predicted days are shown in figures , , and , respectively, for confirmed cases, recovered cases, and death cases in india. the eruption of the novel coronavirus covid- had left extensive and profound impacts worldwide. although this disease appears to be well controlled in india till now, the recent dramatic increase in new cases and deaths outside of india, especially in europe and the united states, indicates that the covid- eruption may have tragic results globally the study of the covid- outbreak pattern of china may help in controlling the disease in other countries. as per the pattern of china, it may be understood that the effect of this disease in india will be at peak during the third and fourth weeks of april . it is essential to discuss that these predictions are made on the basis of a comprehensive study of china. the strategies to reduce/control covid- cases include a national lockdown of days, public transport control, specialized medical support for affected populations, and others. if these measures are strictly followed, then results may be different. our estimate shows that the mortality rate in india is predicted to be around . %. globally, a . % mortality rate is estimated by the who as of march , . this mortality rate may vary in different states of india. it is important to emphasize that the predicted mortality rate could be different from the actual mortality rate looking at the measures taken by the government of india. this study has not taken into consideration several other socioeconomic factors that may affect the spreading of covid- . these factors may be education, economic the covid- pandemic may be controlled if sufficient measures are taken to control the disease. the prediction about the pattern of the outbreak in india may help policy-makers take a comprehensive and necessary action. the number of deaths may be controlled as compared to china because of the precautionary measures that have already been taken in the country. the further study of other factors like education, economic conditions, medical facilities, climatic conditions, religious beliefs, and so forth may strengthen the prediction and help in controlling the outbreak of covid- . also, this study may further be extended for predicting the outbreak in other countries. who. situation report- . novel coronavirus countries where covid- has spread monitoring transmissibility and mortality of covid- in europe coronavirus disease (covid- ) outbreak in iran: actions and problems novel corona virus the weka workbench. online appendix for "data mining: practical machine learning tools and techniques the economic times. share of population over age of in india projected to increase to % in : un. last updated share of elderly population in italy covid- ) mortality rate. last updated the authors have no conflicts of interest to declare. key: cord- -uz hfixk authors: gandhi p, aravind; kathirvel, soundappan title: epidemiological studies on covid- pandemic in india: too little and too late? date: - - journal: med j armed forces india doi: . /j.mjafi. . . sha: doc_id: cord_uid: uz hfixk nan of the tests performed in maharashtra (till rd may ) and sari cases (till nd april ) from sentinel sites, ( . %) and ( . %) patients found positive for covid- . , of the cases for whom data was available from maharashtra (n- ), new delhi (n- ) and sentinel sites (n- ), ( . %), ( . %) and ( . %) were males; and mean/median age was . , . and years, respectively. [ ] [ ] [ ] the details of clinical presentation at the time of testing was available only with new delhi study. of the cases, ( . %) were asymptomatic, and ( . %) had comorbidities most commonly hypertension ( . %) and diabetes mellitus ( . %). of the symptomatic patients, fever and cough ( . %), sore throat ( . %), headache ( . %) and breathlessness ( . %) were the common clinical presentation. a total of ( . %) and ( . %) patients were critically ill and deceased (case fatality rate-cfr) respectively in maharashtra (n- ) and none in new delhi. , though higher cfr has been reported among males of maharashtra ( . %) compared to females ( . %), no significant association was found between gender and mortality (p- . ). the age-specific mortality rate was also high among patients aged - years ( . %), - years ( . %) and above years ( . %). no details are available on clinical presentation and mortality other than sari from sentinel site study. new delhi study was able to trace the source of infection to foreign travel history or to close contact with all cases. however, of the cases for whom source investigation was completed in maharashtra (based on cases reported till th april ), ( . %) had a travel history, and ( . %) had a contact history with confirmed covid- case. source of infection was inconclusive among ( . %) cases. similarly, of the covid- cases among sari patients from sentinel sites, source history was not available, and the source could not be traced among ( . %) and ( . %) cases, respectively. the considerable proportion of cases for whom the source of infection could not be traced indicates that the community transmission may be happened already in india. the discrepancy in tracing the source between these three studies may be due to the differences in approach, study population and the study period. it was a cluster or community-based approach in maharashtra and hospital-based approach in new delhi and sentinel site study. further, new delhi study investigated all covid- positive cases, and sentinel site study investigated all sari cases for covid- . though the above three literature provides insight into some basic demography of the covid- cases in india, they could not provide representativeness and comprehensiveness, together or alone. they also differ with each other in terms of severity, source of infection and clinical outcomes. it has been more than three months that the disease has emerged into the country. yet, india lacks basic and comprehensive epidemiological information like socio-demography, risk factors and comorbidities, modes of transmission and its dynamics, clinical presentations, the different testing strategies and its positivity rates, and clinical outcomes. though the early, extended nationwide lockdown of the country should be applauded, this alone is not sufficient to defeat the covid- . data is the key in the fight against covid- . there are more than a couple of prediction papers published based on this limited epidemiological data with varied assumptions. at times, actions are taken based on these predictions with many limitations, which may affect the country economically and politically in addition to individual-level adverse effects. though the evidence generated so far in india is indeed too low to comment on the complete epidemiology, it is definitely not late to start, streamline and systematically collect the data and disseminate. in this crisis, the research community can be linked with the people delivering healthcare services at various levels for collecting quality-assured data. hence, it is recommended to generate local epidemiological data through robust studies supported with a) timely and adequate funding/resources; b) collaboration with research and development community; c) fast-tracking ethical and administrative procedures and d) prompt dissemination of findings to the stakeholders by fast-tracking the publications for evidence-based decision. the views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of any institute or government. coronavirus disease (covid- ) situation report - global research and innovation forum: towards a research roadmap clinical and epidemiologic profile of the initial covid- patients at a tertiary care centre in india severe acute respiratory illness surveillance for coronavirus disease , india, report of covid- cases. date: covid- : india imposes lockdown for days and cases rise covid- virtual press conference - who chief scientist soumya swaminathan interview: data is key to control coronavirus pandemic -the hindu key: cord- - ofarutr authors: bhat, yasmeen jabeen; aslam, aaqib; hassan, iffat; dogra, sunil title: impact of covid- pandemic on dermatologists and dermatology practice date: - - journal: indian dermatol online j doi: . /idoj.idoj_ _ sha: doc_id: cord_uid: ofarutr the covid- pandemic has directly or indirectly affected every human being on this planet. it's impact on the healthcare system has been devastating. the medical fraternity across the world, including india, is facing unprecedented challenges in striving to cope up with this catastrophic outbreak. like all other specialties, dermatology practice has been profoundly affected by this pandemic. measures have been taken by dermatologists to control the transmission of the virus, whereas providing health care to patients in the constrained environment. preventive measures such as social distancing and hand hygienic practices along with patient education is being prioritized. dermatological conferences and events scheduled across the globe in the first half of year have been either cancelled or postponed to discourage gatherings. rationalization of resources and practice of teledermatology are being encouraged in current scenario. non-urgent visits of the patients are being discouraged and elective dermatology procedures are being postponed. many national and international dermatology societies have recently proposed recommendations and advisories on usage of biologicals and immunomodulators in present context of covid- pandemic. urticarial, erythematous, varicelliform, purpuric and livedoid rash as well as aggravation of preexisting dermatological diseases like rosacea, eczema, atopic dermatitis, and neurodermatitis rash have been reported in covid- patients. self medications and poor compliance of dermatology patients in addition to lack of proper treatment protocols and monitoring are a serious concern in the present scenario. strategies for future course of action, including the dermatology specific guidelines need to be framed. this issue includes a special symposium on dermatology and covid- having recommendations from special interest groups (sigs) of indian association of dermatologists, venereologists and leprologists (iadvl) academy on leprosy, dermatosurgery, lasers and dermoscopy. the outbreak of novel corona virus infection (severe acute respiratory syndrome-sars cov- ) has taken a humongous toll on human lives both physically and mentally. as of april th , . million cases have been reported while . million lives have been lost worldwide to this deadly viral disease and the numbers are increasing exponentially. [ ] the number of cases in india at present is , and deaths. the outbreak which started towards end of has resulted in a serious economic slump throughout the world. healthcare workers all over the world are facing innumerable problems, dermatologists being no exception. [ ] people dwelling in developing countries are more at risk due to overcrowding, lack of proper sanitation and limited healthcare infrastructure. medical fraternity working under such environment are prone to higher risk due to the presence of asymptomatic carriers of the infection and lack of adequate personal protective equipments. family members of the healthcare workers (hcw) are also at greater risk of transmission of infection from them. [ , ] in china, the primary epicentre of the pandemic, an estimated , hcw have been infected and at least have died. about , hcw have contracted covid- in italy as per the italian higher health institute (iss), while doctors have already lost their lives in this pandemic till now. [ ] the impact of the outbreak on hcw is following similar pattern in developing countries like india. the quality of life among healthcare workers is also taking a brunt with most of the doctors complaining of physical exhaustion and mental fatigue with every passing day. higher rates of distress, anxiety, and depression has been seen in hcw caring for patients of corona virus infection. [ ] dermatology practices are also affected, though to a lesser extent than the front-line departments attending emergency and intensive care units dealing directly with suspected and confirmed covid- patients. cutaneous manifestations of covid- may be rare but no other disease has ever had a more profound effect on dermatologists and their practice. [ ] as the outbreak knocked at the doors of india on th jan and subsequently after release of advisories from indian government since then, many policies and precautions have been implemented by the dermatologists in their practice to tackle this pandemic. outpatient consultations have dramatically reduced during the nation-wide lockdown in india from th march to rd may . routine outpatient clinics are nonfunctional or discouraged throughout the country, aided by increasing the gap of follow-up of patients by the treating dermatologists. guidelines for rational use of the resources and manpower in most of the institutions have led to considerable decrease in working hours of routine departments. while taking history pertaining to the cutaneous involvement, suspicion of covid- is kept in mind for those having fever with urticaria, exanthematous or vesicular rash. history of travel and respiratory symptoms are being enquired for. [ ] as dermatological examination requires a close inspection and often palpation, avoiding contact during examination, maintaining adequate distance from the patient, using alcohol based sanitizers, disposable gloves, frequent hand washing with soaps, periodic disinfection of the rooms and working preferably in negative pressure rooms while performing procedures is being practised judiciously by dermatologists. triple layered surgical masks or n masks are being used to prevent aerosol spread. bedside investigations like dermatoscopy are better avoided or done with precautions but essential laboratory investigations are being carried out regularly. elective dermatosurgical procedures, hair transplantation, laser sessions, aerosol generating, and aesthetic procedures have been almost stopped completely as the virus is most stable on plastic and stainless steel. [ ] same is the case with phototherapy since the chamber used can become a source of infection despite adequate sanitation. only very sick patients with dermatologic emergencies and acute skin failures are admitted in hospitals. rational use of biologics with specific avoidance of rituximab and immunosuppressive pulse therapies in newly diagnosed patients is being practiced by dermatologists in india; however, patients are being kept on minimal doses of immunosuppressive therapy to avoid flare of the diseases. a key aspect of risk mitigation is prevention of covid- in at-risk populations. [ ] american academy of dermatology (aad) recommends to discontinue or postpone biologics in covid- positive patients while the physicians need to assess their use in patients who have not tested positive or exhibited signs and symptoms of covid- on case by case basis. [ ] the international psoriasis council recommends dermatologists to discontinue or postpone immunosuppressant medications for psoriasis patients diagnosed with covid- infection, however apremilast can be continued unless severe symptoms are present. [ ] in confirmed cases of covid- infection who are on systemic steroids for dermatological disorders, it can be continued with tapering doses. however, in patients at higher risk or elderly with co-morbidities, benefit to risk ratio of any immunomodulator needs to be carefully assessed with lower doses recommended. [ ] british association of dermatologists (bad) have also provided guidelines with respect to patients on immunosuppressive medications in current times advising patients at definite high risk or with comorbidities who are on two agents within the class of immunosuppressants (methotrexate, azathioprine, mycophenolate, ciclosporin, fumaric acid esters, -mercaptopurine, leflunomide, cyclophosphamide, tacrolimus, sirolimus) or biologics/monoclonals (all anti-tnf drugs, il agents, anti b cell, il agents, il ) or novel small molecule immunosuppressants (apremilast, jak inhibitors); cortocosteroid dose of ≥ mg of prednisolone per day for more than weeks; cyclophosphamide at any dose orally or if received intravenous within last months; rituximab or infliximab; to undergo shielding with self isolation upto weeks. well-controlled patients with minimal disease activity and no co-morbidities who are being treated with single agents of immunosuppresants or biologics or topical treatment need to maintain social distancing. [ ] patients on dupilumab or omalizumab have possibly lower risk of infection than other biologicals. they have further recommended to continue medications like acitretin, isotretinoin, hydroxychloroquine, sulfasalazine or dapsone following proper monitoring protocols along with social distancing. [ ] however these guidelines advise teledermatology for remote patients and avoid hospital visits by patients as much as possible. [ ] recommendation for leprosy patients is to continue multidrug therapy (mdt), provide medications for - months in order to decrease their hospital visits and advise them to take all precautions to control the outbreak. however, patients being treated for leprosy reactions mandate extra caution as therapeutic immunosuppression makes them vulnerable to covid- . [ ] although there are no guidelines recommended for the treatment of advanced skin cancers with regards to covid- , successful management with sonidegib and vismodegib (hedgehog inhibitors) after satisfactory compliance to treatment in advanced basal cell carcinoma has been reported. [ ] patients are also advised to resort to teledermatology though the majority of patients and dermatologists in developing countries as of now are not very familiar with its routine use in clinical practice. telemedicine is a very useful tool in the current scenario where physical contact with the patient can be avoided to curb the outbreak. dermatologists can utilise this tool better than many other specialities mainly because of the advantage of snapshot diagnosis possible in many of dermatological diseases. modes of communication include video, audio and text based. whatsapp, facebook messenger, skype, and email are the virtual tools being used for teledermatology practices. it seems that dermatology practice has shifted from bedside to phone-side in this pandemic. [ ] telemedicine practice guidelines have been established by the board of governors in supersession of medical council of india to enable registered medical practitioners to provide health care using telemedicine. it has been encouraged more than ever before during these times. mci recommends development of an online course to be completed by a registered medical practitioner to practise telemedicine. [ ] there is an updated framework for telemedicine in the covid- pandemic which needs to be applied at a large scale to improve the public health response so as to integrate telemedicine within health systems for postpandemic times as well. [ ] investments in teledermatology, apart from being assets in current times, will reap long-term benefits by serving as remote service both for the patients not able to attend routine appointments and also to dermatologists. [ ] a guest editorial in this issue by ashique and kaliyadan gives detailed recount of teledermatology and its current perspective in evolving covid- scenario. the impact of this outbreak on postgraduate and undergraduate dermatology teaching, as well as the scientific research in medical colleges and institutions is profound. md/dnb postgraduate dermatology examinations scheduled for may-june session have been postponed in most of the medical colleges across india. online seminars, journal clubs, and case discussions have been resorted to combat the academic hour loss in institutions. for continued medical education, digital podcasts and blended learning concepts as well as inverted classroom approaches provide the required solution in this time of crisis. [ ] virtual meetings and webinars are being conducted instead of conventional medical conferences while many healthcare professionals are of the opinion that it is a better way of interaction even after the pandemic is over in view of saving both time and expenses with optimal benefits. [ ] on a positive note, the manuscripts submitted to this journal have increased almost three folds over these weeks likely to be due to dermatologists having more time in hand during lockdown to complete their pending academic work and paper writing. however, it's hard time for editorial team to process many daily submissions amidst limited workings of publisher, technical and supporting teams. as dermatologists, we should be aware of the cutaneous manifestations of covid- . aggravation of previous skin diseases such as rosacea, eczema, atopic dermatitis, and neurodermatitis has been seen in covid patients. [ , ] urticarial, erythematous, and varicelliform rash and even pseudo-frostbite like acro-ischemic lesions have been reported. [ , ] rare presentations mimicking dengue rash and vaso-occlusive unilateral livedoid eruption have also been seen. [ , ] as only limited data are available regarding the dermatological manifestations of the disease as of now and the early pointers to vasculitic or vasculopathic pathogenesis, there is definitely scope for more careful observations and studies in near future. due to frequent hand hygienic practices, many people and hcw dealing with covid- , as well, are complaining of xerosis, fissuring and hand eczema, requiring dermatologists to prescribe use of suitable moisturisers. [ ] some dermatology departments have introduced colour coding system depending upon the severity (white, green and yellow for less, moderate and high severity dermatological pathologies, respectively) to provide consultations accordingly. [ ] many clinicians have resorted to teledematology in routine cases while reserving in-person visits for emergency patients. [ ] following the virus surge, dermatologists in many hospitals are being posted to work in dedicated covid- wards and emergency screening area including training in basic life support and ventilation. [ ] many stringent measures have been taken by the government of india to curb this growing pathological phenomenon. dermatology conferences and events have been cancelled throughout the country in view of the advisory from the government. [ ] the national and international dermatology society meetings are taking place on various online platforms. indian association of dermatologists, venereologists and leprologists (iadvl), one of the largest dermatology association in the world, was also prompt to issue position statement for its members with the objectives of providing strategies to combat covid- in dermatology practice in the form of education about the prevention of transmission; avoiding all non-essential outpatient consultations and elective procedures; stressing upon the dermatolgists to be updated with ever changing scenarios and guidelines, canceling travels and gatherings including cmes, meetings, and conferences and recommendations about the use of immunosuppressives and biologics in patients. [ ] government has even come up with a guide "minding our minds during the covid- pandemic" to make people understand the importance of lockdown as well as advising people not to resort to alcohol or drugs to cope with emotions or boredom during lockdown. [ ] "aarogya setu", a new user data based corona virus tracking mobile internet application has also been launched by the government of india to combat the pandemic which warns people if they had recently come near the infected people and assess their risk to acquire infection. [ ] multiple clinical trials are being carried out thoughout the world to find a cure to this infection. antivirals like remdisivir or favipiravir have been used. anti-malarial drug hydroxychloroquine alone or in combination with azithromycin has been studied the most which has shown promising results though larger studies and metaanalysis is lacking. [ ] the side effects of the these drugs especially cardiotoxicity narrows down its option of wide use. indian council of medical research (icmr) recommended prophylactic use of hyroxychloroquine in high risk populations including hcw. [ ] however, the potential of hydroxychloroquine to treat covid- and thus having huge surge in its demand has created fears of shortage among its chronic users of various dermatology and connective tissue disorders especially lupus erythematousus where disease control is highly dependent on this medication. [ ] there are also reports of exacerbation of psoriasis in a patient of covid- treated with hydroxychloroquine which raises the question whether there will be an increase in number or flare in psoriasis cases during the pandemic. [ ] ivermectin, fda approved drug for parasitic infections, has also been recently reported to inhibit sars cov- virus in vitro. [ ] both these drugs are routinely prescribed by the dermatologists and their rampant use for covid- prophylaxis may lead to scarcity for dermatological patients. self-medication and lack of compliance to prescribed treatments have become a worrisome issue of dermatological patients in present scenario. lack of proper treatment protocols and monitoring is also adding to the misery. measures such as taken by chen et al. for patient safety at chinese dermatology clinics need to be enacted in our setting as well. temperature of the patient and accompanying person should be checked at the entrance of opd and those with fever or history of contact with people with fever or from hot zones and high-risk areas, should be sent to the fever clinic for screening. patients should not be allowed to take off their masks except on indications of facial lesions. dermatologists must wear personal protective equipment and take it off only in a designated disposable area. [ ] we are not sure how long this critical situation will last but we need to frame strategies for future course of action including the dermatology specific research and guidelines. as is rightly said "prevention is better than cure"-the statement is apt for the current situation where even the countries with best healthcare system have succumbed to this microscopic entity. to fulfil our obligation as professional in the house of medicine, we the dermatologists are morally and ethically bound to perform our duty when called upon to fight this medical crisis. [ ] the right approach may be to embrace every moment with courage, precautions and hope that the current milieu is just darkness before the sunshine. humanity will overcome these tough times as they always have in the past, all we need to do is to maintain placidity and show benevolence and do our bit to serve and save mankind. nil. there are no conflicts of interest. coronavirus covid- global cases by the centre for systems science and engineering the impact of novel coronavirus on dermatology presumed asymptomatic carrier transmission of covid- supporting the health care workforce during the covid- global epidemic coronavirus: doctor death toll rises to . fnomceo.ansa. available from factors associated with mental health outcomes among health care workers exposed to coronavirus disease the profound dermatological manifestations of covid- dermatology staff participate in fight against covid- in china dermatology practices as vectors for covid- transmission: a call for immediate cessation of non-emergent dermatology visits use of systemic immunomodulatory therapies during the coronavirus disease (covid- ) pandemic covid- and immunomodulator/immunosuppressant use in dermatology covid- ) outbreak. international psoriasis council dermatology advice regarding self-isolation and immunosuppressed patients: adults, paediatrics and young people. healthcare professionals. british association of dermatologists treatment-specific guidance british association of dermatologists dermatology patients remotely. healthcare professionals. british association of dermatologists guidelines for doctors of the brazilian society of hansen's disease on the possibility of coinfection leprosy and covid- . leprosy and covid .infolep monthly overview of new publications on leprosy patients with advanced basal cell carcinomas in treatment with sonic hedgehog inhibitors during the coronavirus disease (covid- ) period: management and adherence to treatment whatsapp messenger as a teledermatology tool during coronavirus disease (covid- ): from bedside to phone-side global telemedicine implementation and integration within health systems to fight the covid- pandemic: a call to action covid- : challenges and opportunities for dermatology response medical education and care in dermatology during the sars-cov pandemia: challenges and chances medical meetings may be forever changed what are we doing in the dermatology outpatient department amidst the raging of the novel coronavirus? cutaneous manifestations in covid- : afirst perspective le syndicat national des dermatologues-vénéréologues (sndv) covid- can present with a rash and be mistaken for dengue skin manifestations are emerging in the coronavirus pandemic. dermatology news. md edge skin damage among healthcare workers managing coronavirus disease- global coronavirus pandemic ( -ncov): implication for an italian medium size dermatological clinic of a ii level hospital strategic dermatology clinical operations during covid- pandemic with virus surge, dermatologists and orthopedists are drafted for the e.r. the new york times government of india advisory-cancellation of conferences/ events iadvl position statement on current covid- virus pandemic. indian association of dermatologist, venereologist and leprologists- minding our minds during the covid- . ministry of health and family welfare government of india aarogyasetu app for staying informed and alert against covid . ministry of health and family welfare government of india covid- : more hydroxychloroquine data from france, more questions recommendation for empiric use of hydroxy-chloroquine for prophylaxis of sars-cov- infection. technical documents and advisory.indian council of medical research potential of chloroquine and hydroxychloroquine to treat covid- causes fears of shortages among people with systemic lupus erythematosus a case of exacerbation of psoriasis after oseltamivir and hydroxychloroquine in a patient with covid- : will cases of psoriasis increase after covid- pandemic? the fda-approved drug ivermectin inhibits the replication of sars-cov- in vitro dermatology residents and the care of covid- patients key: cord- -e h tq x authors: singh, manish kumar; neog, yadawananda title: contagion effect of covid‐ outbreak: another recipe for disaster on indian economy date: - - journal: j public aff doi: . /pa. sha: doc_id: cord_uid: e h tq x the global outbreak of covid‐ and subsequent lockdowns raises serious economic concern and havoc worldwide. this article tries to provide an economic perspective of covid‐ in india using some statistical figure of economic indicators. analysis is based on the data collected for macro‐economy, travel & tourism, transportation, stock market, human capital and trade. finding revel that india could experience a health debacle at present and excruciating economic contraction in the near future if the government is unable to execute a proper policy framework. based on the discussion, a few policy suggestions have been presented to counter both health and economic crisis. in january , world bank argues that growth in almost all emerging markets and developing economies regions have been weaker than expected due to the global trade tension, sharp downturn in the major economy and financial disruptions. they suggest that there is a need to rebuild macro-economic policy space, pursue decisive reform to bolster governance and business climates, improve tax policy, promote trade integration and rekindle productivity growth while protecting vulnerable groups (world bank, ) . but, the whole scenario has changed, not because of inappropriate policy intervention, it is because of coronavirus diseases . china reported the first case to the world health organisation (who) country office in china on st december . the who on january , has declared it, as a public health emergency of international concern and on march , covid- has been declared as a pandemic by the same organisation. the spread of the virus and its impact on mortality and morbidity can be assessed by the fact that it reached , confirmed cases worldwide and , deaths across the countries and territories (who, march ) and it is going to be more severe because the trend is rising continuously. the covid- outbreak is first and foremost a human tragedy, affecting hundreds of thousands of people. thus, many countries have been lockdown and restrict their economic agents to mobilise from one country to another country and even within the country due to the communicable covid- . it is having a growing impact on the global economy and unfortunately, the global health crisis becomes a global economic crisis due to the cancel of flights, restriction on labour mobility and volatility in stock markets, fall in oil prices, and so on. for vulnerable families, loss of income due to an outbreak can translate to spikes in poverty, missed meals for children and reduced access to healthcare for beyond surveys of china's manufacturing and services sector plunged to record lows in february (business news, ), automobile sales sank a record % (bloomberg news, ) , and china's exports fell . % (bermingham, ) in january and february. as covid- spreads, china's economic recovery will be challenged as demand from other countries drops as they cope with the virus. although the outbreak appears to have slowed in china, covid- and its impacts have gone global. the united states, china, japan, germany, britain, france and italy have contributed % of world supply and demand [gross domestic product (gdp)], % of world manufacturing, and % of world manufacturing exports (baldwin & di mauro, ) but unfortunately, these are in the top- most affected countries by covid- except japan (wto, march ). annual global gdp growth is projected to drop one-half a percentage point (from . to . %) in , with growth possibly even being negative in the first quarter of (oecd, ) . in this addition, the head of the imf (kristalina georgieva) said the world economy had entered a recession "as bad or worse" than the global financial crisis of - (elliott, . this global outbreak reaches to more than countries and india is also one of them. the cases of the virus in india has been rising day by day and upraised the concerns regarding its economic consequences (refer to figure ). india is one of the fastest growing economy and the fifth largest economy of the world (economic survey - , ). the gdp value of india represents . % of the world economy in (treding economics, ) and gdp based on ppp, india represent . % of the world economy in (imf, ). however, many electronic media (bbc, ; subramanian, ) and economist (subramanian & felman, ) was claiming that india is facing the problem of economic slow-down, the decline in demands, rise in unemployment, decline in consumption expenditure especially in the rural area and so on. with the downturn of economic status, india has now stuck in the spread of covid- and the country has been lockdown for st days till april . where, top states of india, which are highly affected by covid- has contributed % of india's state gdp and this outbreak could lead to rapid fall in growth performance. concerns regarding the health facilities are one of the fundamental to this pandemic and india ranked far below in health facilities as compared to world average. india spends very few amounts in health sector in the yearly budgets and this health crisis severely rejuvenates the lacking. in the union budget of - , the budget allocation for heath sector is just , core rupees which is approximately % to the gdp and far below to targeted . % (jayakumar, ) . india has one doctor per , people and one nurse to people as compared to the who norms of : , and : , respectively (business standrad, ). per person health expenditure india is just $ where % of it consist of private spending and % of its public spending (asrar, ) . thus the poor health facilities in india are clearly visible form the above discussion and this pandemic will be a challenging time for indian health sector. this heath emergency has a direct link with economic crisis as any economy cannot survive without healthy and active economic participation of the people. therefore, the present situation ring the alarming bell to the indian government and through this study, we try to provide some possible economic impact of covid- . mishra ( ) , on behalf of business today (refer to table ) recently estimated the expected loss in the component of indian gdp due to the + (additional days of the operating cycle before a material or service can be back to operations days) nationwide lockdown. the loss could be approximately . lakh crore rupees of gross value added (gva) in total, where highest loss may be encountered in financial, real estate and professional service sector with . lakh crore followed by trade, hotel and transport sector with . lakh crore. thus, the time has come when policymakers and government bodies should take deep agitation about to recover people from the tragedy of covid- and, aware and take necessary actions to prevent probable economic damages. based on the above discussion, we develop two main objectives in this study, firstly, we accommodate the theoretical linkages to evaluate potential broad channels through which covid- could impact an emerging economy like india. and secondly, we are focusing on the economic consequences of covid- on indian economy with a present assessment of economic outcomes. covid- does not only bring health sector crisis to the world but also assign economic crisis. restriction on trade, travel and labour mobility will largely create demand and supply shocks. developing countries like india have severe consequences for employment as % of employment is informal in nature (ilo, ). nation wise lockdown has a high economic impact on the lower sections of the society which mostly are daily earner and engaged in the informal economy. nearly % of the workforce in informal sector has survived with no minimum wage or any kind of social security (sharma, ) . even after the unorganised workers social security act ( ), only - % got enrol for social security. according to periodic labour force survey of - , . % had no job contract, . % are not eligible for paid leave and . % has no social security (mohanty, ) . the exact span and deepness of the crisis are not known right now and time will reveal the real picture. however, economist like evans and over ( ) provides some potential economic channel of covid- for low and middle-income countries. we find their arguments and theoretical linkages are applicable for india also. we boone ( ) . the confidence of the consumer/investor is mostly influenced by macro-economic uncertainty. the long-run effect of covid- is mainly run from the health, education and infrastructure sector. sickness and mortality will results in loss in income and human life. in a same fashion, the government mandates and institution decision will impact both the education and infrastructure development which have long-run consequences. after the discussion of the theoretical linkages, following sections devoted to explain economic situations in india at national and subnational level with the use of recent data series. the macro-economic impacts of covid- on india's national and sub-national level are uncertain. india is already running through in table , we have reported the top indian states with their respective gdp sizes. the data for clearly show that these states contribute more than % of the total state gdp and unfortunately most of these states are highly affected by covid- ( march ). complete lockdown of the country will hamper every state's growth performance. the fall out mostly encountered from the industry, manufacturing, construction and real estate sector. and the impact may be long-lasting contagion effect due to interstate and inter-sectoral linkages. restriction on transportation and labour mobility mostly halter the economic activity initially and demand in the economy in the later period. the economic crisis, as far now, predicted as supply shock to the economy. in long-run, supply shock also has the potential to create demand shock. the pandemic raises the concerns regarding travel and tourism industry as the almost entire world is now in isolation. according to the ministry of tourism, india ranked th globally and seventh in asia and the pacific in respect of international tourist arrivals in . the nationwide lock-down will restrict both international and domestic tourist movement. table the indian tourism industry is a highly potential and respect of size, its share is . % of gdp (see table ) people are directly and indirectly benefited from the tourism sector through its wide linkages with other sector and economic activities. table widespread covid- has an important implication on education system in india. gross enrolment rate is highest in case of primary, upper primary and elementary level of education (refer to the table ) and shut down of all schools will lead to a huge amount of student to sit at home. the role of technology in providing remote learning is very much limited and uncertain in india. close down of schools will highly impact educational outcome without remote educational facilities. both the demand and supply shock will hit the global trade and india's trade as well. recent trend in exports and imports show the fluctuation in the first months of (refer to figures and ) . due to the lockdown, it becomes obvious that both exports and imports will experience a drastic decline in march and the upcoming months of . however, the duration is unclear today and will depend upon the lethality of the virus and actions taken by the governments. an important sector that usually affected instantly by lockdown is the transportation sector. disruption in the transport system quickly affecting the demand in the service sector that is crucial for micro, small and medium enterprises (msme) which are more fragile to market demands (bouey, ) . considering three modes of transportation-aviation, railway and road, india is earning huge revenue from the transportation sector. shut down of both public and private mode of transportation will directly affect the demand and supply in the economy. there, likevehicle tax, fines and so on, therefore the shutdown will impact the revenue collection from road transport hugely. stock markets mostly behave accordingly with the people confidence and market conditions. capital market across the world witnessing high volatility due to the outbreak of the virus. in the middle of february , india's share market reports a remarkable downfall in case of sensex and nifty both (refer to figure ). after rd march , this fall is more rapid. without proper policy incentive and reduction in the cases of covid- , it will be very hard to bring investor confidence in the market. based on the above backdrop, there are two things, which government should take serious concern on the priorities basis, first, improving the healthcare services along with the health infrastructures as per the requirement of epidemic. the following remarks may help: • create ventilators through moderate the hotels just like indian government moderating the coaches of passenger rail. • promote the factories for more production of health accessories like mask, hand wash, sanitizer and so on. encourage other factories which are producing similar types of product and those, who can be easily modified. • the government should provide free test of covid- disease as private sector is charging , - , rupees per person. these charges discourage the venerable groups from the voluntary check-ups and this could turn out to be severe for covid- spread. • the government should ensure safety, security and welfare of the front-line workers who at the high risk and should provide monetary incentives. government should also promote the members of "anganvadi," asha and other local governing body for the distribution of basic health accessories and the awareness of people. and second, provide the economic assistance and incentive to the establishment of the economy in present and more likely in future through: • distribution of cash transfers to the informal workers through geographical targeting and this can be done by the local administrative units. • government should provide ecosystem to maintain forward and backward linkages of msme and other exempted sectors along with special packages for msme through moratorium of payments like bank loan, gst and others payments. this will ensure msme to continue economic activity and employment. • increase the scale of amount of direct benefit transfer like jan dhan yojana, mgnrega, pm-kisan and pension scheme along with recapitalisation of banks which will revive the demand in the economy. there should also need to temporarily increase the quantity of food distribution through the public distribution system (possibly free of cost) to ensure the food security of the vulnerable groups. • lockdown of "mandies" will create difficulties in selling rabi crops in india and farmers have to bear the most losses. thus proper functioning of "mandies" and provision of minimum support price should be required for the survival of % population whose livelihood is based on agriculture. above all, the government should increase the productive social sector expenditure without any consideration of fiscal deficit. acknowledgment the author's like to acknowledge the blind reviewers for their productive comments and a special thanks to prof. a. k. gaur (department of economics, bhu) and shruti shuvam (iit, roorkee) for their encouragements and supports. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - sensex nifty f i g u r e trend in stock market. source: www.in.finance.yahoo.com india's healthcare: private vs public sector | india | al jazeera economics in the time of covid- thinking ahead about the trade impact of covid- . economics in the time of covid- . retrieved from www.cepr.org bbc coronavirus: china's exports and imports plummet in january and february china car sales drop a record % as virus empties showrooms tackling the fallout from covid- . economics in the time of covid- assessment of covid- 's impact on small and mediumsized enterprises: implications from china china february factory activity contracts at record pace as coronavirus bites india has one doctor for every , citizens. govt | business standard news government of india ministry of finance department of economic affairs economic division north block new delhi- dozens of poorer nations seek imf help amid coronavirus crisis the economic impact of covid- in lowand middle-income countries | center for global development world economic outlook gold gains as covid-led growth fears spur safety buying. business news healthcare allocation in budget . % lower than last budget coronavirus in india: covid- lockdown may cost the economy rs . lakh crore; here's how labour reforms: no one knows the size of india's informal workforce, not even the govt national database of workers in informal sector in the works great slowdown", economy headed to icu: ex-cea. the economic times india gdp | global economic prospects slow growth, policy challenges key: cord- -f jma d authors: srivastava, a.; tamrakar, v.; moradhvaj, m.; akhtar, s. n.; kumar, k.; saini, t. c.; c, n.; saikia, n. title: geographical variation in covid- cases, prevalence, recovery and fatality rate by phase of national lockdown in india, march -may , date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: f jma d background: since the covid- pandemic hit indian states at varying speed, it is crucial to investigate the geographical pattern in covid- . we analyzed the geographical pattern of covid- prevalence and mortality by the phase of national lockdown in india. method: using publicly available compiled data on covid- , we estimated the trends in new cases, period-prevalence rate (ppr), case recovery rate (crr), and case fatality ratio (cfr) at national, state and district level. findings: the age and sex are missing for more than percent of the covid- patients. there is an exponential increase in covid- cases both at national and sub-national levels. the covid- infected has jumped about times ( from cases in the pre-lockdown period to , , in the fourth lockdown); the average daily new cases have increased from in the first lockdown to , in the fourth lockdown; the average daily recovered persons from to , ; the average daily death from to . from first to the third lockdown, ppr ( . to . ), crr ( . to . ) and cfr ( . to . ) have consistently escalated. at state-level, the maximum number of covid- cases is found in the states of maharashtra, tamil nadu, delhi, and gujarat contributing . percent of total cases. whereas no cases found in some states, kerela is the only state flattening the covid- curve. the ppr is found to be highest in delhi, followed by maharastra. the highest recovery rate is observed in kerala, till second lockdown; and in andhra pradesh in third lockdown. the highest case fatality ratio in the fourth lockdown is observed in gujarat and telangana. a few districts viz. like mumbai ( . ); chennai ( . ) and ahmedabad ( . ) have the highest infection rate per thousand population. spatial analysis shows that clusters in konkan coast especially in maharashtra (palghar, mumbai, thane and pune); southern part from tamil nadu (chennai, chengalpattu and thiruvallur), and the northern part of jammu & kashmir (anantnag, kulgam) are hot-spots for covid- infection while central, northern and north-eastern regions of india are the cold-spots. conclusion: india has been experiencing a rapid increase of covid- cases since the second lockdown phase. there is huge geographical variation in covid- pandemic with a concentration in some major cities and states while disaggregated data at local levels allows understanding the geographical disparity of the pandemic, the lack of age-sex information of the covid- patients forbids to investigate the individual pattern of covid- burden. keyword: covid- ; india; case fatality rate; case recovery rate; period prevalence rate; geographical variation the novel coronavirus , caused by severe acute respiratory syndrome, has been spreading rapidly across the world since it broke out in wuhan city, china in december . covid- outbreak is a global public health emergency and declared as a global pandemic on march , (sohrabia et al., ; who, ) . on may , , this disease has been transmitted to over countries and territories affecting more than . million people and claiming . million lives worldwide (worldometers, ) . out of all these countries, areas, or territories, the united states now has the largest outbreak of covid- with . million (worldometers, ) . in india, the first case of covid- was detected on january , , in kerala (mohfw, ) . with the experience of the overwhelming burden of covid- in european countries, the government of india (goi) was quick to respond to covid- by a number of preventive measures such as tracking individuals with international and national travel history, quarantining covid- patients, canceling visas and international flights, involving media in raising mass awareness on preventive measures and finally a complete nationwide lockdown from march , to may , , by a phase-wise declaration. later, goi also introduced a smartphone-based application, known as "aarogya setu" to trace and detect covid- affected cases. to reduce the peace of contamination, administration across the country sealed and sanitized the areas or housing societies with covid- patients. despite all these measures, the number of covid- cases has been rapidly expanding but with a huge geographical disparity with zero active cases in the northeastern states to , cases in maharashtra (on may , ) (covid india, ). examining the geographical variation in covid- is crucial for understanding the national and local burden of this pandemic. such a study can provide input for intervention and policy and indicate the future trajectory of covid- . the aim of this paper is to analyze the trajectory of covid- cases, period prevalence rate, recovery, and fatality rate by phase-wise during national lockdown at national and sub-national levels. there are a few non-peer reviewed studies in india addressing covid- . using deaths and , confirmed cases, a study examined the effect of covid- on longevity in india and inferred that india may lower the life expectancy by . , . and . years under various assumptions (mohanty & sahoo, ) . the highest observed cfr among most affected states is in maharashtra, whereas the recovery rate has reached percent in kerala, percent in haryana and percent in tamil nadu (dhillon et al., ) . a study on spatial and demographic characteristics of covid- positive cases in india shows that majority of the covid- cases are concentrated in maharashtra, tamil nadu, gujarat, and new delhi (ram, kumar, & kaur, ) . the - aged are the adversely affected groups and twothirds of the positive cases in india were males . if the basic reproduction rate during the second lockdown continues, only a maximum of . percent population will be infected by the middle of august and the prevalence is likely to reach zero by november (kumar, meitei, & singh, ) . a study has used a mathematical model of the spread of covid- in india for both age and . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . social contact structure, where the mortality due to covid- infection showed significant gaps across the age groups, except among elderly where mortality rates rise (r. singh & adhikari, ) the preventive measures may have averted around , confirmed cases and , deaths till april , (dwivedi, rai, shukla, dey, & ram, ) . the aim of our study is of two-folds: first, we analyzed the national and sub-national trajectory of covid- cases, period-prevalence rate, fatality, and recovery rates by lockdown phases and secondly, we analyzed the geographical clustering of covid- infection rates in india. we used publicly available data from https://www.covid india.org/ (covid india, ). it is an application programming interface (api) for daily monitoring of the covid- cases at national, state, and district levels. data compiled in this web portal is based on state bulletins and official handles to update the case numbers. the details of the data are available on the website. this portal data matches with the data provided by the ministry of health and family welfare, government of india (https://www.mohfw.gov.in/) (mohfw, ). we found that age information is missing for percent of the patients, whereas sex information is missing for percent of the total confirmed cases. out of the total deceased, about percent do not have information on age and sex. out of recovered, only percent have age information and about percent have information on sex (see table ). due to such a high level of missing information on age-sex data, we did not carry out our analysis by age-sex disaggregation. about . % of the patients were not assigned to any state, which is excluded from the analysis. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint we analyzed the trends in cases and average daily cases during lockdown periods at national and state levels. we calculated the period prevalence rate (ppr), the case recovery rate (crr), and the case fatality ratio (cfr), using the following methods: where; ii c is total covid- infected people in the i th lockdown; ci is the number of infected cases in the i th lockdown i; ri- is the number of recovered in the i- th lockdown; − is the number of deaths i- th lockdown; cfri is case fatality ratio in i th lockdown period; crri is case recovery rate i th lockdown; ppri is the period prevalence rate in the i th lockdown and pi is the total population of a specific area in i th lockdown. since district level data also provides the number of active cases (cases which has not been recovered/deceased and currently infected) of covid- , we computed infection rate as = * where, i d is the infection rate for particular district d; a d is the number of active cases in district d and p d is the total population of district d. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint india march, - may, we carried out the analysis by the phase of the national lockdown that goi imposed. figure presents the timeline of lockdown phases: pre-lockdown as march , -march , (ten days); first lockdown as march , -april , ( days); second lockdown as april , -may , ( days), third lockdown as may , -may , ( days) and, fourth lockdown as may , -may , ( days)* ,we analysed upto th may . we used qgis software to generate descriptive maps and later exported shapefiles to geoda software to perform spatial analysis. we used first-order queen's contiguity matrix as the weight for conducting spatial analysis since our main aim is to understand spatial interdependence between infection rate and the neighboring natural regions. we estimated moran'i and univariate local indicators of spatial association (lisa). moran's i is the pearson coefficient measure of spatial autocorrelation, which measures the degree to which data points are similar or dissimilar to their spatial neighbors (moran, ) . the lisa cluster map yields four types of geographical clustering of the interest variable (weinreb, gerland, & fleming, ) . here, "high-high" means that regions with above-average infection rates also share boundaries with neighboring regions that have above average values of infection rate. on the other hand, "high-low" means that regions with above-average infection rate are surrounded by regions with below-average values. the "high-high" are also referred to as hot spots, whereas the "low-low" are referred to as cold spots. our analysis was done in r, geoda, and qgis software. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint india has experienced exponential growth of new, recovered, and deceased cases since the second lockdown phase (fig ) . the average daily new cases have increased from in the first lockdown to , in the fourth lockdown; the average number of daily recovered persons from to , ; the average number of daily deaths from to . the average daily total infected people raised from in the first lockdown to , in the fourth lockdown. there is rise in new cases ( to , ); total infected persons ( to , , ); recovered ( to , ) and deaths from to , (see fig ) . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint fig shows ppr per thousand, crr per , and cfr per by lockdown phases in india. it is evident that at national level ppr ( . to . ), crr ( . to . ) has consistently increased over these periods whereas cfr ( . to . ) has declined marginally (fig ) . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint fourth lockdown (average to new cases per day and total new cases to ). among northeastern states, assam ( to persons per day and total new cases to ) has the highest number. interestingly, overall . percent of covid- total infected persons belong to the four states, viz., maharashtra, tamilnadu, delhi, and gujarat. also, the average daily prevalence of covid- is the highest in the six major states and has increased consistently viz. maharashtra ( to , persons per day; total infected persons to , ); tamil nadu ( to , persons per day; total infected persons to , ); delhi ( to persons per day; total infected persons to , ); gujarat ( to persons per day; total infected persons to , ); rajasthan ( to per day; total infected persons to , ) and madhya pradesh ( to per day; total infected persons to , ), though kerala experienced the least increment in average prevalence of covid- ( to per day; to total persons) at the end of the fourth lockdown(see fig ) . state-wise trend analysis of recovered cases also varied during lockdowns. the highest recovered cases belong to maharashtra and the lowest to meghalaya. besides, the highest daily average and number of recovered cases belong to maharashtra ( to average daily cases; recovered from to , ); tamil nadu ( to average daily cases; recovered from to , ); gujarat ( to average daily; recovered from to , ); delhi ( to average daily cases; recovered from to , ); rajasthan ( to average daily cases; recovered from to , ). kerala experienced a decline in average daily recovered cases due to smaller number of infected cases in the fourth lockdown period. the state variation in deaths has been seen from one to another lockdown phase. maharastra recorded the highest number of deaths irrespective of the lockdown phase. in the first phase of lockdown, the second-highest death cases were found in madhya pradesh ( deaths) followed by delhi ( deaths) and gujarat ( deaths) whereas in second and third lockdown phases, gujarat and west bengal ranked the second position respectively. in the fourth phase, gujarat ( ) and delhi ( ) experienced the highest spike in deaths after maharashtra. maharashtra (average daily deaths from to ; deaths from to ) also experienced the highest number of deaths over the lockdown period, followed by gujarat (average daily deaths from to ; deaths to ); delhi (average daily deaths from to ; deaths from to ) and the lowest in kerala with no deaths in third lockdown to deaths in fourth lockdown., . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint however, ppr per thousand population is the highest for delhi ( . ) and the lowest for jharkhand ( . ) in the fourth lockdown among the top infected states ( figure ). the pattern of ppr by states has increased consistently in four states/uts viz., delhi ( . to . ); maharashtra ( . to . ); tamil nadu ( . to . ); gujarat ( . to . ); jammu & kashmir ( . to . ). though in kerala ( . to . ) ppr has slightly increased compared to other states. (see fig ) . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . fig ) . the pattern of crr varied from the first to fourth phase of lockdown. while most of the states observed an inverted "u" pattern, some states such as gujarat, madhya pradesh, maharashtra, orissa, and andhra pradesh experienced increasing recovery rates. on an average haryana ( . ) showed the highest recovery rate followed by kerala ( . ) and rajasthan ( . ) over all lockdowns. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https: //doi.org/ . //doi.org/ . / among the states with at least infected cases, cfr is the highest in gujarat ( . ); telangana ( . ); delhi ( . ); uttar pradesh ( . ) and the lowest in assam ( . ) and bihar ( . ) in the fourth lockdown. pattern of cfr showed that other larger states have also experienced high fatality over the lockdown periods viz; telangana ( to . ); uttar pradesh ( to . ); madhya pradesh ( to . ); rajasthan ( to . ). however, we found a few states experiencing decline in fatality rate, viz. bihar ( . to . ); west bengal ( . to . ); tamil nadu ( . to . ); karnataka ( . to . ); delhi ( . to . ) and, maharashtra ( . to . ) (see fig ) . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint note: there are eleven states with missing information on districts: patients in delhi; in telangana; patients in goa; in assam; in manipur; in tripura; in karnataka; in uttarakhand; in tamil nadu; in meghalaya and in arunachal pradesh. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint note: moran's' i and univariate lisa maps for above map. source: author's calculation . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint covid- is a global challenge where india stands within the first ten affected countries. the share by india to covid- cases may arise in the near future because of its mammoth population size, high population density, and poor public health facilities. the present study provides the national and subnational trajectory of covid- cases, period-prevalence rate, fatality rate and recovery rate in india, over a period of four months, from onset to may , (end of the nationwide fourth lockdown). as of may , (by end of th national lockdown), india has reported a total of , , cases, , recovered and , deaths from covid- in states and union territories. the national daily new cases observed about percent change over lockdown period; daily infected about percent change; daily recovered about percent change and daily deceased about percent change. our analysis also revealed that at the national level, there is consistent improvement in crr over the lockdown period. we also found the cfr was minimal by the end of the fourth lockdown phase. this study also observed that at the national level, the ppr has increased times over four lockdown periods the highest percent change is observed in bihar ( times); tamil nadu ( times); odisha ( times); madhya pradesh ( times) from first to fourth lockdowns; whereas, the percent change of crr is the highest in telangana ( . percent change); tamil nadu ( percent change); rajasthan ( percent change) and kerala ( percent change); from first to third lockdown periods. most of the states observed a decline in cfr over the lockdown periods. however, three states viz., maharashtra, west bengal, and gujarat have to put more effort as they have high cfr and low recovery rates. maharashtra also observed the lowest crr of . percent on average over lockdown periods. the number of confirmed cases in india is found to be lesser than other countries where lockdown is either not strict or not implemented (roser, ritchie, ortiz-ospina, & hasell, ) . a study found that lockdown has averted deaths until april , . thus, lockdown may have played an important role in decelerating the speed. moreover, it has also given the government time to prepare for a possible surge in cases, when the pandemic is predicted to peak in the coming weeks. however, ppr rising at an escalated pace ( . to . percent), more importantly in the last two lockdown periods might be due to two possible reasons; firstly, the exercise of testing samples has been intensified by government authorities, which consequently results new cases; secondly, the nation has witnessed huge flux of migrants returning to home states especially from megacities during third and fourth lockdown periods. moreover, the home secretary of india has made some relaxation for the inter-state movement mainly for distressed migrant workers, stranded tourists, pilgrims, and students (goi, ) . the present study observed huge state-level variations among covid- new, total infected, recovered, and deceased cases. six states (maharashtra . percent; tamil nadu . percent; delhi . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint . percent; gujarat . percent rajasthan . percent and uttar pradesh . percent) together account for . percent of the national new cases, most of them contribute substantially to nation's gdp. among the national recovered cases, percent belongs to just four states, percent belong to maharashtra ( percent), tamil nadu ( percent), gujarat ( . percent), and delhi ( . percent). at the state-level the pattern of new, total infected, recovered, and deceased cases per day have also increased over the lockdown periods. about percent of covid- deaths belong to four states viz., maharashtra ( . percent), gujarat ( . percent), delhi ( . ), and madhya pradesh ( . percent). the percent change of daily new cases and daily total infected cases is the highest in bihar, tamil nadu, odisha, and madhya pradesh. the daily-recovered cases were the highest among tamil nadu, rajasthan, delhi, and telangana. the daily deceased cases were the highest in maharashtra, gujarat, and delhi) from the first to the fourth lockdown periods. however, kerala is the only state experiencing a reverse trend in the daily new cases till third locklockdown but observed times spike in the fourth lockdown. kerala comes out to be the best example to fight this contagious disease. it has flattened the curve of this outbreak and observed a consistent decline in cfr ( . to ) till third lockdown periods and reached . percent recovery rate since the first lockdown period though in fourth lockdown it observed decline in the recovery rate and increase in the fatality rate. early detection, broad social support (masih, ) , together with strong public health system (kurian, ; vibhute & chattopadhyay, ) helped to contain the virus in kerala till the third lockdown. kerala's previous experience of the nipah virus in to use extensive testing, contact tracing, and community mobilization to contain the virus and maintain a very low mortality rate might have also helped. it has also set up thousands of temporary shelters for migrant workers (lancet, ) . another possible reason for lesser infection in kerala may be lower population density in the cities of kerala than the cities from the highly affected states. however, the reason for the spike of cases in the fourth lockdown in kerala might be due to the reemergence of infection due to migration in the state (hussain, ) . the study further finds that the covid- cases are spatially concentrated in the selected districts of india. we observed that out of districts, districts have at least one case of covid- and about districts have at least covid- patients. the pattern of districts revealed that the active covid- cases are mostly concentrated in districts with large population sizes and mostly urbanized. about percent of cases belong to hotspot districts belonging to maharashtra, gujarat, delhi, madhya pradesh and tamil nadu. mumbai ( . per hundred population) observes the highest infection rate followed by chennai ( . per thousand population) and, ahmedabad ( . per thousand population). the smaller districts such as ariyalur, dhalai, leh, kurnool, perambalur also observed a significantly high infection rate of covid- . the risk factors of high infection rates may be due to demographic, socio-economic or contextual factors such as age structure, population density, migration rate living conditions, access to health care etc. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint the age-sex pattern is crucial to understand the pattern of the pandemic spread and recognize the intensity of public health intervention measures required for disease control. it is missing from the data, about percent for age and about percent from sex. we also observed state-level age-sex missing data. it is worthwhile to mention that there is a possibility of under-reporting in infected and deceased cases due to lack of diagnosis. media has highlighted under-reporting of covid- cases in delhi and west bengal (pti, ; s. s. singh, ) . by analyzing the available covid- data, we cannot evaluate the total burden of mortality by covid- . there might be a spike of deaths among people suffering from fatal diseases like cancer, hypertension because non-covid healthcare services have been disrupted. such an indirect effect of covid- on mortality cannot be evaluated since india does not have any data system giving weekly or monthly death records. nevertheless, data used in the study is the only reliable statistic to understand the geographical disparity in the covid- pandemic in india. guardian. retrieved from https://www.theguardian.com/commentisfree/ /apr/ /kerala-. cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint covid- india dashboard case-fatality ratio and recovery rate of covid- : scenario of most affected countries and indian states assessing the impact of complete lockdown on covid- infections in india and its burden on public health facilities a situational analysis paper for policy makers international institute for population sciences guideline on movement of persons and vehicles d.o.no. - / -dm-i(a) india new virus cases take kerala's covid- tally past , . hindustan times projecting the future trajectory of covid- infections in indian-state-flattened-coronavirus-curve india under covid- lockdown aggressive testing, contact tracing, cooked meals: how the indian state of kerala flattened its coronavirus curve. the washington post covid- and mortality: india's perspective covid- india, ministry of health and family welfare, government of india notes on continuous stochastic phenomena facing criticism for 'under reporting' of covid- deaths, delhi issues sop for hospitals spatial mapping and demographic characteristics of the covid- positive cases in india: a situational analysis coronavirus pandemic age-structured impact of social distancing on the covid- epidemic in india. - corona virus.the mystery of the low covid- numbers in west bengal. the hindu world health organization declares global emergency: a review of the novel coronavirus (covid- ) on issues with covid data and why kerala stands out in india hotspots and coldspots: household and village-level variation in orphanhood prevalence in rural malawi who director-general's opening remarks at the media briefing on covid- - covid- coronavirus pandemic key: cord- -n fcf y authors: tyagi, r.; bramhankar, m.; pandey, m.; m, k. title: covid : real-time forecasts of confirmed cases, active cases, and health infrastructure requirements for india and its majorly affected states using the arima model. date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: n fcf y background: covid- is an emerging infectious disease which has been declared a pandemic by the world health organization (who) on march . this pandemic has spread over the world in more than countries. india is also adversely affected by this pandemic, and there are no signs of slowing down of the virus in coming time. the absence of a vaccine for covid- is making the situation worse for the already overstretched indian public health care system. objective: this study is forecasting the confirmed and active cases for covid- until june, using time series arima model. in further analysis, based on predicted active cases, we estimated the requirement of isolation beds, icu beds and ventilators for covid- patients until june. methods: we used arima model, and auto arima model for forecasting confirmed and active cases till the end of june month using time series data of covid- cases in india from march , , to may . we estimated requirement of icu beds as %, ventilators as % and isolation beds as % of the active cases predicted from our calculations. results: we expect that india will be having confirmed cases ( % ci: , ), active cases ( % ci: , ) at the end of june based on our forecasts. maharashtra, punjab, gujarat and delhi (ut) will be the most affected states, having the highest number of active and confirmed cases at the end of june while kerala is expected to have less than confirmed cases and no active cases at the end of june. we expect that india has to prepare isolation beds ( % ci: , ), icu beds ( % ci: , ) and ventilators ( % ci: , ) to accommodate the patients at the end of june. discussion and conclusion: our forecasts show a very alarming situation for india in coming days and, the actual numbers can go higher than our estimates of confirmed cases as india is observing partial lockdown currently. in future, lockdown might be lifted, and in that case, there will be a surge in the number of daily confirmed and active cases. the requirement of isolation beds, icus and ventilators will also be increased in that scenario. migrants returning to their homes due to loss of livelihood and income in the lockdown period may lead to a rise in the number of cases, which could not be accounted for in our projections. we suggest a public-private partnership (ppp) model in the health sector to accommodate covid- patients adequately and reduce the burden of the already overstretched indian public health care system. covid- is an emerging infectious disease which has been declared a pandemic by world health organization. the world health organization (who) has declared the outbreak of the novel coronavirus (covid- ) as a pandemic on march . it is caused by severe acute respiratory syndrome corona virus (sars-cov- ). this pandemic has spread over the world in more than countries, and developed countries like italy, china, australia, the usa are the most affected by this virus. the origin of the virus is yet to be confirmed, but the first person tested positive is from wuhan, china. it is spreading very quickly throughout the world, and the number of confirmed cases is about to reach million, and the recovery rate is around % in the world. (worldometer, may ). in india, the first positive case of covid- was detected on january , in kerala. on may , the country has , active cases, with all india institute of medical sciences (aiims) director randeep guleria stating that according to data released by experts and going by the current trend, the cases are likely to peak in june-july. of the total , active cases, . percent of patients are in icu, . per cent on ventilators, and . per cent are on oxygen support. currently, on may , india had dedicated covid hospitals with , , beds ( , , isolation beds and , icu beds) and , dedicated covid health centres with , , beds ( , , isolation beds and , icu beds) along with , quarantine centres (pib-updates on covid , may ) . however, if infections continue to rise at the same rate in may as they have done so far in april, india could be facing a deficit in isolation beds, intensive care unit (icu) beds and ventilators in the coming time. the infrastructure stress will be especially acute in eight high-burden states, led by gujarat, maharashtra, delhi and tamil nadu as they have more than active cases currently. it is really crucial in this situation to be prepared for healthcare infrastructure when the infections will be at its highest and accordingly the requirement for isolation beds, intensive care unit (icu) beds and ventilators will also be at its peak. according to the report of world population prospects ( ), india has a population of more than . billion and most of the population of urban areas and cities are under the risk of contracting the virus. so, it is important to forecast numbers of confirmed and active cases at the national and state level for india to see which states will be having the highest burden of the increasing confirmed and active cases of covid- by the end of the june. another objective of this study is to forecast the requirements of healthcare infrastructure in the coming months based on the numbers of active cases projected. this will be helpful to do proper future planning for the health facility in india. this will be helpful for the government to provide health facilities like isolation beds, ventilators and icu units in time to time without any overburden on the health system. tiwari et al. ( ) made their prediction for india based on the pattern of china using a machine learning approach. they predicted that the peak of the cases for india would be attained between the third and fourth weeks of april in india. this outbreak is predicted to be controlled around the end of may . the total number of predicted confirmed cases of covid- might reach around , , and the number of deaths due to covid- are predicted to be around april , , in india. however, this prediction does not seem to fit in the current situation as we are observing around daily confirmed cases and (aiims) director randeep guleria also stated that according to data released by experts and going by the current trend, the cases are likely to peak in june-july. another study by singh et al. ( ) to identify the top countries with the spatial mapping of the confirmed cases. a comparison was made between the identified top countries for confirmed cases, deaths, and recoveries, and an (arima) model was used for predicting the covid- disease spread trajectories for the next two months. their predicted values showed that the confirmed cases, deaths, and recoveries would double in all the observed countries except china, switzerland, and germany. chakraborty ( ) also used a hybrid approach based on autoregressive integrated moving average model (arima) and wavelet-based forecasting model that can generate short-term (ten days ahead) forecasts of the number of daily confirmed cases for canada, france, india, south korea, and the uk. guan et al. ( ) in his study on data regarding patients with laboratory-confirmed covid- from hospitals in provinces, autonomous regions, and municipalities in mainland china through january , , found that . % who were admitted to the icu, . % who underwent invasive mechanical ventilation, and . % who died. another study by wu et al. ( ) from china suggests that - % of covid- cases require hospitalization, with around % of cases presenting with severe symptoms and % requiring intensive care. a study by lazzerini et al. ( ) for italy and spain suggested that - % of covid- positive cases have been hospitalized, with - % requiring admission to intensive care units. based on the covid- cases in italy shows that - % of patients will require ventilation, and some patients will need ventilation for several weeks. remuzzi et al., ( ) find that the percentage of patients in intensive care reported daily in italy between march and march , , has consistently been between % and % of patients who are actively infected. in the indian scenario, a press release by pib on may stated that of the total , active cases, . per cent patients are in icu, . per cent on ventilators and . per cent are on oxygen support (pib press release). it is quite evident from the above studies that icu admission rates for covid patients vary for countries depending on the severity of the disease in the patients of that country. for india, as of now, patients requiring icu admission for covid is almost % which is lower than in other countries. however, this proportion might increase in the coming times as the severity of infection might increase as the infection will be at its peak in the month of june-july and therefore the percentage of covid patients requiring icu facility and ventilation support will be at its peak. for our study, the required data of daily total confirmed cases and total active cases of covid- infection collected for india as well as its selected states from the (https://www.covid india.org/), and excel of the patient database is used to build a time-series database for confirmed and active cases. in this study, forecasting is done based on the data from march , , to may . this data is being used to build forecast models for a, particularly short duration. in the past few months, an increasing number of research related to forecasting the trend of pandemic covid- cases are being published using different approaches in various part of the world. benvenuto et al., ) . in this study, the well-known autoregressive integrated moving average (arima) time-series model used for the further forecasting purpose. arima model is one of the generalized forms of an autoregressive moving average (arma) model among the time series forecasting. we fit both models to understand the data better or to predict future points in the series (forecasting) . arima model depends or always represented with the help of some parameters, and the model has expressed as arima (p, d, q): p, d and q are non-negative integers. the parameters have their usual meaning, here, p stands for the order of auto-regression, d represents the degree of trend difference (the number of times the data have had past values subtracted) for the stationary of the trend and q signifies the order of moving average. this model combines auto regression lags under the stationary trend and moving average and predict better future values based on past and recent data. for this model, the degree of parameters p, d and q determine based on the partial auto-correlation function (pacf) graph, the augmented dickey-fuller test to test the stationary of the time series observations and complete auto-correlation function (acf) graph respectively we have applied the arima model and auto arima model using r, to our considered time series data of covid- cases in india for the forecasting the total confirmed and active cases for india and its majorly affected states. we selected states based on the criterion that chosen states should have at least confirmed cases till may . by using this selection criterion, india and other states selected which are andhra pradesh, bihar, delhi, gujarat, haryana, jammu & kashmir, odisha, karnataka, kerala, madhya pradesh, maharashtra, punjab, rajasthan, tamil nadu, telangana, uttar pradesh and west bengal. the cases are forecasted under the assumption that people will be maintaining condition similar to the full or partial lockdown situation. after fitting the model, the built model is used to forecast confirmed and active cases covid- cases for the next days, i.e. from may , , to june . the model for forecasting future confirmed and active cases of covid- cases is represented as, here, xt is the predicted number of confirmed and active covid- cases at t th day, α , α , β and β are parameters whereas zt is the residual term for t th day. the trend of forthcoming incidences can be estimated from the previous cases, and a time series analysis is performed for this purpose . in our study, the forecasted cases are mainly used for preparing the government for the health infrastructure such as the number of isolation beds, icu beds and ventilators etc. in further analysis, based on predicted active cases, we estimated the requirement of isolation beds, icu and ventilators for covid- patients in the coming days. based on the literature, the requirement of icus and ventilator support increases as the infection hit its peak, which india may get in the month of june-july said by the director of aiims. so, based on the previous experiences of china and italy, estimates for health infrastructure requirements on projected active cases should be made at % requirement for icus, % for ventilation support and % active cases requires isolation beds. the requirement of icu, ventilator support, and beds, based on active forecast cases required number of beds = forecast active cases at ith day*( / ) required number of icu = forecast active cases at ith day*( / ) our health infrastructure requirement is estimated based on the active cases as our projections are made on the basis on data till may when our country was observing the complete lockdown. however, india is observing partial lockdown currently and might remove lockdown in the future, so for being prudent, we will estimate health infrastructure requirements based on the estimates of the upper confidence interval of active cases. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint results: in fig (a) shows the previous trend of confirmed cases in india. based on that previous data, we have forecasted the trends for confirmed cases in india which can be seen in the second subfigure. the rd and th subfigures for the acf and pacf plot for the determine the value of q and p for the model. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . fig. (a) , conveys about the forecasting of confirmed cases by the arima model. the model fit based on the three parameters (p, d, q) which found based on augmented dickey-fuller test, acf and pacf plot which given in fig (a) which reveals the best model fit with arima ( , , ) having lower akaike information criterion (aic). this model predicts the future confirmed cases with a % confidence interval based on the previous data, which shaded by blue in the above correlogram figure till june . similarly, from fig (b) at the india level, we have forecasted total active cases with the best fit with model arima ( , , ), which estimates the predicted active cases for the same duration. the analysis result for india level from table and fig , shows that the total confirmed and active cases at the india level will increase in the future. in india, based on our predictions, total confirmed cases may cross . lakhs, whereas total active cases will be close to . lakhs by the end of june . we can see that the gap between confirm and active cases is also increasing as the rate of recovery and death also increases with the increasing cases in the coming time. in the mid of june. from our estimates, we expect that india will be having confirmed cases ( % ci: , ). at the mid of june, we expect that kerala and odisha will be having less than confirmed cases based on our projections from data till may . however, states like maharashtra ( confirmed cases ( % ci: , ), punjab ( confirmed cases ( % ci: , ), delhi ( confirmed cases (ci: , ) & gujarat ( confirmed cases ( % ci: , ) will have a high number of confirmed cases at the mid of june. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint at the end of june, from our estimates, we expect that india will be having confirmed cases ( % ci: , ). at the end of june, we expect that kerala and odisha will be having less than confirmed cases based on our projections from data till may . however, states like maharashtra ( confirmed cases ( % ci: , )), punjab ( confirmed cases ( % ci: , )), delhi ( confirmed cases (ci: , ) & gujarat ( confirmed cases ( % ci: , )) will have a high number of confirmed cases at the end of june. at the end of june, from our estimates, we expect that india will be having active cases ( % ci: , ). at the end of june, we expect that kerala and madhya pradesh might not be having any active cases based on our projections from data till may . however, states like maharashtra ( active cases ( % ci: , )), punjab ( active cases ( % ci: , )), delhi ( active cases (ci: , ) & gujarat ( active cases ( % ci: , )) will face a high burden of active cases at the end of june. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . in fig. (a) , we see different zones according to the prevalent cases by their shaded colour and we can compare the confirmed covid- cases, how changes will occur in forthcoming days at three points of time. it indicates that some states have changes occur over time, the states like gujarat and west bengal showing less than thousand confirmed cases at the end of may , but till mid of june these states will infect cases more than to thousand. further, if we compare map for confirmed cases in uttar pradesh and andhra pradesh also has increases cases from mid of june to the end of june. similarly, in fig. (b) shows the map for the active cases at three-point of time. it indicates that the maharashtra and delhi, gujrat, punjab and other states will have been increasing number of active cases over the three-point of time. from these maps, we can understand some states like maharashtra, delhi, gujrat, tamil nadu, punjab, west bengal, andhra pradesh and some other showing more affected states in countries by the covid- cases. table and fig. (a) shows that the forecast value of the required number of beds for patients that will be suffering from covid- in the coming time. at the end of may, the total number of beds required for india ( % ci: , ). in some states, kerala and madhya pradesh will cure all covid- patients, and another way in some states as maharashtra (ci: , ), panjab (ci: , ), delhi ( % ci: , ), gujarat ( % ci: , ) and tamil nadu ( % ci: , ) will require the highest number of beds. fig. (a) represents the number of beds in the middle month of june. the table suggests that in india, the required number of active beds is ( % ci: , ) and maharashtra will require isolation . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint beds ( % ci: , ), punjab will require isolation beds ( % ci: , ), delhi will require isolation beds ( % ci: , ), and gujrat will require isolation beds ( % ci: , ) will continue to maintain the top four position with an increasing trend in terms of the requirements. the numbers of beds required in kerala, karnataka, odisha, and karnataka will be minimum. as the study suggested that the number of covid- patients will be high in june; therefore, the number of beds also require high in june month. table shows the forecast number of beds require to admit the patients who suffer from covid- at the end of june. india has to prepare isolation beds ( % ci: , ) to accommodate the patients. the required numbers of beds have increased compared to the end of may. maharashtra will require isolation beds ( % ci: , ), punjab will require isolation beds ( % ci: , ), delhi will require isolation beds ( % ci: , ), and gujarat will require isolation beds ( % ci: , ), whereas kerala and madhya pradesh would be removed from the table due to the zero forecasted active cases at the end of june. : - ) ventilators. it is noteworthy that kerala will require ( % ci: , ) icu and ( % ci: , ) ventilators, and mp will require icu ( % ci: , ), and ventilator ( % ci: , )) and are likely to overcome the situation. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . table & (b) shows the forecasted value of the required number of icu and ventilators to admit the patients who suffer from covid- at the mid of june. india has to prepare ( % ci: , ) icu and ( % ci: , ) ventilators to accommodate the patients. the required numbers of the facility (icu and ventilators) are increased compared to the end of may. maharashtra will require icu ( % ci: , ) and ventilators ( % ci: , ), punjab will require icu beds ( % ci: , ) and ventilators ( % ci: , ), delhi will require icu beds ( % ci: , ) and ventilators ( % ci: , ) and gujarat will require icu beds ( % ci: , ) and ventilators ( % ci: , ), whereas kerala and madhya pradesh will not be considered in the calculations due to the zero forecasted active cases at the mid of june. table represents the forecasted value of the required number of icu and ventilators to accommodate the covid- active patients at the end of june. as the number of active cases increases the requirement of the facilities also increase. the required number of icu will be ( % ci: , ) and ( % ci: , ) ventilators. maharashtra will require ( % ci: , ) icu and ( %ci: , ) ventilators, punjab will require ( % ci: , ) icu and ( % ci: , ) ventilators. delhi will fig. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint require ( % ci: , ) icu and ( % ci: , ) ventilators. gujarat will require ( % ci: , ) icu and ( % ci: , ) ventilators will continue to maintain the top four position with an increasing trend in terms of the requirements. the numbers are increasing very slowly in odisha. the world is going through a pandemic, and almost every country is affected by it. a country needs to know how much burden of active and confirmed cases it will have to bear in the coming time. it will help the country in taking pro-active measures to prepare adequate health infrastructure for the coming time based on future needs. we used arima model and auto arima model on the time series data of covid- cases in india for forecasting the total confirmed and active cases till june end. based on our forecasted values of active cases, we calculated the healthcare infrastructure required in the coming time. based on our forecasts, confirmed cases for india at the end of may are expected to be ( % ci: , ). india will be having confirmed cases ( % ci: , ) in the mid of june from our estimates. we expect that india will be having confirmed cases ( % ci: , ) at the end of june. our current estimates for confirmed cases are in line with the actual number of confirmed cases as on may , india has , confirmed cases, while our estimates suggested , confirmed cases ( % ci: , ). aiims also suggested that peak will be achieved in months of june-july. our results also show that daily confirmed cases are increasing at a faster pace even at the end of june with around , daily confirmed cases, so it is likely that peak will be attained afterwards. by the end of the june, maharashtra ( confirmed cases ( % ci: , )), punjab ( confirmed cases ( % ci: , )), delhi ( confirmed cases (ci: , ) & gujarat ( confirmed cases ( % ci: , )) will be the most affected states. while kerala and odisha will be least affected having less than confirmed cases based on our projections from data till may based on our forecasts of active cases for india, we are expecting active cases ( % ci: , ) at the end of may. india will be having active cases ( % ci: , ) in the mid of june from our estimates. we expect that india will be having active cases ( % ci: , ) at the end of june. our current estimates for active cases are also in line with the actual number of active cases as on may , india has , active cases, while our estimates suggested active cases ( % ci: , ). maharashtra ( active cases ( % ci: , )), punjab ( active cases ( % ci: , )), delhi ( active cases (ci: , ) & gujarat ( active cases ( % ci: , )) will face a high burden of active cases at the end of june. while kerala and madhya pradesh might not be having any active cases based on our projections from data till may . in terms of health infrastructure requirement at the end of june, we expect that india has to prepare isolation beds ( % ci: , ) to accommodate the patients. when it comes to states, maharashtra will require isolation beds ( % ci: , ), punjab will require isolation beds ( % ci: , ), delhi will require isolation beds ( % ci: , ), and gujarat will require isolation beds ( % ci: , ). for critically ill patients, there is a requirement of icu beds and ventilators. based on our forecasts for the end of june month, the required number of icu beds for india will be ( % ci: , ) and ventilators ( % ci: , ). maharashtra will require icu beds ( % ci: , ) and ventilators ( % ci: , ), punjab will require icu beds ( % ci: , ) and ventilators ( % ci: , ), delhi will require icu beds ( % ci: , ) and ventilators ( % ci: , ) and gujarat will require icu beds ( % ci: , ) and ventilators ( % ci: , ). at present, india seems to be well prepared for the challenge as on may , india had dedicated covid hospitals with , , beds ( , , isolation beds and , icu beds). . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . according to our forecasts, it is a very alarming situation for india in coming days. however, the actual numbers can go higher than our estimates of confirmed cases, active cases and healthcare infrastructure as we made this forecast based on the data till may , when india observed complete lockdown. currently, india has a partial lockdown with restrictions varying for three zones (red, orange and green zone) based on the current assessment of the situation in there. in future, lockdown might be lifted, and in that case, there will be a surge in the number of daily confirmed and active cases. the requirement of isolation beds, icus and ventilators will also be increased in that scenario. the migrants are returning to their homes due to loss of livelihood and income in the lockdown period, which may lead to a rise in the number of cases, and could not be accounted for, in our projections. so, india and its majorly affected states like maharashtra, gujarat, tamil nadu and delhi need to be well prepared for the pandemic challenge in coming time and focus on increasing their healthcare infrastructure, and other states should also remain alert till the pandemic completely recedes. we suggest a public-private partnership (ppp) model in the health sector to accommodate covid- patients adequately and reduce the burden of the already overstretched indian public health care system. the forecasting of covid- cases is done based on the data under the lockdown duration. so, the forecasted cases in future will be showing the same trend as india would have observed, had it been observing complete lockdown. since may , india is observing partial lockdown, and which might be removed in the coming time so that actual cases will be more than the forecasted cases. for some states like punjab showing more covid- infection and madhya pradesh showing decline trend in future, but the situation may not occur in future because of the nature of the previous trend-pattern is different from now. forecasted cases based on arima model in our study for some states having lower bound for the % ci comes negative values which we have considered zero cases in that situation. in our study, the seasonality factor did not consider which is important in india, and maybe it affects our forecasting in future because of monsoon diseases. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint estimation of the final size of the covid- epidemic application of the arima model on the covid- epidemic dataset real-time forecasts and risk assessment of novel coronavirus (covid- ) cases: a data-driven analysis. chaos, solitons, and fractals, , . advance online publication analysis and forecast of covid- spreading in china a sidarthe model of covid- epidemic in italy. arxiv preprint clinical characteristics of coronavirus disease in china trend analysis and forecasting of covid- outbreak in india forecasting the dynamics of covid- pandemic in top countries in april through arima model with machine learning approach application of an autoregressive integrated moving average model for predicting the incidence of hemorrhagic fever with renal syndrome an arima model to forecast the spread and the final size of covid- epidemic in italy updates on covid- covid- and italy: what next? the lancet a statistical analysis of the seasonality in pulmonary tuberculosis pandemic for the top affected countries: advanced autoregressive integrated moving average (arima) model. jmir public health and surveillance coronavirus (covid- ): arima based time-series analysis to forecast near future coronavirus (covid- ): arima based time-series analysis to forecast near future outbreak trends of coronavirus disease- in india: a prediction. disaster medicine and public health preparedness, - . advance online publication applications and comparisons of four time series models in epidemiological surveillance data note ) *** shows active decline cases to zero in the respective duration and states. ) ' ' show the minimum case or lower bound. key: cord- -o loo d authors: yadav, pragya d.; raut, chandrashekhar g.; patil, deepak y.; d majumdar, triparna; mourya, devendra t. title: crimean-congo hemorrhagic fever: current scenario in india date: - - journal: proc natl acad sci india sect b biol sci doi: . /s - - - sha: doc_id: cord_uid: o loo d india is considered as a hot spot for emerging infectious diseases. in the recent past many infectious diseases of emerging and re-emerging nature have entered this subcontinent and affected a large number of populations. a few examples are nipah, avian influenza, pandemic influenza, severe acute respiratory syndrome corona virus and chikungunya virus. these diseases have not only affected human and animal health but also economy of the country on a very large scale. during december , national institute of virology, pune detected crimean-congo hemorrhagic fever virus specific igg antibodies in livestock serum samples from gujarat and rajasthan states. subsequently, during january crimean-congo hemorrhagic fever virus was confirmed in a nosocomial outbreak, in ahmadabad, gujarat, india. retrospective investigation of suspected human samples confirmed that the virus was present in gujarat state, earlier to this outbreak. this disease has a case fatality rate ranging from to %. earlier presence of hemagglutination inhibition antibodies have been detected in animal sera from jammu and kashmir, the western border districts, southern regions and maharashtra state of india. the evidences of virus activity and antibodies were observed during and after the outbreak in human beings, ticks and domestic animals (buffalo, cattle, goat and sheep) from gujarat state of india. during the year , this virus was again reported in human beings and animals. phylogenetic analysis showed that all the four isolates of , as well as the s segment from specimen of and were highly conserved and clustered together in the asian/middle east genotype iv. the s segment of south-asia type was closest to a tajikistan strain tadj/hu of . the present scenario in india suggests the need to look seriously into various important aspects of this zoonotic disease, which includes diagnosis, intervention, patient management, control of laboratory acquired and nosocomial infection, tick control, livestock survey and this, should be done in priority before it further spreads to other states. being a high risk group pathogen, diagnosis is a major concern in india where only a few biosafety level laboratories exist and it needs to be addressed immediately before this disease becomes endemic in india. the crimean-congo hemorrhagic fever (cchf) was first characterized in the west crimean region of the former soviet union in during a large outbreak and was isolated in from a patient [ ] [ ] [ ] [ ] . the virion is spherical, * - nm in diameter and is in the form of enveloped particles with a tripartite, single-stranded rna genome having negative polarity. this virus belongs to the genus nairovirus in the family bunyaviridae and causes fatal viral hemorrhagic fever (vhf) in humans, with a reported high mortality rate [ ] . the genus nairovirus includes described viruses, which are placed in seven serogroups based on the antigenic relatedness. the groupings have subsequently been sustained through demonstration of morphological and phylogenetic relatedness. only three viruses of this genus are known to cause human disease: they are cchfv, dugbe and nairobi sheep disease virus [ ] . in india, among nsd group, ganjam virus is considered a variant of nsdv. ganjam virus, also known to cause human infection, is transmitted through hyalomma species of ticks. the antibodies against this virus have been recorded in animals and humans [ ] [ ] [ ] [ ] [ ] . cchf virus has tri-partite genome segments; small (s), medium (m) and large (l), which encode for the nucleocapsid protein (np), the envelope glycoproteins g and g and an rna dependent rna polymerase respectively [ ] [ ] [ ] . cchf infections have been found in parts of africa, asia, eastern europe and the middle east [ ] [ ] [ ] [ ] [ ] [ ] [ ] . among the tick-borne hemorrhagic viruses cchfv has an extensive geographic range [ ] . in nature, humans get infected either through a tick bite or by contact with an acute phase cchf patient or by contact with blood or tissues from viremic livestock [ ] .this review elucidates the current scenario including presence of this virus in india, consequences on public health, issues with diagnostic system, surveillance program to monitor this disease, network of laboratories, and requirement of infrastructure to address cchf outbreaks. the review was prepared after an extensive search for literature on vhf and cchf using different online web pages including pubmed, world health organization (who) and centre for disease control and prevention (cdc). all the recent literature published on cchfv from india was thoroughly studied and also epidemiological data from the national institute of virology (niv), pune, india was considered while compiling this review. since the discovery of cchf virus, nearly outbreaks involving more than , cases have been reported all over the world from almost countries [ ] . the known distribution of cchf virus covers the greatest geographic range as compared to any other tick-borne virus. there are reports of viral isolation and/or disease in africa, asia, southeast europe and the middle east [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the average case fatality rate is - %, but variable mortality rates from to % have been reported in various outbreaks. the mortality rate is higher with nosocomial infections than through tick bites which may be related to the virus dose [ ] . india has been considered as a hot spot for many emerging and re-emerging infectious diseases [ ] .there has been suspicion of cchfv presence in india due to confirmed cchf positive cases in adjoining countries like pakistan, china, and afghanistan [ , ] . india has an ancient history with these countries and also trade records of livestock and human movements. the presence of this virus in india raised high suspicion, when it was isolated from the tick species hyalomma anatolicum and also from a mixture of hyalomma and boophilus species collected in pakistan [ ] . in , shanmugam et al. [ ] , tested a total of human sera from all over india. of these, nine samples from kerala and pondicherry were found positive for cchf virus specific antibody. in the same study, out of serum samples, collected from sheep, horse, goat and other domestic animals from all over india showed evidence of cchfv antibodies. most of the positive sera in southern india were collected from goats. evidence of hemagglutination inhibition antibody positivity was recorded in the animal sera tested during a serosurvey conducted in jammu and kashmir and in the western border districts of india in . in the same study antibodies were also detected in domestic animal sera from different states/territories of southern india and from maharashtra state. mainly goat serum samples from south india were found to be positive [ ] . subsequently, in , kaul et al. [ ] , conducted a survey of ixodid ticks to determine the cchfv activity in jammu and kashmir state, india, but cchfv isolation was not obtained from pools comprising eight species under six genera of ticks. all these studies were based only on serological findings in which no virus isolation could be achieved and hence no clear evidence of this virus could be obtained. during december , just prior to cchf outbreak, blood samples were collected by the niv, pune to examine livestock for the presence of cchfv specific igg antibodies from abattoirs in the northern adjoining state of rajasthan and some more distant areas of maharashtra and west bengal. the serum samples of buffalo, goat and sheep from sirohi district, in southern rajasthan were found positive for igg antibodies against cchfv. in january , cases with hemorrhagic manifestations among hospital staff were reported from ahmadabad of gujarat state, india. out of samples screened, one hospital and one family contact (both asymptomatic) were positive for the presence of igm antibodies against cchfv and three cchf positive cases showed high titer of igm antibodies [ ] . speculation was made that higher number of suspected cases were present in gujarat state [ ] . animal serum samples from northern west bengal and pune district of maharashtra were negative for cchfv igg antibodies. evidence of cchfv infection (igg positive) was also found in a follow-up study of livestock (buffalo, cattle, goat, and sheep) from kolkata and the surrounding villages of changodar, jivanpara and navapura. overall it was observed that igg antibody positivity in small sample sizes varied between villages ( - %) [ ] . earlier phylogenetic studies based on complete s genome segment sequences showed that cchfv strains cluster in seven distinct groups while molecular epidemiology of cchfv isolates (based on ''s'' segment) have revealed the three groups of genetically related isolates; group a (african clade and asian clade comprising isolates from, china, iran, russia and madagascar), group b (south and west africa and iran) and group c (greece) [ , ] . recent, s segment analysis had shown that cchfv strains cluster in six to seven distinct groups as west-africa in group i, central africa in group ii, south-africa and west africa in group iii, middle-east and asia in group iv, europe in group v and greece in group vi. the group iv may split into two distinct groups, asia and asia . complete genome analysis of cchfv isolates not only revealed high genetic diversity but also showed recombination and re-assortment which resulted in more complicated evolutionary routes of the virus, than a mutationbased selective forces [ ] [ ] [ ] [ ] [ ] . earlier data on serological testing has suggested that there are very few significant differences among strains of cchfv at different geographic locations. however, more recent data based on nucleic acid sequence analysis have revealed the extensive genetic diversity [ ] . sequence-based molecular characterization of the indian cchfv showed that they possess the functional motifs, known to occur in the s, m and l gene segment products as in other cchfv. phylogenetic analysis showed that all the four isolates of , as well as the s segment from isolates of were highly conserved and clustered together in the asian/middle east genotype iv. the s segment of south-asia type was closest to a tajikistan strain tadj/ hu of ( . % nucleotide identity) while the m segment was closest to type m . both m and l segments were closest to an afghanistan strain afg - of ( and % nucleotide identity respectively). thus, the indian isolates were identified as a south-asia /m fareast virus combination and the differing parental origin in the s and l/m segments suggested that it might be an intragenotypic reassortant. the molecular clock studies further revealed that the ancestry of these viruses was not very recent and dated back to about years on the basis of the s segment, whereas it was about years based on the m segment. however, the outbreak may not have resulted from a very recent introduction. considering this, so far there was no evidence which confirmed multiple circulating strains in the country. the cchfv sequences of human case from showed similarity with cchfv sequences of year and , reported from india, which indicates that same virus strain was in the circulation (niv, unpublished data). subsequently, the possibility of a recent re-introduction of the virus from any of the neighboring countries cannot be ruled out [ ] . this virus circulates in the nature in an ''enzootic tick-vertebrate-tick'' cycle and there is no evidence that the virus causes disease in any animal other than newborn laboratory mice. cchfv infection has been demonstrated more commonly among smaller wildlife species such as hares and hedgehogs that act as hosts for the immature stages of the tick vectors [ ] . cchfv has been isolated from numerous domestic and wild vertebrates; cattle, goats, sheep, hares, hedgehogs, a mastomys spp. of mouse and even antibodies against cchfv have been detected in the sera of domestic animals [ ] [ ] [ ] [ ] . large herbivores have the highest seroprevalence rate for cchfv [ ] . seroprevalence rates of - % have been reported in some studies, while others suggest that more than % of adult livestock in endemic regions have antibodies against the virus. cchfv infections are asymptomatic in animals other than experimentally inoculated newborn rodents (laboratory mice, rats and syrian hamsters) [ ] . the potential roles of migratory birds and the movement of livestock carrying ticks in the spread of the virus over distant geographical areas have been described. although birds carry cchf infected ticks, they don't show presence of the virus or cchfv specific antibodies [ , ] . cchf virus has been detected in at least species of ticks, from seven genera of the family ixodidae (hard ticks). however, members of the genus hyalomma seem to be the principal vector. transovarial, transstadial and venereal transmission of the virus occurs in this genus. cchfv has been reported from a biting midge (culicoides spp.) and also been found in two species of argasidae (soft ticks). however, experimental infections suggest that this virus does not replicate in this family of ticks and even in other several species of ticks [ , [ ] [ ] [ ] [ ] [ ] . cchfv specific igg antibodies were detected in cattle, goat and buffalo from surrounding villages of the ahmadabad city in gujarat state, india and virus was isolated from the pool of male hyalomma anatolicum anatolicum ticks, collected from a buffalo in the affected area, which suggested that this disease was not due to the recent introduction of cchfv to this area [ ] . ornithodorus tick pool was found positive for cchfv by rt-pcr in routine screening after the outbreak from ahmadabad, gujarat state (unpublished data niv, pune). rodent's serum samples screened from the affected area by real time rt-pcr were found negative. during the gujarat outbreak, follow-up studies revealed that sheep, goats, buffalo were the main hosts for cchfv, in which not only igg antibodies but viral rna was also detected in serum samples [ ] . humans appear to be the only host of cchfv in which the disease is manifested. clinical progress of cchf differs from mild to moderate or severe. initial symptoms of cchf differ from patient to patient. the typical course of cchf shows that the disease progresses through four distinct phases, i.e., incubation, pre-hemorrhagic, hemorrhagic and convalescence [ ] . the clinical features observed commonly in cchf patients from india were high grade fever, headache, body ache, nausea, vomiting, abdominal pain, dizziness, malaise, photophobia, diarrhea, petechiae, ecchymosis and visceral bleeding. bleeding from other sites including the vagina has also been reported in the very severe cases [ , , ] . the common laboratory findings of cchf patients who died due to this infection from india demonstrated elevated prothrombin time (pt) and activated partial thromboplastin time (aptt), alanine aminotransferase (alt), aspartate aminotransferase (ast), lactic dehydrogenase (ldh), creatinine phosphokinase (cpk), leucopenia and thrombocytopenia [ , , ] . it has been found that in some patients cchf develops into a serious or fatal disease while in others it is only mild or asymptomatic but in india most of the cases showed severe manifestations [ , ] . one of the major reasons for nosocomial infection of cchf could be the high viral load which helps in virus dissemination [ ] . in severe cases, hemorrhagic manifestations develop within - days after onset of disease. hence, it becomes imperative to provide a differential diagnosis for cchf with respect to other viral diseases mimicking the similar signs and symptoms which will be helpful in early treatment of affected patients. the pathogenesis of cchf is not well understood due to the limited number of biosafety level- (bsl- ) laboratories and unavailability of proper animal model. however, a common pathogenic feature of viruses causing vhf is their ability to disable the host immune response by attacking and manipulating the cells that initiate the antiviral response [ ] . early diagnosis of cchf is critical for the management of patients, to prevent the transmission of the disease to the community and potential nosocomial infections. the differential diagnosis of cchf differs depending on that particular geographic region. in india, overlapping symptoms of hemorrhagic fevers like dengue, kyasanur forest disease, hantavirus hemorrhagic fever and other diseases (malaria, meningococcal infections and leptospirosis) are of major concern in cchf diagnosis [ ] . the diagnosis of vhf is mainly based on typical clinical presentation and thereafter confirmed by detection of either virus or viral rna or by demonstration of a rise of antibody titers against it [ ] . laboratory diagnosis of cchfv includes the reverse transcription polymerase chain reaction (rt-pcr) and real-time rt-pcr assay, which is the method of choice for the rapid detection of viral rna in the acute phase, considered highly specific, sensitive and rapid [ ] [ ] [ ] . the consumables and instrumentation required for these techniques are cost expensive and out of the financial reach of many local laboratories. this can delay the timely diagnosis and in turn early management of patients. detection of immunoglobulin m (igm) during the acute phase and immunoglobulin g (igg) antibodies in convalescent phase sera is detectable by enzyme-linked immunosorbent assay (elisa) and immunofluorescent antibody (ifa) [ , ] . patients with fatal disease as well as patients in the first few days of illness do not usually develop a measurable antibody (igm) response and in these individuals diagnosis is achieved either by virus detection in blood, serum, plasma, urine or tissue samples using molecular techniques. diagnosis of suspected cchf sample is strictly performed in specially-equipped, high biosafety level laboratories. in india, niv, pune and high security animal disease laboratory (hsadl), bhopal are the only two laboratories which have the capacity to provide diagnosis on cchf virus. the national institute of communicable diseases (nicd) also played a major role in outbreak investigations of communicable diseases and was involved in the early phase of cchf investigations. the niv is india's premier virology research institute and is identified as the who collaborating center for arboviruses reference and hemorrhagic fever reference and research. it has functional state of the art bsl- laboratory to provide diagnosis on highly infectious pathogens and also has a newly constructed bsl- laboratory. during the first outbreak of cchf in gujarat state of india, all the human samples were sent to the niv, pune for diagnosis of suspected samples. the laboratory provided the diagnosis using elisa, and/or molecular methods and also isolated cchf virus. the entire cchf diagnostic assays have been thoroughly validated and standardized approach has been followed in the laboratory to provide a correct diagnosis on cchf. quick and accurate diagnosis were provided to ensure early patient management. the hsadl is one of the premier facility recognized by office international des epizooties (oie) (the world's apex organization for animal health for handling exotic and emerging pathogens of animals) by virtue of its bsl- containment laboratory and animal experimentation facility. the real-time rt-pcr assay for diagnosis of cchfv has been standardized and validated. during cchf outbreak around veterinary samples were sent to the hsadl for surveillance of cchf in domestic animals. both of these laboratories have the independent capacity to provide cchf diagnosis as they have specialized laboratories with appropriate facilities and expertise. the process, system and test method used for diagnosis are consistently validated for quality assurance. these laboratories are accredited internationally which assures the clinician and the patients that the test reports are reliable and also gives a feedback to the laboratory on its performance as per international standards. as this virus belongs to risk group- , there are limitations for diagnosing cchf in several affected areas. also there is high risk involved in the infectious sample collection and transportation to diagnostic laboratories which are important issues that needs to be addressed by hospitals or any agency involved in it. at the source while collecting samples in outbreak scenario, personal protection equipment, packing of samples should be performed as per international guidelines described by who and cdc [ , ] . to cope up with all these problems, diagnostic capacities for cchf should be increased mainly in affected areas. also a national network of local, state, public health, hospital-based and veterinary laboratories should be developed which will respond to the public health emergencies and provide laboratory diagnostics on cchf. after an outbreak of cchf in gujarat state of india during , directorate general of health services, ministry of health and family welfare, government of india issued a protocol for treatment of cchf in india [ ] . as per the protocol the patients are categorized into three types as follows. supportive care is necessary based on the patient's physiologic condition. because most patients requiring prehospital evaluation and transport are in the early stages of the disease, universal precautions should be adequate. in patients with respiratory symptoms, use of face shields and high-efficiency particulate air (hepa) filter masks should be compulsory. general supportive therapy is the mainstay of patient management in cchf. intensive monitoring to guide volume and blood component replacement is required. supportive care includes fluid management by intravenous crystalloids, oxygen, cardiac monitoring and administer blood and blood products as clinically indicated. intramuscular injections and the use of aspirin or other anticoagulants should be avoided. invasive procedures should be minimized because of the risk associated with viral transmission from sharp objects. there is currently no specific antiviral therapy for cchf. however, the antiviral drug ribavirin has been found effective against the cchfv in vitro, although its exact mechanism of action against this virus is unclear. although its clinical use in cchf treatment is controversial, it is the only antiviral drug currently available [ ] [ ] [ ] . however the benefits of ribavirin treatment have not been examined under the strict conditions of a randomized clinical trial and the drug is not approved for the treatment of cchf by the us food and drug administration [ ] . ribavirin therapy was found to be effective in cchf patient when administered in the early phase of illness during cchf outbreak in gujarat [ ] . the optimal route of administration of ribavirin is by mouth preferably taken with food. during the course of cchf patients have nausea, vomiting, gut bleeding, hematemesis and malena and hence potentially poor uptake of oral ribavirin. blood count needs to be monitored at least weekly. ribavirin was generally well tolerated. the most common side effect of ribavirin is mild to moderate hemolytic anemia which is reversible. anemia associated with ribavirin therapy is often asymptomatic and can be managed by monitoring blood count and serum biochemistry. ribavirin is contraindicated for treatment in pregnant women. given the high risk of cchf-related mortality for both pregnant women and fetuses, ribavirin still may be recommended. ribavirin is contraindicated in patients with chronic anemia and hemoglobin levels below g/dl, and in patients with severe renal impairment (creatinine clearance \ ml/min). the drug may accumulate in patients with impaired renal function. these patients should be carefully monitored during therapy with ribavirin for signs and symptoms of toxicity, such as anemia. in case of hypotension and hemodynamic instability patients should be managed on standard guidelines for the treatment of shock which includes resuscitation, fluid supplements (crystalloids/colloids) and ionotropic support. in suspected secondary bacterial infection patient should be treated on standard guidelines/practice for community acquired/nosocomial infections. platelet transfusion may be considered if there is significant bleeding with thrombocytopenia. ventilatory/renal support may be provided as per the standard guidelines. prophylactic administration of oral ribavirin to the contacts of cchf patients is not recommended. symptomatic contacts can be given therapeutic dose. the complete therapeutic dose of ribavirin should be given to health care workers with severe exposure (needle stick injury, direct contact with blood/body fluids). for a person with mild exposure observe and closely monitor hcw for any symptoms. management of cchf patients with hyper-immunoglobulin administration might be a very promising new treatment approach, especially for high-risk patients [ ] . there are some non-pharmaceutical interventions for patient management that should be followed such as placing patients in an isolation room, prevent non-essential staff and visitors from entering the room, all staff entering the room should wear personal protective equipments, biomedical waste management as per sop, supervision of infection control practices by hospital infection control committee, the persons handling the dead body in hospitals should wear personal protective equipments, spraying dead bodies with : liquid bleach and disinfecting ambulance/transport vehicle. currently, there are no standardized case definitions for cchf notification and contact tracing within india. after the documentation of first positive case of cchf in gujarat state a special team was sent to the society where the deceased cchf positive patient lived and the surveillance on members of the society was conducted for unusual fever symptoms. a similar process was carried out in the case of shalby hospital by the doctor who had attended one of the cchf cases. in a special move, the ahmadabad municipal corporation carried out surveillance in all cattle sheds within corporation limits and abattoirs that operate both legally and illegally. the major concern was the hyalomma ticks that are present on the cattles which are the transmitters of the deadly disease. the strategic actions taken by the state government included active human, animal and entomological surveillance. isolation and treatment of cases following universal precautions, contact tracing and monitoring contacts, spraying cattle in the affected area with anti-tick agents, spraying human dwelling with residual sprays and communicating the risk to the public. in view of the cchf outbreak, department of health, government of india alerted the states neighboring gujarat to pick up cases of hemorrhagic fever at the earliest and to review the situation in their states and remain prepared to detect, verify and respond to outbreaks of cchf. the national institute of virology, pune has been actively involved in surveillance of cchf in gujarat and has proposed to carry out nationwide serosurvey of cchf in domestic animals. such surveillance will reveal the clear scenario of the existence of cchfv in different states of india and will help in assessing the possibility of risk by cchf virus to all the animal handlers in the dairy industry. in the view of the potential consequences during its outbreaks, cchfv is classified as an agent of bioterrorism. this has resulted in its inclusion as a cdc/niad category-c priority pathogen [ ] . after first confirmed cchf outbreak in india; some important factors have been noticed in hospital settings such as the irregular use of personal protective equipments or barrier nursing methods, minimal use of surgical masks (except in the intensive care units) which might have led to a nosocomial outbreak. certain universal precautions, such as hand wash was not appropriately followed. patients did not wear masks in wards or when being transported for medical procedures (e.g., x-ray examination). disposal of waste, collection of soiled linen, laundry, cleaning of floors and other surfaces in the wards was carried out by personnel who did not follow infection control practices. after the announcement of the cchf outbreak in india during , stringent infection control practices were introduced, including isolating patients in the hospital, barrier nursing techniques were initiated, and housekeeping procedures and waste management were improved. all these practices and timely diagnosis of suspected cases helped in the management of outbreak and ended with four deaths and one recovery, but again during similar kind of cchfv transmission from patient to medical practitioner was reported in hospital settings of gujarat state [ , , niv unpublished data] . prevention and control of cchf infection can be achieved by avoiding or minimizing the exposure to infected ticks. insect repellents containing n, n-diethylmeta-toluamide (deet) are effective in protecting against ticks. wearing protective clothing and early and correct removal of ticks are recommended. in endemic areas, control of ticks has been achieved by environmental sanitation of underbrush habitats. acaricides may be useful for domestic animals to control cchf virus-infected ticks, if used - days prior to slaughter or during export of animals from enzootic regions. nonspecific preventive measures such as tick eradication has proved to be expensive, inefficient and in many instances impractical. a vaccine derived from the inactivated mouse brain is used in bulgaria, but it is not widely available and its efficiency and safety needs to be re-evaluated. specific human immunoglobulin is used for post-exposure prophylaxis. a dna vaccine containing the cchf genome m segment has shown to produce neutralizing antibodies in mice [ ] ; however, the protective efficacy of the vaccine has not been evaluated. after the nosocomial outbreak in january, , gujarat state government has taken initiatives to track each cchf case based on syndromic approach and is undertaking anti-tick measures. however, during june , another episode of nosocomial infections was noticed from ahmadabad city which resulted in two fatal cases. exposure history revealed that the treating physician had an accidental contact with the patient (the index case, resident of bawla taluka, ahmadabad), who had similar symptoms of hemorrhagic fever and had died a week earlier. the sample of the treating physician (case a) was found to be positive for cchfv (unpublished data niv, pune). suspected family contact and hospital contacts and samples of animals and ticks were screened for cchfv, out of which only animal samples were found to be positive while other contacts and ticks were found negative. during the period of - , a large number of referred cchfv suspected human samples from gujarat state and other parts of the country were screened by the niv, pune but no evidence of positivity recorded from any other state apart from gujarat. in the recent years a number of zoonotic viral diseases have emerged in southeast asia [ ] . cchf was recently recognized in india; whereas from so many years its presence has been reported from the neighboring countries. the short incubation period and many of the non-specific symptoms overlapping other hemorrhagic fevers, raises the risk of humans carrying the cchf virus to naive areas. this can lead to secondary infection amongst travel companions, close contacts, and healthcare providers. the environmental factors, climate and human behavior are critical determinants for the establishment and maintenance of cchf endemicity within an area. even though the explanations about cchf emergence or re-emergence have been formulated, the contribution of each of these factors has not been quantified. those persons who fall in the high risk group populations can reduce the risk of cchfv transmission through changes in the land use, recreational activities and livestock movement. increasing awareness about this dreadful disease among people might help in reducing its incidence rate. introduction of cchfv to a non-endemic area could take place either through legal or illegal trade of infected animals, animals infested with infected ticks, through geographic expansion of infected hyalomma ticks from cchf-endemic areas. the reasons for the emergence and re-emergence of cchf are multifactorial, which are partly understood. effective surveillance and reporting of the cases is necessary to monitor the spread of the disease in near future. multidisciplinary research focusing on developing sensitive diagnostic tools, building biobank of clinical samples, development of new antivirals and vaccines will be useful to prevent or counter/ tackle future outbreaks. livestock sector plays a critical role in the welfare of india's rural population. animal husbandry is responsible for a very large economic support to the country and it is estimated that the yearly turnover is in several hundred crores of rupees. it contributes nine percent to gross domestic product and employs eight percent of the labor force. this sector is emerging as an important growth leverage of the indian economy. india is progressing continuously in the dairy industry. with an annual production of million tonnes in - , india is the largest producer of milk [ ] . initiation of operation flood in early seventies provided a stimulus to milk production. gujarat being a hub for the dairy industry, animal exchange, movement and rearing has increased in this state. hence this disease also raises a crucial concern with respect to the food safety and security point of view in india. in india, livestock sector in - has contributed rs. billion, . % of total gdp at constant price (gdpls). according to th livestock census in india cattle, buffalo, goat and sheep contributed . , . , . and . millions respectively to the economy by various means [ ] . the fact that such huge population of the above mentioned livestock is in close contact with the human beings indicates the possibility of spread of this virus in different parts of india. currently, there is no information available for the presence of this virus in other states. looking at the scenario a survey is required to understand the prevalence of this disease and risk involved in human health. as earlier described by lahariya et al. [ ] , a national inter-sectoral surveillance and response system, and crossborder sharing of information and establishing special community based laboratory surveillance programs for atrisk population groups should be developed. laboratory capacity for timely diagnosis with a regional network of accredited laboratories and training of scientific and technical staff, infection control and vector control activities through integrated vector management, biosafety practices and techniques, case management and health education for high-risk groups and by public health preparedness to address the emerging and re-emerging diseases are the ways to prevent and control this disease. in a developing country like india only a few biosafety level- laboratories are available, and out of those only a few are capable to carry out viral diagnosis, is one of the main limitations to deal with this infectious disease. indian council of medical research has taken initiative in strengthening virology 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hemorrhagic fevers and other arboviral infections). materials of the th scientific session of the institute of poliomyelitis and viral encephalitides emerging viral diseases of southeast asiaand the western pacific india's milk revolution department of animal husbandry dairying & fisheries, ministry of agriculture, government of india ( ) th livestock census key: cord- -g ke h authors: singh, vaibhav pratap; haribabu, p.; bindhumadhava, b.s. title: covid curve guides india’s health infrastructure growth needs date: - - journal: j emerg nurs doi: . /j.jen. . . sha: doc_id: cord_uid: g ke h covid- has led to many unprecedented situations across the world. with lockdowns and severe restrictions on movement and activities, countries have managed to slow down the covid curve but developing countries like india are likely to face a humongous task of containing the virus spread in coming months. high population density, continuing economic activities, movement of people etc. will keep causing newer hotspots across india. we look at the compounded daily growth rates (cdgr) of usa, spain, india and brazil over the duration of the virus spread since january, . we also analyze the correlation between the total cases and active cases across india. we estimate the projected number of beds, icu beds, oxygen support and ventilators for different cdgrs in the coming months and also define a metric target to control the virus spread through various preventive measures. abstract covid- has led to many unprecedented situations across the world. with lockdowns and severe restrictions on movement and activities, countries have managed to slow down the covid curve but developing countries like india are likely to face a humongous task of containing the virus spread in coming months. high population density, continuing economic activities, movement of people etc. will keep causing newer hotspots across india. we look at the compounded daily growth rates (cdgr) of usa, spain, india and brazil over the duration of the virus spread since january, . we also analyze the correlation between the total cases and active cases across india. we predict the projected number of beds, icu beds, oxygen support and ventilators for different cdgrs in the coming months and also define a metric target to control the virus spread through various preventive measures. be effective measures in slowing the covid curve in many countries. with the world starring at an economic recession, many countries across the world have slowly and steadily started easing their respective lockdowns in the hope that the above stated measures will prevent an uncontrollable rise in covid cases. in this letter we discuss why the cases will keep on increasing especially in the countries with high population density pockets, analyze the growth rate of covid cases, define metrics leading to flattening of the covid curve and also discuss the rate at which countries should scale up their health infrastructure in the coming months. although the analysis is generic and shall apply to other countries as well, we take the example of india which has conditions like high population and its density, large economically vulnerable population due to multiple lockdowns, developing health infrastructure etc. multiple lockdowns, since th march , have immensely helped in slowing the covid curve in india and have given the much needed time to the central and state governments to scale up the health infrastructure as well as to sensitize the population on various preventive measures which will go a long way in keeping the curve within control in the coming months. economic slowdown has caused large scale migration from urban pockets which in turn have led to an increase in the covid curve in india. thus the government has started relaxing the lockdown to start various organized and unorganized economic sectors, ease the movement of people etc. in a bid to give relief to the ones in need. such relaxations, coupled with the large population and its density, are likely to increase the covid- cases in the coming months. highlighting the federal government structure in india, the covid containment strategy has been implemented state wise. various indian states are adopting a strategy of -days quarantine for any individual coming from outside the state. but the number of individuals coming from outside the states is huge. for e.g. bihar is expecting a total of lakhs migrants to come back . institutional quarantine has its own infrastructural limitations. home quarantine seems to be a possible option for asymptomatic and mildly symptomatic cases but should be implemented in a strict manner. the social fabric and the culture of joint families shall help in the successful implementation of the home quarantine scheme. we focus on combing only the hotspots, the high number of asymptomatic cases will keep on causing more hotspots at different locations and further a person tested today might get infected tomorrow due to easing of lockdown norms. the disease incidence usually decreases only once herd immunity is reached in a community. herd immunity is a phenomenon where a considerable size of a community becomes immune to a particular communicable disease thereby reducing the number of disease carriers . usually vaccination assists in achieving herd immunity but a vaccine for covid- looks far away. the other method is of natural infection where a sizeable portion of the community is exposed to the virus in a controlled manner such that they develop antibodies in response and become immune to the disease . in such natural infections is predicted to be between and . thus according to the below given equations, the threshold population to reach herd immunity shall be between to . % . in a country like india, with a population of . billion , the threshold to reach herd immunity will be . crore. the covid- curve will flatten either when the total number of covid- cases will start approaching the threshold herd immunity population or when all the current cases (both symptomatic and asymptomatic) will be strictly isolated and no new positive cases will be allowed into the population. both the conditions are extremely difficult to achieve making it clear that covid- is going to stay for a very long time. the compounded daily growth rate (cdgr) calculated over days for india, usa, brazil and spain is plotted in figure for a duration from th jan, to th may, . the initial spikes are majorly due to small number of cases but a generic trend observed in the plot is that lockdowns have played a significant role in slowing down the cdgr of the countries. developed countries i.e., usa and spain have a cdgr over days of . % and . % as on th may whereas developing countries i.e., india and brazil have a cdgr over days of . % and . % as on th may . figure gives taking these numbers into consideration, table gives the health infrastructure needs in the coming months in india. india needs to focus all its might at reducing the cdgr of health infrastructural needs to as close to zero. at zero the need of scaling up the health infrastructure will seize to exist. coronavirus cases. accessed nitish govt gets to work to bring lakh migrants, students back but says it'll take months concepts of herd protection and immunity the flaws of "herd immunity: whose duty is it to protect the very young/old, pregnant, vaccine allergic, and the immunosuppressed? understanding herd immunity comment what policy makers need to know about covid- protective immunity the reproductive number of covid- is higher compared to sars coronavirus covid- : herd immunity and convalescent plasma transfer therapy public health measures and the reproduction number of sars-cov- herd immunity -estimating the level required to halt the covid- epidemics in affected countries our world in data. coronavirus pandemic (covid- ). accessed covid curve guides india's health infrastructure growth needs ministry of home affairs g of i. consolidated guidelines: st lockdown press information bureau government of india. extension of lockdown up to lakh passengers travel in shramik special trains till may : indian railways. published press information bureau government of india. our recovery rate has improved at . %, and more than lakh tests have been conducted the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work ☐the authors declare the following financial interests/personal relationships which may be considered as potential competing interests key: cord- -eocse xa authors: gowrisankar, a.; rondoni, lamberto; banerjee, santo title: can india develop herd immunity against covid- ? date: - - journal: eur phys j plus doi: . /epjp/s - - - sha: doc_id: cord_uid: eocse xa world health organization declared the novel coronavirus disease (covid- ) outbreak to be a public health crisis of international concern. further, it provided advice to the global community that countries should place strong measures to detect disease early, isolate and treat cases, trace contacts and promote “social distancing” measures commensurate with the risk. this study analyses the covid- infection data from the top affected countries in which we observed heterogeneous growth patterns of the virus. hence, this paper applies multifractal formalism on covid- data with the notion that country-specific infection rates follow a power law growth behaviour. according to the estimated generalized fractal dimension curves, the effects of drastic containment measures on the pandemic in india indicate that a significant reduction of the infection rate as its population is concern. also, comparison results with other countries demonstrate that india has less death rate or more immunity against covid- . the novel coronavirus disease (covid- ) is an emerging epidemic responsible for infecting lots of people and killing lakhs globally since the first report till today, according to the world health organization (who). the who china country office has informed of cases of pneumonia unknown aetiology detected in wuhan, hubei province of china, on december . a total of case patients with pneumonia of unknown aetiology have reported to who by the national authorities in china since december through january . further, who received the information from the national health commission china that the outbreak is associated with exposures in one seafood market in wuhan on and january . the chinese authorities identified a new type of coronavirus, which has been isolated on january . china shared the genetic sequence of the novel coronavirus for countries to use in developing specific diagnostic kits. during the period - january , the ministry of public health, thailand, reported the first imported case of laboratoryconfirmed novel covid- from wuhan, china, and the ministry of health, labour and welfare, japan (mhlw), reported an imported case of laboratory-confirmed covid- from a e-mail: santoban@gmail.com (corresponding author) particularly, some countries are in the process of measures public health and social processes based on local epidemiology, while others are considering shrink these interventions. besides, countries have employed public health and social measures based on local risk assessments, such as full lockdown, restricted local movement, and educational institutes are implementing the virtual classes and industries are encouraging work from home, and regulated universal travel measures. numerous papers have appeared modelling the forecasting the trends of epidemiology of the disease [ ] [ ] [ ] [ ] [ ] , and many analyses have been done for the currently available epidemic data [ ] [ ] [ ] . the analysis made by using practical data shows that the power law kinetics with fractal exponent provides a better fit to the current data for the number of deaths and spared rate compared than the classical epidemiological approach that assumes an exponential growth of the disease [ ] [ ] [ ] [ ] . the idea of fractal dimension is useful in the categorization and quantification of shape and texture which is used to describe systems with simple self-similarity and regular fractals [ ] . however, it is not enough to characterize sets having heterogeneous scaling properties like growth of epidemic disease. for such a characterization grassberger has generalized the analysis with the notion of multifractals which implies a continuous spectrum of exponents for the characterization of the system [ ] . in this oversimplification, an inhomogeneous fractal is considered to be associated with countably many subfractal sets of dissimilar dimensions [ ] [ ] [ ] [ ] [ ] [ ] . we analyse the covid- infection data from the top affected countries in which we observed the growth and death patterns of the covid- are heterogeneous. hence, this paper applies the multifractal formalism on covid- data with the notion that country-specific transmission rates follow a power law growth nature. herd immunity is related to a scenario under which people develop immunity against contagious infectious disease that materializes when the people is immune either through vaccination or immunity developed through former infection and they become immune to that disease. this provides indirect protection or herd immunity to those people who are not immune to the disease, see for instance fig. . as on may , india is under the top most infected countries with over per day recorded cases for four consecutive days. data from johns hopkins university [ ] show that the total number of cases in india has surpassed that of iran. after a sharp spikes of cases since the second week of may, it can be predicted that the scenario will continue till it can attain a maximum peak, may be in the month of june. after this intense period, herd immunity can occur by a natural course of infection. in this report, using a brief comparative analysis, we have shown that india can develop a significant mutation against the disease. we have restricted our data analysis till nd may. the work is organized as: in sect. , necessary materials and method of multifractal formalism are presented. in sect. , the covid- infection data from the top affected countries are described and discussed the heterogeneous nature of covid- growth patterns. further, multifractal formalism is applied on covid- data with the notion of power law growth behaviour of virus. the generalized fractal dimension curves are estimated, and using these results comparison is made between india with other countries. conclusions of the work are provided in sect. . this section presents the explanation of the material and method description applied in this paper. prediction of the number of infected case for different diseases is the foremost task in the healthcare system. in general, epidemiological analysis models assume that the number of confirmed positive cases of covid- grows exponentially with respect to fixed reproduction rate n. each person infected by the covid- transmits to n number of new persons when n > , and then the total number of covid- cases grows as n t τ = e at ( ) here τ is the incubation time which depends on the nature of covid- . the limitation of exponential approaches is that it assumes each person transmits to n number of new person without considering the inhibition due to the interaction with already infected people such as lockdown, quarantine, restricted local movement, distance-learning, teleworking, regulated travel, and other prophylactic measures. therefore, in order to create short-term predictions to prepare for the extent of the global pandemic infection data from the top affected countries have investigated in [ ] . also, all country-specific infection rates follow a power law growth behaviour and the scaling exponents per country are calculated in [ ] . in this paper, the partition function of covid data for top affected countries has been estimated to apply analogy of multifractal formalism with covid- transition, since the partition function exhibits the power law distribution. a set s of points describing an object can be divided into boxes labelled by an index i such that the ith box has n i points of the total n points of the set. these points are sample points describing the content of the underlying measure. let us use the mass or probability eur. phys. j. plus ( ) : the mass exponent τ (q) for the set depends on the moment of order q chosen. like n (δ) of bare d-measure the partition function (if we may call) z (q, δ) also often exhibits power law distribution where the exponent τ (q) is called the mass exponent not the fractal dimension if it is nonlinear in q. the mass exponent is more revealing than the simple fractal dimension as we shall soon find it out. it can equivalently be defined as the generalized fractal dimension (gfd) d q can be defined as as q −→ , d q converges to d , which is given by where d is the information dimension and d q is a monotonically decreasing function of q such that d ≥ d ≥ d . here d and d denote the fractal dimension and correlation dimension, respectively. the set s is a country and it can be divided into boxes labelled by an index i such that the ith box has n i number of person affected by covid- of the total number of persons infected by every positive case n of the country s. let us use the mass μ i = n i /n in the ith cell to estimate the generalized fractal dimension by using eq. ( ). covid- data have been downloaded from the publicly available jhu-csse ( ) data repository provided by the johns hopkins university center for systems science and engineering (jhucsse) [ ] and statistics and research coronavirus pandemic (covid- ) available in the website of our world in data [ ] . we have selected the data sets with the most infections as presented in [ ] on - - : p.m. ist. the countries and their infection counts and death counts are given in table . figure a shows generalized fractal dimension result for the confirmed cases of countries. for each country day zero is considered to be the day of the first confirmed case of covid- . in each day the confirmed cases are normalized by dividing them by the total number of case and obtained the partition function z (q, δ) by eq. ( ) . also, fig. b reveals generalized fractal dimensions of confirmed deaths corresponding to the confirmed case of top countries. in fig. a , a comparison of the days of different countries' case counts shows that india has ranked th spread rate higher growth than uk, canada, france, germany, iran. mexico, russia and china, but lower growth than usa, brazil, turkey, spain, peru and italy. it is important to note, however, that due to the discrepancies of covid- testing, these . , . , . , . , . and . , respectively, which are shown in subplot. we observed that the transmit rate of usa, uk, spain, brazil, canada seems to follow the same patterns, whereas france transmit rate is irregular not gradually increasing. figure figure shows the daily confirmed cases and confirmed deaths of italy, turkey, india, and their generalized fractal dimensions are revealed in subplot. figure c clearly shows that generalized fractal dimension of death rate of india is monotonically decreasing from . , whereas italy and turkey have initial value . , . , respectively. it should also be noted that remaining all countries initial mortality rate starts above the value . ; hence, death rate of india is lesser than any other countries. this discrepancy might eventually get decreased or increased when more data on the outbreak in india will become available. however, the empirical data available as on . . are evident that india has more immunity eur. phys. j. plus ( ) : against covid- . this is likely to be connected with many culture-related behaviours and to the presumed diversity in health conditions of the people. the analyses presented in this study demonstrated that india has less mortality rate of covid- as its total infected population is concern. across the world, countries have executed a number of control procedures to respond to covid- , with the aim of slowing down transmission and dropping mortality. particularly, india is in the process of scaling up public health and social measures based on local epidemiology and on local risk assessments, such as continuously four full lockdown, restricted local movement, and educational institutes are implementing the distance-learning and businesses to teleworking, and regulated international and national travel measures. finally, the death rate is likely to be connected with many culture-related behaviours and to the presumed diversity in health conditions of the people. notice that mortality and transmit rate might eventually get decreased or increased when more data on the outbreak of all countries will become available. preliminary estimation of the basic reproduction number of novel coronavirus ( -ncov) in china, from, to : a data-driven analysis in the early phase of the outbreak analysis and forecast of covid- spreading in china, italy and france herd immunity-estimating the level required to halt the covid- epidemics in affected countries mathematical prediction of the time evolution of the covid- pandemic in italy by a gauss error function and monte carlo simulations short-term forecasting covid- cumulative confirmed cases: perspectives for brazil covid- data repository by the center for systems science and engineering coronavirus pandemic (covid- ). published online at ourworldindata.org who, coronavirus disease (covid- ) situation reports short-term predictions of country-specific covid- infection rates based on power law scaling exponents fractal kinetics of covid- pandemic the fractal time growth of covid- pandemic: an accurate self-similar model, and urgent conclusions scaling features in the spreading of covid- the fractal geometry of nature generalized dimensions of strange attractors the infinite number of generalized dimensions of fractals and strange attractors multifractal and generalized dimensions of gray-tone digital images fractal patterns in nonlinear dynamics and applications mid-sagittal plane detection in magnetic resonance image based on multifractal techniques acknowledgements lamberto rondoni acknowledges partial support from miur grant dipartimenti di eccellenza - . key: cord- -wfiqbu m authors: upadhyay, ranjit kumar; chatterjee, sourin; saha, satvik; azad, rajeev k. title: age-group-targeted testing for covid- as a new prevention strategy date: - - journal: nonlinear dyn doi: . /s - - -x sha: doc_id: cord_uid: wfiqbu m robust testing and tracing are key to fighting the menace of coronavirus disease (covid- ). this outbreak has progressed with tremendous impact on human life, society and economy. in this paper, we propose an age-structured siqr model to track the progression of the pandemic in india, italy and usa, taking into account the different age structures of these countries. we have made predictions about the disease dynamics, identified the most infected age groups and analysed the effectiveness of social distancing measures taken in the early stages of infection. the basic reproductive ratio [formula: see text] has been numerically calculated for each country. we propose a strategy of age-targeted testing, with increased testing in the most proportionally infected age groups. we observe a marked flattening of the infection curve upon simulating increased testing in the – year age groups in india. thus, we conclude that social distancing and widespread testing are effective methods of control, with emphasis on testing and identifying the hot spots of highly infected populations. it has also been suggested that a complete lockdown, followed by lockdowns in selected regions, is more effective than the reverse. covid- , a respiratory disease caused by a new strain of coronavirus (sars-cov- ), has spread to almost every part of the world, since first reported in december [ ] . who declared this outbreak a 'public health emergency of international concern' on january . as of april , it has caused , , deaths with , , confirmed cases of infection. till date, usa has the largest number of fatalities, followed by italy. usa reports , , cases, with cases per million people, though the statistics have still been evolving due to the large variability in testing performed by different countries as of now [ ] . in the absence of any vaccine to prevent and contain the spread of novel coronavirus disease, covid- , as well as the lack of an established treatment regimen to cure this disease (beyond mitigation of symptoms), effective non-pharmaceutical interventions are needed to contain the epidemic and minimize morbidity and mortality associated with this respiratory disease. as the covid- pandemic has swept across the globe, now affecting almost all countries, measures for mitigation have been put in place that include strict lockdown to less restrictive people movement but all aiming to achieve social distancing of different degrees to balance the socio-economic impacts of the lockdown and the disease. robust testing and tracing are key to containing the pandemic and effectively 'flattening' the infection curve, both by distributing cases over a longer period of time and by reducing the total number of cases, and thus lowering the epidemic peak. governments and health agencies have banked on mathematical models to guide towards the goal of optimizing available resources to attain maximal benefits of mitigation measures. mathematical models are often based on certain assumptions; however, these are continually improved upon through adjustments guided by emerging data, and eventually, these models become more reliable in helping navigate through such situations. here, we leverage the emerging information from covid- in different countries, mainly usa, italy and india, to develop a covid- specific model that can inform on effective interventions for coronavirus containment. as people of different age groups have responded differently to coronavirus, we utilized the age-stratified data of covid- to develop a system that can inform on more effective prevention strategies. we particularly focused on india where covid- seems to have not peaked yet despite the most restrictive lockdown imposed for over a month now. our model recommends that testing and tracing be ramped up in the - -year age-group population in india in order to flatten the infection curve in shortest time possible in the current situation. we further demonstrate this by computing the basic reproductive ratio r at different times and following an age-grouptargeted intervention. the novel coronavirus is thought to have originated in bats and eventually infected humans, due to the similarity in the genome sequence of sars-cov- to that of a bat coronavirus [ ] . human-to-human transmission has also been established. so far, we observe different transmission and fatality rates in different countries. one of the main reasons for this is differing age groups and social contact structures. in order to study this effect, we use social contact matrices, which show contact patterns of an age group with others and are used to parametrize mathematical methods to understand the transmission patterns. schenzle [ ] used an age-structured seir model with age groups to study the spread of measles, a disease which mostly affects children. this method has previously been applied to respiratory diseases like influenza [ ] , pertussis [ ] and varicella [ ] . given that covid- transmission patterns are very similar to those of respiratory diseases caused by other viruses, we can get valuable information by studying covid- disease dynamics through an age-structured model. it has been observed that social distancing, isolating infected populations and quarantine are effective ways of containing the epidemic. after receiving the best available medical intervention to date, a quarter of critically ill patients still die, signifying that the host response to the virus is an important factor [ ] . thus, the government and hospitals need to procure supportive care equipment in sufficient amounts. initiating the process of flattening the curve by these abovementioned methods provides the time to prepare for supportive care. with social distancing becoming a preventive strategy, many countries have announced partial or complete lockdowns. numerous companies are also advising their employees to 'work from home'. due to this, patterns of mixing between people change, the effects of which are hard to represent with classical compartmental disease models. however, it is essential to understand these changing contact patterns in order to more accurately model the disease dynamics. considering the differential impacts of an infectious disease on people in different age groups, perhaps due to a number of reasons including physiology, immunity, mobility, and social contact and behaviour, an infectious disease model must consider differential age-group disease dynamics. recently, some new approaches about age structure population models have been proposed in [ , ] . age-structured models offer better approximations of reality and also give health organizations better tools to develop age-group-targeted control strategies. here, we have simulated the spread of novel coronavirus using such an age-structured siqr model. we have fitted our model to the current situations in italy and usa and have estimated age-wise mortality rates. side by side, we compared this with the scenario in india. we have also analysed the success of lockdown measures adopted by these countries qualitatively and have projected the effects of further lockdowns. we examine whether starting off with a complete lock-down which is then gradually lifted in specific areas is more effective than the reverse, i.e. declaration of lockdown regionally followed by a nationwide lockdown. finally, we have proposed a novel method of age-group-targeted testing to tackle the situation and have also showed how it can help in flattening the curve effectively. this manuscript is organized as follows. in sect. , we formulate the mathematical framework of an siqr epidemic model. in sect. , we analyse the predictions made by a numerical simulation of our model. in sect. , we propose control strategies and their intended impacts. finally, in sect. , we discuss the conclusions. the basic reproductive ratio r is calculated in "appendix a", and various parameters used in our numerical simulation are tabulated in "appendix b". the mathematical framework of an age-structured siqr epidemiological model is formulated. in order to construct the model, our assumptions are stated as follows: . the entire population, n , is divided into four compartments: susceptible population, s (which are under risk of contracting the infection), infected population, i (which consists of infectious, both symptomatic and asymptomatic, or untested individuals), quarantined population, q (which are removed from all contacts within the entire population and are hence not infectious) and recovered class, r (which are recovered from infection). therefore, we have n = s + i + q + r. in order to keep track of disease-induced death, we assign an additional compartment of fatalities, f. . each population of siqr and f is further subdivided into m age classes. individuals within the same compartment interact with other individuals proportional to a coefficient of interaction c i j , which specifies the average contact between age classes i and j, with < i, j ≤ m. . there is no recruitment of the susceptible population and no natural death in any compartment. there is also no aging of individuals. . the disease is transmitted from the infected to the susceptible population with age class i, i.e. compartment s i , at a rate βλ i . here, β is the transmission probability, and λ i is the weighted coefficient fig. schematic diagram of the interacting population within a certain age class, for the model ( ) of contact of age class i with the entire infected population. individuals from compartment s i move into compartment i i and become infective immediately. . individuals from compartment i i move into compartment q i at a rate δ i and are no longer infectious. . the infected and quarantined populations, i i and q i , recover and move into the recovered population, r i , at rates and γ , respectively. . the populations i i and q i suffer disease-induced death, at a common rate of μ i . a schematic diagram of the interacting population is presented in fig. . thus, the transmission process is formulated by the following system of differential equations: the initial conditions are s i ( ) > , all the parameters in the system are positive quantities. we break down the age-structured social contact matrix, c = [c i j ] m×m , into the contributions from households, workplaces, schools (all educational institutions) and other areas (market places, restaurants, cinema halls, shopping malls, etc.), represented by c h , c w , c s and c o , respectively. each of these is weighted with coefficients α h , α w , α s and α o , which we change over time to reflect the effect of lockdown on social contact. for example, during the time period when all educational institutes are closed, we set α s = . we note that when italy and usa announced partial lockdowns, the coefficients α have been fitted to the existing data. it must also be noted that even during a complete lockdown, the contributions to the contact matrix from work and other areas are never zero, as people involved in essential services continue work and marketplaces must operate to some degree. lockdowns also induce an increase in household contact, as people are staying at home more [ ] . for numerical simulation, we have collected data on the times and nature of lockdown imposed, starting from the closure of schools and universities to complete lockdowns [ ] [ ] [ ] . a complete lockdown in india was declared on march . usa declared a national emergency on march , followed by various statewise guidelines and orders to 'stay at home'. italy had also proceeded towards lockdown step by step, with a lockdown of the northern provinces on march and a nationwide lockdown from march onwards. the parameters δ i , γ and have been assumed, using known rates of infection, recovery and the first appearance of symptoms. we assume the onset of symptoms, detection and isolation in . days on average [ ] for infected individuals. we also assume that an individual stays quarantined for days, which is the average recovery period for a symptomatic individual [ ] . in addition, we assume that unidentified infected individuals, either asymptomatic or untested, can proceed straight to recovery after days of infection on average. the parameters β and μ i have been fitted to existing case and fatality data. the values of β for india, usa and italy are . , . and . , respectively. the values of the remaining parameters are listed in "appendix b" (tables , ). it must be noted that we choose to interpret currently reported cases to belong in the quarantined compartment, q, which is a subset of the total infected population. we have also chosen our initial conditions such that i i ( ) = q i ( ), on the assumption that cases are underreported where exactly half of all infected individuals are identified (quarantined). for india and italy, we use m = age classes, equally dividing the range of ages - years. due to unavailability of data, we use m = age classes for the usa, over a range - years. for each country, we have set up m differential equations, which we have integrated using the python module 'numpy'. we have collected covid- case and mortality data up to april for each country from worldometers [ ]. we have also collected age-structure data from popu-lationpyramid [ ] and social contact data from prem et al. [ ] . the age classes and initial susceptible population data are presented in table . the infection curves predicted by our model are shown in fig. . we note that our model predicts a fairly symmetric infection curve, whose peak trails behind the peak of the quarantined population. usa and india continue an upward growth, while italy's infection curve has begun to drop. if current conditions continue without any new measures being taken, active cases are predicted to reach peak within months for usa and around months for india. we also predict that everything will be normal in months for italy, without considering the effect of herd immunity. on the other hand, it may take a year at worst for india and usa to fully recover. by 'normal', we mean that the number of infected individuals has dropped below one thousand, which represents a sufficiently small number of cases relative to the populations of the countries in consideration to be fully identified and isolated. we observe a common trend in infected age groups across all three countries, in that the young-and middleaged groups (between and years of age) have the largest numbers of infected people, relative to the initial susceptible population size of that age group. we estimate this by measuring the drop in s i from its initial value across all age groups i over time, as shown in fig. . this may be explained by larger contact coefficients α among themselves and other age groups. the population within this age group is also highly mobile, in each country. on the other hand, data suggest that infection is less common in children [ ] . dr. calum semple, professor at liverpool university, stated that 'we know that lung development doesn't finish until teenage years. ace is highly regulated in lung development. because of that the "lock" might be expressed differ-ently in kids' lungs' [ ] . hence, we have identified the - -year-old age group to be the most infected age group across all three countries (fig. ) . in our proposed control strategy, we thus place less emphasis on individuals younger than years. considering different mortality rates across different age groups has very little effect on the total infection and mortality curves, both qualitatively and quantitatively. we note that italy's mortality curve in fig. f has begun to flatten, far quicker than our model would sug- gest. we may explain this by noting that the reported mortality rates, which we used to fit our model, are likely inaccurate due to factors such as sampling bias and the changing capability of health care system. with time, as italy continues to improve medical facilities and mobilize doctors and nurses, patients receive better care and facilities are no longer swamped as they were in the early stages of the pandemic. we also note that with time, the mechanisms by which covid- causes death might be better understood by scientists and practitioners, so the observed lower mortality rate may also be explained by better, more effective treatment and the identification of drugs which improve survival chances. presently, the overall mortality rate is the highest in italy, followed by india and the usa (fig. ) . interpreting these mortality rates is complicated by the fact that pre-existing medical conditions play a major role and are somewhat correlated with age. fatality rates may also be inflated by limited testing and the resulting selection bias in which asymptomatic individuals are not accounted for. in addition, the fact that our model omits - -year age group in the usa, despite a high expected mortality rate in that group, may explain why our model predicts a lower mortality rate in usa, compared to india and italy. the basic reproductive ratio r can be interpreted as the expected number of cases directly caused by a single infected individual in a completely susceptible population. when r > , the infection spreads in the population, and it does so more rapidly with higher r . when r < , the infection eventually dies out, and the system proceeds towards the disease-free equilibrium. we have calculated r for the three countries, as presented in table . a lower r value for india initially indicates a comparatively slower spread of disease than in usa and italy. figure illustrates the decrease in r with the implementation of social distancing measures. the drop in r is significant in all cases, although only italy shows r < , which is enough for the disease to die out. concerningly, our model shows very little impact of the lockdown in india, compared to the projections without one. after fitting our model to case numbers before the implementation of social distancing measures, our model predicts that complete stop of contact between people outside their home, or even a % reduction in such contact, is not consistent with subsequent reported cases. the three different countries show different degrees of reduction in contact, in terms of different control coefficients α. this effective reduction in contact in india seems to be far less than in usa, which in turn is less than in italy. in the case of italy, data look promising, suggesting that the implementation of lockdown was more successful. the effectiveness of control strategies can be measured by the basic reproductive ratio r . the parameters which can practically reduce r are the contact coefficients, α and the rate of quarantine of infected individuals, δ i . social distancing works well at reducing interpersonal contact, but we can see that implementation issues can severely damage its effectiveness. by sufficiently increasing the number of tests carried out, we can identify and quarantine infected individuals more quickly, thus indirectly increasing δ i . this means that infected individuals would have a lower probability of infecting a susceptible individual. on the other hand, testing rates are limited by the medical resources of each country. while south korea has managed to test a large fraction of their population, in countries with very large populations such as india, randomized testing for the entire population is not feasible. hence, we suggest an age-group-targeted testing initiative, where the age groups with the largest number of infected individuals are targeted. in addition, economic activities have come to a halt during lockdown in india. barclays has estimated a loss of up to . billion usd in india [ ] . practically, it may not be possible to continue a complete lockdown indefinitely. only a multipronged approach can successfully combat an outbreak of infectious disease. though we have not provided any medical insights, they should go hand in hand with the strategies we propose here. we discuss two strategies below. . keeping in mind that individuals in the age group - years are most likely to catch infection, we emphasize testing more people from this age group rather than randomized testing. this will help in isolating infected people and restrict their disease transmission. the impact of such a strategy is evident from the curves in fig. . the corresponding change in r is illustrated in fig. b . we see that although r has not dropped below , our strategy offers a significant improvement. for this simulation, we have increased the value of δ i for the targeted age group - years, which corresponds to i ∈ { , , , , } ( table ). the initial population sizes of these age groups are shown in table . we have assumed that infected members of these groups can proceed to quarantine in . days, on average. for the remaining groups, we increase the detection period to . days. concentrating testing on groups most likely to have infected members helps bring them out of contact with the susceptible population and hence flatten the infection curves. this in turn lowers the peak number of critical cases, thus distributing the workload of medical facilities over a longer period of time. the peak is also observed far later than with normal rates of testing, although normalcy is restored not much later. . we suggest that a complete lockdown, followed by lockdowns in selected regions, is more effective than the reverse. as symptoms take time to manifest, infection can spread very rapidly to areas not under sufficient lockdown. however, if the majority of infected individuals can by identified and isolated by testing during the lockdown period, subsequent lockdowns can target those areas with larger infected populations. this would effectively reduce disease transmission across a country. we suggest that introducing a lockdown in slow phases, as was done in italy and usa, may not have been as effective as a complete lockdown introduced in the early stages of the pandemic. however, we do acknowledge differences in the socio-economic structures and dynamics of different countries, which demand differential strategies tailored individually to their underlying structures. our model is ill equipped to model lockdowns in selected regions, but we have approximated this effect with reduced contact coefficients α. our model of covid- dynamics allows us to make some useful predictions and modify pre-existing strategies to obtain better results. this model has been tuned with available data of social contact matrices and reported deaths and infected individuals available till april . methods of testing and social distancing are known to tackle this kind of situation. in the context of this novel disease, we have re-examined these methods. it must be noted that in our model, we have interpreted the number of reported cases as the number of symptomatic or tested cases, and we assume that they are transferred to quarantine as soon as they are confirmed positive. the actual number of covid- cases is much higher than reported, which is consistent with the nature of the reported infection curve. we must note that as of april , india has conducted , , tests. this is a major step up from the initial , tests before the declaration of lockdown. at this milestone of tests, india has recorded around , positive cases, as opposed to usa's , , and italy's , cases [ ] . india has also observed a comparatively lower mortality rate. this can be explained by her disproportionately young population, together with the low rate of infection and transmission in the younger age groups. the mean age of india's population is . , compared to usa's . and italy's . [ ] . we acknowledge that there are uncertainties in determining the model parameters due to unavailability of proper data and that this may lead to incorrect predictions. we note that the use of mortality data is partially motivated by the fact that such figures are more likely to be reliable, as opposed to infection numbers which suffer from under-reporting. the choice of a single transmission coefficient β across all age groups is because of the lack of age-group-specific estimates on transmission probabilities, as well as the complexity of fitting such coefficients for each of the age groups even if available. similarly, disease-induced mortality rates across the infected (both symptomatic and asymptomatic) and quarantined populations have been assumed to be the same, μ. while these rates may indeed differ among these groups in reality since severe cases are frequently quarantined, we justify this assumption with our simulation which closely mimics the trends in available data without introducing additional parameters. furthermore, we emphasize, again because of these reasons, that factors such as agedependent immunity have not been incorporated into our model, and the coefficients λ i merely reflect normalized amounts of contact between age classes. our initial conditions i i ( ) = q i ( ), which reflect the assumption that half of the cases are reported, may be adjusted with better estimates of the fraction of reported cases. the assumption that births, natural deaths and aging are absent is valid only over relatively short periods of time. we have also focused on the population below years of age, as the rest of the population is significantly small. with these assumptions, we can clearly say that our model can make short-term predictions, but cannot reliably make long-term forecasts. in this instance, we have run our simulation for a maximum time period of months. we also acknowledge that partial lockdowns of infection hot spots are not well modelled by our method, which considers a given region as a whole. with the availability of reliable data, we may be able to apply our model on smaller populations and make region-wise predictions. we also post-pone the application of targeted testing to other countries, such as usa and italy, for further study. through this study, we have offered a more efficient, country-specific covid- model for informing on strategies to contain the sars-cov- pandemic. our contribution of a new age-stratified model will aid government and health agencies and will spur further research in covd- modelling. the implications of our proposed work are timely as this is still an emerging situation in many countries and perhaps broad as well, as viral pandemics are predicted to keep re-emerging in the near future, perhaps in different shades or shapes. keeping in mind that all models are merely approximations of reality, we hope that this model can aid in developing policy, with economic and medical perspectives. here, we find the basic reproduction number using the next-generation method [ ] . we first linearize the system of equations ( ) at disease-free equilibrium, where hence, when the infected and quarantined populations are small, their dynamics are described by the following system. we collect the infected and quarantined compartments in the vector v = (i · · · i m q · · · q m ) t . we can thus rewrite the system ( ) in the form d we further break l = t − v , where the transmission matrix, t , represents the influx of newly infected individuals, and the transition matrix, v , represents the movement between the infected compartments. they are calculated numerically as follows: the basic reproductive number r = ρ(t v − ) is simply calculated as the spectral radius of the matrix t v − (table , fig. ). here, we list the parameters used in our numerical simulation (tables , and ). all population numbers are in millions covid- ) situation reports- a pneumonia outbreak associated with a new coronavirus of probable bat origin an age-structured model of pre-and postvaccination measles transmission the contribution of social behaviour to the transmission of influenza a in a human population clustering of contacts relevant to the spread of infectious disease contact network structure explains the changing epidemiology of pertussis surviving covid- nonlinear physiologicallystructured population models with two internal variables on first-order hyperbolic partial differential equations with two internal variables modeling population dynamics of two physiological structures modeling infectious diseases in humans and animals the incubation period of coronavirus disease (covid- ) from publicly reported confirmed cases: estimation and application who: report of the who-china joint mission on coronavirus disease projecting social contact matrices in countries using contact surveys and demographic data characteristics of pediatric sars-cov- infection and potential evidence for persistent fecal viral shedding scientists seek reason why coronavirus has less impact on children reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission key: cord- -b mzk p authors: pandit, nitin; vanak, abi t. title: artificial intelligence and one health: knowledge bases for causal modeling date: - - journal: j indian inst sci doi: . /s - - - sha: doc_id: cord_uid: b mzk p scientists all over the world are moving toward building database systems based on the one health concept to prevent and manage outbreaks of zoonotic diseases. an appreciation of the process of discovery with incomplete information and a recognition of the role of observations gathered painstakingly by scientists in the field shows that simple databases will not be sufficient to build causal models of the complex relationships between human health and ecosystems. rather, it is important also to build knowledge bases which complement databases using non-monotonic logic based artificial intelligence techniques, so that causal models can be improved as new, and sometimes contradictory, information is found from field studies. abstract | scientists all over the world are moving toward building database systems based on the one health concept to prevent and manage outbreaks of zoonotic diseases. an appreciation of the process of discovery with incomplete information and a recognition of the role of observations gathered painstakingly by scientists in the field shows that simple databases will not be sufficient to build causal models of the complex relationships between human health and ecosystems. rather, it is important also to build knowledge bases which complement databases using non-monotonic logic based artificial intelligence techniques, so that causal models can be improved as new, and sometimes contradictory, information is found from field studies. been designed to support researchers and interested citizens in collection and collation of biodiversity related data sets. concurrently, many other systems for biodiversity data have been created around the world, such as gbif , with applications ranging from species identification to reintroduction . modern algorithms using big data driven machine learning (ml) and neural networks (nn) , coupled with sensors with new capabilities such as bioacoustics and analytical approaches such as genomics , are used to complement traditional approaches of biodiversity conservation in situ and in vivo. meanwhile, data and models about human health are also becoming increasingly complex, as medical discoveries utilize new computation assisted approaches for health management from prevention to cure for the human body . in fact, biomedical technologies for curing human health ailments are being projected as the next frontier of growth for the global economy toward an ageless generation . looking to quickly tide over this global emergency, the medical community has been spurred on to develop a vaccine to protect the public and reduce individual risk. whereas a vaccine from the best minds in biomedical research will be welcomed by one and all, public health and biodiversity experts are now under pressure to speed up their work on preventive approaches which include early warning systems, delaying and hopefully even preventing such outbreaks, and if it occurs, better management of such outbreaks. the existing surveillance apparatus rightly concentrates on early outbreak detection among people, and includes containment and response. while new standards for interoperability are being adopted in india for clinical health of individuals, standards are silent about including causal information, such as wild and domestic animal surveillance for understanding the dynamics of the pathogen-host cycles between outbreaks. such long-term longitudinal surveillance provides insight into disease burden and helps detect possible predictable patterns in outbreaks at a much lower economic cost than responding after the pathogens emerge . in an attempt to create an integrated mechanism for surveillance, detection and treatment of such zoonoses, a multi-disciplinary engagement in the form of the roadmap to combat zoonoses in india (rczi) initiative was established in . the rczi had identified key thrust areas and provided several strategies for research and action. yet, largescale and long-term integrated surveillance, involving human, veterinary and wildlife monitoring have failed to materialise . as a consequence, we still lag in our understanding of the burden and dynamics of emerging and reemerging infectious diseases (erid). the indian government's integrated disease surveillance project (idsp), launched in , sought to establish a decentralised staterun india-wide surveillance programme. this programme began with the establishment of surveillance units at the district level, led by a district surveillance officer and a rapid response team to respond to outbreaks. the idsp has generated clear information flow on outbreaks of conditions and publishes periodic reports of outbreaks on their website . while the outbreak detection and rapid response functions are taken care of by the idsp, the programme is unable to integrate human and animal (livestock and wildlife) surveillance. this is not surprising given that the idsp is structured within the department of health and thus, there is limited scope for convergence with other departments. independent evaluations of the idsp have pointed out the need for its strengthening and have identified key limitations in achievement of timely outbreak detection and proactive monitoring of erids . an integrated human and animal surveillance system that collects primary data on disease parameters from people, livestock and wildlife is needed as it will improve our understanding of the dynamics of erids and as well as our response (both locally and also policies). globally, there are increasing demands for the establishment of responsive and scientifically sound surveillance systems to better understand the connections between deforestation, wildlife, and pandemic risk and, possibly to predict outbreaks and the spread of erids. recent reviews of surveillance systems have recognized that these need to be strengthened in developing countries. there is also moderate evidence to suggest that most efforts in strengthening response to zoonoses have been focused on "laboratory capacity and technical training, with relatively little attention given to the collection of field data, particularly at the interface between human and livestock populations" . health the biomedical profession is developing advanced algorithms using machine learning and neural networks to derive hypotheses with strong correlations to enable drug discovery for medicines and vaccines to address human health . the health industry has been captivated by cost savings through efficient transactions and better diagnostic outcomes through the use of artificial intelligence (ai) techniques . in fact, current systems of medical informatics focus on human biology only, with most of the research efforts evolving to solve health problems of the individual . even in the developed health care systems in the west, the vision of future medical systems does not include much about zoonotic diseases . some ai techniques are being used to further derive correlations using large data sets for individual human-centric medicine . meanwhile, there is much to be done to develop proactive, in silico models of one health for public health related applications for prevention and management of outbreaks. when causal models of outbreaks are known, j. indian inst. sci. | vol xxx:x | xxx-xxx | journal.iisc.ernet.in e.g., free-ranging dogs causing zoonotic diseases, targeted management approaches can be designed using modern tools such as agentbased modeling . however, the main difficulty with developing in silico causal models of one health are founded on the lack of data which can help us characterize the ecosystem of pathogens in which the human is simply one actor, who we tend to focus on. scientists are calling for the nmbh to create a decentralized, national system of surveillance of zoonotic disease outbreaks which also will collate data about ecosystems and biodiversity, since it is their degradation due to human actions which leads to erids. but is that enough? in fact, modeling such complex ecosystems requires us to understand the myriad behavioral patterns of pathogens and other actors who possess different contextual mechanisms of problem solving intelligence best described in the "ants on a beach" parable in herbert simon's classic book, sciences of the artificial, . it is, therefore, quite understandable that research in one health calls for decades long, painstaking, and heroic efforts to discover causal linkages which can provide sufficient data for deriving correlations with confidence , and which then can be used as predictive causal models. surveillance databases need to be coupled with such causal models in the form of knowledge bases to create useful artifacts, i.e., in silico models of one health. the one health system for data management is a necessary and immediate requirement to enhance our understanding and for rapid response to outbreaks. when such a data management system is available and continually updated, and if we know a well founded causal "law of nature", we can deduce conclusions from observations. for example: causal law: if all < humans with ixodes tick bites in the us > have < lyme disease > . observation: < arundhati > is a < human with ixodes tick bite in the us > . deduction: then < arundhati > has < lyme disease > . deductive rules are represented by the famous syllogism that: causal law: if all < men > are < mortal > . observation: < socrates > is a < man > . deduction: then < socrates > is < mortal > . however, the complexity of ecosystems and zoonotic diseases rarely present such simple situations for the application of rules of deductive logic. definitive causal laws of nature simply are not established or well founded. therefore, the analytical approach will still be reactive in nature and largely dependent on correlations between observations and hypotheses generated by the integration of knowledge from the diverse disciplines such as public health, epidemiology, and biodiversity. the research question is whether knowledge from disparate sources can be captured and utilized to create causal models which, in turn, are capable of generating hypotheses for a proactive response to erids. recent developments in ml and nn have proliferated in the data analytics community to solve many complex problems. similar to traditional time series forecasting methods, ml and nn algorithms work well when there is no dearth of data . some slight variations in the applications of such algorithms also allow for "learning" and deriving models that fit reality to an acceptable degree . in fact, all such more or less statistical methods allow for deriving causal models from large datasets for which virologists created the metaphor in fig. the rules of inductive logic are not as automatically applicable as the rules of deductive logic. however, when one has statistically representative datasets of the population, inductive rules can enable low-risk reasoning with some predictive capabilities. history is replete with stories of poor, inductive reasoning leading to beliefs which were difficult to revise. galileo would have agreed. perhaps the most interesting case of reasoning for problem solving arises when there is paucity of data. in such cases, problem solving requires that we make hypotheses and test them as we obtain more information. the painstaking gathering of information, leading to incrementally improving hypotheses leads scientists to causal models such as the one developed by scientists working on kfd. the causal models, often represented as directed graphs, show the current state of knowledge based on whatever information is available. that is: causal law: if all < migratory birds from russia > have < encephalitis > . observation: < kfd > has same origins as < encephalitis > . abduction: then < kfd > will be in < migratory birds from russia > . but, < kfd > could be indigenous! and, in fact, this was the logic that was used in the quest to find kfd, and found to be an erroneous assumption. abductive rules are represented by the famous syllogism that: causal law: if all < men > are < mortal > . observation: < socrates > is < mortal > . abduction: then < socrates > is a < man > . but < socrates > could be a dog! abductive reasoning carries significant risk, and can lead to dangerous assumptions which can have subsequent knock-on effects. furthermore, such hypothetical models carry the inherent risk of being disproved when additional information conflicts with the information gathered to date. the scientific method essentially incorporates such "abductive" reasoning based on hypothesis testing, and it was in full display in the mystery of the kfd outbreaks which re-emerged after half a century as an erid in india. abductive reasoning was applied to develop hypotheses that small mammals on the forest floor could be the reservoirs for kfd and yet again, was proven wrong. through a process of hypothesis testing, causal chains such as 'small mammal-haemaphysalis-small mammal' chain, the 'small mammal-ixodes-small mammal' chain, and 'small mammal-haemaphysalismonkey' chain were all eliminated. before the development of data intense techniques like ml and nn, the science of ai cultivated sophisticated methods to enable building artifacts, i.e., in silico problem solving knowledge bases to emulate such reasoning and support incremental development of causal models. the current causal model (fig. ) for the reemergence of kfd was traced to human interventions which reduce biodiversity and provide opportunities for the virus to infest species that they otherwise may not have. the important lesson from the kfd story is that for different types of reasoning to be applied, it is important to develop tools which go beyond simple databases to store and retrieve datasets. it will be important to develop statistical approaches to enable the use of large datasets. but more realistically, it will be important to assist the ecologists, field biologists, epidemiologists, and other scientists with systems which can represent the current state of knowledge, that can be changed as more information is obtained to consolidate and revise the best known models of the time. models based on incomplete information can be dangerous. they can set up societal trends that can influence societies in good and bad ways . as the world responds to the covid- crisis with emphasis on health financing , it would behoove us to invest in technologies that actually assist one health scientists in building not only databases, but also their knowledge bases toward prevention and management of zoonotic diseases. investment in developing such comprehensive artifacts for one health is the need of the day. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. received: august accepted: september j. indian inst. sci. | vol xxx:x | xxx-xxx | journal.iisc.ernet.in nitin pandit is the director of the ashoka trust for research in ecology and environment (atree) in bangalore, india. previously, dr. nitin pandit was the director of priority initiatives at the world resources institute (wri) in washington, dc, usa, focusing on restoration and energy efficiency. prior to this assignment, he was the ceo of wri india and led wri's work in india. he was responsible for formulating and implementing wri india's strategy, including a new program in the restoration of degraded lands. before wri, nitin was president of international institute for energy conservation (iiec), with offices and programs in a dozen countries, for implementing novel sustainable energy approaches for developing countries, such as market transformation, energy-efficient buildings, and demand-side management using renewable energy hybrids and energy efficiency improvement. in the s, nitin formed a boutique high-tech consultancy specializing in artificial intelligence (ai) applications in environmental and renewable energy systems. using ai, he developed tools and solutions for integrated "closed-loop" systems of water, energy, and materials, synoptic climatology, air pollution, and nonpoint source pollution. in the s, nitin worked with reputed consulting firms in the areas of pollution prevention and waste management, geohydrology and geotechnical construction, and water resources engineering. nitin has a bachelors and couple of masters' degrees in engineering, and a doctorate in public policy. abi t. vanak is a senior fellow (associate professor), and convener of the centre for biodiversity and conservation with the ashoka trust for research in ecology and the environment (atree). he is also a fellow of the dbt/wellcome trust india alliance clinical and public health program. his research areas include animal movement ecology, disease ecology, one-health, savanna ecosystems, invasive species and wildlife in human-dominated systems. much of his research work focuses on the outcome of interactions between species at the interface of humans, domestic animals and wildlife in semi-arid savannas and agro-ecosystems. under onehealth systems and disease ecology, he studies dynamics of rabies transmission in multi-host systems and the role of small and medium mammals in the transmission dynamics of kyasanur forest disease. abi vanak has a master's in wildlife biology from the wildlife institute of india and a ph. d. in wildlife science from the university of missouri. current causal model for kfd (credit: ita mehrotra -model ling-the-chall enges -of-manag ing-free-rangi ngdog-popul ation s?commi t=bee e adbc a dbd c cf -at-antintel ligen ce-the-wrong -way- #:~:text=in% his % % boo k% c% the ,the% com plexi ty% in% the % ant . accessed date com/ -facts -about -time-serie s-forec astin g-that-surpr ise-exper ience d-machi ne-learn ing-pract ition ers- c ee . accessed date com/a-short -intro ducti onto-model -selec tion-bb bb c . accessed date /press relea sepag e.aspx?prid= . accessed date research options for controlling zoonotic disease in india integrating one health in national health policies of developing countries: india's lost opportunities key: cord- -qyxko authors: malani, a.; mohanan, m.; kumar, c.; kramer, j.; tandel, v. title: prevalence of sars-cov- among workers returning to bihar gives snapshot of covid across india date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: qyxko india has reported the fourth highest number of confirmed sars-cov- cases worldwide. because there is little community testing for covid, this case count is likely an underestimate. when india partially exited from lockdown on may , , millions of daily laborers left cities for their rural family homes. rna testing on a near-random sample of laborers returning to the state of bihar is used to estimate positive testing rate for covid across india for a -week period immediately following the initial lifting of india's lockdown. positive testing rates among returning laborers are only moderately correlated with, and % higher than, indian states' official reports, which are not based on random sampling. higher prevalence among returning laborers may also reflect greater covid spread in crowded poor communities such as slums. the burden of sars-cov- (covid) in india is high and rising. india has roughly the same population ( . billion ( )) as china, but already quadruple the number of cases. since it is the world's nd most populous country, it is unsurprising that india ranks th in number of cases and th in number of deaths reported as of june . yet these absolute numbers likely drastically undercount the burden: india ranks th in the world in testing rate, at , tests per million ( ) . there are no reliable and consistent estimates of the extent of the prevalence of infection across india. while india conducts testing in every state and territory, it is just beginning representative community testing ( ) . early efforts by the indian council of medical research (icmr) conflated prevalence among patients admitted for non-covid symptoms with community prevalence ( ) . moreover, most ongoing efforts to conduct community-level testing in india are serological, so they measure the share of population previously infected or recovered, rather than currently infected ( ) . the number of cases reported on a daily basis by the indian government comes from nonrepresentative rna testing. these data are products of testing policies and rates that vary across states and are hard to track, making interstate comparisons difficult ( ) . some states have implemented tight restrictions on which patients can be tested, doctors' ability to prescribe tests, and the number of labs that are permitted to conduct testing ( , ) . here, we rely on a unique dataset of rna tests conducted on , workers from around the country who returned to their home state of bihar between may -june , , to provide a snapshot of covid burden across india. in the aftermath of the lockdown and ensuing job losses, india experienced a large flight of daily laborers (hereafter workers) migrating from urban areas back to their familial home states ( ) . bihar (population million) received roughly . million such workers between may and june (supplement table ). bihar implemented a testing program that included a random sampling of returning workers. combining data from this testing with demographic information on the returning workers, we present information on the prevalence of covid in states across india, compare these positive test rates with those reported by the states, and report positive test rates by demographic group. india's first confirmed covid case, on january , , was a student who had returned home to kerala state from wuhan, china. other states had introductions by foreign travelers who had visited other countries. the first recorded introduction in bihar was on march , , by a traveler from qatar. after imposing a series of increasingly strict travel restrictions, india . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint imposed a nation-wide lockdown on march , . it was one of the most stringent lockdowns worldwide: mobility to workplaces and retail fell % and %, respectively ( ). india has nearly million persons who work in one state, but regularly return to their rural homes in another ( ) . the lockdown was imposed hours after it was announced and barred travel between districts, so many workers were unable to return to their rural homes. many wanted to return home, as the lockdown prohibited work opportunities, especially in cities, which had a higher burden of covid cases. on may , india announced a partial release from lockdown, allowing workers to return to their out-of-state homes with the consent of destination states ( ). reverse migration surged to over million persons within a few weeks ( ) . roughly . million workers were expected to return to bihar ( ) . we study the rate at which workers returning to bihar tested positive for covid during a day period from may -june , . between may and ("period "), bihar imposed a -day quarantine in government facilities on all returning workers. the government's policy was to test all symptomatic workers, and randomly test the remaining workers, with a heavier weight on pregnant women, children under age , and elderly above ( ) . between may and ("period "), bihar focused its institutional quarantine policy on workers from a few cities that were believed to have higher rates of infections: the national capital region (ncr) around new delhi, mumbai and pune in maharashtra, surat and ahmedabad in gujarat, kolkata in west bengal, and bengaluru in karnataka. for these workers, the testing policy remained the same as in period . all remaining workers were placed under -day home quarantine. they, or the members of their household, were tested only if they were symptomatic. from june to ("period "), bihar continued its quarantine policy from period . it tested workers in government quarantine as in period . for workers in home quarantine, bihar switched to random testing of workers regardless of symptoms or demographics. returning workers were typically tested within days of arriving in the state (supplementary figure ) . initially, screening tests were conducted using truenat machines; positive samples were confirmed by rt-pcr ( ) . the sensitivity and specificity of truenat machines are % according to the manufacturer ( ) . after that was confirmed in a validation test on may , , ( ) , the indian council of medical research stopped requiring rt-pcr confirmation ( ) . therefore, we assume that the positive test rate measures covid prevalence. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint the data have information on the workers' state of origin, age, and sex. test results are aggregated from daily data up to roughly week intervals, because there is a great deal of daily variation in the states from which workers arrive. the exact intervals correspond to periods during which testing policy is constant. for between-state comparisons, we drop states with less than tests due to lack of precision. to address concerns that the testing rate may indirectly be a function of disease status, i.e., selection bias, or that sampling weights are unknown, we do two things. first, we focus on subsamples, e.g., adult males, who were both selected at random and weighted equally in selection (supplement table a ). second, we estimate nonparametric bounds on prevalence, a method known as partial identification ( ) (supplement table b ). lower and upper bounds assume all non-tested persons are uninfected and infected, respectively. such upper bounds are uninformative because testing rates are so low ( ) . therefore, we only present lower bounds. testing rate. of the . million workers who returned to bihar from the origin states that met our inclusion criteria during all periods in our study (table ) , , were tested (supplement table ), yielding an overall testing rate of . %. this is higher than the average official testing rate of . %, defined as the number of tests conducted by an origin state on their residents divided by that state's population (supplement table ). the number of tests conducted on returning workers was fairly constant at , per day. the ostensible rate at which workers were tested declined in period and jumped in period , mainly because the number of workers per day increased in period and then collapsed in period . moreover, period is nearly twice as long ( v. days) as later periods. prevalence among returning workers. prevalence of covid was . % among returning workers in period ( table ). this rate rose (p< . ) to % in period and then declined (p< . ) to . % in period . overall, the rate increased % during the duration of the study. these overall changes mask substantial variation in changes across states. in period , workers returning from delhi ( . %), maharashtra ( . %), and west bengal ( . %), had the highest prevalence (table ). since these workers were largely employed in cities, these numbers likely reflect prevalence among the poor in urban centers such as new delhi, mumbai, pune and kolkata. in period , prevalence remained high in workers from delhi ( . %) and maharashtra ( . %), though the latter now had the highest rate. however, haryana ( . %) and uttar pradesh ( . %) had higher rates than west bengal ( . %) in this period. growth was largest in uttar . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint pradesh (+ . %) and maharashtra (+ . %), while rates fell most in west bengal (- . %) and jammu and kashmir (- . %). notwithstanding these changes, the within-state correlation between the positive rate in the two periods is . (p<. ). in period , prevalence was highest in workers from delhi ( . %), haryana ( . %) and uttar pradesh ( . %). workers from most states experienced declines in prevalence from period , with the largest, significant declines associated with maharashtra (- . %), uttar pradesh ( . %) and delhi (- . %). the correlation between prevalence in periods and is high ( = . p<. ). comparison with state testing results. the positive test rate observed among returning workers is moderately correlated with the positive test rates measured by workers' origin states ( = . , p< . ). however, the positive rate among workers returning to bihar was on average percentage point (pp) ( %) higher than the prevalence reported by the origin state's testing data across the periods. moreover, there is variation in the discrepancy between these two measures of covid burden. part of the variation is temporal. while positive rates rose gradually in the data from states, it rose and then fell among returning workers. part of the variation is geographic. the discrepancy is widest in maharashtra ( . pp), haryana ( . pp), and uttar pradesh ( . pp) and lowest in delhi ( pp), madhya pradesh ( . pp), and odisha ( . pp). a challenge with making state-wise comparisons using official data is that states adopted varying testing policies with large differences in testing rates (supplement table ) and composition of individuals tested. this is somewhat mitigated when using data from returning workers because all testing was done under a common testing policy by bihar. however, even the representativeness of bihar's testing may be questioned because the state had different sampling weights for symptomatic persons; pregnant women, children and the elderly; and remaining persons. moreover, the state did not estimate the number of migrants in each health and demographic bin, so sampling weights cannot be computed. to address sampling bias, supplement table a presents the prevalence for different groups of workers (symptomatic workers, non-symptomatic workers, non-child and non-elderly men). the correlation between prevalence in these subgroups and overall prevalence among workers was quite high (versus prevalence for whole sample all periods: = . , p< . for symptomatic; = . , p< . for non-symptomatic; = . , p< . for men ages to ). the supplement also presents a lower bound on the positive rate for both data from origin states and from workers returning to bihar (supplement table b ). the lower bounds for delhi and maharashtra workers remain the highest among states across all periods. however, the . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint correlation between lower bounds based on states' own testing and tests of returning workers across all periods is weak ( = . , p= . ). prevalence by demographic group. prevalence was lowest among girls under (table ) , who had significantly lower rates than any group other than adult women (supplement table ). prevalence was highest among elderly and non-elderly men, though only the differences between these two groups and children (of both sexes) were significant. comparison with states' data. while prevalence among workers returning to bihar was moderately correlated with the positive test rate reported by origin states, there are important differences. one is that, while the positive test rate rose gradually in state reports, it rose and then fell in data on returning workers. it is possible that changes in bihar's testing policy or the composition of returning workers explains the discrepancy. however, the non-uniform changes in prevalence among workers from different states suggest that bihar's testing policy, which is largely uniform, is not responsible. moreover, the variable changes in prevalence over time among workers across states suggest that selection of workers is not the explanation. an alternative explanation for the discrepancy is that data on returning workers may be more representative than state data of the non-monotonic patterns in prevalence common in epidemics. a national epidemic is a sum of local epidemics ( ) . the data on workers is compatible with this view. external validity. returning workers may not be representative of the entire state or city population. these workers, often daily laborers, tend to be less wealthy as measured by consumption (cite). they likely live in more dense communities ( ) , which may increase covid transmission. however, workers in our sample are likely to be representative of poor communities in their origin cities. testing was unlikely to detect infections that the workers acquired on the crowded trains used to transport workers home ( ) . train journeys were less than day and bihar tested most returning workers within days of arrival. rt-pcr does not yield positive results within days of infection ( ) . imperfect sensitivity. given indian council of medical research's validation of bihar's testing procedure, we equate positive test results with prevalence. however, imperfect specimen collection could lead to lower sensitivity than rates estimated in a lab setting ( ) , which would lead to an underestimation of infection rates unfortunately, it is difficult to estimate the impact . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint of imperfect specimen collection on sensitivity. if it were possible, one would adjust prevalence upwards using standard formulas ( ) . the analysis here suggests that random testing of travellers may be a useful method of national surveillance when there is variability in local testing protocols and rates. moreover, to ensure prevalence is correctly estimated, backchecks should be conducted by experienced technicians to determine if sensitivity of testing in the field corresponds to that in the lab. finally, our results suggest that poor communities in india may have higher prevalence of covid than suggested by official statistics, perhaps due to crowding in their densely populated communities. these communities may require extra attention and support in infection control policies. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint table . difference between positive test rates among returning workers and among residents of state, by state or territory of origin and period. notes. statistics for states from which testing results are not available are marked as missing. for some states, the dates for test result data do not correspond exactly to the dates of each of the periods; in those cases, we take data for the closest period corresponding to each of the periods. state-reported positive rate is the number of confirmed cases reported by a state divided by the number of tests conducted by that state during the relevant time period. asterisks (*/**/***) are used to mark statistical significance (at the / / % level). . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint united nations department of economic and social affairs population division covid- coronavirus pandemic icmr to test for community transmission in districts severe acute respiratory illness surveillance for coronavirus disease icmr to check for community spread everything you wanted to know about india's test numbers, in five charts hindustan times testing is key to fighting coronavirus -so why does india have such a low testing rate? millions of indians are fleeing cities, raising fears of a coronavirus 'land mine' in villages covid- community mobility report -india may -mobility changes covid- : expected migrant movement as lockdown eases first batch of stranded migrant workers arrive in bihar on special train directions for random testing performance evaluation of truenattm sars cov- test on truelabtm workstation: validation report revised guidelines for truenat testing for covid- econometrics with partial identification. the handbook of economet estimating the covid- infection rate: anatomy of an inference problem multiple peaks patterns of epidemic spreading in multi-layer networks real-time rt-pcr in covid- detection: issues affecting the results estimating false-negative detection rate of sars-cov- by rt-pcr. medrxiv estimating prevalence from the results of a screening test key: cord- -eoabmyg authors: nicoletti, marcello title: new solutions using natural products date: - - journal: insect-borne diseases in the st century doi: . /b - - - - . - sha: doc_id: cord_uid: eoabmyg most antibiotics are derived from natural products, like penicillin, as well as recent insecticides, like pyrethroids. secondary metabolites are produced by plants as ecological chemical mediators, and can therefore possess intrinsic physiological properties against other organisms. these benefits are far from being fully explored. in particular, attention is here focused on the multipurpose neem tree (azadirachta indica), reporting several experiments of applications in the field of seed oil and neem cake. the latter product seems to be promising because of the low cost, the possible production on a large scale, and the selection of effects in favor of beneficial organisms. neem cake is able to act on different sites, as required by integrated pest management. several utilizations of neem products are reported and their potentiality evidenced. some considerations in this chapter may appear distant from the title of the book, but only by applying the general natural rules can the reason of the single phenomenon be understood. other studies on resistance mechanisms of plasmodium are enabling new possible methods of control always based on natural products activity. and biotic targets, which are important to the individual homeostasis and survival. one form of evidence in accordance with this interpretation is the strong correlation between natural products' producers and biodiversity, therefore indicating a matter of adaptation. however, it is possible to argue that if differences can characterize each organism from another, the some is not true in case of a molecule. once determined the structure, a molecule is a molecule, even if generated by the metabolism or by a synthetic route, and therefore the living rules cannot be applied to the molecular world. this is true only in part. we must consider, in particular for natural products, the conformational forms, which are different ways of the same molecule to react. an organic molecule can change easily its d structure adapting to the environmental needs, like we open and close our hands. furthermore, once inside the metabolism, the molecule, even if inorganic, is integrated in the organic network and it is forced to collaborate to an integrated living system. the cell environment is far different from the test tube of the chemist. in practice, the molecule is simply part of an advanced complex integrated dynamic system, limiting its freedom. beside the consideration that physical forces work in the same way in the assembling matter, as we can know and distinguish a giraffe from a wizard, we can study natural compounds and distinguish them on basis of the structures and assign their place and role. about the role, we must remember that natural products are chemical mediators inside the environment, meaning that they must act on the receptor of the target organisms. therefore, the structures of natural products are derived from their activity, the same argument we use in the consideration of a pharmacological drug. here, the importance of natural products inspiring all the molecules tailored to affect living organisms. in particular, among the detected activities in plant species, the defensive against herbivorous is highly reported. plants cannot counteract by movements like animals and therefore an arsenal of chemical weapons is essential in their fight for survival. therefore, it is highly possible to find natural products toxic or repellent to phytophagous, like insects, as well as active constituents against pathogens. natural products with such properties should be extracted and found in the complex and confused reservoir of secondary metabolites, but the presence into the plant is not sufficient. it is necessary to realize the mechanism of action and the potentiality to be used as marketed products. therefore, the pathway should comprehend the discovery, the isolation, the sources, the bioactivities, and the possibility to be obtained in high quantity, the method of utilization, the environmental impact and the cost of production. the natural products have been already reported for antibiotic activity. in particular, essential oils and phenols are stated in many papers as being responsible of antibacterial and insecticide properties (ghosh et al., ; gibbons, ) . however, the activity seems to be too general. most essential oils are composed of the same main constituents, the difference being mainly quantitative for each compound or hidden deeply inside the plethora of secondary constituents. furthermore, excluding the phenols typical of essential oils, the quantity of known phenols is very large and complicated, with thousands of structures reported and different activities connected. therefore, special research must be performed, including the possibility to test new substances never reported. among secondary natural products with insecticide activity, a special place must be assigned to essential oils. in this regard, several papers report the utilization of essential oils as the active ingredient against pests. the antimicrobial activity of essential oils is also well-reported and evident in nature. several plants accumulate essential oils in the inner parts of roots and rhizomes, in order to avoid the devastating attack of micropathogens, wherein the plant often accumulates precious reserve substances. in other cases, the aerial parts are focused on defensive or cooperative actions. some birds defend their clutch by surrounding the nest with aromatic plants. the human utilization of essential oils of different kinds against insects has a long story. herodotus reported the use in ancient egypt of mosquito nets and towers impregnated with fish odor to avoid mosquito bites. an essential oil is a complex chemical mixture of substances volatile at ordinary temperature (figs. . and . ), and therefore the constituents must have low molecular weight. in other words, they are micromolecules, with average molecular weight of - uma and hydrocarbon prevalence. essential oils can be extracted from the raw materials by utilizing their volatile properties, such as in the steam distillation method. the antimicrobial activity of essential oils is usually a consequence of the content of phenols, but other properties must be considered. on the basis of the structures of the active constituents, there are two types of essential oils. the first one, mainly present in less advanced angiosperm dicotyledons, like magnolidae, contains mainly root and fruit drugs rich in simple phenolic phenylpropanoids, which are mainly utilized by the plant in protection of pathogens. in rosidae and sympetalae, the terpenoids progressively become predominant. the new volatile constituents, in addition to the protective and toxic effects, afford a positive attraction on pollinatory agents, evidencing the plant position and allowing a memory of the selected species. in this way, the scenario of the interaction between animals and plants changes from defensive to collaborative. the new plants to be selected and appreciated can enrich the offer to the collaborative animals fig. . a typical current apparatus for the production of essential oils by steam distillation. with fruits of inebriant flavors, colored flowers and other nice experiences. therefore, utilized essential oils are mainly complex mixtures of volatile plant secondary metabolism and consist mainly of monoterpenes and sesquiterpenes, which means lipid secondary metabolites, and, to a lesser extent, of aromatic compounds. the choice of essential oil depends firstly on the taxonomy of the selected plant and the effects depend on the nature of the constituents of the essential oil. the conclusion, based also on direct experiments, is the presence of a general antibiotic and insecticide activity; however, another real need is a selective toxicity in favor of the useful organisms. therefore, some kind of activity is expected for an essential oil, but there is a necessity to maximize its effectiveness. they are exploited in several fields, such as perfumery, food, pharmaceutics, and cosmetics, but essential oils have also long-standing uses in the treatment of infectious diseases and parasitosis in humans and animals. essential oils, currently more than of which are known, are highly variable in their complex composition. usually, at least a mixture of more than main different constituents of low molecular weight is present. among the single species, the qualitative composition of the essential oil is respected, although a quantitative variability is common between population according to the environmental pressures. however, some terpenes can be easily found, like the hydrocarbons (myrcene, pinene, terpinene, limonene, cymene, αand β-phellandrene) and the oxygenated ones, like the alcohols (geraniol, linalool, menthol, terpineol, borneol) , the aldehydes (citral, citronellal), ketones (menthone, pulegone, carvone), bicyclic monoterpene ketones (thujone, verbenone, fenchone), acids (citronellic acid, cinnamic acid), oxides ( , -cineole) and esters (linalyl acetate), but the aromatic phenols (carvacrol, thymol, safrole, eugenol) are also common. a few essential oils may also contain sulfur-containing constituents, methyl anthranilate, coumarins, and special sesquiterpenes such as zingiberene, curcumin, farnesol, sesquiphellandrene, turmerone, nerolidol, etc. often these components are at low concentrations (less than % each), but the opposite is also possible, with major compounds that can represent up to % of the total volume of oil, as much as % like eucalyptol in eucalyptus or limonene in citrus or pinenes in turpentine of pinus. therefore, the antiparasitic activity of an essential oil can vary according to differences in its chemical composition, but it is usually present. nowadays, there is an increasing interest in the utilization of essential oils against endoparasites and ectoparasites of animals and humans, in particular when they are resistant to conventional drugs. however, the use of essential oils is in general restricted for the high cost and considering that usually they are not adequately specified for the considered target (bagavan and rahuman, ; shaalan et al., ; tikar et al., ) . again, also in the case of essential oils, the insurgence of the insecticide resistance must be considered (brown, ) , although usually less common in these cases. therefore, in consideration of their general but also weaker effectiveness of essential oils in comparison with synthetic insecticides, their utilization requires the insecticidal properties of essential oils to be investigated in different approaches of selection of the studied plants and their uses. some examples of researches, in which i had occasion to participate, involving essential oils in insect-borne diseases are reported here. the leading idea was to utilize the essential oil properties in an innovative way, such as in mixture or selected types. in (benelli et al., a,b) , the activities of five essential oils were investigated. the essential oils were obtained from different plants: pinus nigra var. italica (pinaceae), hyssopus officinalis subsp. aristatus (lamiaceae), satureja montana subsp. montana (lamiaceae), aloysia citriodora (verbenaceae), and pelargonium graveolens (geraniaceae) against culex quinquefasciatus (diptera: culicidae), which is a vector of lymphatic filariasis and of dangerous arboviral diseases, such as west nile and st. louis encephalitis. the research was original in its focus on the potential synergistic and antagonistic effects, testing them in binary mixtures on c. quinquefasciatus larvae. mixtures of essential oils are very easy to obtain, since the constituents are perfectly soluble in the final solution and the selected oils were cheap and easy to find on the market. in such a way, knowing the composition, it is possible to combine constituents, enhancing the range and the quality of activity. the pool of the investigated species was highly varied, but this was considered a positive factor. first, the chemical composition of each essential oil was investigated by gc-ms analysis, which is the best analytic method in such mixtures of volatile compounds. therefore, it was also necessary to test the activity of each essential oil and later to try the best combination on the basis of its effectiveness. the highest effectiveness was obtained by s. montana subsp. montana essential oil (lc ¼ . μl l À ), followed by p. nigra var. italica (lc ¼ . μl l À ), and a. citriodora (lc ¼ . μl l À ). it was possible to obtain an enhancement of the larvicidal activity by preparing simple binary mixtures of essential oils (ratio : ), such as s. montana+a. citriodora, which showed higher larvicidal toxicity (lc ¼ . μl l À ). on the other hand, testing s. montana + p. nigra ( : ), an antagonistic effect was detected, leading to an lc ( . μl l À ) higher than the lc values calculated for the two oils tested separately. therefore, these results indicate the extreme need for innovation and imagination in natural products research, against many papers repeating the same procedure that change only the plant used. another work (pavela et al., a,b) was based on geographic distribution and the traditional use. six medicinal and aromatic plants-azadirachta indica (see later in this chapter), aframomum melegueta, aframomum daniellii, clausena anisata, dichrostachys cinerea, and echinops giganteus-have been traditionally used in cameroon to treat several disorders, including infections and parasitic diseases. the aim was to evaluate the activity of the essential oils of these plants against trypanosma brucei tc and determine their selectivity with balb/ t (mouse embryonic fibroblast cell line) cells as a reference. essential oils from a. indica, a. daniellii, and e. giganteus proved to be the most active ones, with half maximal inhibitory concentration (ic ) values of . , . , and . μg/ml, respectively. these essential oils were characterized by different chemical compounds, including monoterpenes and sesquiterpene hydrocarbons and oxygenated sesquiterpenes. some of their main components were assayed as well on t. brucei tc , and their effects were linked to those of essential oils. in this way, the research partially confirmed the ethnopharmacological indications, validating their traditional use and confirming the utility of popular information in the search for useful plants. the synergic action of binary mixtures of similar constituents of essential oils against larvae of the filariasis vector culex quinquefasciatus was also the inspiration behind research (benelli et al., a,b) on four apiaceae species: trachyspermum ammi, smyrnium olusatrum, pimpinella anisum, and helosciadium nodiflorum. initially, all the essential oils proved to be highly toxic to the larvae, but short-term exposure to both binary mixtures strongly reduced emergence rates, fertility, and natality of the c. quinquefasciatus that survived after the treatment at the larval stage. in addition, larvicidal acute toxicity of essential oils main constituents, i.e., germacrone, isofuranodiene, and (e)-anethole, were carried out, with lc being . mg l À , . mg l À , and . μl l À . the results demonstrated the promise of these essential oils and their constituents to develop cheap and effective mosquito larvicides. in another paper (pavela et al., b) published in the same year, the vector target was the same but the selection of the plant totally different, as endemic to madagascar. the reason is that in some parts of the world, there are interesting examples of endemic flora whose species could contain different essential oils and therefore different activity. for this reason, pharmaceutical companies often explore remote parts of amazonia or isolated zones in search of new active compounds. there were examples of exploitation of rare african rauwolfia species to obtain their indole alkaloids. working with endemic species is important considering that in many cases, populations are in limited numbers and at risk of extinction, and we need to identify their molecular treasure before they disappear. this was also the motivation for my trips to several parts of the world, focusing in particular on deserts and islands, in search of special plants. madagascar's fauna and flora are diverse and unique. when the unique gondwana continent braked up in several pieces, india started to move to asia living africa. however, a consistent block remained near to africa, becoming a great island, now known as madagascar. this happened more than million years ago. the isolation of madagascar gave rise to a particular case of biodiversity. this is the story of the beginning of madagascar, as far as we know. here, it is important to report that the island is characterized by at least seven very different habitats, each with different endemisms. the potentiality of cinnamosma madagascariensis, an endemic species widely present in the forests of madagascar, was reported to us thanks to the exceptional collaboration with professor philippe rasoanaivo, who had a deep knowledge of the flora of the island and their economic importance. this plant has important traditional uses ranging from management of dementia, epilepsy, and headache to malaria (rakotosaona et al., ) . few data have been reported about the chemical composition of its essential oils, and no studies have been published on its bioactivity against mosquitoes. once again, we first investigated the chemical composition of essential oils extracted from stem bark and leaves of the plant, and later their larvicidal potential against the filariasis vector culex quinquefasciatus. the reason was that when you have little information, you must consider that different parts of a plant can contain very different essential oils. in fact, gc-ms analysis revealed differences between the volatile profiles of leaves and bark oils. in the former, linalool ( . %), limonene ( . %), myrcene ( . %), and α-pinene ( . %) were the major constituents, while in the latter one, β-pinene ( . %), α-pinene ( . %), and limonene ( . %) were the most representative compounds. acute toxicity experiments conducted on larvae of the filariasis vector c. quinquefasciatus led to an lc of . and . μl l À for the bark and leaf essential oils, respectively. overall, cinnamosma madagascariensis bark and leaf essential oils against filariasis vectors proved to be promising, since they are effective at moderate doses. the insecticidal activity of the essential oil of another malagasy plant was also studied (benelli et al., ) . hazomalania voyronii is popularly known as hazomalana and its use to repel mosquitoes and resist against insect attacks has been handed down from generation to generation in madagascar. the property of the essential oils obtained from the stem wood, fresh and dry bark of h. voyronii were able to repel important mosquito vectors (aedes aegypti and culex quinquefasciatus). furthermore, the toxicity of the aforementioned essential oils was investigated by who on three insect species of agricultural and public health importance (cx. quinquefasciatus, musca domestica, and spodoptera littoralis), respectively, as well as the adequate topical application methods and compared with the commercial repellent n,n-diethyl-m-toluamide (deet). repellence assay revealed almost complete protection (> %) from both mosquito species for min when pure fresh bark essential oil was applied on the volunteers' arms, while deet % repelled more than % of the mosquitoes up to min from application. the research validated the traditional use of the bark essential oil to repel insects, although an extended-release formulation based on h. voyronii essential oils is needed to increase the repellent effect over time. furthermore, it evidenced the wide spectrum of insecticidal plants potentially useful in the fabrication of green repellents and insecticides useful to control mosquito vectors and agricultural pests, avoiding the utilization of synthetic products. another interesting study (benelli et al., b) was dedicated to helichrysum faradifani (asteraceae), which is a perennial endemic shrub growing in rocky and sandy places of madagascar. the ethnopharmacological about malagasy traditional medicine reports that this plant is used as a wound-healing agent, disinfectant, and for the treatment of syphilis, diarrhea, cough, and headache. the chemical composition of the essential oil distilled from the aerial parts of h. faradifani, and analyzed by gc-ms, evidenced that monoterpene hydrocarbons ( . %) were the major fraction of the essential oil, with bicyclic α-fenchene ( . %) being the predominant component. sesquiterpene hydrocarbons ( . %) were the second major group characterizing the oil, with γ-curcumene ( . %) being the most abundant component. its insecticidal activity was evaluated against second, third, and fourth instar larvae of the lymphatic filariasis vector culex quinquefasciatus by acute toxicity assays. the most sensitive were second instar (lc ¼ . μl l À ) larvae. for the third and fourth instar larvae, the estimated lc were . and . μl l À , respectively. finally, a different approach to volatile substances was performed, considering that smoke is often traditionally used against mosquitos (ansari and razdan, ) . therefore, the larvicidal, pupicidal, and smoke toxicity of senna occidentalis and ocimum basilicum leaf extracts against the malaria vector anopheles stephensi were evaluated (murugan et al., ) . in larvicidal and pupicidal experiments, s. occidentalis lc ranged from . (i instar larvae) to . ppm (pupae), and o. basilicum lc ranged from . (i instar larvae) to ppm (pupae). smoke toxicity experiments conducted against adults showed that s. occidentalis and o. basilicum coils evoked mortality rates comparable to the pyrethrin-based positive control ( %, %, and %, respectively). furthermore, the antiplasmodial activity of these plant extracts in antiplasmodial assays was evaluated against chloroquine (cq)-resistant (cq-r) and cq-sensitive (cq-s) strains of plasmodium falciparum. the s. occidentalis % inhibitory concentrations (ic ) were . μg ml À (cq-s) and . μg ml À (cq-r), while those for o. basilicum ic were . μg ml À (cq-s) and . μg ml À (cq-r). the high potentiality of the reported data must be considered. these smokes, as the essential oils, can be quite easily obtained in good quantity and low cost and therefore locally produced and directly utilized. this is important for countries with limited economic resources. the distribution of individuals in accordance with the boltzmann curve is the result of the current chemical-physical environmental pressure, concentrating the organisms of the species in the most adapted form. however, sooner or later situations are destined to change, and some of the individuals confined in the wings of the curve are ready to profit of the change and enter in the center, as soon as the conditions will be favorable to them. another consequence of this typical statistical distribution is the careful preservation of individual types inside the population. in practice, on the genetic point of view, the best species or the favored community do not exist in absolute, and any declaration or pseudo-scientific argumentation about the primacy of a race, also human, must be considered as a guilty stretch. as confirmation, this is also in accordance with the distribution of the constituents of matter at a subatomic level. the final consideration is that the chemical composition of a plant is limited, being the expression of the genome of the species, but it may change at any time in response to internal and external stimuli. let us use these concepts to evaluate insecticides used in insect-borne diseases. the interest in the use of biocidal products of natural origin began in the s and grew until the s, when it was obscured by the arrival of synthetic insecticides on the scene. for a long time, the pesticides scenario was dominated by synthetic products, until several factors caused a decline in their utilization. however, in the last years, interest in natural products has reappeared intensely, especially for the control of noxious insects at larval stage. this situation has matured, as is well known, following the indiscriminate (and not always necessary) use of excessive amounts of pesticides which, once released into the environment, are difficult to eliminate, as evidenced by the paradigmatic case of ddt (see chapter ). at the same time, incidence of insect resistance has increased, resulting in partial product inactivity and/or increasingly massive dosage requirements. all this led to a need for the formulation of a new generation of pesticides, and to focus research and production efforts on natural products. in , the world health assembly reported in resolution . , section . , the need to develop bio-insecticides. slowly but inexorably, the pesticides market registered the rise of biopesticides from natural products. the change in favor of natural products is the result of two concomitant facts: the evidence of the environmental damage due to massive utilization of synthetic products, and a new and growing sensibility in favor of respect for habitats, asking for more compatible solutions. in the current search for the production of a new generation of pesticides, useful for mankind's battle against superbugs and other threats, to face challenges to food supply and health, plant sources play a relevant role. the current prevalence of natural products evidences that a consistent number of biocides and antibiotics have been obtained from substances produced by living organisms, which are part of the great book of mother nature, whose lessons are still useful. that probably means that attention in chemistry is finally moving from the free synthetic approach to natural products, already selected during the long story of molecular evolution. in an article that appeared in acs' journal of natural products, charles l. cantrell and colleagues pointed out the impact of natural productssubstances produced by living plants, animals, and other organisms-on the production of pesticides. the article reports the percentages for registered insecticides obtained from new active ingredients in the period - (cantrel et al., ) . the paper's aim was focused on the impact of natural product and natural product-based pesticides on the u.s. market, obtained on the basis of nai registrations of new active ingredient registrations with the u.s. environmental protection agency (epa). the ingredients are categorized into four categories: biological (b), natural product (np), synthetic (s), and synthetic natural derived (snd). in particular, nps are considered substances produced by living plants, animals, and other organisms. the report evidences that nps, snds, and bs all have origins in natural product research. nps accounted for . %, ss for . %, bs for . %, and snds for . %, arising from the combination of conventional pesticides and biopesticides. in the registered conventional pesticides, the category of biopesticides alone registered an evident majority of nps (with . %), followed by bs ( . %), snds ( . %), and ss ( %). in contrast, on the conventional pesticides alone, the category s clearly dominated with %, followed by snd with . %, np . %, and b . %. the review indicates that in the same period, more natural products were registered as nais for conventional pesticides and biopesticides than any other type of ingredient. the authors report that when biological ingredients and natural products recreated in laboratories are included, more than % of all nais registered in that time frame have natural origins. more than two out of every three new insecticides approved in the last years are directly derived from natural substances produced in plants or animals or have significant roots in them. it is noteworthy that these numbers are very similar to those obtained if we compare with a similar projection concerning registered medical drugs in a similar period, and published in the same scientific journal. it is also noteworthy that a similar trend can be observed in the case of the registration of medical drugs in the period - , as previously reported in the same scientific journal by david j. newman and gordon m. cragg (newman and cragg, ): % of registered drugs directly or indirectly derived from np of secondary metabolism, % from b, % from snd, and only % from s. again, the details reveal differences in the sectors, with np and b dominating in anticancer and antibiotics, whereas the opposite concerns antiinflammatories, with s clearly dominating. these data, obtained on a total number of new approved drugs, are the results of several reviews that confirmed these percentages. in particular, the authors stress the role of microbes in the production of new drugs derived from natural products: "we wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated," and therefore "it is considered that this area of natural product research should be expanded significantly." in other words, the future of pharmaceutical drugs could be related to natural products obtained by natural synthesis. once conceivable that the shift from synthetic pesticides to biopesticides seems to be incontrovertible, as fueled by the resistance phenomenon and the general tendency for "natural," the key argument is the choice of the raw material for the best bioinsecticide. as evident from the above reviews, bioinsecticides could be extracted from a living organism, like a plant, or produced by a living organism, like a bacterial strain by hemisynthesis, or obtained by synthesis in accordance with the structure of the active natural product. here, the debate is open between those affirming that "a molecule is a molecule" and those in favor of "original" natural products. anyway, in the case of an extract, the complexity of ingredients cannot be reproduced or performed by synthesis. the main characters of a natural "ideal" insecticide should be: biodegradability, environmental care, sustainability (obtained from renewable materials) and selectively (harmful to beneficial insects). it should also satisfy some conditions to be economic appealing and relevant, like be easy to produce, low cost, derived from raw materials that available and abundant in the country where the insecticide should be utilized. the last conditions are important to avoid accumulation by multinational agencies, as is happening for coffee and cacao. finally, but not in order of importance, the ideal natural insecticide must be able to compete in the market with the insecticides currently in use. the research for the ideal bioinsecticide is open, starting from the plant to be used. evident that this role should be assigned to neem. at that time, the tree was practically unknown in the occident, since its distribution and utilization were confined to the indian subcontinent. therefore, i wrote an article about neem to explain the importance of this plant, and some years later, i was contacted by an italian industry using neem oil because of the curiosity and interest raised by that article. the references about this plant and its use appear since time immemorial, as reported in the ayurveda and unani systems of traditional medicines, and even in the earliest sanskrit writings referring to the medical uses of fruits, seeds, oil, leaves, roots, and bark (gupta, ) . neem can be found all over the indian subcontinent since the time of the sanskrit-speaking aryans. so important was the species for the aryans, they even mentioned and included it in their sacred ayurveda, which is the sacred book of indian medicine. the species was later dispersed throughout the old tropics, including indonesia, either naturally or brought back by the ancient austronesian sailors after visiting and trading in india at least around years ago. through the centuries (kumar and navaratnam, ) , the medical importance of neem never waned in the indian subcontinent and it is now considered the "village pharmacy" for its importance in the ordinary life of indians, who use this plant to treat several illnesses (nix, ; girish and bhat, ) . many other news and references increased my interest. the marvelous tree, the problem-solving tree, the divine tree, india's tree of life, nature's drugstore, the pharmacy tree, the panacea for all diseasesthese are just some of the terms used to evidence the respect for this plant and its importance (ruskin, ; brahmachari, ; puri, ; national research council, ) . neem's relevance and its beneficial properties has been reported by the who/unep ( ), which considered neem as an effective source of environmentally powerful natural pesticide and one of the most promising trees of the st century for its great potential in pest management, environmental protection, and medicine koul and wahab, ) . furthermore, the u.s. national academy of sciences dedicated a report to neem, significantly titled "neem-a tree for solving global problems" (nas, ) . the importance of neem has increased exponentially in recent years. considering the enormous quantity of results and scientific data concerning the validation of medicinal and biological properties, the international scientific community included neem on the list of the top plants to investigate and use for the sustainable development of the planet and the health of mankind (tewari, ; foster and moser, ) . however, in the occident, insecticidal activity is the most common application for neem oil and its derived products. the plant, besides neem, is also known as nimba, nimtree, margosa, and indian lilac. in botany, neem is azadirachta indica a. juss and belongs to the meliaceae family. meliaceae are angiosperm rosidae, closely related to simaroubaceae and rutaceae (schumutterer, ) . the family includes genera and c. species. these are woody plants, like trees, shrubs, and shrublets, pantropically present, with a few temperate representatives in china and south africa. it is estimated that c. million years ago, two subfamilies diverged, cedreloideae with genera and melioideae with genera, including aglaia, dominating with c. species, and azadirachta with only two species. meliaceae are commonly known as the mahogany family, being known mainly for some important timber species, such as the true mahogany (swietenia mahagony). however, losses due to overexploitation and genetic erosion, as well as toxic effects on workers, limited the use of this true mahogany, nowadays widely replaced by spanish mahogany (s. macrophylla). azadirachta indica is an evergreen tree that grows up to a height of - m, but in favorable conditions it can to a height of about - m, with a trunk diameter up to . m (fig. . ) . the leaves of neem, composed of - leaflets, meaning - leaflets with a single terminal, are abundant, suspended by a strong and long petiole which lacks stipules, crowded near the ends of the branches. the leaflets are toothed, deeply serrated, their margins irregularly serrated, sharply pointed, and curved like a scythe. young leaves are pale, tender green, and tinted with rust, but during the favorable season the tree profits from the fresh, green color and shining surface of the leaves, giving a delicate and charming appearance. white small flowers are abundant, very fragrant, bisexual, or staminate in male exemplars. they are arranged in clusters at the axils of the leaves. they present five separated petals arranged in the form of a star. they appear in spring, and open in the afternoon giving out a delicate smell, which increases during the night. the fruit is a smooth, yellow-green, small, round drupe with a sweetflavored pulp. during the monsoon, when the flowers have fallen and the tree is in full foliage, the curved, toothed leaves, massed round the branches, have a distinctive appearance, which is easy to recognize. from march to may, the flowers, with five whitish petals, appear in great numbers on long, drooping stems. flowers are used to produce a bitter honey. the fleshy fruits are purplish-black, single-seeded drupes, which turn yellowish when ripe. elliptical in shape, they have a sweet-tasting juice loved by birds and bees. however, after the rains, the fruits change, giving off a strong unpleasant smell. in autumn, fruits fall down in great quantities if not harvested. the tree is believed to be native at least of north-east india and burma, or indonesia, but now widely distributed in the indian subcontinent, and it grows naturally throughout the dry regions of the country. it is usually planted along roads and avenues in towns and villages, because it grows fast and easily, and has an irregularly rounded crown with a canopy of leaves, making it a useful shade tree ( fig. . ) . the central regions of india are considered the patria of neem. if you go to coimbatore, in tamil nadu, you can find neem trees everywhere, in towns and in the countryside. it is mainly used for shade, lining streets or in most people's back yards. in india, it grows throughout the states of uttar pradesh, bihar, west bengal, orissa, delhi, maharashtra, gujarat, and andhra pradesh, but the original natural distribution is obscured by widespread cultivation. cultivation is easy, since neem usually grown from seed but can be propagated also from cuttings or root suckers, and it is a fast-growing species. potential utilizations of neem concern human, animal, and environmental health. the last one is a recent but very important acquisition. neem is cultivated for two main reasons: environmental care and the production of seed neem oil. the tree's tolerance and adaptation to hot and dry climates has made it one of the most commonly planted species in arid and semi-arid areas (tiwari et al., ) . the survival capacity of neem is mainly due to its highly expanded root system. neem trees are extremely useful to counteract desertification and furnish the only source of wood in arid and nutrient-deficient zones. the plant does not need particular care and grows rapidly up to m tall. neem trees attain maturity in - years in areas where the sunlight is intense, weather is warm, and good well-drained soil is found. the tree is stable in windy zones and can live for years or more. to survive in arid climates, neem depends on a wide strong root system with a deep tap root and extensive lateral roots, which are ideal for soil conservation. furthermore, its planetary presence can contribute to positive carbon sequestration to minimize climate changes, considering that adult neem trees can retain ae . g of co per m and per hour, which means - tons of co per hectare. therefore, neem trees can be considered to be air purifiers as well as air fresheners. for all these reasons, neem is widely cultivated in warm countries, and its areal distribution is expanding rapidly by massive cultivations in sub-tropical regions of america (caribbean cuba, central and southern america), asia (nepal, pakistan, bangladesh, sri lanka, myanmar, thailand, malaysia, indonesia, iran, china, turkey, indonesia), africa (kenya, cameroon), and australia. the cultivation of neem trees is in particular increasing in the drought-prone areas, like in south arabia (arafat valley) and in the uae. in , northern nigeria, thanks to the governmental project arid zone afforestation (azap), saw , neem trees being planted. in europe, some cultivations are reported only in southern spain and portugal (sara and folorunso, ) . the presumed current global neem trees presence and production are reported in table . . the data were obtained by cross-referencing several sources and are only indicative, considering that a real census was never completed in many countries (in particular in china) and many plantations are in progress. india is still by far the homeland of neem, but the scenario has changed rapidly in the last years and will continue to do so in the future, as can be deduced from the data in table . . visiting oman, i noted the presence of planted neem trees in areas where acacia was the only other woody plant (usually the only plant) able to survive. the neem tree is resistant to drought and it grows in many different types of soil, but it thrives best in well-drained deep and sandy soils. normally, it flourishes in areas wherein the neem is a life-giving tree, especially for dry coastal, southern districts. its capacity to survive in arid zones improved cultivation in sub-arid to sub-humid conditions, with annual rainfalls between and mm. it can tolerate high to very high temperatures, but it does not tolerate temperatures below °c, making cultivation in temperate climate very difficult. however, the future worldwide distribution of neem is not predictable. indians are convinced that it will be difficult to obtain similar ideal conditions to their country and others in the orient; however, the story of the cultivation of cinchona by dutch botanists in indonesia tells us that the results of the cultivation can be successful and the results even superior. in the complete linnaean binomial name of neem we found a. juss, which is the mark of the author of this species, designating the scientist who first published the name and a complete and scientifically reliable description of the species. a. juss refers to antoine laurent de jussieu ( - ), a great french botanist, who was the first to publish a complete and valid natural classification of flowering plants, named genera plantarum, published in , the same year as the french revolution, surpassing the sexual system presented by linneus. antoine laurent jussieu was the member of a family of a plant enthusiasts; his uncle was the botanist bernard de jussieu, whose transferred knowledge and unpublished work were the starting point of the book of antoine laurent, and his son andrien-henri also became a botanist. the merit of his work was the use of multiple characters to define taxa. in this approach, he achieved a significant improvement over the "artificial" system of linneus, mainly based on the number of the reproductive characters, i.e., stamens and pistils. many people know the work and name of linnaeus, but the impact of jussieu's work was fundamental in taxonomy, founding the principles that served as the foundation of plant classification in a natural system. many presentday plant families are still attributed to him, as the species is to linnaeus. that's what who can find in ordinary sources of information. the consequent idea is that jussieu, though living in france at a historical revolutionary time, was totally dedicated to botany, but his work was also revolutionary, through a strange pathway. deeper information about his life is a source of important lessons. his uncle, bernard de jussieu, invited the young antoine to paris, where he was trained in medicine for years. however, his uncle, via his position as a demonstrator at the jardin du roi (royal garden), had other plans for antoine. he guided his nephew's studies and prepared him for a lecturer's position at the garden, which was soon to become vacant. at just -years old, antoine was transferred to that position and his botanical training was limited because the subject then was viewed only as an accessory to his medical course. the inexperienced jussieu had to study botanical topics by night, since he had to teach by day. using the plants in the garden to teach plant morphology, which were arranged according to the current artificial system of joseph pitton de tournefort, jussieu started to realize the inadequacy of that system. this progressively changed his interest into a true passion for botany, and classification began until, as part of an application for a place at the academy of sciences, he produced a treatment of the ranunculaceae, starting a complete revision of the plant taxonomy system. continuing in his study, it became apparent to jussieu that the artificial system of tournefort was inadequate, and from he began arranging the plants in the royal garden in his own way and finally transferring the knowledge in the construction of his own system of plant classification. despite the initial success obtained by linnaeus' sexual system, it was clear to jussieu that the swedish naturalist had used a counting method, whereas it was necessary to grade the characters, considering some of them more important than others, depending on how variable they are within a species. this was a necessary lesson to consider the variability of living organisms correctly. however, he continued practicing medicine, chiefly devoting himself to the health of very poor people. in , he was put in charge of the hospitals and charities of paris. in the final years of his life, jussieu, by then almost blind as well as deaf, dedicated the last part of his extraordinary life to meditation and prayer. the neem tree has few diseases and enemies (boa, ; schmutterer, ) . in general, it is considered a very resistant and healthy plant . however, it is possible that after its spread around the world, something is changing. we must move our focus from india to the new settlements, in africa. in northern nigeria, neem now is planted in towns and villages, as a highly evaluated source of shade and firewood, as well in the establishment of shelterbelts. in nigeria, like in other parts of africa, the small twigs of neem are used to clean and whiten teeth, in consideration of its antibacterial properties. in particular, reports of pests and damages comes from east africa, like gall mites (phyllocoptes sp.) on older plants, but the most potentially dangerous pest is aonidiella orientalis, known as oriental scale (ofek et al., ; lale, ; elder et al., ) . this insect was widespread in western kenya but is not currently harmful. likely to be native to asia, it has been introduced to many regions via shipments of plants and then began its slow spread. some ports check for this and other scales in plant shipments. in africa, neem has been widely planted in the sahel region. oriental scale first appeared in the sahel during the mid- s and caused widespread damage to neem trees planted there. infestations were first detected in nigeria in along its border with cameroon and by the mid- s, widespread damage had been reported to neem trees throughout northeastern nigeria. the oriental scale is a flattened, circular or oblong insect, about . mm in diameter. it varies in color from yellow to light reddish brown. it frequently forms large colonies and sucks the sap of small stems and branches, which is phloematic sap, rich in sugars and other organic substances. infestations often spread to the foliage, fruits, and even seeds. feeding damage causes the foliage to die, giving infested trees a burnt appearance. this is followed by progressive dieback of branches and eventual tree mortality. the heaviest infestations appear to be on large trees located either in marketplaces or around human settlements. the female attaches to the surface of a plant and causes the disease by the larvae, which roam the plant, feeding on sap by inserting their stylets, sucking sap, and weakening the plant progressively. the physical damage includes discoloration and deformation of leaves. flowers and fruits fail to develop. it is noteworthy that the effects of the pest attacks are very similar to those already reported for olive trees, including exsiccation of leaves and wood. the lesson is that, in this outbreak, we have an explosive negative mixture of alien species and man's activity on the habitat. the enormous spread of neem trees in recent years is an unusual phenomenon, whose consequences should be better monitored. before going into detail about the constituents, we must consider the typologies of the forms of the marketed products containing natural products. we are referring to insecticides, but the same considerations are simply applicable to nutraceuticals, phytomedicines, cosmetics, and even food. it is possible to find the plant drug, meaning a part of the plant utilized. the plant drug is usually utilized exsiccated, or as a derived product, like an extract, resin or oil, which can be obtained as such, or be enriched in one or more constituents, which are considered responsible for the activity. in this sequence, the original starting point, which makes the plant useful, has been betrayed in favor of increased efficacy. however, following this treatment, there are products registered as food supplements containing % of a pure substance and usually the origin is not at all natural (although this is not declared on the label). in such cases, the product is more similar to a medicinal drug than an extract and it should be considered and used in medicinal form. the distinction between such marketed products is not evident and not reported to the unaware consumer, who may well prefer the product due to its apparently "natural" origin. knowledge of the chemistry is therefore fundamental and the basis of any decision about the appropriate use of a plant. however, we cannot know exactly what is inside a plant. all our methods of investigation are limited and may be misleading, although papers and books are full of information about the compounds contained in plants or their derived products. this is the consequence of plants' extreme chemical complexity. in a single leaf of hemp, more than constituents have been detected, considering the secondary metabolites alone, and hemp can contain high levels of thc or cannabinoids can be practically absent. in such cases, the morphology does not give any help and only a reliable chemical analysis can indicate what kind of hemp we are handling. since its beginning, phytochemistry has sought knowledge of all natural products. in about one hundred of years of activity, innumerable analyses were made and an enormous quantity of data collected in a very useful data base, but recent advancement in analytical devices and novel interpretation ask for a revision of the result of this job (kaushik et al., ; forin et al., ) . we must remember that the molecular world is not detectable by our senses and therefore we have secondhand and probably only partial information. sometimes, this information is considered sufficient to assign the compound/activity relationship, but only until other analyses confirm the presence of other molecular candidates. the seeds of neem contain at least identified biologically active compounds (govindachari, ) . among them, major constituents are nortriterpenes, named limonoids, i.e., azadirachtin, nimbin, nimbidin, nimbolides, and many others (ragasa et al., ) . however, each year other new limonoids are discovered. more constituents mean more possible activities. preparations from the leaves or oils of the seeds are used as general antiseptics (mossini et al., ) . due to neem's antibacterial properties, it is effective in fighting most epidermal dysfunction, such as acne, psoriasis, and eczema. ancient ayurvedic practitioners believed high sugar levels in the body caused skin disease. neem's bitter quality was said to counteract this sweetness. during the last desert locust plague in africa, it was noticed that these insect, schistocerca gregaria (forskal), ate almost any vegetal around, leaving a bare landscape when they fly away, except for neem trees, probably because of the antifeedant effect of the very bitter leaves, due to the presence of limonoids. traditionally, indians bathed in neem leaves steeped in hot water. since there have been no reports of topical application of neem causing adverse side effects, this is a common procedure to cure skin ailments or allergic reactions. neem also may provide antiviral treatment for smallpox, chicken pox, and warts, especially when applied directly to the skin. its twigs are commonly used to clean and disinfect teeth. the brushing of teeth with neem to prevent gum diseases and for teeth whitening is very common, and not only in india. there are also various kinds of natural toothpaste on the market that contain neem extracts. it is also possible to prepare a homemade toothpaste to achieve shiny, cleaner teeth. neem powder is made by grinding dried neem leaves, which is traditionally used by mixing one teaspoon of neem powder with one teaspoon of baking soda and enough water to make a useful paste. these preparations can help to avoid the plaque and tartar that build up in gums, which are the root causes of bad breath. in addition to cosmetic uses, neem's antimicrobial activity to maintain dental health is also worth noting (chava et al., ) . a preparation can be obtained by boiling neem leaves in water until they reduce to a quarter of the original volume. finally, gargling with this concoction contributes to good breath and whiter teeth, as it kills the bacteria inside the mouth. the teas of neem leaves are utilized in indonesia and oman for their digestive properties (sujarwo et al., ) . neem's effectiveness is due in part to its ability to inhibit pathogens from multiplying and spreading (benelli et al., ) . neem produces painrelieving, antiinflammatory, and fever-reducing compounds that can aid in the healing of cuts, burns, sprains, earaches, and headaches, as well as fevers (chopra et al., ) . several studies of neem extracts in suppressing malaria have been conducted, all supporting its use in treatment. neem has broad applications to human and animal health, as well as organic farming (bhowmik et al., ) . it is reported as a powerful antiviral and antibacterial, with peculiarities that set it apart from other herbs in that class of broad antimicrobials (sandanasamy et al., ) . neem oil is also commonly added to a variety of creams and salves. it is effective against a broad spectrum of skin diseases including eczema, psoriasis, dry skin, wrinkles, rashes, and dandruff. these are just a few examples of the possible utilization of neem, and the potentiality of neem is considered by everybody, including the onu and other institutions, to be very high, but so far little has been done to develop appropriate products from it to help mankind. in particular, considering insect-borne diseases, in vivo activity of neem seed oil (nso) against malaria plasmodium has also been reported (dahiya et al., ; trapanelli et al., ) . today's exploding growth in human population is seriously depleting the world's natural reserves and economic resources. unless the runaway human population growth rate is slowed down, there will be little hope for raising everyone out of poverty in the developing world. besides educational constraints, the nonavailability of inexpensive methods of contraception, which do not cause trauma or impose on the esthetic, cultural, and religious sensitivities of people, limit the success of birth regulation programs. however, recent findings indicate that some neem derivatives may serve as affordable and widely available contraceptives. a recent controlled study in the indian army proved the efficacy of neem as a contraceptive. in , the report of the washington-based international food policy research institute predicted a world even more unequal than the present, with food surpluses in the industrialized world and with chronic instability and food shortages in the global south, particularly in african countries. the main product of neem seed oil (nso) is the fixed oil obtained by expressing the seeds, still enclosed in the kernels. therefore, the fleshy pulp is removed or dried, to obtain the inner part. nso can be obtained by different extraction methods. most nso is produced in india by small-scale producers at ordinary temperatures using very simple machinery, which is utilized in other periods of the years for other oily extraction, like arachnids or soya seeds (figs. . - . ). however, modern apparatus is also used in india and many other countries are now producing and refining nsos. therefore, considering also the possible different geographical origin of the raw material, combined pre-and postharvesting factors can result in great differences in constituents present in marketed nsos, as already reported. therefore, despite the common definition for all the oils obtained from kernels of neem, it is necessary to consider that there is no single nso, but many nsos differing in shape, color, viscosity, chemical constitution, and activity. medicinal and cosmetic utilizations are relevant and continuously increasing. cold pressed neem oil is commercially known as margose oil and considered as pressed directly from seeds. there are hundreds of marketed products worldwide based on margose oil. neem, or margose, oil has a brown color, a bitter taste, and a garlic/sulfuric smell. the oil is usually obtained by simple pressing, but extraction by organic solvents, like hexane, is also used, though in such cases traces of the residue of solvent are always present in the final product. the type of insecticide is commonly registered as biocide, insect repellent, and antifeedant, intended for use on outdoor and greenhouse agricultural food and ornamental crops as a repellent and insect growth regulator. the products are considered to have no risk to human health because of their low toxicity via all routes of exposure. there is no reason to believe that any nontarget organisms, including honeybees and other beneficial insects, would be adversely affected, as tested by the environmental protection agency (epa). the environmental protection agency (epa) is probably the most important agency in charge of environmental care and health. it is an agency of the united states federal government whose mission is to protect human and environmental health. the epa is also in charge of the regulations of carbon emissions from power plants, automobiles, and other contributors to climate change. the epa became popular in europe because of a civil enforcement case against volkswagen and other car manufacturers, subject to reservations set forth in each of the partial settlements. in , the u.s. department of justice resolved a criminal case against volkswagen ag with a plea agreement for the offenses of conspiracy, obstruction of justice, and entry of goods by false statement, and the u.s. customs and border protection resolved civil fraud claims with volkswagen arising from the illegal importation of affected vehicles. the epa was established in december by an executive order of president richard nixon, with headquarters in washington, d.c., in response to widespread public environmental concerns that gained momentum in the s and s. epa is a giant public agency with a budget of billion us $, and it is born as reaction to the public movement in favor of the environment due to the carson's book (see chapter ). it is considered reliable because independent. the epa is responsible for creating standards and laws to protect and preserve the natural environment and improve the health of humans by researching the effects of and mandating limits on the use of pollutants. the epa's aims include the regulation of the manufacturing, processing, distribution, and use of chemicals and other pollutants. in addition, the epa is charged with determining safe tolerance levels for chemicals and other pollutants in food, animal feed, and water. the best presentation of neem insecticide properties and the rationale of its utilization is the report of the epa about the registration of cold pressed neem oil, concerning a product named plasma neem. the report has a significant subtitle: "reasons why neem oil is an effective way to control insect hoppers" (epa (us environmental protection agency), ). the target of the product cold pressed neem oil is insect hoppers, because of their special liking for cash crops. the consequence is a crisis because of insect hoppers infesting these cash crops by chewing and sucking the leaves, as reported by many farmers. the reasons to use neem are focused on the effects of chemical fertilizers, which "provide a remedy but tend to kill beneficial insects as well." the report identifies three reasons why neem oil should be considered an effective way to control insect hoppers which feed on cash crops. reason : selectivity. "neem oil is usually sprayed on the leaves and stalks of a cash crop. so it is aimed at only the insect hoppers who spoil the cash crop by chewing the leaves or biting off bits of the stalk. the insect hopper which attacks the plant by consuming it will end up consuming the neem oil as well and hence die as an aftermath. beneficial insects, who replenish the soil in a natural fashion, do not consume the plant and hence do not get affected by neem oil." reason : eco-friendly efficacy. the content of azadirachtin in neem oil is considered very good at controlling and eliminating insect hoppers, avoiding the negative effects on the productivity of cash crops. furthermore, the neem oil exerts no damage to the soil or disruption of the chemical composition of a fertile soil. the product affects biological functioning of the insect hopper, and therefore the insect hopper forgets to feed or breed after devouring a cash crop with neem oil sprayed on it. the conclusion about this point is clear: "this leads to the complete elimination of the insect hopper and the infestation cycle without any other adverse chemical side effects." the action is mainly larvicide, but also deterrent and adult insecticide in most species. reason : cost-effectiveness. the utilization of neem oil for preserving cash crops from insect hoppers is considered very cost-effective. in comparison to chemical fertilizers, neem oil is expensive, but other positive effects must be evaluated. there is another consideration about the cost/benefit effect: eliminating negative insects and worms by neem oil, farmers need not spend money on buying supplements for the enrichment of soil. the heavy investment to preserve soil quality is totally avoided when a farmer uses neem oil. in conclusion: "overall, it can be said that neem oil as a source to control insect hoppers in cash crops is extremely beneficial for farmers." the final consideration of the epa is the advice not to use the content of the report as an endorsement of nso. in fact, it is important to remember that the report is based on scientific and experimental data. the epa is not working in favor of the industry or the market, but its judgments must be considered objective although its aim is environmental improvement. nso, obtained by the cold expression method, is the only natural productderived insecticide, whose registration was approved by epa. the epa's authority is so far internationally recognized. therefore, in the report there are three main key items of information: the evaluation of the selective insecticide activity; the preference for synthetic products in consideration of the eco-friendly properties; and the indication of azadirachtin as necessary for the activity. let us consider the report as a guide and evaluate each of these points. later, we will add other considerations. it is noteworthy that all these indications can be found already reported and present in the information about the ethnobotany and traditional medicine of neem. in the cultivation of rice, when the plantlets are underwater, the addition of extracts of neem to the usual fertilizer, not only decreases the mosquitoes number, but also has beneficial effects on the production. the utilization of neem to increase soil fertility and treat medicinally plants and livestock is recommended in the upavanavinos, an ancient sanskrit book on agriculture. the dried leaves and the oil are used as preservatives against insects and microorganisms for the postharvesting conservation of foods. conservation is guaranteed for more than a year. panels derived by the extraction of the oil are used as food additives for livestock, and the animals are washed with this diluted oil to prevent the attacks of parasites or harmful insects. in the last decade, the focus was on the potentiality of a new analytical technique, hptlc (high performance thin layer chromatography) ( fig. . ) . hptlc is the last evolution of planar chromatography and allows the evidence of most of the constituents of an extract in an identifying track, named fingerprint, wherein identification of constituents can be obtained by direct comparison in the same plate with the correct standards, utilizing the rf value and the reaction with adequate derivatization (nicoletti et al., a,b) . improvements in separation and visualization of the spots are obtained by reduction of the size of the particles of the silica gel, constituting the fixed phase. the mobile phase can be selected on the ample repertory of solvents and their mixtures, as well as the several methods of derivatization and detection. the final effect, in comparison with ordinary planar chromatography (tlc), is like a myopic person wearing glasses. the advantages in comparison to the tlc are in the total control of the environmental conditions and the automatization of the procedures. each step of the analysis is performed entirely by a series of devices, and the operator is only asked to produce the program of actions by the software. plates can be visualized and derived in several ways, obtaining multiple information (figs. . and . ). they can be easily preserved and stored as digitalized images inside the computer, and immediately sent everywhere or compared with a data bank. however, the most important feature of hptlc is that the results of the analyses are very clear, thanks to careful preparation work that enabled optimal chromatographic conditions, as demonstrated by the quality of the images. in other words, our idea was to "see the molecules" (nicoletti, ) and obtain simple and clear evidence of the metabolic production. molecules are too small to feel their presence with our senses or directly by any sort of device, but it is possible to evidence their chemical properties in the plate, recording the rf value, the fluorescence, and the color after derivatization. an hptlc or nmr graphic needs an expert for correct interpretation, such as any specialized analysis, like a cardiogram . in hptlc, without any knowledge of chemistry, the presence or absence of a determined spot is evident (figs. . and . ). hptlc was selected to obtain a metabolomic approach, meaning the study of many constituents as possible, focusing on secondary metabolites (toniolo et al., ) . metabolomic is one of the -omic sciences generated by the dissection of the dogma of biology, based on the sequence dna➔rna➔proteins. it is necessary to propose some comments about the dogma of biology and why its crisis generated a series of other points of view. first of all, the use of the word "dogma" should be avoided in biology, since the matter is more complicated than a simple sequence, as actually happened. the central dogma of biology was first proposed in by francis crick, as a consequence of his discovery of the structure of dna. the dogma describes process by which the instructions contained in dna are converted into a functional product. another definition is: "the coded genetic information hard-wired into dna is transcribed into individual transportable cassettes, composed of messenger rna (mrna); each mrna cassette contains the program for synthesis of a particular protein (or small number of proteins)" (sources: definition from chapter : the dynamic cell, of molecular cell biology). the flow of genetic information within a cell follows the sequence: dna codes for rna via the process of transcription (occurring within the nucleus), rna codes for protein via the process of translation (occurring at the ribosomes), and proteins are responsible for the synthesis of the other metabolites (proteins are spread everywhere). cell data are organized within the database of dna and reversed in the metabolic flux, through rna. although clearly deficient, the central dogma of biology dominated genetics for decades, but through ongoing research, many exceptions were discovered. for example, most dna is silent, since it does not encode proteins. retroviruses, which are relevant for our arguments, present the possibility that rna transcribes into dna through the use of a special enzyme called reverse transcriptase, and other cases of deviance can be reported. however, the biggest revolution consists in the direction of the arrows. it is necessary that information could follow also the reverse pathway, allowing an appropriate response by the genome potentiality. therefore, at least the dogma must be rewritten with two-way arrows. in principle, a metabolomics study should be the determination of the pathway of cell production from the genome through transcription, but the term "metabolome" is now used to evidence the whole pool of metabolites, in particular for natural products, whereas transcriptomics is related to proteins. transcriptomics involves serious difficulty to obtain reliable results. a protein seems perfectly comfortable inside the cytoplasm, but outside, irreversible denaturation causes definitive degradation and consequent difficulty in understanding the protein's functionality. in contrast, small molecules are more stable in any environment and their molecular structures at least can be determined by phytochemical analysis (nicoletti and toniolo, ; toniolo et al., ) . however, in the metabolome we have hundreds of thousands of different constituents to be studied, and the classic approach to study the molecules one by one is impracticable, and other methods must be utilized. the lesson is that the role of any metabolite cannot be discarded a priori, and also a secondary influence in the evaluation of the property of an extract can be important to definite and obtain the final reaction. once again, the "magic bullet" paradigm is under discussion, but the total utilization of plant extracts must also be considered an unsatisfactory solution. the aim of our approach was to adapt the method to other subjects outside the pharmaceutical applications. therefore, our first studies focused on the determination of adulterants in nutraceuticals and other pharmaceutical products, like the "green viagras." later, we adapted the method and the devices to use the metabolome as a source of information about what is going on in a complex system in which living organisms are acting. therefore, we are able to study the effect of environmental factors, like ozone, on the quality of wine (valletta et al., ) . however, probably the most impressive application was the study of the environmental effects of the costa concordia disaster (toniolo et al., ) . on the night of january , , the costa concordia, a giant yacht with approximately cabins, passengers, and crew, was wrecked off the rocks of the italian coast a few hundred meters from the port of giglio, a little island on the tyrrhenian coast in tuscany. like an injured helpless mastodon, the cruise ship inclined dangerously, until the inclination stopped with most of its starboard side under water. because of the inclination and the amount of people, the overnight evacuation of the costa concordia was a challenging process, and people died. the cost of removing the ship was us$ million. for scientists like us, interested in environmental damage, it was a unique occasion. for year, months, and days, the enormous hull of the boat altered the underlying marine habitat, interrupting the normal flow of sunlight over a surface of more than , m . the seagrass posidonia oceanica was chosen as the target organism of the impact evaluation, since, like in other parts of the mediterranean sea, it forms large underwater meadows. using hptlc analysis, it was possible to determine the health of each collected plant and make a map of the metabolic damage, which accorded with the shadowed area. however, albeit the negative conditions, the rhizomes turned out to be mostly still alive and able to reproduce the meadow again. therefore, the final task of our research was simply to wait until nature carried out its work. however, there is a further chapter of this story, written after our study. to remove the ship, a platform was transported from north europe. the problem was that the bottom of the platform was full of mytilus. when the platform was exposed to the hot mediterranean sea temperature, the mussels died, releasing their bodies, covering down the sea background and causing a further source of damage. a clear example of human stupidity and superficiality. anyway, devoted to our task, we are now repeating our analyses to understand what happened and what is still going on, relying on the quality and reliability of our indisputable results. the study of neem oil was based on the experiences obtained by improving the hptlc devices via the metabolomics approach. the central idea was to collect as much information as possible about the constituents of the neem products, without any preference for any kind of metabolite, considering any product and any extract like a unique molecular system. in the hptlc analyses on nsos, the objective was to achieve the total chemical characterization of the used oil, and then the derived products, by means of the production of a chromatographic reference profile of the metabolites' production. this objective is not easy to achieve due to the complexity and variability of neem oil. neem products are subjected to great variation in composition, due to preharvesting factors, like environmental situation, genomic differences, influences of the habitat, and others, including postharvesting situations, like harvesting and stocking, treatment of the raw material, separation of different parts, extraction methods, production of the final product, and others. in fact, analyzing different marketed neem oil from several productions and countries, we decided that it was not possible to refer to a single neem oil, but to neem oils in the plural, due the great differences in composition. therefore, we decided to obtain and adopt a reliable reference metabolomic hptlc profile for the neem extracts or products to be utilized in our biological experiments in vitro and in the field. in fact, one of the typical problems in activity tests is the differences in raw material giving rise necessarily to different results in activity and utilization. another important aspect of our metabolomic study was that the complexity of the neem profile was even greater than expected. this result is the consequence of the generalist approach. in other molecular chromatographic or spectroscopic analyses, like hplc, the result is sub judice on the detector's settlement. therefore, if the molecule does not possess the adapt chromophore, the molecule, even if it is the main component, is invisible to the detector. in hptlc, there are universal derivatization methods, like h so , to reveal the organic substances, but it is possible when necessary to adopt a particular agent. in this way, it was possible to exclude the presence of a relevant percentage of azadirachtins and the occurrence of other constituents relevant for the activity. this is another recurring lesson for those studying natural products. although a plant has been the object of several phytochemical studies, new constituents can be obtained. an example is the discovery of gossypol in cotton oil. insecticidal activity is reported in a hundred or so published papers, concerning a wide range of species of arthropods, as confirmations of many traditional uses (schumutterer, ; amirthalingam, ; jones et al., ; van der nat et al., ; biswas et al., ) . leaves are used in houses to repel and keep away insects. when half of a sample of soya leaves are sprayed with nso and offered as food to the japanese coleopteran (popillia japonica), the insects feed only on the nontreated parts of the leaves. in nicaragua, farmers spray their cultures with an aqueous extract obtained by leaving the seeds for h in water. in general, nso-based products have proven to be very effective against a huge range of pests of medical and veterinary importance, mainly including mosquitoes. the insecticidal properties of neem and its many formulations are based on experimented antifeedant, fecundity suppression, ovicidal and larvicidal activities, including growth regulation and repellence against a great number (around ) of different insects, also at very low dosages, whereas useful insects were shown to be unaffected isman, ; sharma et al., ; schumetter and singh, ; forin et al., ) . the deterrent activity was also important, which can be easily determined as reported in fig. . . other studies, like the molting and the growing of the selection under investigation, need special devices, as those reported in fig. . . in particular, a concentrated extract of neem seeds, named mitestop, developed by the university spin-off company alpha-biocare (d€ usseldorf, germany), proved to be very effective against a huge range of pests of medical and veterinary importance, including ixodes and rhipicephalus ticks, house dust mites, cockroaches (blatta, blattella, and gomphadorhina), raptor bugs (triatoma), cat fleas, bed bugs, biting and bloodsucking lice, poultry mites, and beetle larvae parasitizing the plumage of poultry. neem leaves can also be used to protect stored woolen and silk clothes from insects. concerning mosquitoes, emulsified formulations of a. indica oil showed excellent larvicidal potential against different mosquito genera, including aedes, anopheles, and culex, also under field conditions. insect growth regulatory activity of neem-borne molecules alter or block the metamorphoses of larvae (toniolo et al., ) . neem weakens the cuticle defense system of the young instars, causing easy penetration of pathogenic organisms, or interferes with the molting mechanism. concerning biological control, an increase of the control of aedes populations was observed after the combined application of predatory copepods and neem-based larvicidal products, since repeated application of nso does not affect populations of predatory copepods. however, relevant limitations are related to the relatively high cost of refined products and the low persistence on treated surfaces exposed to sunlight. in the soil, the half-life of azadiracthins, meaning the time necessary to degradate the compounds, is from min to days, depending on the environmental conditions, like moisture, high temperature, and sun. the breakdown is faster on plant leaves, due to the exposure and the surface. in the attempt to assign the active constituents of nso, we must consider that the chemistry of neem is very complicated in terms of numbers and types of constituents. despite the great quantity of dedicated research, chemical research is far from complete. hundreds of compounds have been isolated and identified from various parts of neem, with seeds being the most investigated for their commercial value. the seeds may contain approximately % of a brownish yellow oil, mainly constituted by several fatty acids, i.e., oleic acid cis- -ottadecenoic ( - %), palmitic esadecanoic acid ( %- %), stearic acid ottadecanoic ( %- %), linoleic acid cis, cis- , -ottadecadienoic ( %- %), and arachidic acid ( %- %), although several other compositions have been reported. after a certain time, fatty constituents tend to separate and appear as white amorphous material. the main characteristics of the oil are its unpleasant strong alliaceous odor and acrid taste, attributed to sulfurous constituents. the shape and consistence can be very different according to the extraction method and the source. in fact, the composition of neem oil is highly variable, depending on preharvesting factors, like the cultivar, the geographic and environmental origin of the raw material, collection seasons, and postharvesting, like the extraction method, preservation, and conservation. extraction can be executed with different apparatus, temperatures, pressures, and methods, affecting the yield as well as the content. as later reported, these aspects have been deeply considered and hptlc analyses can be utilized to ensure the chemical composition of the neem oil utilized in the biological experiments. among the c. compounds characterized from the neem seeds, more than one-third of them are nortriterpenoids, which are triterpenoids lacking some carbon atoms (kaushik et al., ) . nortriterpenoids are chemotaxomically well located in a few related families of rosidae angiosperm dicotyledons, i.e., rutaceae, simarubaceae, cucurbitaceae, and meliaceae, within the rutales order. generally, in the plants of the rutales order, the partial loss of the lateral chain is followed by a complicated rearranging of the remaining part, giving rise to different polycyclic molecular skeletons, full of oxygenated functional groups, partially acylated. syntheses of complex natural compounds are costly and therefore they are usually used only for special activities. it is necessary to consider this point, which is in favor of the use of the plants as source of these compounds, since the synthesis can reproduce the chirality of nortriterpenoids only with extreme difficulty and cost. nortriterpenes are a very interesting part of the plant's chemical ability, that we call biosynthesis, to produce active complex molecules. nortriterpenes present very complicated structures and high numbers of active parts. we must remember that in natural products, activity is based on the presence of functional groups, made by heteroatoms, which means mainly o and/or n. if nitrogen is present, you have alkaloids, otherwise the range is higher, comprising phenols, alcohols, ketones, and others. however, the introduction of an oxygen inside a derivative usually is obtained to increase the activity, but also introduces instability in the molecule. we must remember that a natural product started from co and is likely to become co again at the end of its life. this is the necessary turnover of atoms and energy in organic matter. the first process accumulates energy and it is based on reductive reactions (endothermic reactions), whereas the second one is based on oxidation and produces energy (exothermic reactions). in other words, life is based on subtraction of negative entropy from the habitat, and at the end of its life, the organism releases this energy to the system. during its life, the molecule is expected to carry out its role inside the biosystem, which is the reason for its synthesis inside the plant. to understand the role, the nature of the target is essential. in insect-borne diseases, the natural product should interfere in the life of herbivorous insects or dangerous pathogens. in the case of neem, the activity is mainly larvicidal, blocking the metamorphosis to the next pupal stage. the larvae are unable to develop and change their state. to obtain this result, a lot of chemical and finalized activity are necessary, in this case consisting of hormonal interference in the insect metamorphosis process. in other words, the molecule must be able to mimic the internal complex chemical apparatus that allows drastic changes in the forms of the insect, until it stops the process. let us consider in particular the class of nortriterpenes. we have already had occasion to meet monoterpenes in the essential oil constituents. owing to their biosynthetic origin derived from progressive accumulation of isoprene units, each made by five carbon atoms, terpenes are classified according to the increasing molecular weight in monoterpenes (c ), diterpenes (c ), triterpenes (c ), and tetraterpenes (c ). squalene, the unique precursor of all triterpenes, is a linear unsaturated hydrocarbon, but its derivatives, for stability reason, are all cyclized with hexagonal and pentagonal cycles in the final structure. among triterpenes, the most famous class is certainly the steroidal one. steroids are present in any organisms, where they carry out several fundamental roles. without steroids, starting from the cholesterol stabilization of cell membranes to the influence on metabolism, no cell, and therefore no organism, could survive. however, each organism synthetizes its own steroids. in fact, animals possess simpler steroids usually with few oxygenated functional groups, bacteria produces steroidal triterpenes mainly dedicated to the stability of the cell envelope, and plants biosynthetize quite complex structures, named phytosterols. generally, phytosterols possess more cycles respect to the ordinary structure of the steroid model and an increase of the number of functional groups (roy and saraf, ) . animal steroids are based on a simple, easy-to-remember sequence of four fused cycles: three hexagonal and the last pentagonal. the basic structure of a steroid is quite easy to write and remember by students, including the stereochemistry, whereas the structures of limonoids are very complex and not so easy to remember. the problem is that in the basic structure of a steroid the sequence of the cycles is linear, whereas in limonoids there are complicated re-arrangements, causing a circular total structure. the insect's molt and metamorphosis are triggered and directed by hormones, usually consisting of steroids, such as prohormones (pheromones or juvenile hormones) and ecdysones. the term "ecdysone" was introduced by the german biochemist peter karlson ( karlson ( - in in "chemische untersuchungen € uber die metamorphosehormone der insekten" (karlson, ) . the etymology of this word is interesting, from the greek ekdusis "shedding," or more precisely ἐκ(ς) ("external" or "from inner to out") + δύω ("dress oneself") + -si(s) ("action") + -ona ("hormone"). however, ecdysones have typical steroidal structures, whereas limonoids are the result of a complex chemical rearrangement. thus, to interfere in insect life, special triterpenes are necessary. several plants, like those in rutales and sapindales and related families, are specialized in the synthesis of such molecules, probably made to defend the plant from phytophagous insects. to obtain this result, great chemical ability is necessary. first, part of the typical hydrocarburic lateral chain, typical of most steroids, is lost ("nor" in chemistry means exactly this passage obtained by cutting c-c bonds), and the remaining part is both oxygenated and compressed in a complicated polycyclic structure, which is quite stable in the cell environment, but easily degradable in contact with atmospheric oxygen and sunlight. in this way, the nortriterpenes can be produced in the plant and transferred to the insect with mortal effects through a subtle toxic effect. the idea is to interfere with the growth regulators, interrupting the balance of hormones, named juvenile, in particular interrupting the transition process from the larval instar stages to pupae and adults by juvenile hormone analogues. therefore, on learning this lesson from nature, we can find solutions and inspirations. on the basis of these considerations and the structural diversity ( fig. . ), nortriterpenes can be divided into two main groups: limonoids (c ), with partial loss of the lateral chain (manners, ) , and quassinoids (c and c ), with total loss of the lateral chain (vieira and braz-filho, ) . in ancient times, plants containing these kinds of compounds were mainly famous for the bitterness of their drugs, utilized in the production of tonics, digestifs, and medicines. limonoids are part of our ordinary experience with some fruits and are crucial for the dissemination process. when we eat a citrus fruit, such as a lemon or an orange, we taste the agreeable flavor of the juice, but the seeds are discarded because they contain the nortriterpene limonin, which is very bitter and unpleasant. by throwing away the seed, we contribute to the reproduction of the plant. several other properties of limonoids have also been reported, including antioxidant, antimicrobial, and antitumoral activities, the insecticidal of neem being so far the most important. limonoids are considered the most active ingredient of insecticide neem products. they are classified into nine basic structures, with three main skeleton types: (a) azadiracthins, highly polioxygenated and acylated, with a saturated first ring, a tetrahydrofurane ring between the two first rings, and a final dihydrofurane ring chained with the other part of the molecule; (b) nimbins, less oxygenated and acylated with a skeleton evidently similar to that of the steroids, the furane ring with only a link with the remaining part of the molecule; and (c) a third type similar to the azadirachtins one, but the polycyclic part containing the dihydrofurane ring is less complicated, giving rise to a more linear general skeleton. such variability is necessary to sustain the large range of targets. in fact, these differences are just as important for the biological activity as for the decomposition. however, in terms of market considerations, azadirachtins, in particular azadirachtin a, are considered the reference constituents to evaluate the quality, and therefore the activity, of neem oil. azadirachtin a is a highly oxygenated c-secolimonoid, whose content in the seeds is highly variable ( . %- %), mainly depending on the producing zone and the seasonal trend. this compound acts as a biocidal on insects after ingestion or contact, with several effects: (a) interference on the growing processes, inhibiting the molting or blocking the hormone ecdysone synthesis; (b) antifeedant, with reduction of feeding; (c) negative effects on adult fecundity and egg fertility; and (d) diminution of the defense capacity of the cuticle, easing the penetration of pathogens. in particular, the larvicidal effect consists in the formation of the "permanent larvae," i.e., larvae are able to complete the molt as a consequence of destruction of the cuticle or of hormonal perturbation of the metamorphoses. this study consists in the careful observation of the larvae transformations and in the daily count of the consequence of azadirachtins and related compounds on the molting of phytophagous with buccal apparatus, either biting-sucking and chewing, comprised in all systematic categories: orthoptera including grasshoppers, locusts and crickets, etheroptera, homoptera, aphides, cicadellidae, hymenopterous, thysanoptera, aleurodidae, dipera, beetles, and others, including acarus and nematodes. neem's oil formulations usually show a range of different azadirachtins amounts, ranging from to mg/kg, meaning that products can be obtained either by using directly poor neem oil or a dilution process of neem extracts containing different quantity of azadirachtins, up to %. in addition to neem oil, azadirachtins are also marketed, in particular azadirachtin a. the amount of production of this substance amounts to about tons, with % coming from india, and china as the second producer. other data about the activities of nso and its products can be found in the references at the end of this chapter. our first experiments clearly demonstrated strong larvicidal activity of nso and neem cake on asian tiger mosquito (nicoletti et al., a,b) . however, our hplc and hptlc analyses showed a low content in azadirachtins in the nso and in the methanol extract . the result was interesting, since it is well-known that insecticidal activity is strictly related to the chemical composition, but in contrast to most reports evidenced a relation between the activity and the presence of these limonoids. this consideration prompted research to identify a relationship between composition and activity in the case of nsos marketed by different producers. first, the hptlc analysis indicated great differences in the fingerprints of the analyzed oils, with special reference to limonoids (nicoletti, ; toniolo et al., ) . a second analytical step consisted of a fractionation of three selected neem oils in three fractions of increasing polarities (i.e., ethyl acetate fraction (ea), butanol fraction (bu), and water (we)). the initial neem oil and the obtained fractions were evaluated for larvicidal toxicity and field oviposition deterrence against the asian tiger mosquito, aedes albopictus. the experiments showed good toxicity of the entire neem oil and ea fractions against a. albopictus fourth instar larvae (with lc values ranging from . to . ppm), while little toxicity was exerted by bu and we fractions. the differences of activity were in accordance with the results of hptlc analyses, since the nsos more concentrated proved to be more active. these results were confirmed by deterrence of a. albopictus oviposition in the field (effective repellence values ranging from . % to . %), while no effectiveness of bu fractions was found. concerning ovideterrent activity, no difference due to the production site was found. these experimental data evidenced the possible use of neem constituents against culicidae in the field. the constituents must be found in the apolar fraction, but the hptlc analysis showed a complex composition, wherein limonoids were not prevalent. therefore, neem oil and ea fraction seem promising, since they are effective at lower doses, if compared to synthetic products currently marketed, and could be advantageous alternatives to develop newer and safer mosquito control tools, but other studies are necessary to obtain a better definition of the active constituents and tailor the neem products in accordance with the required utilization (benelli et al., c; . therefore, when we started our work on neem products, we found several incongruities between the reported studies in the literature and our results . in case of incongruence of the experimental data, two main interpretations are possible. the anomalous data could be the consequence of some error in the experimental procedure or the previous reported data must be reconsidered on the light of the new ones. in fact, many scientific important discoveries have been as consequences of unexpected results. there is a strong tendency in pharmacology to assign the activity of a plant drug to one constituent, or eventually a few of the same chemical class. this is mainly a consequence of the pharmacological tests, which are tailored on the magic bullet axiom and the difficulties in determining precisely the composition of an extract. however, in an extract, and consequently in the plant, there are hundreds of compounds, with effects on bioavailability, solubility, and synergic and antagonist activity. in opposition to the magic bullet, there is the approach of the phytocomplex, invoked by many researchers in phytochemistry and pharmacognosy. an important part of research on neem was dedicated to increase its availability and properties, focusing in particular on stability and cost, toward the production of the ideal insecticide. the first aspect was assigned to the production of nanobioparticles containing neem extracts, which demonstrated clear larvicidal and deterrent activity on vectors, like ae. aldopictus, also in field conditions (chandramohan et al., ; murugan et al., ) . several factors must be considered in the case of a product based on natural substances. in theory, the plant could be available for everyone and therefore it cannot be patented. therefore, so far natural products are available for everyone and thus have been explored very little. natural products are the chemical part of the environmental interactions between living organisms and therefore they are natural candidates for the production of active drugs. the chemical production of a plant is strictly subjected to the environmental conditions that can highly influence this production. first, the exactly determined species must be used and determined in composition. once the raw material is obtained, the process of transformation can significantly influence the composition of the product. the technological transformation is essential to the quality and efficacy of the product. therefore, this second step is vital for the success of the product. the third step consists of the target being assigned to the product and the consequent marketing. in future, natural products will be even more important in the production of new drugs and foods and feeds, able to face the challenges of a continuously changing market. technology is key to this. the natural products market is expanding rapidly in previously unexplored areas, in particular as an alternative to products based on synthetic compounds. the prospects and possibilities in this situation are immense, but knowledge of nature and activity of natural products must be revised utilizing recent devices and research approaches. importance and role of natural products will increase if the multidrug resistance continues, asking for new bacterial and insect possibilities of control. the common composition of a botanical product is based on a single herb or on the combination of more species based on recipes and formulae mainly derived from the historical literature and empirical experiences. the long and accurate work of phytochemistry based on the sequence extraction-separation-identification, derived from the correspondence of one drug to one illness, generated a huge catalogue of identified natural substances that can be employed as useful standards to determine the composition of the botanical drug. the knowledge about composition must be as complete as possible; not a single constituent should be unused, and utility depends strictly on the utilization. natural products are derived mainly from plants as the result of coevolution between organisms and environment (tehri and singh, ) . for this reason, they have been used for centuries in popular and traditional medicines, as well as often being employed as spices and insecticides. unlike modern pharmacology and drug development, which are based on a single chemical entity, natural product preparations are multiingredient. a single herbal drug contains at least compounds making a complex matrix, named a phytocomplex, in which the single active constituent is not considered solely responsible for the overall efficacy. the utilization of the phytocomplex is based on experimental basis, since many data afford the validity of this approach, although further confirmations could be obtained using modern pharmacological devices. in other words, the same botanical raw material can be used directly, or extracted in different ways or used as a source of selected substances, or modified according to the product and target. in , a mixed team of experts from mit (massachusetts institute of technology) and the broad institute of harvard university, both in the usa, reported an interesting and innovative study for a scientific evaluation of the effectiveness of natural products. the argument is strictly inherent to the endless debate about the role of natural products and their efficacy, causing a fighting contrast, but useless and boring, between supporters of "natural" versus defenders of synthetic drugs. the key aim of the study was to understand what is going on between the two main levels of the metabolism (primary and secondary), on the basis of the consideration of the functional connection between genes and gene products, as well as between genes and targets. an innovative feature of the study is that the researchers decided to commit the argument to neutral judgment, submitting the elaboration of collected data to the computational work of artificial intelligence. the work was based on the comparison of cumulative connectivity distribution of small molecules, natural or synthetic, grouped according to connectivity associated with the target. assuming that proteins form biological networks and that metabolism and health depend on these networks, we should be able to assign a role to the molecules considered as possible medicines. the result showed that natural products target the proteins with a high number of protein-protein functional interactions (higher network connectivity), whereas the synthetic ones act on a limited protein network. the conclusions of the study, based on a computational approach, were evident: "we observe that approved drug targets that are not also natural product targets exhibit a connection distribution much closer to the case for human disease genes that natural product targets, which remain the most highly connected targets." this sentence indicates a positive and useful consideration about the role and activity of natural products. natural products tend to target more essential and general protein networks to an organism than other groups of small-molecule targets, like those more related to specific disease genes. therefore, the dichotomy between natural and synthetic active constituents must be considered mainly as a consequence of a cultural heritage, unable to assign a complementary or differently appropriate role to the two classes of molecules. the results of the study are coherent with the nature of natural products, whose production is the consequence of environmental interactions, including defense against predators or pathogens. this kind of defense cannot be specific, and therefore natural products act on more highly connected network of proteins, interrupting or limiting the activity of the essential proteins in environmental competitors or invaders. they may be tailored for a positive or negative influence in physiologic activities and basic metabolism of an ample range of organic targets. these arguments are in favor of the potential use of natural products as insecticides. in any case, there are several difficulties in assigning the activity to single constituents, causing several cases of wrong or misleading assignments of all the activity to single substances in the case of a plant extract, like in valerian (valeriana officinalis), whose extracts are largely marketed and utilized for their mild sedative effects. with the discovery of valepotriates, the effects were assigned to these constituents, but after the evidence that extracts with low content in instable valepotriates also exerted similar action, the essential oil was considered additionally responsible for the effect. another case consists of a current debate about hemp. besides cannabinoids, its essential oil and other constituents are now considered important for the multiple activities of hemp. in other words, there are hundreds of marketed products of hemp and many related claimed activities, and this can be related to the complex cannabidioma and/or the different compositions of the products, although they are all derived from the same raw material. it is very important to stress that important new features can appear, also in the case of species highly studied in their chemical composition, as shown in the scientific literature. recently, a new cannabinoid was isolated from cannabis sativa (citti, ) . as is wellknown, (À)-trans-Δ -tetrahydrocannabinol (Δ -thc) is the main compound of hemp and it is considered the main one responsible for intoxicant activity. however, the chemical constitution of this species is subject to high differences in accordance with its varieties and cultivars. cannabinoids possess a unique structure, derived by junction of a monoterpene and a polyketide unit. most of them have a side alkyl chain, whose length influences the biological activity of this cannabinoid. in fact, analogues of Δ -thc with a longer side chain were synthetized and they have shown cannabimimetic properties far higher than Δ -thc itself (seven c against five). in this study, a new phytocannabinoid with the same structure of Δ -thc, but with a seven-term alkyl side chain, was isolated and identified, and its stereochemical configuration confirmed by a stereoselective synthesis. this new phytocannabinoid has been called (-)-trans-Δ -tetrahydrocannabiphorol (Δ -thcp). the binding activity of Δ -thcp against human cb receptor in vitro (k i ¼ . nm) proved to be similar to that of cp (k i ¼ . nm), a potent full cb agonist. in the cannabinoid tetrad pharmacological test, Δ -thcp induced hypomotility, analgesia, catalepsy, and decreased rectal temperature, indicating a thc-like cannabimimetic activity. as confirmation, the corresponding cannabidiol (cbd) homolog with a seven-term side alkyl chain (cbdp) was also isolated and unambiguously identified by matching with its synthetic counterpart. the presence of this new phytocannabinoid could account for the pharmacological properties of some cannabis varieties that are difficult to explain by the presence of the sole Δ -thc and indicate the importance of the interaction between constituents of the so-called cannabidiome. therefore, we were not totally surprised when we found good larvicidal activity against aedes albopictus also in nsos with low content in azadirachtins . this was quite a novelty on the basis of the literature, but it is necessary to consider the importance of the metabolomics approach and the possibility with hptlc to obtain several views of the same plates. each view means a revelation of different compounds on the basis of their chemical structure and present functional groups. using an appropriate revelation agent, it is possible to see compounds that are not visible with another derivatization. this approach is contrary to the tendency of current analytical chemistry to focus on a single class of compounds or even unique constituents, which obtain perfect and reliable but limited results. another incongruence consisted of the presence of insecticide activity also in neem products after years of production, when limonoids should be highly degradated. the first experimental evidence we obtained on the activity of neem oil was the inability of the larvae of ae. albopictus to complete the molt from larva to pupa. the larvae proved to be initially immature, their bodies imperfect, and finally before the third instar, most insects died and none was able to fly. the delicate mechanism of the development stage was jammed and the cruel destiny of the unfortunate insects assigned. each organism has its weakness. mosquitos, like any arthropod, possess a rigid exoskeleton, which offers efficient strong and secure protection, also against pesticides, which is one of the reasons for the success of these creatures. the exoskeleton of insects is primarily made of proteins (sclerotin) and chitin (a polysaccharide), which are interwoven and linked together to form strong but flexible bundles. interestingly, chitin is also the main constituent of the fungal cell wall. the ratio of the components of the exoskeleton varies from one body part to another on an insect. however, the exoskeleton is too rigid, and acts like a cover that encases the entire insect, and being a nonliving formation, the exoskeleton does not change size and grow with the insect. the exoskeleton is too ridged to be recycled or modified, and it must be substituted, but it must also protect the insect until the new exoskeleton is ready. during the growth period, insects must shed the exoskeleton in order to assume a new form. as a result, it is necessary for the insect to shed its old exoskeleton to make way for a new, larger one through a process called molting. this is a hormone-controlled phenomenon. during the molting stages, the hormones are released to start and finalize each step of the metamorphosis, until the mature insect finally emerges. however, the chemical constitution of the exoskeleton is variable in each insect species and this is the reason for the selective toxic effects, such as those reported in the case of neem. regarding the structures of insecticides acting as growth regulators, albeit in the case of ecdysones the relation with insect hormones is evident, in other cases the similarity is not so clear, as well as the real mechanism of action. the stages between the subsequent molts are generally called instars. these correspond to altered body proportions, colors, patterns, and changes in the number of body segments or head width. for most insect species, an instar is the developmental stage of the larval forms, but an instar can be any developmental stage including pupa or imago. the larval stage is in particular a delicate stage of the insect metamorphosis. however, we were totally aware that confirmation of the neem insecticide activity, albeit with a demonstrated chemical constitution, in a laboratory experiment was a weak starting point. the open questions were numerous: (a) how to obtain the same result in the field; (b) whether the larvicidal activity could be connected to other properties, in order to improve the use; (c) what the cost of neem oil would be, considering the large-scale spread of the insects; (d) how limited the stability of the active ingredients of neem would be; (e) what determination of chemical content of neem oil would be required, to be connected to the determination of the activity; and (f) what the ambit of utilization would be and the possible damage to the habitat. other advantages arising from the use of neem-based products are the rare induction of resistance, due to their multiple mode of action against pests, the low toxicity rates that have been detected against vertebrates, and finally the necessary environmental care. there is a little confusion about the plant species named azedarach, and very similar denominations. the name azedarach was given by the famous persian physician avicenna ( - ) to indicate some poisonous trees; however, azadirakhti literally means "free book of india." in , linnaeus reported about melia azadarachta in his species plantarum ( : with habitat: india). in the same book ( : ), we can find melia azedarach (habitat: syria) and melia azedarach var. sempervirens (habitat: zeylona). actually there are two distinct species, azadirachta indica a. juss, attributed to neem (or nimba, meaning "who gives good health," as reported in the sanskrit books) and melia azedaracht linneus, attributed to melia, a very similar tree. this is the typical taxonomic situation in botany and zoology. the differences between taxa are often very narrow and only specialists are able to find them. in any case, the problem of the significance of these differences is always a matter of debate. god bless taxonomists, because they are necessary to obtain order out chaos, but please do not spend your precious intellect on endless discussions with no final consistent result! in fact, the matter is complicated by synonymous, parental disputes, errors of any type, including wrong transliteration (i.e., gingko and ginko), disputable rules of the international codices, and more. neem and melia are very similar, but there are several tricks to distinguish between the two species. the first is commonly known also as indian lilac and the second one as persian lilac or simply melia. neem has usually white flowers whereas melia presents an explosion of blue flowers; the fruits of the former have an elongated shape, whereas the latter's are totally rounded. if the trees do not have flowers or fruits, and you are not a botanist, you may be in trouble, but you can remember that neem cannot live in temperate climate regions, whereas melia can be easily cultivated in such places. therefore, if you are in europe or the usa, you can be % sure on the matter. melia azedarach is known by several common names, such as melia, chinaberry tree, pride of india, bead-tree, cape lilac, syringa berrytree, persian lilac, and others. it is usually a large tree growing up to m tall, with leaves -pinnate, rarely -, with primary pinnae in two to six pairs, usually three to seven leaflets per pinna, narrowly ovate or subovate, serrate, acuminate, irregularly toothed, or crenate. flowers are abundant and small, sweet-scented, in large axillary panicles. all parts of this tree are reported to have medicinal uses, but in particular, in terms of insecticide properties, seedlings are reported to present aphid attacks. a leaf used as a bookmark will deter insect pests. in italy, the tree is known as the tree of rosary, since in the past, before the advent of plastic, its hard and round kernels were used to make the grains of a rosary. our research on melia azedarach, as well as the references on this plant, evidences a significant difference in the chemical composition. limonoids are present, but different from azadirachtins and other constituents make a marked relevant dissimilarity in composition. the initial conclusion was that melia probably cannot compete with neem as an insecticide, but other utilizations can be explored. however, once again a limit in the references is an irresistible task for a researcher in search of innovations. in addition to the insecticidal properties, we were initially particularly interested in the antimicrobial activity. people often associate antimicrobial activity with infection and effects on their health, but microbes are everywhere and most damage affects cultivation of plants. agricultural methods of reproduction of plants with economic value were totally transformed by the introduction of micropropagation and stem cell culture. micropropagation allows the rapid cultivation of selected cultivars, saving time and resources. however, although the first steps of micropropagation were performed in aseptic conditions, the possibility of infection of calla, shoots, and seedlings is high. avoiding the infection must be done via an appropriate and sensitive approach, avoiding damage to the delicate meristems-a typical job for natural products. the antibacterial study (marino et al., ) aimed to investigate the antibacterial activity of unripe fruits of melia azedarach collected in different periods. the activity was tested on the shoots of a hybrid of prunus cerasifera x prunus spinosa and calla lily of zantedeschia aethiopica against several bacterial species. the data reported evidenced a positive antibacterial activity and the absence of any negative effect on the growth of shoots surviving at the second subculture on a standard medium. hptlc analysis showed the prevalence of polyphenols, such as chlorogenic and caffeic acids, which, on the basis of the literature, are consistent with the antimicrobial activity. this activity is important considering that many plant species of economic relevance are now obtained by micropropagation, and this cultivation in vitro is necessary to avoid any sort of contamination. further research is essentially the rational collection of most of the arguments previously considered, as evident in the title: "green-synthesised nanoparticles from melia azedarach seeds and the cyclopoid crustacean cyclops vernalis: an eco-friendly route to control the malaria vector anopheles stephensi?" (anbu et al., ) . in this research, once a single-step greensynthesis of silver nanoparticles (agnp) using the seed extract of m. azedarach was obtained, we tested its mosquitocidal activity. in laboratory assays on anopheles stephensi, ag np showed lc ranging from . (i instar larvae) to . ppm (pupae). in the field, the application of ag np ( Âlc ) led to complete elimination of larval populations after h. finally, we decided to test the nanoparticles on nontarget aquatic predators. the application of ag np in the aquatic environment did not show negative adverse effects on predatory efficiency of the mosquito natural enemy cyclops vernalis. the reason for this additional research lies in the fact that numerous aquatic arthropods attack and devour preparasites. as we already know, the utilization of the insecticides, though with plant-derived active constituents, could be dangerous for the environmental equilibria. in particular, it could affect the natural biological control, based on the presence predators of the vector in the common habitat, remembering that all the insect stages, except the adult insect, need water. in such sites, there is fresh water everywhere, such as lakes, pools, and similar places, enabling life along the plant-covered banks of stagnant and slow-flowing bodies of water. in such places, mosquitos can proliferate as can any other predator, which in an aquatic environment is fundamental to limit the proliferation of the vector. in fact, after coupling, and the consequent blood feeding necessary to assume the proteins necessary for the eggs maturation, the female is looking for an appropriate place for the deposition of - eggs. a single anopheles, like other insect, is able to produce a quantity of eggs and larvae enough to invade all the neighboring habitats, as in the classic case of a locust invasion. this is not possible only thanks to the natural enemies. the microaquatic environments are the scenario of a continuous fight for survival, where often two or more species of arthropods are involved, as predator or as prey. in our study, we selected the genus cyclops, which is one of the most common of freshwater copepods, comprising more than species. copepods are very little crustaceans, commonly called water fleas. they have a single large eye, which may be either red or black, and therefore they are named for the cyclops of greek mythology. cyclops prefers fresh water, and is less frequent in brackish water, where it feeds on small fragments of plant material, animals, or carrion. it swims with characteristic jerky movements and has the capacity to survive unsuitable conditions by forming a cloak of slime, with an average lifespan of about months. several microscopic crustaceous, including copepod species, feed small and very small preys. in high-density, unstructured environments such as eutrophic lakes, predatory copepods commonly coexist with certain smallbodied prey, where encounters are frequent with ineptness on the part of the predator and counter-tactics by the prey. in particular, laboratory studies showed that copepods are effective predators on early-instar culex larvae, involving an important role in suppressing mosquito populations, because of their feeding behavior and abundance. they are very efficient in this role, since the presence of alternative abundant food, like bacteria and protozoa, does not deter their attacks on their preferred prey. copepods are capable of killing and eating at least four preparasites within min and a predator density of copepods/liter is expected to reduce the mosquito larvae by %, with the rate of predation inversely proportional to the water volume. neem cake: from by-product of an industrial process to multipurpose resource for a sustainable agriculture chain during our research activity, we were highly interested in industrial plantborne by-products, since they can offer new products to the market with lower cost and high usefulness. our attention was immediately attracted by neem cake, a cheap by-product of nso extraction, obtained as a residue after mechanical pressing of the neem seeds, considered of low economic value and utilized to enrich the soil of some mineral components, such as nitrogen. the laboratory test indicated neem cake activity against aedes albopictus and a number of culicidae species (nicoletti et al., ) . in the case of biocidal treatments, it is important to demonstrate that insecticide activity is associated with antimicrobial activities in consideration of the high possibility of infection and the severe consequences for health, in particular in the case of the animals, both pets and livestock. the importance of insecticidal and antimicrobial activities for animal treatment has been evidenced in the experiments with nso and neem cake further reported, including larvicide, deterrent, and repellent activities (benelli et al., a,b; nicoletti et al., a,b) . the complex range of different compounds in the neem seeds open the possibility to utilize the derived products to solve many current problems. the challenge now is to obtain marketed products tailored for different utilizations. the reported experiments evidenced these potentialities, which are only waiting a realization and a wider utilization. despite diseases, wars, and environmental disasters, the human population is growing. first of all, more people will need more food. this forecast shows in particular a massive increase in animal protein demand, needed to satisfy the growth in the human population, wherein billions of people require an increase of caloric input and better food. therefore, attention is focused on the sources of feed protein and their suitability, quality, and safety for future supply. in addition, the quantitative production aspect is causing a series of problems. there will need to be a considerable increase in feed manufacture, requiring a thriving, successful, and modern feed industry, including a key aspect concerning the protection and preservation of the food produced and marketed. this aspect is strictly related to safety issues, which will remain paramount in the minds of consumers following recent food crises. it is time to consider that the need of more food to feed due to increasing planet population perhaps cannot simply be solved by massive production, but reduction of food waste and conservation can increase food availability by %- %. "feed the planet and energy for life" was the theme of world expo in milan, italy. among the activities occurring at the expo, research and proposals concerning the utilization of neem products were presented in a call for projects in favor of sustainable progress and production of future foods. the neem project was selected as the best one due to its possible applications in the production of food and feed. the expo event projected feeding as the main challenge for humankind and showed the extreme urgency of elements of innovation in technology and science connected to the production and conservation of food. it was demonstrated how serious feed problems still plague several areas of the world today, and the possibility of new solutions was mentioned. the neem project was focused on the agricultural utilizations of neem cake concerning its advantages as soil fertilizer and as a natural ectoparasiticide for the treatment of sheep and goats. neem products were proposed as being able to affect the biotic composition of the soil. neem cake must be preferred to neem oil for its cost and its form as a powder immediately available. several experiments evidenced the improvements of the utilization of neem cake in agrarian ecosystems: ( ) availability of nutrients, in particular nitrogen and phosphorus, more consistent with the requirements of the crop; ( ) development of the microbial beneficial biomass of the soil, which increases in quantity and activity, but with selective influence against nematodes and other negative components. in agricultural practices, plants in addition to nutrients should count on a greater variety of useful microorganisms and on acquisition of nutrients themselves, through the activation of complex symbiotic systems. if you want to understand the state of health of a tree, you must look down, not up; and ( ) development of pest control system of insects and other arthropods of agricultural and livestock interest. neem cake, as an industrial by-product, is a heterogeneous material that maintains a high added value due in large part to its chemical composition, which confers its biological activity. neem cake is widely available on the global market, considering the increasing presence of neem trees in the world and production of nso. the exploitation of its characteristics in the food chain to improve consumer health, increase the productivity of agricultural products, and feed the planet is the logical consequence of the urgent need to develop new sustainable agricultural systems in a world where many highly polluting pesticides are no longer allowed to be used. however, more research, in particular in field conditions, is necessary to understand the real value of its microbiological, insecticide, fertilizer, and nematocide activity, involving collaborations between different experts in individual sectors-import companies, organic farms, and research institutions-in order to determine the manner and timing of land application of this valuable product of "waste," still underestimated. neem cake could lead to a revolutionary improvement in the fertilization of agricultural plants, adding to the characteristics of chemical fertilizers those of a soil improver. in agriculture, we could define neem cake as a prompt nutrient-release fertilizer, effective in allowing rapid absorption of nutrients and promoting development of the plant, with the capacity to increase the activity of the microbial biomass and organic matter, favoring the sequestration of carbon. the idea was to join the fertilizer, insecticide, and antimicrobial utilities of neem cake. exploitation of the use of neem cake as an insecticide came from this first test: some pots of impatiens (impatiens balsamina) were fertilized with % by volume of neem cake, and mosquito larvae were reared starting from eggs. the eggs were hatched in control and treated in pot saucers, but none of the newborn larvae survived in the water saucers of pots treated with neem cake, while in the water saucers of pots unfertilized with cake, the control larvae completed their development in less than a week, becoming adult mosquitoes. other major beneficiaries of the use of neem cake as insecticide are undoubtedly sheep farmers, who can use an organic product of natural origin and low cost that is simultaneously effective against the larvae of culicoides and other pests, while respecting the natural biotic communities. direct beneficiaries of neem cake, as a fertilizer, are farmers seeking pest and nematode control, in particular for nematodes. currently, some highly toxic products are still on the market by virtue of the absence of suitable alternatives. particular attention must be focused on the changes on soil micro-composition, as evidenced in several field experiments. in conclusion, we can report the following important advances in the use of neem cake as a functional fertilizer: (a) energy saving flows from the use of a waste of an industrial chain; (b) environmental sustainability, as documented by the analyses attesting the absence of heavy metals, aflatoxins and residues of pesticides; (c) neem cake is an excellent alternative to methyl bromide (bm) (banned as being responsible for the "thinning" of the ozone layer of the atmosphere); (d) neem cake is an excellent alternative to temephos and other organophosphates used to treat water infested with disease-carrying insects including mosquitoes, midges, and blackfly larvae; (e) neem cake is a great alternative to nematicides, like , -dichloropropene; and (f) neem cake in the field trials carried out in sardinia had efficacy similar to azadirachtin biological products already established in organic farming, but were very expensive and not really effective. in addition, neem cake showed very low effect on "nontarget" insects that live in the same environments as culicoides larvae. ectoparasites are organisms that inhabit the skin of another organism, causing significant infestations and pathologies. many micropathogens can profit from the work of ectoparasites, either to colonize the skin injury and lesion, or be inserted in the host during the feeding. the vast majority of ectoparasites are arthropods, e.g., insects and arachnids. again the triangle host-vector-etiological agent is reproduced. many ectoparasites are vectors of pathogens, which are typically transmitted while feeding on or from other hosts. several ectoparasites (e.g., most lice) are host-specific, including livestock, pets, poultry, fish, and bees, but others parasitize a wide range of hosts, including humans. typical effects of infection on the host are irritability, dermatitis, secondary infection (other parasites profit of the skin necrosis), fecal hemorrhages, blockage of orifices, inoculation of toxins, and exsanguination. as a consequence, the host's general health can be seriously affected with low weight gains, particularly important in livestock. subdermally located parasitic larval stages of certain flies can be favored by the ectoparasited infection, causing a condition termed "myiasis." when insects (order hemiptera) are involved, the infection mechanism is similar to that previously described for any insect-borne disease. the vector contains several hematophagous ectoparasites, including approximately species of kissing ("cone-nose") bugs (reduviidae, triatominae) and bed bugs and bat bugs (cimicidae). these parasites make physical contact with the host principally when ingesting a blood meal. these kissing bugs usually prefer domestic animals, from which relatively large blood volumes may be imbibed; in such a way they can cause a great deal of damage and transmit important diseases. ectoparasites play a very detrimental role in terms of decreasing the productivity of livestock, such as sheep and goats. nso was utilized in the field as an antibacterial in the case of ectoparasites' stings and bites resulting from goat wounds. common external sheep and goat parasites include ticks, lice, and mites. they cause restlessness and irritation. weight loss and reduction in milk production may occur as a result of nervousness and improper nutrition, because animals spend less time eating. bites can damage sensitive areas of skin (teats, vagina, eyes, etc.) . some parasites feed on blood, causing anemia, especially in young animals. the bite and the sting of ectoparasites allow bacteria to proliferate in wounds from abrasions or lesions from scratching, and cause levels of tissue reaction of different entities, super-infection, and cervical lymphadenopathy. ectoparasites cause many problems in livestock production. they seriously damage sheep and goat skins, resulting in the rejection or downgrading of the skins. this causes huge economic loss, as this skin damage renders it unsuitable for the leather industry due to the decrease in quality. lower production of meat is also a typical consequence. pseudomonas aeruginosa wound infections are characterized by a change in the color of the skin around the wound area and the formation of lesions. the bacterium products and pigment cause yellow discoloration of wool and consequently reduced quality and market value. nso treatment in the field on as a natural ectoparasiticide for sheep and goats proved to be successful in preventing and curing the attacks of endoparasites ( fig. . ) . the experiments were performed on selected livestock (fig. . ) by a specialized team of crea researchers (de matteis et al., ) . the effects on the parasites were evident (figs. . and . ) and even after the first treatment with nso, protection against ectoparasites was obtained. more important, the health of the treated livestock improved, as testified by the hematological profile of goats. in vivo and in vitro tests on blood cells from siriana, sanen, cashmere, and maltese goat (capra hircus) breeds showed no significant difference (p <. ) between nso treated and untreated goat hematological parameters at each sampling time considered. in addition, the nso effect on goat pbmc cultured in rpmi medium was evaluated at : Â to : Â dilutions at , , and h of exposure. the in vitro test revealed that the response of goat pbmc viability is dependent on concentration, incubation time, and nso dose. in conclusion, the nso should be considered useful, safe, and innovative for development of topical solutions for the care of wounds. among the most relevant typology of neem products, we focused on selectivity. the antibacterial activity of nso was assayed against isolates of escherichia coli, considering that this bacterium can produce beneficial and pathologic populations. the molecular biology characterization showed that isolates resulted in diarrheagenic e. coli. nso showed biological activity against all isolates. however, there were significant differences between the antibacterial activities against pathogenic and nonpathogenic e. coli, as well as between nso and ciprofloxacin activities. on the basis of the results obtained, nso is able to counteract e. coli and also influence the virulence of e. coli-viable cells after treatment with nso. the preservation of marketed food is an important aspect of the smart utilization of the produced food (maruchecka et al., ) . furthermore, the consequent waste of unutilized food is a relevant problem in overcrowded towns (hlpe, ) . a large quantity of food is lost or wasted throughout the supply chain, from initial agricultural production down to final household consumption (hlpe, ; kader, ) . the loss or waste for high perishable food, such as fresh fruit and vegetables, fish and livestock products, has been estimated at as much as half of all food grown before and after it reaches the consumer. approximately one-third of all ffvs produced worldwide are lost during food supply chain production. shelf life plays a central role in food spoilage. the impact of the enormous quantity of packaging is evident in any planet environments. increase of the shelf life means reduction of cost and waste. everything pivots around the material utilized for packaging, and new solutions are emerging (otoni et al., ; singh and singh, ; cooksey, ; appendini and hotchkiss, ) , including passive packaging (brockgreitens and abbas, ; ozdemir and floros, ) , active packaging (coma, ) , intelligent packaging (lee et al., ; de kruijf et al., ) , and smart packaging (dobrucka and cierpiszewski, ) . although the results are not evident in our ordinary life, the galaxy of packaging is rapidly moving and increasing in research and proposals, based on new technologies and advanced techniques recently available, like nanotechnology and molecular biology. efforts are focused on solving the food preservative problems, to extend the shelf life of perishable foods, by reducing the need for additives and preservatives. "smart packaging" is based on the production of functional methods to obtain the following goals: be tailored depending on the product being packaged, including several types of food, beverages, pharmaceuticals, household products, etc.; reduce food waste, increasing the shelf life; and maintain, and eventually enhance, product attributes (e.g., look, taste, flavor, aroma). the key words are protect, preserve, and present. several methods and approaches, such as oxygen scavenging and antimicrobial technologies associated to the production of modified films, have been considered . they are different solutions to serve the basic and fundamental properties of packaging. so far, the dominant packaging is the basic one, using low-cost material and involving no interaction with the food inside. this is passive packaging, wherein the traditional packaging systems are included, as the use of covering material characterized by some inherent insulating, protective, or ease-ofhandling qualities. usually, the ordinary packaging of food is mainly a used to method to attract and select the consumer, beside a preservation. the consequence is the enormous amount of waste, and the consequent damage to the environment. this situation is increasing due to the increasing numbers of consumers in emerging countries, where these consequences are not adequately considered. packaging is considered active when it can interact in the same way and/or react to various stimuli, in order to keep the internal environment favorable for the maintenance of product quality. several environmental, biotic, and abiotic factors must be considered, in order to respond to the degradation process successfully. the activity involved could be the presence of an oxygen scavenger (this can absorb high-energy oxygen inside a package and therefore increase the shelf life of a product) or an anti-ros (a scavenger of radicals by oxygen or other origins), such as in the typical case of phenolic natural products. smart packaging relies on the use of chemicals, electrical, electronic, or mechanical technology, or any combination of these. technology is used to modify the packaging by adding constituents to change its features and properties (kerry et al., ; malhotra et al., ) . active and intelligent packaging is particularly dedicated to the preservation of fresh products, like vegetables, in accordance with increasing requirements for this kind of food (nicoletti and del serrone, ; nicoletti, a,b) . intelligent packaging systems monitor the condition of packaged foods to give information regarding the quality of the packaged food during transport and storage (aguilera et al., ) . probably the most innovative aspect of intelligent packaging is that it can be supported by the utilization of systems of detection in meat and meat products, obtained through the use of sensor technologies indicators (thakur and ragavan, ) , including integrity, freshness, and time-temperature indicators (ttis) and radio frequency identification (rfid). therefore, active and smart packaging performs additional functions to the basic one by the introduction of innovations in the design of packaging, with the aim of increase the shelf life, but also to add conveniences for the user and usefulness for the consumer, to be introduced also in the supply chain. in this way, the product can respond not only to the need for a longer life, but also make the product more available, more useful, and more safe. since our invisible enemies are asked to play their role again, antibiotic activity is required. packaging is mainly used to separate food from environmental conditions, utilizing simple material made of paper or plastic. however, it cannot prevent internal attacks by microorganisms, but can only limit or delay the effects. therefore, additional treatments are required to limit their action, like the utilization of low temperatures, which involves additional costs and energy consumption and pollution. a new idea is to associate to the packaging some antimicrobial agent. before and during packaging, storage, and shelf life, food is subjected to a continuous attack by microorganisms. these microorganisms are working to benefit themselves by demolishing progressively the molecular structure of the food, as soon and as completely as possible. therefore, by preserving the food, we are working in a thermodynamically unfavorable situation. in term of shelf life, the food is in competition with its natural recycling, and, working to maintain as possible this limbo, we can utilize the food efficiently as it is possible. the resistance phenomenon interests also zoonotic food-and waterborne pathogens becoming more resistant to antibiotics (del serrone et al., ) . resistant strains of pathogens have been isolated from food, causing an increasing incidence of food-borne diseases. through the food, these microorganisms could be entering the human gastrointestinal tract on an almost daily basis. the antimicrobial activity of nso and related products have already been reported (palanappian and holley, ; baswa et al., ; sairam et al., ) . a possible utilization of antibacterial activity of neem cake against meat spoilage bacteria was tested using a broth model meat system . the tests were positive, since the growth inhibition zone (mm) varied significantly (p!. ). with respect to ciprofloxacin activity, the antibiotic value ranged as follows: . ae . to . ae . mm and . ae . to . ae . mm, respectively. the percentage of bacterial growth reduction (gr%) also varied significantly (p !. ) in function of considered nce concentrations ( : - : , ), with the highest gr% for μg nce ( . ae . to . ae . ). the numbers of viable bacterial cells never significantly (p . ) exceeded inocula concentrations used to contaminate the meat. all the results of the experiments showed that neem cake is able to counteract the main microorganisms responsible of meat spoilage, like strains of gram-positive and gram-negative, as well as facultative anaerobic bacteria. the antimicrobial activity of neem products was confirmed also for nso against spoilage bacteria, such as carnobacterium maltaromaticum, brochothrix thermosphacta, escherichia coli, pseudomonas fluorescens, lactobacillus curvatus, and l. sakei. after the second day after nso, only c. maltaromaticum-viable bacterial cells were detected. these data could be used to create new intelligent packaging. utilizing a nanotechnology already employed for other materials, neem cake may be incorporated into the cavities of nanoparticles, maintaining its antiparasite activity. once incorporated into the packaging material, the neem cake, also in minimum quantity, should be able to effect its preservative food action, acting against the demolishing microorganisms. the increase of the shelf life of meat should compensate for the additional cost of the packaging material, not considering the decrease of waste. it is possible that the first activity of luca was to find the energetic source for survival, and the second was to compete with the other lucas. the results are an endless transformation of forms and production of new molecules. the living organisms had a long time to organize their molecular weapons and the secondary metabolites are there, produced and organized to be considered and utilized in the right way. the neem tree is an example of nature's treasure. the advent of homo sapiens (lucy) changed in part the rules of the natural game, but natural products still remain a necessity for our life. recently, parenteral artesunate has replaced quinine and many other antimalarial products for the treatment of severe malaria. however, several reports have demonstrated the emergence of resistance to the efficacy of artemisinin-based combination therapy monotherapy, such as in western cambodia and other regions in south-east asia. to face the phenomenon, artemisinin-based combination therapies are now recommended by the who. the aim is to reduce the morbidity and mortality associated with malaria with artemisinin-based combination therapies, including chloroquine plus other drugs, like sulfadoxine-pyrimethamine. meanwhile, with increasing resistance to chloroquine, quinine is reconsidered, being so far the only substance for which plasmodium did not develop resistance. the consequences are that in uganda quinine was prescribed for up to % of children younger than years with uncomplicated malaria, and from , african countries recommended quinine as a second-line treatment for uncomplicated malaria, as a first-line treatment for severe malaria, and for treatment of malaria in the first trimester of pregnancy. recent surveillance data from other sites are in accordance. however, quinine was substituted due to its limits and therefore in , who ( ) guidelines recommended reinforcing quinine's activity by combining it with other antimalarial agents, like doxycycline, tetracycline, or clindamycin as a second-line treatment for uncomplicated malaria (to be used when the first-line drug fails or is not available) or quinine plus clindamycin for treatment of malaria in uncomplicated cases and in the first trimester of pregnancy. the development of effective cocktails is a current trend of medical treatment of several diseases, including forms of cancer. in addition, the combination of natural products and synthetic drugs is recommended. natural products can be utilized as resistance-modifiers or chemosensitizers, and may be able to restore chloroquine sensitivity in resistant strains of plasmodium. the idea of years of research from different research groups was that the antimalarial treatment combined with natural products could be based on lower doses of chloroquine, in order to minimize the resistance insurgence and to avoid the collateral effects in the case of prolonged use, necessary in areas where the disease is endemic. this approach came from an ethnopharmacological investigation by professor rasoanaivo (rasoanaivo et al., ) . most people consider ethnopharmacology to be a collection of ancient utilizations of natural sources, and as knowledge that is going to disappear. on the contrary, in addition to traditional uses there are new ones emerging, even as consequences of the utilization of modern drugs. considering that oms reports that % of the planet population relies on traditional medicine, the utilization of medicinal plants is not limited to ancient times and past populations, but it changes according to needs and evolution of treatments. ethnobotanical knowledge is still passed from one generation to another in the majority of populations living in rural areas, and in urban areas, where malaria has been revealed to be resistant or incurable by modern scientific medicines, people have turned to traditional treatments. it is therefore of paramount importance to preserve and transmit this ethnobotanical heritage. therefore, this discipline must be regarded as a multidisciplinary science in movement, where botany, chemistry, and pharmacology play central roles for scientific evaluation and validation of popular uses. however, economic and social aspects must also be considered, in order to develop new drugs and treatments of both old and new diseases. most antimalarial drugs currently in use belong to the classes of aminoquinolines (chloroquine, amodiaquine, primaquine), quimolinomethanol derivatives (quinine, mefloquine, halofantrine), diaminopyrimidines (pyrimethamine), sulfonamides (sulfadoxine, sulfadiazine), biguanides (proguanil and derivatives), antibiotics (tetracyclines, doxycyclin, clindamycin), sesquiterpenes (artemisinin, dihydroartemisinin, arteether, artemether, artesunate) , and naphtoquinones (atovaquone). among them, only quinine and artemisinins are natural products, but also a relevant part of the current antimalarial arsenal. the potentiality of natural products is very high. a review by willcox and bodeker ( ) on traditional herbal medicines for malaria in three continents reported plant species from families. however, the clinical trials are largely lacking, since only eight clinically controlled trials have been reported, involving p. falciparum and p. vivax. in the case of malaria, alkaloids are the first candidates responsible for the activity. there is a long tradition in popular medicine of plants containing these compounds to control fever. these plants also have a bitter taste, which is usually connected to the alkaloid presence, as already reported for the aforementioned quinine bark case. two important considerations attracted our attention, in view of the possibility to explore new strategies: the special endemic flora of madagascar and the occurrence of information about a popular treatment of malaria as yet unreported. madagascar is a land of endemism, consisting about , species of vascular plants, of which % are endemic, and eight families totally endemic. malaria is practically endemic in all madagascar and therefore the population harbors a very rich and unique knowledge on antimalarial plants. after a resurgence of malaria in the early s, as a consequence of plasmodium falciparum resistance and due to the high costs of conventional drugs, local populations returned to the uses of herbal remedies. two hundred and thirty-nine plant species, of which about % are endemic to madagascar, have been reported as having antimalarial uses in malagasy traditional medicine. prof. rasoanaivo discovered the use by some populations in madagascar of decoctions of some local plants in association with low doses of chloroquine to complement chloroquine action against chronic malaria . the lower use, one or two tablets of chloroquine ( - mg), is probably adopted to avoid collateral effects due to prolonged use of chloroquine, but such a dose could be considered inadequate to favor chloroquine resistance. therefore, we have a mixture of recent learning and ancient knowledge, evidencing the reality of ethnopharmacology. however, popular uses of medicinal plants need scientific validation with advanced tools. therefore, research started from the knowledge that some populations in madagascar use decoctions of some local plants in association with low doses of chloroquine to complement chloroquine action against chronic malaria. in such a way, resistance insurgence and collateral effects are both lowered. on the basis of the ethnobotanical work conducted by rasoanaivo and his collaborators, plants were selected and investigated for in vitro and in vivo antimalarial activity and a chloroquine-potentiating effect. in the case of validation of the activity, the determination of the active constituents followed. the results of these selections were that the alkaloids of loganiaceae, menispermiaceae, and rutaceae were the most promising compounds showing significant effects, some of them potentiating the action of chloroquine. from a phytochemical point of view, alkaloids are in pole position among natural products utilized in traditional medicine against malaria. mono-and bis-indole alkaloids have been isolated from several plants that are traditionally used to treat malaria on different continents. the most active compounds are those that originate from plants belonging to the genera strychnos (loganiaceae) and alstonia (apocynaceae). a review covering the indole alkaloids that have high antiplasmodial activities in vitro and in vivo, and favorable selectivity indices (si¼cc /ic ), was published by frederich et al. ( ) . in the case of malaria, alkaloids are the first candidates as being potentially responsible for the activity. there is a long tradition in popular medicine of plants containing these compounds to control fever. these plants also have a bitter taste, which it is usually connected to the alkaloid presence, as already reported for the aforementioned quinine bark case. two important considerations attracted our attention, in view of a possibility to explore new strategies: the special endemic flora of madagascar and the occurrence of information about a popular treatment of malaria so far never reported. madagascar is land of endemism, consisting about , species of vascular plants, whose % are endemic, and even families totally endemic. malaria is practically endemic in all madagascar and therefore the population harbours a very rich and unique knowledge on antimalarial plants. after resurgence of malaria in the early 's, as a consequence of plasmodium falciparum resistance and due to high costs of conventional drugs, local populations back to the use of herbal remedies (blanchard, ; maggi et al., ) . two hundreds and thirty-nine plant species, of which about % are endemic to madagascar, have been reported as having antimalarial uses in the malagasy traditional medicine. prof. rasoanaivo discovered the use by some populations in madagascar of decoctions of some local plants in association with low doses of chloroquine to complement cq action against chronic malaria . the lower use, one or two tablets of chloroquine ( - mg) , is probably adopted to avoid the collateral effects due to a prolonged utilization of chloroquine, but such dose could be presumed inadequate to favour chloroquine resistance. therefore, we have a mixture of recent acquirement and ancient knowledge, evidencing the actuality of ethnopharmacology. however, popular uses medicinal plants need a scientific validation with advanced tools. therefore, the researches started from the knowledge that some populations in madagascar use decoctions of some local plants in association with low doses of chloroquine to complement chloroquine action against chronic malaria. in such way, resistance insurgence is lowered, as well as collateral effects. on the basis of the ethnobotanical work conducted by rasoanaivo and his collaborators plants were selected and therefore investigated for in vitro and in vivo antimalarial activity and a chloroquinepotentiating effect (maggi et al., ) . in case of validation of the activity, the determination of the active constituents followed. the results of this selection were that the alkaloids of loganiaceae, menispermiaceae and rutaceae were the most promising compounds showing significant effects, some of them potentiating the action of chloroquine. mono-and bis-indole alkaloids are traditionally used to treat malaria in different continents (ramanitrahasimbola et al., (ramanitrahasimbola et al., , . the most active compounds were mainly related to the genera strychnos (loganiaceae) and alstonia (apocynaceae). a review covering the indole alkaloids that have high antiplasmodial activities in vitro and in vivo, and favourable selectivity indices (si¼cc /ic ) was published by frederich et al. ( ) . strychnos is a pantropic genus, with about species, present in three continents: in africa, in america, and in asia and oceania (only s. potatorum is present in both asia and africa). asiatic species are mainly small trees, whereas in the new world lianes are generally dominant. the most famous strychnos species is the asiatic s. nux-vomica, because of strychnine contained in the seeds with other related alkaloids. strychnine is also known and used for its bitter taste. south american species are characterized by different mono and bisindole alkaloids, important as constituents of some curare preparations of indios amazonia tribes (see introduction) . during the preparation of curare, the tribe curandero selects local plants and extracts the mixture by hot water. finally, the extract is filtered on leaves and concentrated to obtain a paste, which is preserved into a container, like a calebassa or a tube, maiden by a cane, or a pottery. active constituents in curare are bis-indole alkaloids from bark of strychnos ssp. and bis-tetrahydroisoquinoline alkaloids from menispermaceae. the genus strychnos is represented in madagascar by species, of which five are endemic to the island. among them, s. diplotrocha leeuwenberg and s. myrtoides gilg & bussse are used as antimalarial in the northeastern part of the country (rasoanaivo et al., ) . the phytochemical analysis allowed the separation and the structural determination of several indole alkaloids, some already known and others never reported, including mixtures of epimers, which is very unusual in the same plant (rasoanaivo et al., (rasoanaivo et al., , (rasoanaivo et al., , . the in vitro and in vivo chloroquine-potentiating effect of the crude extract of dried and powdered stem barks of s. myrtoides exerted chloroquine-potentiating effects on p. falciparum fcm , but it was devoid of intrinsic antimalarial activity. the extract was also devoid of cytotoxic effects on hela and l fibroblast cells. the two compounds exhibit a closely related structure but different basicity. therefore, the latter parameter can be excluded from the factors affecting the chloroquine-potentiating effect. these results were confirmed by other experiments, demonstrating that the crude extract of s. myrtoides showed higher chloroquine-enhancing activity than its major bioactive constituents. these data support the use of the plant as a phytomedicine to treat malaria, but minor components of the extract may act synergistically. among the main isolated alkaloids, malagashanine was very interesting. malagashanine is an unusual indole alkaloid of the strychnos type. its pentacyclic structure contains seven consecutive stereogenic centers and, most important, a transfusion between the c and d rings, against all the other similar natural alkaloids. therefore, malagashanine is the parent compound of a new type of indole alkaloids (fig. . ) (kong et al., ) , named n b c( )-secocuran, isolated so far from the malagasy strychnos species, which are traditionally used as chloroquine adjuvants in the treatment of chronic malaria (rasoanaivo et al., a (rasoanaivo et al., , . malagashanine showed only weak in vitro intrinsic antiplasmodial activity (ic ¼ . ae . μm), but did display marked in vitro chloroquine-potentiating action against the fcm chloroquine-resistant strain of plasmodium falciparum. another study allowed clarification of the mechanism of action of the major constituent, malagashanine, being able to prevent chloroquine efflux from the cell, and stimulates chloroquine uptake into drug-resistant p. falciparum strains. malagashanine appears able to act more on plasma membrane than inside the parasite, allowing the toxicity of chloroquine against plasmodium, even at sublethal doses. in the attempt to confirm the reversal of chloroquine resistance by the bark of s. myrtoides, a double-blind randomized controlled clinical trial of a standardized alkaloid extract titrated at % malagashanine took place in a government-run outpatient clinic in the town of ankazobe (northwest central highlands of madagascar), but the results of the treatment showed no significant efficacy, indicating a need for other confirmations. however, in conclusion, the approach, in accordance with recent tendencies on multidrug resistance control, based on mixtures of natural products and classic antimalarial drugs, with a relevant coincidence between the ethnobotanical reports and the scientific evidence, may offer interesting possible solutions for the treatment of malaria. many aspects about the mechanism of action of malagashanine as chloroquine adjuvant to reverse the resistance need further study. malagashanine could increase drug accumulation by interacting with a dysregulated ion exchanger, avoiding the decrease inside the food vacuole, or acts by a mechanism related to drug binding to hematin (perisco et al., ; rafatro et al., ) . in particular, in relation to the ph role in the blood red cell, it would be necessary to determine if malagashanine acts inside or outside the food vacuole, including the membrane periphery. the capacity of malagashanine to reverse cq resistance may be related to the well-known properties of verapamil ( fig. . ) and related substances (martin et al., ; martiney fig. . verapamil and other compounds studied for cq-resistant reversal by membrane calcium channels blocking. adovelande et al., ) . verapamil was the first calcium channel antagonist to be introduced into therapy in the early s. it is a phenylalkylamine calcium channel blocker used in the treatment of high blood pressure, heart arrhythmias, and angina. in short-term incubations, verapamil was found to increase chloroquine accumulation in the lysosome of erythrocytes infected with both chloroquine-sensitive and -resistant organisms, but only to affect the chloroquine susceptibility of the latter. verapamil works independently of the overall ph gradient concentrating cq into a trophozoite's digestive vacuole. the activity is therefore related to the inhibition of membrane ion channels, interfering in the chloroquine transit within the parasite's cytoplasm. other substances like chlorpheniramine and others are reported as candidates for cq-resistant reversers. in any case, again the key role of natural products and ethnoparmacology information, such as for quinine (cinchona sp.) and artemisinin (artemisia annua), is fully confirmed. another attempt to explain the activity of malagasy plants alkaloids explored the role of glutathione. l-glutathione reduced (gsh) (fig. . ) is a simple tripeptide, consisting of glutamic acid, cysteine, and glycine. it is considered one of the most powerful endogenous antioxidants, capable of preventing damage to cellular components caused by reactive forms of oxygen, radicals, and heavy metals, although its role in stress management and efficient defense against pathogens are still under study (mangoyi et al., ) . besides its antioxidant defense and free radical scavenging, glutathione regenerates important antioxidants such as vitamins c and e. gsh exists in every cell of the human body, but it is also present in many other organisms, including fungi and bacteria. there is a linkage between gsh and malaria. some parasites are superprotected by gsh. they are endowed with powerful and host-independent mechanisms, which de novo synthesize or regenerate gsh and protect the parasites from oxidative damage and other outside attacks. gsh in particular protects the gametocytes against oxidative stress and inhibits the action of arginine, which produces no and expels it from the food vacuole. at the trophozoite stage of p. falciparum in human erythrocytes, gsh takes part in detoxifying processes of heme, produced by hemoglobin digestion, by polymerizing some % of heme to insoluble hemozoin. some authors suggest that the nonpolymerized heme, existing in the food vacuole, is subsequently degraded by gsh, increasing the role of this metabolite. chloroquine could interact with gsh, competitively inhibiting the degradation of heme by gsh or allowing toxic heme to accumulate in membranes and damaging parasites. this argument merits some explanation. the prooxidant damage and inflammation process created by excessive heme, hemozoin, and fragments from rupture of the digestive vacuoles in blood vessels and plasma can be mitigated by glutathione. in other words, the inside of the infected erythrocyte glutathione is beneficial to the parasite; outside of the erythrocyte it reduces the negative effects of the malarial infection. high oxidative stress could actually be detrimental for the survival of young parasites (gallo, ; patzewitz and m€ uller, ) . glutathione transferases (gsts) are versatile enzymes involved in the intracellular detoxification of numerous substances. gsts have been investigated in parasite protozoans, like those involved in malaria, with respect to their biochemistry and as targets in synthesis of new antiparasitic agents. p. falciparum possesses high quantity of these enzymes (pfgst) and their activity was found to be increased in chloroquine-resistant cells, and it has been shown to act as a ligand for parasitotoxic hemin. pfgst represents a promising target for antimalarial drug development. a pfgst isolated from p. falciparum has been associated with chloroquine resistance. plant extracts have been found to act at different vulnerable metabolic sites of pfgst, disturbing gsh-dependent detoxification processes, increasing cytotoxic peroxides levels and possibly increasing the concentrations of toxic hemin in the parasites. in the case of s. myrtoides alkaloids, malagashanine was found to prevent chloroquine efflux from and stimulated chloroquine influx into drug resistant p. falciparum, suggesting that its effects are more on the plasma membrane than inside the parasite. malagashanine ( μm) reduced the activity of pfgst to %, but showed a time-dependent inactivation of pfgst, suggesting a role of malagashanine as a chemomodulator in cases of pfgst overexpression in chloroquine-resistant strains. the malaria cycle of a parasite is based on two cycles, one involving the host and the other affecting the vector. during the mosquito cycle, again there are metamorphoses and reproduction by the parasite. in consideration of the resistance phenomenon, new transmissionblocking agents, able to interrupt malaria transmission, are required. these blocking drug components can be effective in reducing gametocyte density in the human host (gametocytocidal activity) or disrupting parasite development in the vector (sporontocidal activity), resulting in a reduced number of infective vectors and, as a consequence, decreased incidence of malaria cases. in other words, control malaria's parasites through the cure of the vectors infested by the disease. in the sexual stages of plasmodium parasites, gametocytes are critical for the transmission of the parasite to its vectors. p. falciparum gametocytes are also important in the disease diffusion, since being exceptionally long-lived, they cause clinically cured patients to be reservoirs of infection. the cycle of propagation of the malaria parasites starts when the female anopheles feeds on blood from an infected vertebrate. immediately, the first metamorphosis starts. by the ingestion, the mature male and female gametocytes, namely micro-and macrogametocytes, enter the mosquito host. immediately after reaching the mosquito's midgut, the two types of gametocytes undergo dramatic metamorphoses. we must remember that such transformations are a response to environmental stimulation, like a decrease in temperature, an increase in ph, and an influence of xanthurenic acid. within - min, the rounded macrogametes leave the erythrocytes and diffuse inside the blood, together with the flagellates microgametes. now comes the last change. within the next h, the motile male gametes can fecundate the macrogametes, and round zygotes develop that mature to elongated motile ookinets and move to the outer midgut surface, completing early sporogonic development. these changes can be obtained by severe transformation inside the intrinsic cell organization, involving the cytoskeleton directly. an equatorial position of chromosomes in the metaphase plate in the middle of the spindle is necessary for mitosis and symmetric cell divisions. a symmetric metaphase plate position is essential for symmetric cell divisions, explaining why it is conserved in all metazoans, plants, and many fungi. control of this parameter is essential, since differences in cell size have been linked to cell fate and generate a class of anticancer drugs. movements of chromosomes are in charge of microtubules, which are elements of the cytoskeleton. the cytoskeleton is a network of protein fibers forming the "infrastructure" of eukaryotic and prokaryotic cells. in eukaryotic cells, protein filaments and motor proteins form a complex mesh of protein filaments and motor proteins. the cytoskeleton aids the inside cell movement and transportation of subunits, like organelles and molecule groups, stabilizes and maintains cell shape, and gives support and order. the cytoskeleton is not a static structure but it is able to disassemble and reassemble its parts in order to enable internal and overall cell mobility. intracellular movements include in particular manipulation of chromosomes during mitosis and meiosis from the equatorial plaque to the polar positions, in the formation of daughter cells, and also it is implicated in the immune cell response to pathogens. the cytoskeleton is composed of at least three different types of fibers: microtubules, microfilaments, and intermediate filaments. these fibers are distinguished by their size, with microtubules being the thickest and microfilaments being the thinnest. the assemblement of the proteins, tubulines a and b, makes microtubules, in form of long cave filaments. these hollow rods function primarily to help support and shape the cell and as "routes" along which organelles can move. therefore, without the action of microtubules, the cell is unable to reproduce. the cell is blocked in a limb, with part of the mitosis already done and the final act in progress. the result is a polyploid cell, meaning a cell with double or more than the normal number of chromosomes. because chromosomes cannot move alone, they must be dragged by the cytoskeleton. the mechanisms of action of several important antitumoral drugs derived from natural products are characterized by promotion of the assembly or disassembly of microtubules, meaning stabilization or destabilization of the tubules against depolymerization, resulting in mitotic arrest. treated cells have defects in mitotic spindle assembly, chromosome segregation and movements, and consequently in cell division. the main problem of the utilization of these compounds in combination chemotherapy for sensitive tumor types concerns their selectivity against malignant cells. cancer is basically a disease of uncontrolled cell division, including too-active mitosis, multiplying the cancerous mass. in most cases, these changes in activity are due to mutations in the genes that encode cell cycle regulator proteins. however, although cancer cells are a selected target, in consideration of their high level of mitosis, other tissues can be involved in the action of positive regulators of cell division. molecular agents of plant origin are of primary importance in cancer treatment. those acting on the cytoskeleton can be classified into two main groups: antimicrotubule agents like colchicine and the vinca alkaloids, which induce depolymerization of microtubules, and taxol and taxotere, which induce tubulin polymerization and form extremely stable and nonfunctional microtubules (rowinsky et al., ) . neem products have been seriously explored in recent years, in several sectors, mainly in the fight against insect-borne diseases. however, it seems that so far the potentiality of neem has been only lightly touched on. neemazal is a marketed neem product consisting of a quantified alcoholic extract obtained from azadirachta indica seeds, with a reported limonoid concentration of . %, consisting of azadirachtin a %, azadirachtins b-k . %, salanins %, and nimbins % (dembo et al., ; habluetzel et al., ) . neemazal completely blocks transmission of the rodent malaria parasite p. berghei to anopheles stephensii in vivo, when administered to gametocytemic mice at a corresponding azadirachtin a dose of mg/kg. other in vivo transmission blocking studies suggested that na may have stronger transmission blocking activity than azadirachtin a alone, evaluating the activity of nonazadirachtin a constituents of neemazal. in an ex vivo assay, which exploits a major target process of azadirachtin a against p. berghei, microgamete formation inhibition of plasmodium was used to estimate the pharmacodynamics of two varying doses of neemazal and azadirachtin a. a team led by prof. g. chianese (university of salerno, italy) explored the possibility of influencing plasmodium gametocytes by neem products, demonstrating the potential of blocking the reproduction stages of the parasite. neemazal is a marketed neem product consisting in a quantified alcoholic extract obtained from azadirachta indica seeds, with a reported limonoid concentration of . %, consisting in azadirachtin a %, azadirachtins b-k . %, salanins %, and nimbins %. neemazal completely blocks transmission of the rodent malaria parasite p. berghei to anopheles stephensii in vivo, when administered to gametocytemic mice at a corresponding azadirachtin a dose of mg/kg. other in vivo transmission blocking studies suggested that na may have stronger transmission blocking activity than azadirachtin a alone, evaluating the activity of nonazadirachtin a constituents of neemazal. azadirachtins exert relevant effects on microtubules assembly and organization, interfering with the expression and/or function of adhesive proteins during the genesis of microgametocytes, through disruption of the organization of mitotic spindles and cytoskeleton formation and activity. these molecules can interfere with cytoplasmic microtubule organization and distribution, causing severe depletion of actin levels. in this action, neemazal proved to be more effective than azadirachtin a. in confirmation, another study showed that the product completely inhibits the growth of p. falciparum field isolates in an. coluzzii mosquitoes at a dose of ppm in direct membrane feeding assays. microorganisms have not finished producing surprises and breaking the boundaries reported in books. meanwhile researchers are investigating malaria parasites more and more deeply in search of their weak points, but their study is complicated by the parasite's metamorphosis, which involves not only the shape but also fundamental aspects of the metabolism (becker and kirk, ) . asexual stages of the parasite contain a single mitochondrion, whereas gametocytes can have several mitochondria. the energy production is very important. plasmodium falciparum, as well as other similar apocomplexa protozoans, possesses an intriguing nonphotosynthetic plastic, discovered in the s. the surprise was that apicoplastides possess their own nucleic acid. regarding their role, they were considered by kilejian ( ) as "a source of some substrate essential for energy production of mitochondrion." in view of their other characteristics, they could be considered a possible bridge between organisms or the ancestral point of divergence from green algae and protozoans. in conclusion, apicoplastides could be part of the endosymbiosis pathway, wherein degenerated chloroplasts were useful to increase a mitochondrial efficiency still in evolution. thus, endosymbiosis started with the inclusion of the two main bacterial forms, the hetero-and the autotrophic one, but later the ancestral (green or red) primordial alga degenerated the chloroplast in favor of a clear evolution toward the heterotrophic metabolism ( fig. . ) . usually the shift to the eukaryotic cell is considered a consequence of environmental factors, such as the increase of oxygen in the oxidative atmosphere; however, it is possible that in some cases interactions between organisms could also have played an important role. the study on apicoplastides allowed researchers to evidence similarities (keeling, ; kilejian, ; k€ ohler et al., ) between different arthropod-borne diseases, such as avian malaria, eimoriosis, and toxoplasmosis, confirming once more the occurrence of common survival strategies in different organisms. other differences concern the enzymes network and the membrane transport mechanisms. the new knowledge about parasitespecific organelles could be of fundamental importance to the development of future antimalarial drugs, increasing efficiency and decreasing side effects, like resistance. another important research front full of possibilities is focused on the membrane mechanism of cq's extrusion by permeability pathways induced by the parasite in the host red blood cells (saliba et al., ) . this is related to the cq of interfering with the detoxification of toxic heme monomers. the studies showed that - h after the invasion by the parasite, the socalled new permeability pathways act on the interchanges, i.e., the entry of nutrients, as well as mediating the efflux of metabolic wastes. several groups advanced the hypothesis of a number of channel types, activated by particular stress or stimuli (ginsburg and stein, ; kirk et al., ; duranton et al., ; staines et al., ; thomas and lew, ) . all these references testify to and confirm the presence of a wide range of studies in search of an answer to the challenge of resistance. the front is still too large and undetermined, but every year the knowledge of host cell reaction is increasing and there is a high probability that the problem will be solved in the coming years. during the development of the arguments contained in this book, it was necessary link the insect-borne diseases argument to several collateral items. the idea in particular was concentrated on a possible utilization of this particular topic as an epiphany, meaning an enlightening subject, which allows a revision of the problem from a new perspective. the interpretation of a new and key piece of information can allow the process of significant thought about a problem, until, in accordance with the original significance of the term in ancient greek, the ἐπιφάνεια (epiphanea) appears like a manifestation, with a striking appearance. this book started with considerations about gaps and books. let us now return to these two points. the lesson from carson's book about the fundamental role of beneficial insects in the survival of mankind, has arguably not been understood. throughout all warm terrestrial ecosystems, insects are a dominant component and they are part of the lives of any organism. the insect-plant relationship is a fundamental biotic interaction, and plants account for a large part of the planet's biomass, many times the biomass of all animals together (new, ; jankielson, ; dunn, ) . the animal biodiversity is dominated by that of insects. they are a beautiful example of variability, in terms of both number of species (more than million) and abundance (more than half of all living organisms), although at most only about %- % of insects are scientifically described. this diversity, consisting of large numbers of individuals and great intra-and interspecific variety, is a consequence of the enormous functional significance of insects in habitats. primitive insects appeared very early in the silurian period, when plants and animals finally emerged from the sea and colonized dry land, and over the last million years the number of insect families has been rising. they were able to colonize any part of the territory, including the sky. today, the number of reported insect families is about and they have survived various negative major impacts, including the mass extinction event at the end of the cretaceous period. a review analysis, published in the journal biological conservation by francisco sánchez-bayo, at the university of sydney, australia, and kris wyckhuys, at the china academy of agricultural sciences, beijing china, attests a current insect collapse. the decline's hypothesis is based on a study of recent selected studies. the causes and significant factors include intensive agriculture, the heavy use of pesticides, urbanization, and climate change. the loss of insect population is calculated in an annual . % rate over the last - years, and the future tendency is evaluated to % in the next years and increasing continuously until only half left in years. this scenario is already underway. in puerto rico, a recent study revealed a % fall in ground insects over years. the catastrophic cascade effects on the planet's ecosystems include ants, aphids, shield bugs, and crickets, which are the food for many birds, reptiles, amphibians, and fish that eat insects. there are many indicators supporting the scenario (sánchez-bayo and wyckhuys, ; diamond, ) . in england, between and , the number of widespread butterfly species fell by % on farmed land, suffering the biggest recorded insect falls overall-though that is probably a result of this area being more intensely studied than most places. a particular alert concerning bees being seriously affected has also been raised in europe and the usa; for example, only half of the bumblebee species found in oklahoma in the usa in were present in (alburaki et al., (alburaki et al., , aizen, ). the number of honeybee colonies in the usa was million in , but . million have since been lost. in , according to eu data, there were around , beekeepers and million hives in the eu, producing , tons of honey per year, but the same source tells us that many insect pollinator populations are now in clear decline. there is similar news from brazil, with half a million bees dead. on one side, this is considered the effect of the use of some pesticides, toxic to bees. on the other side, it is a classic example of rapid and intense environmental change to improve agricultural intensification and pasture, with the systematic elimination of all trees and shrubs that normally surround the fields, so there are plain, bare fields that are treated with synthetic fertilizers and pesticides. dr. sanchez-bayo said: "we are not alarmists, we are realists. we are experiencing the sixth mass extinction on earth. if we destroy the basis of the ecosystem, which are the insects, then we destroy all the other animals that rely on them for a food source." he added, "it will collapse altogether and that's why we think it's not dramatic, it's a reality." the situation comprehends micro-and macroepisodes, like the continuous devastation of equatorial tropical forests, in particular the amazonia territory. the sequence is clear and well-known, and it always works: first, the fire destroys the vegetation, in particular the woody plants; second, the soil is cleaned, otherwise the plants could replace the habitat rapidly; and third, the territory is declared totally compromised and ready for further utilizations. however, as observed by samways in biodiversity and conservation ( , and later confirmed by this author in a series of further papers) in a paper titled "insects in biodiversity conservation: some perspectives and directives," the main concerns are the "lack of human appreciation of importance, coupled with the general disregard and dislike of insects, is an enormous perception impediment to their conservation. this impediment coupled with the taxonomic impediment must be overcome for realistic biodiversity conservation management. as it is not possible to know all the species relative to the rate at which they are becoming extinct, it is essential to conserve as many biotopes and landscapes as possible." there is a sentiment of urgency for measures "essential to preserve species dynamo areas as an insurance for future biodiversity," such that "preserved areas must also be linked by movement and gene-flow corridors as much as possible." the last point of view is crucial. preservation must be considered not only as an opportunity to maintain the presence of species in selected habitats against their disappearance, but it must be considered changes as opportunities to perform a positive future. in this regard, entomologists are asked to contribute in control of vectors affecting humans, crops, and livestock, but also to take an active part in the consideration due to the beneficial species. the central task is the possibility to predict accurately the environmental effects of any intervention. once the inherent risks connected with traditional control methods have been considered, the consequences of new introductions must be carefully predicted, including any synergist effect. the rate of insect species extinction is estimated as being eight times faster than those of mammals, birds, and reptiles (barnosky et al., ; dirzo et al., ) . another important current gap concerns scientific information. most ordinary people do not have access to data obtained by the scientific community, as well as opinions and models produced by experts and scientists. information, when available, is usually distorted and adapted to the dominant axioms by a plethora of generalist supposed experts. the proposed idea is that these kinds of people are able to know and comment on everything. the distortion, sometimes voluntarily pursued and often a consequence of general confusion, generates progressive modification of the starting points and even the concealment of important facts. the recent phenomenon of fake news is clearly generated from the same situation. although most research information is now easily accessible and can be obtained directly from the internet, its utilization remains restricted to dedicated people. in contrast, some scientific information is amplified far away from its real impact. how many times did you read about the discovery of a definitive cure to cancer? or about the already obtained solution to any physiological problem using staminal cells? in our era of globalized knowledge, news are obtained and fluxed indirectly, without few possibility of checking the origin and the reliability. it is necessary to consider that more than % of the human population, consisting of . billion people, are connected via the internet, and . billion utilize social networks regularly. these numbers are likely to increase % every year. all these people have access to information only through selected channels and although they are in a condition to verify it, science and general information are on different and distant levels. the main problem is that the information is reduced to a few soundbites, and there is no place for elaboration or proposals of other possible interpretations or points of view. this is not a recent case, produced by digitalization of communication. beside the sources, the problem of the quality of scientific information was fully evidenced more than years ago, in the "public understanding of science." this is the title of a report requested in by the royal society and prepared by a group of experts, whose leader was the geneticist sir walter fred bodmer. the report evidenced the general lack of knowledge about scientific themes. on one side, most of the population, accounting for two-thirds of europeans, was confident about science and technologies, considering that scientists were able to solve human problems and make human life "easier, healthier and comfortable." on the other side, the sequence "more communication ¼more knowledge¼more social adherence to scientific arguments" appears largely inadequate. the dominant problem about scientific communication is that ordinary people need an alphabetization to understand and meet the complexity of the scientific items. the conversion of the original scientific information is usually distorted and changed, at best "adapted," but more often polluted by political, social, and cultural interests. the result is a reductive metamorphosis, in the best case, or complete revision to be adapted and useful to already-made opinions. among the various examples of this operation we find neverending debates, such as those concerning ogm, vaccines, or the consequences of climate changes, without considering abnormal and artificially created themes, such as the contraposition between vegans and meat-eaters. the manipulation is based on a presumed "democratic" interpretation of scientific data. no vote is necessary to assure the consistency of a scientific law based on adequate experimentation, but the aim is that reliability must be obtained by public consensus and even agreement. independence has always been a necessary character of science, but manipulation was never pursued. history tells us that any political or social manipulation of science led to disaster. in contrast, priorities, when based on correct scientific information, as well as consequent implications and decisions, must be subject to the most ample democracy. at the end of this little journey through macro-, micro-, and nanoworlds, it is undeniable how long the road still is to understand and discover the mysteries of insect-borne diseases. in the meantime, we await the next surprises. the covid- pandemy dramatically evidenced all the current limits of science and technology to face this kind of challenges. the virus was faster and clever. predictively and prevention were insufficient. despite the potentiality, the debacle and medicine was evident and the consequent economic and social damages were enormous. microorganisms will continue to play their role 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composition determination by hptlc of chemical composition variability in raw material used in botanicals costa concordia disaster: environmental impact from phytochemical point of view trasmission blocking effects of neem (azadiracha indica) seed kernel limonoids on plasmodium berghei sporogonic development ecophysiological and phytochemical response to ozone of wine grape cultivars of vitis vinifera ethnopharmacognostical survey of azadirachta indica a juss quassinoids: structural diversity, biological activity and synthetic studies public health impact of pesticides used in agriculture: reportage of a world health organization and u.n. environmental programme malaria treatment guidelines. world health organization key: cord- - xxevp authors: patel, piyush; gohil, piyush title: role of additive manufacturing in medical application covid- scenario: india case study date: - - journal: j manuf syst doi: . /j.jmsy. . . sha: doc_id: cord_uid: xxevp this paper reviews how the additive manufacturing (am) industry played a key role in stopping the spread of the coronavirus by providing customized parts on-demand quickly and locally, reducing waste and eliminating the need for an extensive manufacturer. the am technology uses digital files for the production of crucial medical parts, which has been proven essential during the covid- crisis. going ahead, the d printable clinical model resources described here will probably be extended in various centralized model storehouses with new inventive open-source models. government agencies, individuals, corporations and universities are working together to quickly development of various d-printed products especially when established supply chains are under distress, and supply cannot keep up with demand. mankind has seen different pandemics since the starting where a portion of them were more horrendous than the others to the people. the worldwide emergency of novel coronavirus also referred to as covid- initially detected in the wuhan region of china. as of august , there is no proven vaccine for covid- , but numerous continuous clinical preliminaries are assessing expected medicines [ ] [ ] [ ] . d printing [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] is an essentially unique method of creating parts contrasted with conventional subtractive or formative manufacturing technologies. in d printing the part is made directly onto the built stage layer-wise, which prompts a novel arrangement of advantages and confinements -more on this beneath. the d printing technique needs to think outside the standard for changing human services. in a few words, d printing consists of empowering specialists to treat more patients, without sacrificing results. hence, similar to any innovation, d printing has presented numerous favorable circumstances and conceivable outcomes in the clinical field [ - ]. manufacturing industries and investors are continually trying to improve procedures to bring down cost, vitality and grow their ability (table ). at this stage, exploration and industry intrigue lie in figuring out where am can supplant or make new assembling frameworks [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . am might have the option to assume a job in assisting with supporting modern gracefully chains that are influenced by constraints on conventional creation and imports. co-ordinations of the supply chain are likely j o u r n a l p r e -p r o o f the primary enormous scope business that might be influenced by d printing innovation. as shown in fig. (a) traditional method involves prolonged process starting from taking raw materials, acquiring materials, manufacturing, distributing and selling to end-user. fig. (b) represents changes in the supply chain that quick part production possible through the use of d printing [ ] [ ] [ ] [ ] . (a) traditional supply chain (b) d printing supply chain fig. traditional versus d printing supply chain [ ] makers are on the whole being compelled to develop and actualize new and coordinated ways to deal with item observing and quality control. one of their greatest calculated difficulties includes guaranteeing their creation lines are running, despite the absence of accessible staff because of social distancing rules [ ] . this is the place computerized developments in smart manufacturing [ ] [ ] [ ] can offer numerous advantages. the decision of the most appropriate procedure for each kind of model depends on the meaning of the target behind the creation of the model and different factors: innovation, creation time, weight, materials, cost, aesthetic, functional, investigational, surface completion, post processing requirements, assurance, spares and consumables things. consider the ideal characteristics for your specific application and contrast them with the available choices in a given manufacturing processes. (fig. ) the present advanced cloud-based innovation services [ - ] and arrangements offer an uncommon degree of adaptability, with factory managers ready to remotely monitor and deal with their creation lines from any area with a web association [ ] [ ] [ ] . the designer must realize the deciding components of the finished result so as to have the option to choose the most appropriate assembling strategy, make the essential changes to the geometrical data file (stl or amf), and survey the nc code. the designer must, therefore, have a full outline of the times of the cycle as appeared in fig. . this highlights the impact of design for additive manufacturing (dfam), when an item has been intended for a particular machine or cycle [ ] , just as the significance of print settings to optimize production [ ] [ ] [ ] [ ] . key advantages of d printing over traditional manufacturing are digital storage, quicker creation, detectability of part files, reduction in delivery time and the capacity to deliver segments regardless of the complexity of part geometry. three iso/astm d printing measures, in particular material extrusion (me), powder bed fusion (pbf) and vat photo-polymerization (vp) are most usually used to create medical parts in the current covid- pandemic [ , ] . the current government has made some excellent strides in pushing for assembling with ventures, for example, prime minister narendra modi's domestic task 'make in india', and the nation has seen critical enhancements in its 'ease of doing business' rankings [ ] . there still is sufficient time for india to get up to speed, yet lead the world by concentrating on building the next generation of pioneers [ ] [ ] [ ] [ ] . according to the th edition of the world bank's (wb) report on october , , "doing business -comparing business regulation in economies", india has ranked rd in the list with the score of . . it has improved by places among nations as against th position in the - list. industry . [ - ] has likewise brought the capacity of consistent advanced physical change through robotics and am innovations like d printing. am advancements are reshaping worldwide worth chains and hold the guarantee of new creation capacities [ ] . india right now represents just around percent of the am introduced base across asia and oceania consolidated, however, organizations such as ge, wipro and intech are driving d printing appropriation in the nation. while the current market size might be little, the future has conceivably numerous situations and the state of the industry relies upon imaginative new use instances of receptions. ( fig. ) in the indian market, there are some limitations in terms of diagnostic kits and a sufficient standard quantity of personal protection equipment (ppe). presently to change india into a worldwide design and manufacturing hub, it is a powerful call to action to citizens and business pioneers to discover gaps and satisfy the necessity of the customer by make in india initiative. the utilization and selection of d printing services are expanding step by step. there will be a more noteworthy requirement for training and capability building inside the associations with expanded infiltration of am. there is additionally a growing concern that am items can't be copyrighted yet should be patented dependent on obvious differentiation. an industry wide joint effort is required to create clarity on what meets all requirements for patent security to control the multiplication of replica parts. [ ] covid- pandemic is the most noticeably terrible unnerving episode of humanity's rule on earth to date. not just it has asserted over a hundred thousand lives afterward, however, it has likewise given many restless evenings to clinical and investigates experts over the globe give concrete solutions for healthcare workers and all those exposed in this time of crisis of lack of medical equipment shortages [ ] [ ] [ ] . hospitals around the globe confronted disturbing deficiencies of clinical apparatus basics like face shields and covers, testing swabs, ventilators, and more. while traditional supply chains [ , ] diverse to respond, d printing outfits have begun dealing with transient curiosity [ ] . most d printers can't produce stock as fast as other assembling techniques like injection molding, however, they can create a wide variety of designs without the need for new molds. by sharing design files and pooling assets, individuals from the d printing network have joined together to become something of an assembling hive mind during this pandemic [ , ] . the world health organization has published a list of covid- critical items facing a global shortage, grouped into three categories like personal protective equipment (ppe), diagnostic equipment and critical care equipment. governments around the globe are approaching makers to briefly repurpose their assembling lines to meet this deficit. normally, various degrees of repurposing are required to produce covid- basic things, depending on the items' level of complexity. covid- is setting off the assembling segment to re-evaluate its conventional creation forms, driving digital transformation and smart manufacturing over the creation lines [ ] [ ] [ ] [ ] . ppe refers to protective clothing, helmets, gloves, face shields, goggles, surgical masks, respirators, and other equipment designed to prevent wearer exposure to infection or illness in this covid- pandemic. some of the equipment required for the general public are covered in this article for the benefit of society. a large number of the ppe designs featured here are works in progress, and the viability of privately fabricated subordinates of these gadgets ought to be carefully evaluated locally [ ] [ ] . face shields are personal protective equipment devices that are utilized by numerous specialists for protection of the facial zone and related mucous membranes (eyes, nose, mouth) from sprinkles, splashes, and scatter of body liquids. in common surgical masks and n masks, the assurance is only for nose and mouth, yet eyes are uncovered. these face shields will assist them with protecting their general face for a more extended time without much discomfort [ ] . indian institute of technology madras-bolstered new businesses has created ppe, such as face shields (fig. )from d printers just as generally accessible materials besides to protect healthcare professionals fighting covid- [ , ] . weighing under gm, the d-printed face shields utilize an adaptable plastic casing to fit people without the requirement of elastic bands and can be worn for long hours. it utilizes a replaceable transparent sheet, which is cheap and can be handily taken off [ ] . the stopgap face mask (fig. ) is created as an emergency action to protect frontline workers and secondary support service health care professionals. it consists of two main parts mask body and filter cover [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the mask and filter cover is printed from a biocompatible nylon material using selective laser sintering technology. the others feature for the attachments are flexible straps and rectangular filter patch are disposed of after every use of this device [ ] . mask adjuster (fig. ) plays an important role for hospital staff who need to wear a face mask for an extended period [ , ] . a designer is fabricating thousands of d printed buckles to improve comfort and alleviate associated ear pain for medical workers treating coronavirus patients. another critical factor in the battle against coronavirus is widespread diagnostic testing. the common processes consist of inserting a five-inchlong nasal swab along the nasal septum until the nasopharynx is reached. the swab must then be rotated for up to seconds to collect secretions before being removed and placed in a sterile container for lab testing [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the d-printed swab (fig. ) design is thin at the top and gets gradually thicker throughout the neck and handle. it has a well-designed tip for efficacy in sample collection for a medical professional, and also for patient comfort and safety [ ] . but for large-scale testing ( fig. ), medicinal services experts get tired and exhausted of tedious work. the robot has extraordinary potential for mass screening for covid- in the healthcare sector. so to fulfill these gap robotics researchers from the university of southern denmark have built up the world's first completely programmed robot to do throat swabs for covid- [ ] [ ] [ ] . the d printed robot swabs the patients with the goal that human services experts are not presented to the danger of contamination. e) ventilator parts hp has declared achievement in empowering frontline workers and communities to react to the difficulties of covid- through d printing. hp has collaborated with redington d in india, to effectively create , ventilator parts for agva healthcare (fig. ) . as a major aspect of this activity, classes of parts have been d printed, to make , ventilators [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . these ventilators are being sent across india for the treatment of covid- patients. the parts incorporate breathe in and breathe out connectors, valve holders, oxygen nozzles and solenoid mounts among others. by using the conventional process to prepare such types of complex parts it requires - months to manufacture theses quantities but with hp d printing innovation, these parts were printed in only days [ ] [ ] [ ] [ ] [ ] [ ] . the infection that causes covid- can live on surfaces for a long time which implies it may infect yourself by reaching a contaminated surface. people often have to enter and exit rooms so it may be possible to infect yourself by touching the door handle [ ] . to shield from such kind of polluted surface a d printable door opener (fig. ) can be fitted onto entryways in clinics and organizations, permitting individuals to open entryways without hands. there has been an increased need for facilities to quarantine oneself in this critical situation of covid- . in this demand, winsun, a d printing firm has found an ingenious solution [ ] . by using d-printing powers on an architectural scale firm is preparing coronavirus isolation wards (fig. ) in a single day. the isolation wards are also furnished with electricity and water supplies. this will help overcome the shortage of hospital rooms at a time when the country and the world are facing the covid- crisis. the ficci drone committee comprehend that drones (fig. ) are playing a huge job in a battle against the coronavirus in help to the accompanying activities undertaken by police, healthcare and municipal authorities like surveillance and lockdown enforcement, public broadcast, checking monitoring body temperatures, medical & emergency food supplies delivery, surveying & mapping, spraying disinfectants, etc [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . drone for covid- [ ] "corona killer", as now popularly known, the quick sanitization drones possess the capacity to cover almost km/day and it is times more efficient than manual sprayers and cost-effective, and got its recognition from the government of india. d printing shortens lead times during product development, brings down creation expenses, and engages designers and manufacturers to face more challenges with new d printed drone structures that give new expected applications to the innovation [ ] . digital aerolus, a worldwide innovator in autonomous advancement has developed the essential indoor drone (fig. ) to fight the spread of the covid- contamination with a % cleansing rate. the battel against coronavirus elimination requires a multi-sectoral approach by focusing on treatment, supportive care, prevention and quickly initiate research projects on medical equipment and vaccine development. as per the world bank data shown in the below fig. & fig. point to the strong possibility that the strength of the healthcare system and the base level of health in the general population are two other important factors that matter crucially. numerous articles have been written in the clinical field identified with the covid- flare-up that has encircled the world and killed numerous individuals. around the world, the episode brought about by covid- makes individuals have restricted social opportunity. general wellbeing activities, for example, social distancing, can cause individuals to feel confined and desolate and can build pressure and nervousness. however, these activities are important to decrease the spread of covid- [ , ] . then again, reductions in greenhouse gas emissions are seen because of altogether reduced street transport, reduced industrial, educational and other activities. with restrictions on up close and personal clinical meetings in the covid- pandemic and the difficulties looked by medical care frameworks in conveying patient care, innovations like telemedicine and smartphone are playing a key role [ ] [ ] [ ] . to avoid a potential pandemic-level outbreak of coronavirus, recommendations to utilize advanced manufacturing resources to provide hospital services in a short duration of time. medical parts are available but because of logistical and supply issues, they may not reach at requiring place in time. d printing has gotten an opportunity to prove itself as an answer for the quick creation of basic segments for life-saving machines in the tragedy of covid- . the government of india (goi) launch different schemes/services (fig. ) to raise funds and adopt new technologies in manufacturing and another sector. india is an important player and tremendous potential for diffusing new technology in the indian market and get economic benefits with affordable additive technology price, and future possibilities continue to rise. government of india schemes / services [ ] [ ] [ ] in this context, the objective of the study is to scrutinize the motivational factors of entrepreneurs that encouraged to adopt additive technology and how its function as responsible innovation. additive manufacturing society of india's vision for aims to put a d printer in every educational institute in india, so its help to education is a practical based. in this regard, they organize a business summit such as gujarat vibrant, the plastic summit, etc. moreover, the examination additionally looks at specific chances and difficulties that impact the adjustment procedure; and describe explicit plans of action contributes towards reliable development. portuguese specialists are working with lisbon university, fan d and others to create formats and legitimate systems to bring resident drove d printing into clinical arrangement. elsewhere in europe, the european commission is working with the european association for am on [ , ] . am has the upside of facilitating the production of complex building structures, for example, clinical gadgets including ppe that can't be easily produced using traditional methods. customization is tedious and costly when by conventional manufacturing techniques. this is the place am makes well and aides in the plan of customized product. metal cutting pioneer, sandvik coromant [ ] , has built up another d demonstrating procedure that can d print up to plastic face shields in the time conventional methods require to print one. this innovation makes ideal fit of the customized product, saves time as well as cost [ ] . a short review identified with the most recent d printing endeavors against covid- is represented in table . overall information from this examination shows that face shields are essentially faster to d print than face masks, requiring less material, less d printed parts, and along these lines costing less to d print, which might be contributing variables to the prominence of face shields among producers compared to face masks. subsequently the determined d printing potential on the globe is in truth moderately assessed to be in any event - times bigger, and along these lines can huge affect the lack of clinical flexibly in the current circumstance. moreover, it ought to be noticed that specific d printing advances are better for assembling explicit kinds of items than others. based on the discoveries, our investigation gives measurable proof that the most potential medical services items that can be fabricated utilizing d printing are those that have a high profitability with a single set of equipment and with boundless accessibility of hardware in the market. in any case, this new unregulated flexibly chain has additionally opened new inquiries concerning product certification and ip. there is a squeezing need to create d printing clinical norms for current and future pandemics. indian governments are likewise observing all the points and effectively reassuring advancement in this space. the first impact is to improve as-is forms by quickening the structure period of new item advancement, upgrading quality by different rounds of testing of models well in time and modifying the manufacture of tooling to improve profitability. the subsequent effect is on item development by decreasing driving weight, production cost and assembly process through part simplification and empowering quick customization of parts. the third effect is to investigate the reduction of after-market part inventory through disseminated producing and improving business sector responsiveness and reducing lead time for customization of embellishments or elite parts. at long last, overall disruptions in the plan of action are normal as am can help the worth creation portion of original equipment manufacturer (oems) and investigate choices for on location manufacture to quicken support and fix for costly segments. in such manner, a forward-thinking survey has been led to decide the capacity of am for giving elite advantages to mankind inside the clinical medical services supplies division. notwithstanding the numerous advantages identified with utilizing am in medical care applications, there are some significant limitations, and consequently the focal points and impediments of this innovation have been introduced. the findings show that experts and investigators who used to with am can focus on the current situation of am from their perspective. it brings another change in perspective in shaping and performing creative thoughts for designers and innovators. additive manufacturing 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shields under covid- quarantine: optimizing the use of university fabrication facilities and volunteer labor d printing to support the shortage in personal protective equipment caused by covid- pandemic examplatory use of d printing to provide medical supplies during coronavirus (covid- ) pandemic in mumbai-based startup d prints protective face shields for doctors. boson machines, a mumbai-based d printing firm iit-madras startups develop ppes from d printers and regular stationery materials hyderabad start-up is d printing face shields, hands-free door openers to stave off covid's spread china pushes all-out production of face masks in virus fight iit kanpur to produce , masks per day available at govt panels flag issues with agva ventilators bought by pmcares fund d printed multipurpose door opener tool for covid . defence research and development laboratory (drdl), drdo ministry of defence, kanchanbagh, hyderabad. . d printing centre(poland) the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. key: cord- - ebw x r authors: gupta, ritesh; misra, anoop title: clinical considerations in patients with diabetes during times of covid : an update on lifestyle factors and antihyperglycemic drugs with focus on india date: - - journal: diabetes metab syndr doi: . /j.dsx. . . sha: doc_id: cord_uid: ebw x r background: diabetes is recognized as an important comorbidity in patients with covid- and a large amount of literature has become available regarding this. the aim of this article is to review the literature regarding various aspects of association between diabetes and covid- and to highlight clinically relevant points with focus on india. methods: we searched pubmed and google scholar databases for articles regarding diabetes and covid- published between march , and august , . results: diabetes and poor glycemic control are associated with increased severity and mortality in patients with covid- . several clinical scenarios about hyperglycemia and covid- are identified and each of these needs specific management strategies. conclusion: it is prudent to maintain good glycemic control in patients with diabetes in order to minimize the complications of covid- . there is a need for well conducted studies to asses the role of individual antihyperglycemic therapies in covid- and also the behavior of new onset diabetes diagnosed either after covid- infection or during this time. we searched pubmed and google scholar databases for articles regarding diabetes and covid- published between th march and th august . diabetes and poor glycemic control are associated with increased severity and mortality in patients with covid- . several clinical scenarios about hyperglycemia and covid- are identified and each of these needs specific management strategies. it is prudent to maintain good glycemic control in patients with diabetes in order to minimize the complications of covid- . there is a need for well conducted studies to asses the role of individual antihyperglycemic therapies in covid- and also the behavior of new onset diabetes diagnosed either after covid- infection or during this time. after the first reported case of covid- in china in december , the pandemic has rapidly spread worldwide. the association of diabetes and covid- was identified initially and clinical considerations about the same were published by us in a highly cited article, one of the first on this subject, in march . present article is an update of the previous article since j o u r n a l p r e -p r o o f much information has become available about the relationship between diabetes and covid- since then, with focus on india. we searched pubmed and google scholar for articles regarding diabetes and covid- published between th march and th august . in this article, we present pertinent points relating to clinical aspects and new evidence which has emerged during this period. c. effect of glycemic control on disease course and severity: there is evidence that good glycemic control could reduce the severity of covid- .well controlled diabetes was associated with significantly lower mortality compared to individuals with poorly controlled diabetes (adjusted hr, . ; % ci, . - . ; p = . ) in a recent study. information about diabetes in covid- in indian patients is sparse at present. in a study in patients hospitalized with covid- till th april in jaipur, western india, diabetes was present in . % of patients . another study in patients from rajasthan reported a prevalence of diabetes to be . % in patients with covid- . clearly, further studies are needed to ascertain this limited data. the imposition of lockdown and restrictive measures in many regions to contain the pandemic has posed challenges in access to healthcare, supply of medicines and insulin . moreover, dietary irregularities, reduced exercise, and mental stress have led to weight gain as seen in a questionnaire-based study by in patients with type diabetes as shown by us . in a study in patients with diabetes in central india, % patients reported worsening of hyperglycemia . a small study on patients with type diabetes in north india showed a statistically significant increase in average blood glucose and hba c during lockdown . this is in contrast to the findings of improved glycemic control and reduced glycemic variability in studies in type diabetes done in spain, italy and united kingdom , , . restrictions during lockdown could also be an important contributing factor in development of diabetes in predisposed individuals. in a study in people without diabetes, weight gain was reported by % respondents and this led to about % increase in number of people with high ada diabetes risk score . this is especially important for south asians who have a higher risk of conversion from prediabetes to diabetes pmid: . not only does this finding have an implication for future burden of diabetes and its complications, it could also lead to increased morbidity because of covid- . as the understanding of infection with sars cov has evolved, two factors have come to be table shows the studies examining the effect of metformin on mortality due to covid- . the largest study showed that metformin use for at least days in the preceding months was significantly associated with reduced mortality in hospitalized patients with covid- ; however this benefit was observed in women only. this could be attributed to the preferentially greater anti-inflammatory effect (preferential effect on interleukin- ) of metformin in women . considerations about the use of other anti-diabetic agents remain the same as in any acute infection however, good glycemic control is prudent while using steroids. also indiscriminate use in mild disease is detrimental and is strongly discouraged. telemedicine has proved to be useful in providing consultation and education to patients in times of restricted social mobility and continues to be utilized in view of the need to minimize direct contact of patients with hospital/healthcare facility , . however, there are challenges and limitations of telemedicine especially in developing countries. these include poor internet connectivity, poor digital literacy, hearing problems, among others . apart from the usual preventive measures like social distancing and use of masks, good glycemic control needs to be emphasized in order to minimize severity of covid- . there is no chemoprophylaxis recommended in patients with diabetes. benefit of nutritional supplements like vitamin c, zinc, selenium, vitamin a and vitamin d etc. has been seen in vitro, however clinical evidence is not sufficient to recommend their supplementation . vitamin d deficiency has been shown to be correlated to mortality in covid , however benefit of intervention has not been demonstrated . it is reasonable to advise a healthy balanced diet with increased servings of protein, fruits, vegetables and nuts . in light of the evidence about role of diabetes and hyperglycemia in determining the severity of covid- , and the effect of the disease and lockdown on the glycemic status of people with and without diabetes, it is becoming increasingly important to recognize the different scenarios where diabetes and covid- interact. a recent article by a consortium of diabetes experts in j o u r n a l p r e -p r o o f india has identified five categories of patients with hyperglycemia who need consideration in today's times of covid- pandemic . each of these need appropriate management as given in table . mortality due to covid- is high even in those individuals not known to have diabetes. with a large pool of undiagnosed people with diabetes in india, it is reasonable to recommend a blood glucose check in asian indians above years who have covid- . clinical considerations for patients with diabetes in times of covid- epidemic preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease -united states hospitalization and -day fatality in , covid- outpatient cases diabetes in covid- : prevalence, pathophysiology, prognosis and practical considerations association of blood glucose control and outcomes in patients with covid- and pre-existing type diabetes diabetic ketoacidosis precipitated by covid- : a report of two cases and review of literature proposed guidelines for screening of hyperglycemia in patients hospitalized with covid- in low resource settings fasting blood glucose at admission is an independent predictor for -day mortality in patients with covid- without previous diagnosis of diabetes: a multi-centre retrospective study epidemiology and determinants of type diabetes in south asia diabetes in developing countries covid in south asians/asian indians: heterogeneity of data and implications for pathophysiology and research treatment outcomes and role of hydroxychloroquine among covid- hospitalized patients in jaipur city: an epidemio-clinical study characteristics and outcomes of hospitalized young adults with mild covid - a cross sectional study reveals severe disruption in glycemic control in people with diabetes during and after lockdown in india effects of nationwide lockdown during covid- epidemic on lifestyle and other medical issues of patients with type diabetes in north india observational study on effect of lock down due to covid on glycemic control in patients with diabetes: experience from central india impact of lockdown in covid on glycemic control in patients with type diabetes mellitus impact of covid- lockdown on glycemic control in patients with type diabetes glycemic control in type diabetes mellitus during covid- quarantine and the role of in-home physical activity assessment of the effect of the covid- lockdown on glycaemic control in people with type diabetes using flash glucose monitoring increase in the risk of type diabetes during lockdown for the covid pandemic in india: a cohort analysis contentious issues and evolving concepts in the clinical presentation and management of patients with covid- infectionwith reference to use of therapeutic and other drugs used in co-morbid diseases (hypertension, diabetes etc) diabetes and covid- : evidence, current status and unanswered research questions basal-bolus insulin regimen for hospitalised patients with covid- and diabetes mellitus: a practical approach. diabetes ther early treatment of covid- patients with hydroxychloroquine and azithromycin: a retrospective analysis of cases in marseille, france efficacy and safety of anti-malarial drugs (chloroquine and hydroxy-chloroquine) in treatment of covid- infection: a systematic review and meta-analysis. front med (lausanne) telemedicine for diabetes care in india during covid pandemic and national lockdown period: guidelines for physicians diabetes care during covid- lockdown at a tertiary care centre in india roadblock in application of telemedicine for diabetes management in india during covid pandemic enhancing immunity in viral infections, with special emphasis on covid- : a review vitamin d deficiency and co-morbidities in covid- patients -a fatal relationship? nfs journal national diabetes obesity and cholesterol foundation, and nutrition expert group, india. balanced nutrition is needed in times of covid epidemic in india: a call for action for all nutritionists and physicians strict glycemic control is needed in times of covid epidemic in india: a call for action for all physicians metformin use is associated with reduced mortality in a diverse population with covid- and diabetes. medrxiv coronado investigators. phenotypic characteristics and prognosis of inpatients with covid- and diabetes: the coronado study observational study of metformin and risk of mortality in patients hospitalized with covid- . medrxiv metformin treatment was associated with decreased mortality in covid- patients with diabetes in a retrospective analysis the authors declare no conflict of interest with reference to the manuscript titled "clinical considerations in patients with diabetes during times of covid : an update on lifestyle factors and antihyperglycemic drugs with focus on india". anoop misra j o u r n a l p r e -p r o o f key: cord- -nm ladlm authors: satyanarayana, srinath; thekkur, pruthu; m. v. kumar, ajay; lin, yan; a. dlodlo, riitta; khogali, mohammed; zachariah, rony; david harries, anthony title: an opportunity to end tb: using the sustainable development goals for action on socio-economic determinants of tb in high burden countries in who south-east asia and the western pacific regions date: - - journal: trop med infect dis doi: . /tropicalmed sha: doc_id: cord_uid: nm ladlm the progress towards ending tuberculosis (tb) by is less than expected in high tb burden countries in the world health organization south-east asia and western pacific regions. along with enhancing measures aimed at achieving universal access to quality-assured diagnosis, treatment and prevention services, massive efforts are needed to mitigate the prevalence of health-related risk factors, preferably through broader actions on the determinants of the “exposure-infection-disease-adverse outcome” spectrum. the aim of this manuscript is to describe the major socio-economic determinants of tb and to discuss how there are opportunities to address these determinants in an englobing manner under the united nations sustainable development goals (sdgs) framework. the national tb programs must identify stakeholders working on the other sdgs, develop mechanisms to collaborate with them and facilitate action on social-economic determinants in high tb burden geographical areas. research (to determine the optimal mechanisms and impact of such collaborations) must be an integral part of this effort. we call upon stakeholders involved in achieving the sdgs and end tb targets to recognize that all goals are highly interlinked, and they need to combine and complement each other’s efforts to end tb and the determinants behind this disease. tuberculosis (tb), caused by the bacteria mycobacterium tuberculosis (mtb), is one of the top leading causes of death world-wide and the leading cause of death from a single infectious agent [ ] . mtb spreads from person to person through airborne droplet nuclei. when a person with active tb of the lungs or throat, coughs or sneezes, droplets containing mtb are expelled into the air and inhalation of this contaminated air may cause tb infection [ ] . once infected, about - % of the people develop in , to rid mankind of the enormous burden of tb, the th world health assembly adopted a resolution to make the world free of tb by the year . who's "end tb strategy" provides a holistic overview of this resolution and has four principles and three pillars [ ] . the three high-level target indicators of the end tb strategy are reductions in tb deaths by %, reductions in the tb incidence rate by % and the percentage of tb patients and their households experiencing catastrophic costs being maintained at zero. these indicators and targets are relevant to all countries, with interim milestones to be achieved by , and . by the end of , at the global level, most of the who regions and many high tb burden countries were not on track to reach the end tb strategy's milestones ( % reduction in tb incidence rate, % reduction in the number of tb deaths and reduction in the households experiencing catastrophic costs to %). the reduction in the cumulative global tb incidence rate between and was only . %, and the reduction in the total number of tb deaths between and was % [ ] . table shows the reduction in the tb incidence rate, tb mortality, and catastrophic costs in the high tb burden countries in the asia pacific region (which comprises south-east asia and the western pacific). however, with this rate of decline in incidence and mortality, and with the data on catastrophic costs unavailable, it is unlikely that any of the countries in the asia pacific region will be able to reach all the end tb strategy's milestones. there are two important aspects to understanding the tb epidemiology. first, mtb infection in humans results in a spectrum of clinical presentations. as mentioned earlier, most infections are subclinical and asymptomatic, with mtb replication contained by the host immunity-a condition called latent tb infection (ltbi)-and only a small subset of infected individuals presenting with symptomatic, active tb disease. even within and between these two states, there is a wide ranging spectrum of mtb bacterial load, immune responses, pathologies and clinical presentations [ ] . second, like all other infectious diseases, the risk of infection and disease is dependent on the characteristics and interaction of the bacteria, the human host and the environment [ ] . a good understanding of these factors and their unique complex interactions-at both the population level and the individual level-is crucial for designing the intervention strategies to mitigate the tb burden. the factors that influence the risk of exposure to mtb, infection, the progression of infection to disease, and adverse treatment outcomes (such as death) are shown in box [ , ] . the factor that is essential for tb infection and disease is close contact with a person with a person with infectious tb disease; the greater the closeness, bacterial load and duration of contact, the higher the chances of infection. other factors such as age, sex, tobacco use, alcohol use, malnutrition, human immunodeficiency virus (hiv) infection, diabetes mellitus and silicosis increase the risk of infection, the progression from infection to disease and adverse tb treatment outcomes, and are therefore called major health-related risk factors. factors such as poverty, socio-economic and/or gender inequality, food and/or job insecurity and weak health systems affect not only all aspects of the "exposure-infection-disease-adverse outcome" spectrum, but also several aspects of the health of populations in general, and are therefore called the critical underlying 'determinants' or the 'root causes' of tb. while age and sex are not modifiable, all the other factors listed in box can be modified by human interventions. table shows the health-related risk factors and the corresponding lifetime increase in the risk of tb disease and the 'population attributable fraction (paf)' of these factors [ ] [ ] [ ] [ ] [ ] [ ] [ ] . * source: global tb report [ ] ); ** these are approximates and vary widely across countries; *** paf indicates the proportion of all cases of a particular disease in a population that is attributable to a specific exposure and is estimated based on the relative risk and the prevalence of the risk factor in the population [ ] . factors influencing the "exposure-infection-disease-adverse outcome" spectrum of tb. • major health-related risk factors (factors that increase the chances of infection, disease, adverse tb treatment outcomes) • age, sex, tobacco use, alcohol abuse, malnutrition, hiv infection, diabetes mellitus, exposure to indoor air pollution, silicosis, intake of immunosuppressive drugs/medications (e.g., tumor necrosis factor-alpha (tnf) antagonists, corticosteroids) • poverty, socio-economic and gender inequality, overcrowding, food and job insecurity, weak health systems in the past, the trends in tb incidence rates in high-income countries clearly show that efforts towards improving the socio-economic status, living conditions and nutritional status (as was seen before and soon after the world wars) resulted in the rapid decline in the tb burden, and, deterioration in these conditions (during times of war) increased the tb incidence rates. both in high and low-income countries, tb predominantly affects people of lower socio-economic status [ , ] . most of the risk factors for tb are associated with poverty, socio-economic and gender inequalities, and living conditions [ ] . malnutrition, poor housing/living conditions, and overcrowding are direct markers of poverty [ ] . people from lower socio-economic groups are more likely to live and/or work in overcrowded settings, experience greater food insecurity, have lower levels of awareness about healthy behavior, and are less likely to have access to quality health care services [ ] . they are also more likely to come into contact with people with active tb disease. the prevalence of tobacco use, alcohol use, hiv, and diabetes mellitus is relatively higher in people of low socio-economic status groups in various settings [ ] [ ] [ ] [ ] [ ] . the multisectoral accountability framework to accelerate progress to end tb (maf-tb) by developed by the who in [ ] urges governments to address a wide range of socio-economic of determinants through collaborations and partnerships. although the primary responsibility to pursue public health in all policies rests with different ministries within governments, the national tb programs, as champions and implementers of the tb care and prevention services in the countries, should take the lead in developing partnerships and support the implementation of the multisectoral accountability framework, both through advocacy and by helping to address the social conditions of patients and their families. tb (as described earlier) is a multifactorial disease, and the achievement of the end tb strategy milestones requires universal access to quality-assured diagnosis, treatment, and prevention services promptly. for this, it is necessary to strengthen the national tb programs, by ensuring adequate resources for deploying latest who-endorsed rapid tb diagnostics and drug susceptibility testing (dst) facilities, the provision of appropriate treatment services for drug-susceptible and drug-resistant tb, preventive treatment for high risk individuals (people living with hiv and household and other close contacts of tb patients), and the implementation of infection control measures in all health facilities. while these are necessary, it is being increasingly recognized that end tb targets are ambitious and unlikely to be achieved by these measures alone [ , , ] . massive efforts are needed to mitigate the prevalence of health-related risk factors, preferably through broader actions on the determinants of the "exposure-infection-disease-adverse outcome" spectrum, such as health system strengthening, poverty alleviation, addressing socio-economic and gender inequality, limiting job loss and food insecurity, improving housing quality and reducing overcrowding. an increase in the health-related risk factors of tb or the worsening of the determinants of tb (as is currently happening due to the socio-economic consequences of the sars-cov- pandemic [ ] ) can harm the global progress made towards ending tb. the sustainable development goals (sdgs) [ ] no poverty . good health and well-being . gender equality . clean water and sanitation . affordable and clean energy . [ ] . these goals necessitate collaboration and the alignment of all actions to secure a fair, healthy, and prosperous future for everyone on this planet-earth. these sdgs provide a framework for action on the determinants of tb disease. action on the determinants of tb through the sdgs framework will also mean endorsing the socio-ecological model of health which outlines that disease prevention and its mitigation may require action at five levels: individual, interpersonal, organisational, community and public policy [ ] and addressing every tb determinant may require actions at these five levels. as discussed above, poverty is a significant determinant of several aspects of health including tb [ , ] . globally, more than % of tb cases and deaths occur in low and middle income countries [ ] . there is an inverse correlation between a country's gross domestic product (gdp) per capita and tb incidence rates [ ] . therefore, efforts to reduce poverty will have a substantial impact on the tb burden. despite great progress made globally in reducing poverty levels, some countries in the who south-east asia and western pacific regions, such as india (~ %) and papua new guinea ( %), have high reported levels of people living below the international poverty line (sdg indicator . . in table ( sdg indicator . . in table ). hunger leads to undernutrition, which is one of the significant determinants of tb [ ] . it is estimated that in india (the highest tb burden country in the world), where the prevalence of undernutrition is high, nearly % of tb cases are attributable to undernutrition [ , ] . undernutrition is also ubiquitous in all high tb burden countries in asia and the pacific region (sdg indicator . . in table ). therefore, ending hunger and improving the nutritional status of populations can dramatically reduce the burden of tb. one of the key targets of this goal (target ) is to achieve universal health coverage (uhc) by [ ] . uhc means that everyone can access and receive sufficient and quality health services that they need without suffering financial hardship. there are two key indicators to monitor progress. they are: a) uhc service coverage index (sci)-sdg indicator . . (table ) , and b) the percentage of the population experiencing expenditures on health care that are relatively large in relation to the household expenditures or income-sdg indicator . . ( table ). the achievement of uhc and improved patient-centered tb care will have a direct effect on the reach and delivery of quality tb services and on catastrophic costs incurred by tb patients and their families [ ] . apart from this, the sdg goal also has indicators for dramatically reducing the prevalence of hiv, tobacco and alcohol use, and diabetes mellitus, all of which will have a considerable impact on reducing the tb burden. quality education typically leads to better and secure jobs, more money and higher purchasing power, resulting in better access to quality health care (including for tb) [ ] . higher earnings also allow people to afford homes in safer neighbor hoods, as well as consume healthier diets. incorporating health within the ambit of 'quality education' builds knowledge, skills, and positive attitudes about health and all other determinants of health, which can directly or indirectly have a considerable impact on efforts to end tb [ ] . education also improves the ability to identify the symptoms suggestive of tb and seek timely care for diagnosis and treatment of tb [ ] , thus, limiting the delays in the diagnosis of tb and the community spread of the disease. tb can affect either gender. in almost all countries, the notification rates of tb are higher in males than in females. although more men than women develop tb disease and die from it, tb is nevertheless a leading infectious cause of death among women. higher tuberculosis notification rates in men partly reflect epidemiological and biological differences in exposure, risk of infection, and progression from infection to disease [ ] . despite this, in several countries, gender inequality, socio-economic, and cultural factors act as barriers to accessing health care among women. these may lead to the under-detection and under-notification of tb in women. the stigma and discrimination associated with tb and certain co-morbidities, such as hiv infection, adversely affect women more than men, often leaving them in a more vulnerable position [ , ] . it is also widely believed that the medical care-seeking behavior of men and women with tb is mostly determined by how they and those around them perceive the symptoms, regard the diagnosis, accept the treatment, and complete it. gender may influence each of these components and affect the early detection of the disease and its outcome [ ] . studies that have assessed gender differences have shown that, on average, women are either undiagnosed, or diagnosed late in the course of tb disease when compared to men [ , ] . promoting gender equality in all spheres of life helps to mitigate some of these issues and contribute towards ending tb. access to clean water and sanitation is essential to reduce illness, malnutrition, poor physical and cognitive development, and death due to water-borne diseases [ ] . in countries of the asia-pacific region, the proportion with access to clean water ranges from . % in rural cambodia to . % in urban china. the proportion with access to safe sanitation ranges from . % in rural democratic people's republic of korea to . % in urban china. the provision of clean water and sanitation can affect the tb burden by reducing infections and improving nutritional status. there is evidence of an association between indoor air pollution (such as that caused by the burning of solid fuels for cooking at homes), outdoor ambient air pollution and tb infection and tb disease [ ] [ ] [ ] [ ] . depending on the prevalence of indoor air pollution, the fraction of tb cases attributable to indoor air pollution varies across countries. the proportion of the population using clean fuels in the south-east asia and western pacific regions ranges from % in dpr korea to % in thailand (table ; indicator . . ). interventions such as clean cook stoves to reduce the adverse effects of indoor air pollution merit rigorous evaluation [ ] , particularly in high tb burden countries in asia and the pacific, where the prevalence of both indoor air pollution and tb is high. clean energy is also expected to reduce outdoor air pollution and improve ambient air quality, which can reduce the risk of tb [ ] . tb predominantly affects people in the economically productive age-groups [ ] . apart from providing stable and regular job opportunities for the economically productive age groups, provision for early diagnosis and treatment of tb at workplaces, making workplaces safe by reducing the chances of airborne transmission of infections, adopting favorable policies towards social/job security in case of diseases and reducing occupational diseases like silicosis, will help in reducing the tb burden and improving the economic productivity of the workforce [ ] . stable/formal employment also increases access to employer-sponsored social health insurance programs and paid sick leaves, both of which are known to be associated with the reduced risk of occupational diseases and all-cause mortality [ ] [ ] [ ] . empowering and promoting social, economic and political inclusion of all, irrespective of age, sex, sexual orientation, disability, race, ethnicity, origin, religion or economic or another status will help in mitigating the effects of socio-economic disparities-disparities that are key drivers of all the risk factors of tb [ ] . rapid industrialization, urbanization, and migration-dominant occurrences in most developing countries in the asia pacific region-can create ideal conditions for infectious diseases (including tb) to flourish [ , ] , unless accompanied by proper urban planning, social reforms, environmental protection, adequate housing, transportation, and a well-coordinated and robust health system. climate change that manifests itself in the form of higher variations in temperatures and rainfall is known to have a substantial effect on several aspects of human health and behaviour (such as crowding, migration, changes in food habits), either directly or through several intermediaries, resulting in an increase in the burden of infectious diseases including tb [ , ] . the linkages between the various sdgs and tb are pictorially depicted in figure . also increases access to employer-sponsored social health insurance programs and paid sick leaves, both of which are known to be associated with the reduced risk of occupational diseases and all-cause mortality [ ] [ ] [ ] . empowering and promoting social, economic and political inclusion of all, irrespective of age, sex, sexual orientation, disability, race, ethnicity, origin, religion or economic or another status will help in mitigating the effects of socio-economic disparities-disparities that are key drivers of all the risk factors of tb [ ] . rapid industrialization, urbanization, and migration-dominant occurrences in most developing countries in the asia pacific region-can create ideal conditions for infectious diseases (including tb) to flourish [ , ] , unless accompanied by proper urban planning, social reforms, environmental protection, adequate housing, transportation, and a well-coordinated and robust health system. climate change that manifests itself in the form of higher variations in temperatures and rainfall is known to have a substantial effect on several aspects of human health and behaviour (such as crowding, migration, changes in food habits), either directly or through several intermediaries, resulting in an increase in the burden of infectious diseases including tb [ , ] . the linkages between the various sdgs and tb are pictorially depicted in figure . together, tb and poverty form a vicious cycle: tb decreases people's capacity to work and adds to treatment expenses. this, in turn, exacerbates their poverty. poor people also go hungry and live in close, unhygienic quarters, where tb and its risk factors flourish. progress in ending tb will accelerate the progress on sdg goal , and through it, progress on other related sdgs [ ] . according to the who's "a multisectoral accountability framework to accelerate progress to end tuberculosis by (maf-tb)" [ ] , the following are recommended actions for national tb programs: • development of national (and local) strategic and operational plans to end (or eliminate) tb, with a multisectoral perspective involving government and partners, consistent with the end tb strategy. • development and use of a national maf-tb. • establishment, strengthening or maintenance of a national multisectoral mechanism (e.g., inter-ministerial commission), tasked with providing oversight, coordination and a periodic review of the national tuberculosis response. • implementation of multisectoral actions on the social determinants of tuberculosis. revisions to plans and policies, and associated activities, based on monitoring, reporting, and recommendations from reviews. who has identified the following fourteen sdg indicators as relevant to tb. these include the levels of these seven within sdg- indicators at the end of is in the high tb burden countries in who south-east asia, and western pacific regions is given in table . national tb programs, ministries of health and governments in the high tb burden countries must realize that interventions beyond diagnosis and treatment of tb and ltbi are needed to reduce the risk factors and determinants of tb. tb programs must take a lead and list the stakeholders in their countries who are working on the other sdgs and equip themselves with resources and the necessary skillsets to engage with them. since tb is not homogenously distributed within the country, there will be geographical areas/communities with high tb burdens. as a first step, tb programs should share details/information of high tb burden geographical areas, assess the socio-economic determinants that are locally relevant/prevalent, and facilitate concentrated action on those socio-economic determinants as a priority in these areas wherever possible. the list of sample interventions that can be undertaken to reduce the prevalence of the socio-economic determinants of tb (based on needs assessment) are given in table . (in this table, using india as an example, we have highlighted public programs [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] that can be galvanized to address the determinants at the local level.) the stakeholders/partners who can be involved in carrying out the interventions could be respective government departments (who have the mandate and jurisdiction to perform the intervention), non-governmental/community based organizations, private sector, developmental partners etc., who may share the common vision of improving the lives of the people. identifying suitable partners will help the national tb programs, in facilitating their interventions in such geographic high tb burden areas. this holistic approach may contribute towards ending tb in such communities or geographic areas in a sustainable manner. demonstration projects on how to operationalize intersectoral coordination and build partnerships (at the local level) are urgently needed to generate evidence and to show that the impact of such initiatives goes beyond the simple sum of its immediate returns. research-to find out the optimal mechanisms for collaboration and to measure the impact of such collaborations-must also be undertaken, so that the lessons learnt are disseminated widely. apart from this, national tb programs must also find themselves represented in all in-country developmental committees and agendas of the government, so that ending tb is seen, not just as a responsibility of the health sector, but seen as a necessity for human development in all spheres of life. international technical and funding agencies/organizations, like who, the global fund, etc., should advocate for progress on broader sdgs and provide technical and financial assistance on this aspect to tb programs. table . sample policies/interventions that can be implemented at the community level in high tb burden geographical areas within a country by the national tb program and its partners to address determinants of tuberculosis. • provision of improved cookstoves, cleaner and drier fuels which aim to burn fuel more efficiently and therefore produce fewer harmful combustion products; • improving natural and artificial ventilation, to avoid air pollution inside the household; • changing cooking behavior and patterns, to reduce the amount of time an individual spends in proximity to a fire or stove; • altering regulatory or financial policies, with intent to improve access to advanced cookstoves or fuels and provide incentives for changes within communities or towards community development. reduced inequalities (sdg- ) • local programs aimed at financial inclusion and social security or linkages to existing social security schemes • jan dhan-aadhaar-mobile programs (for financial inclusion to ensure access to financial services, namely banking savings and deposit accounts, remittance, credit, insurance and pension in an affordable manner and to prevent leakage of government subsidies) [ ] sustainable cities and communities (sdg- ) • local implementation of slum development schemes/ slums upgrading programs which includes improvements in housing conditions, water supply and sanitation, roads, ground stabilization, storm water drainage etc., • jawaharlal nehru national urban renewal mission (a city-modernization scheme) [ ] climate action (sdg- ) • efforts to reduce carbon emissions through increased generation of power using renewable sources of energy • increase additional forest and tree cover • national solar mission [ ] • national afforestation program [ ] achieving end tb targets with the current pace of progress is highly challenging and un-realistic if the thrust is mainly medical and focusing only on 'diagnosis and treatment' of tb and ltbi, without addressing the underlying determinants of tb. while the strengthening of national tb programs under the framework of universal health coverage is quintessential for accelerating the progress towards end tb targets, the sdg framework provides an excellent opportunity for acting on several determinants and risk factors of tb. all stakeholders, be it government ministries, non-governmental organizations or private sectors involved in achieving sdgs and the end tb targets must recognize that most of their goals are strongly interlinked. failure to acknowledge this fact may result in ineffective and inappropriate actions and a delay in the achievement of both sdg goals and end tb targets. world health organisation. the top causes of death revisiting the timetable of tuberculosis is mycobacterium tuberculosis infection life long? the global burden of latent tuberculosis infection: a re-estimation using mathematical modelling global tuberculosis report the importance of heterogeneity to the epidemiology of tuberculosis heterogeneity in tuberculosis drivers of tuberculosis epidemics: the role of risk factors and social determinants modelling the social and structural determinants of tuberculosis: opportunities and challenges hiv and aids in the asia and the pacific regional overview epidemiology of alcohol use in the who south-east asia region hunger notes. asia hunger facts world health statistics data visualisation dashboard: prevalance of tobacco smoking pdf;jsessionid= dc b d bd b d e a?sequence= indoor air pollution and tuberculosis: a systematic review and meta-analysis population attributable fraction a century of tuberculosis tuberculosis and world war i an ecological analysis of incidence of tuberculosis and per capita gross domestic product the impact of social protection and poverty elimination on global tuberculosis incidence: a statistical modelling analysis of sustainable development goal socioeconomic disparities in health: pathways and policies. health aff tobacco and poverty: a vicious circle income inequality, alcohol use, and alcohol-related problems tb, and hiv infection: a vicious cycle disparities in diabetes: the nexus of race, poverty, and place type diabetes incidence and socio-economic position: a systematic review and meta-analysis multisectoral accountability framework to accelerate progress to end tuberculosis by ; 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timsina, jagadish; khadka, sarba raj; ghale, yamuna; ojha, hemant title: covid- impacts on agriculture and food systems in nepal: implications for sdgs date: - - journal: agric syst doi: . /j.agsy. . sha: doc_id: cord_uid: cve mqd the objective of this study was to understand the impacts of covid- crisis in agriculture and food systems in nepal and assess the effectiveness of measures to deal with this crisis. the study draws policy implications, especially for farming systems resilience and the achievement of sdgs and . the findings are based on (i) three panel discussions over six months with policy makers and experts working at grassroots to understand and manage the crisis, (ii) key informants' interviews, and (iii) an extensive literature review. results revealed that the lockdown and transport restrictions have had severe consequences, raising questions on the achievement of sdgs and , especially in the already vulnerable regions dependent on food-aid. this crisis has also exposed the strengths and limitations of both subsistence and commercial farming systems in terms of resiliency, offering important lessons for policy makers. traditional subsistence farming appears to be somewhat resilient, with a potential to contribute to key pillars of food security, especially access and stability, though with limited contributions to food availability because of low productivity. on the other hand, commercial farming - limited to the periphery of market centres, cities, and emerging towns and in the accessible areas - was more impacted due to the lack of resilient supply networks to reach even the local market. lower resiliency of commercial farming was also evident because of its growing dependence on inputs (mainly seeds and fertilizer) on distant markets located in foreign countries. the observation of crisis over eight months unleashed by the pandemic clearly revealed that wage labourers, indigenous people, and women from marginalized groups and regions already vulnerable in food security and malnutrition suffered more due to covid- as they lost both external support and the coping mechanisms. the findings have implications for policies to improve both subsistence and commercial farming systems – in particular the former by improving the productivity through quality inputs and by diversifying, promoting and protecting the indigenous food system, while the latter through sustainable intensification by building reliant supply network linking farming with markets and guarantying the supply of inputs. the novel coronavirus pandemic has revealed how the global food systems can become vulnerable and lead to increase in food insecurity, malnutrition and poverty especially among marginalized groups (world bank, a; wfp, ; nguyen, ; stephens et al., ; fore et al., ) . nepal, a landlocked and least developed country located in south asia (fig. ) , has also been witnessing various adverse impacts of covid- in terms of human casualties and physical and mental health and on country"s diverse farming systems and food security. as of nd november, , total cases of infection with , active cases and total deaths were reported (worldometer, ) . nepal imposed a lockdown to control the spread of the coronavirus since march and partially opened since the first week of september . the lockdown has affected the overall physical, mental, social and spiritual health of the people and posed unique challenges with vulnerable populations and limited resources to respond to the pandemic (poudel and subedi, ) . it has also negatively impacted on education, especially for the agricultural students who should be conducting the practical fieldwork that will not be possible through online classes or videoconferencing . like in other developing countries, nepal also faced a question as to whether the real crisis from covid- would come from health or from hunger, or to what degree the crisis could setback in the achievement of the sustainable development goals (sdgs) by (un, ) . however, nepal"s farming systems also have some resilience that helps to cope with and adapt to the crisis. for example, diversification of crops and income generating activities within the farming system in the hills and mountains was considered as adaptation to face the crisis brought by severe earthquake in (epstein et al., ) . government and other actors in nepal have also implemented new ways to deal with the disruption caused by covid- in food production and food security, and some of them have helped farmers and the broader population. the objective of this study was to assess the immediate impacts of covid- on different farming and food systems as well as their consequences on sdgs (no poverty) and (zero hunger) in nepal. this paper looks into: how local farming systems are being affected and which systems are likely to be resilient; how food security has been impaired; and how effective are the current measures taken by the government and the community to deal with the impact of covid- on farming systems and food security. we also aim to offer some insights into appropriate responses required to deal with the crisis in nepal. the paper is based on a series of three virtual panel discussions organized by the nepalese association of agriculture, forestry and environment in australia as a part of its continuous conversation on this topic the first one was organized on april and the last one on october , which led to an understanding on how the crisis and its impacts progressed over time and how the government"s and community"s responses worked. these virtual discussions were open in which authors participated as discussants and presented the information and data they collected. two of the authors have been working at the grassroots levels in nepal to observe the impact, provide help to people, and influence policy changes to deal with the crisis. other authors collected data and information through secondary sources. researchers and students (ranging from - in each of the virtual panel discussions) based in different countries and interested in this research theme participated in these discussions and provided comments. these discussions were supplemented by findings from key informants" interviews with selected government and non-government agriculture officers and farmers and literature review. ten government officers and fifteen civil society and ngo officials working at different administrative levels were interviewed through telephone once in mid-april and again on mid-october (see table for details on checklists and questions used in panel discussions and interviewing the key informants). nepal has now become a net importer of food. its ability to produce enough food has been hampered by several factors, some of which are small farm sizes, remoteness of farms, insufficient support to general spread of covid- ; general impact on the lives of peoplehealth, food, social, psychological and economic impact across the country; impact on farmers and farm production, distribution of food or farm products through trade/transportation; ground reality in terms of access to food, various safety nets implemented, how people suffered, who suffered; media reports and reality observed; forecasting as to what will happen in coming months in terms of food production, marketing, access to food, and health services; people"s (farmer"s) response to cope with the crisis on their own initiative and how is it helping; what should be done to improve food security. key informants -government policy makers ( ) ) mid-april ( ) ) mid-oct ( ) government policies to deal with such crisis; what supports are provided, how and to whom; policy gaps in agricultural sector in general and food security in particular as exposed by the crisis; experience/idea with regard to resiliency of prevailing farming systems to cope with such crisis; role of indigenous food systems in such crisis; what new initiatives taken at different government levels to deal with the crisis and continue with food production, marketing, distribution through trade/transportation, supply of inputs, new incentive structures; effectiveness of these new initiatives and which seem to work effectively; what could be the policies options for the future to deal with the crisis. key informants-ngos and civil society organizations (csos) ( ) ) mid-april ( ) ) mid-oct ( ) ngos provide emergency services, food provision; livelihood support; agricultural knowledge; and support services. checklists and questions used: effects on people in general, especially to marginalized groups and women; practical measures taken by csos/ngos, communities to deal with the crisis and support people in problems; gaps in such support mechanisms; kind of emergency services required; how the work of csos/ngos affected by the crisis and how this, in turn, affected people/farmers; supports available for farm production, marketing, storage, supply of inputs and the like; effectiveness of various measures taken to support farmers and other people; role of indigenous food systems in such crisis; measures to be taken make safety net, food production and marketing effective so that overall food security is ensured for all. farmers in terms of access to inputs like seed, fertilizer, irrigation, and technical know-how (adhikari, a) . the farming systems have largely been oriented towards subsistence living. indigenous food systems have also been obliterated, and regions where indigenous populations dominate have largely been food insecure, and where malnutrition is widespread (singh, ) . only in the peri-urban areas and in terai plains, there is some commercial farming, where farmers grow crops and keep animals mainly for the market. nepal"s farm products generally cannot compete with cheaper products coming from india (nepal and india have open border and free trade policy), where cost of production is low due to subsidies in fertilizers, irrigation, machineries and services like technical help, and guaranteed marketing through minimum support price (sunam and adhikari, ) . on the other hand, since the s, opportunities to work in foreign countries expanded with globalization that also coincided with nepal government"s openness in letting its people go out for work. slowly labor migrationwithin and outside the country -emerged as a major source of livelihood contributing equivalent to about % of gdp (about usd . billion in - ) (world bank, c) with remittances entering to % households (cbs, ) . many poorer people including marginalized indigenous groups go to india or to cities within nepal for work, whereas lower and upper middle class generally seek jobs in malaysia, gulf, and other wealthier countries. it is mainly because of migration of youths and use of remittance to purchase food from the market that a significant proportion ( %) of cultivated land, especially in the hills and mountains, has been abandoned from farming (upadhyay, ) . nevertheless, nepal still produces about % of the basic required cereals in the country, even though there are annual fluctuations as farming is mainly dependent on monsoon rain for irrigation (moad, ) . nepal also made some significant improvements in poverty reduction (people living under the line of poverty came down from % in to . % in ) and food security and nutrition in the past two and a half decades (gon-npc, ) thanks mainly to increase in remittances and non-farm income contributing about one-third to one-half of the poverty reduction (world bank, b). government has developed plans for sdgs with the aim that it would be able to achieve most of the goals by (un, ; gon-npc, ) fig. . map of nepal showing seven provinces and districts (province no. is named as "karnali", no. as "gandaki", no. as "bagmati", no. as "lumbini", and no. as "sudur pacchim"). the country runs from east to west with high altitude northern areas covering high hills and mountains, mid-altitude middle areas with mid-hills, and low altitude southern areas with plain lands called terai (map source: http://nepalsbuzzpage.com/new-map-of-nepal-with- -province/). impact of covid- on farming systems and food security, and sdgs - a rapid assessment of socio-economic impact of covid- in nepal revealed that the virus will seriously derail the achievement of sdgs if external donor supports are not made available on scale needed to fight the disease and its impact (undp, ). our analysis from the current study reveals that the consequences will spill over to multiple sdgs with an immediate threat to two intricately interrelated goals (goal : no poverty; goal : zero hunger) and negative effects on all pillars of the food security (i.e., availability, access, utilization, and stability). of the four pillars, the profound impact in short-term is seen in availability and access to food and in long term, it will impact all the four pillars of food security. similarly, different farming systems are also being affected differently. farming systems resilience and impacts on farming there are around . million landholdings (family farms) in nepal, % of which are ownercultivated (fao, ) . average size of a farm family is of only . ha. these smallholders produce a wide range of foods, using mainly family labour and consume a main part of the production in-house. they sell just % of their production in the market and generate just % of their total income due to low productivity, limited surplus to sell and lack of access to market and infrastructures like road and transportation networks (fao, ) . on the other hand, these smallholder farms were found to be somewhat resilient in the face of covid- as they depended on local inputs -local indigenous seeds, compost, and family and community labour exchange (personal communication with bakhat khadka, agriculture development office, ministry of agriculture, karnali province and with amrit gurung, gandaki province) and did not need market as the products were consumed at home or locally. these smallholder farms also had potential to initially absorb about half a million youths who returned to their villages from cities from nepal or from india and other countries because of covid- pandemic (undp, ). some of these returnee migrants already started cultivating some of their abandoned fallow land. for instance, in dailekh, a mid-hill district in the karnali province, these returnee migrants have now started ginger and turmeric farming in the traditional fallow lands employing themselves (dhamaka daily, ) . the strong community that is built around this type of farming is also useful in sharing the resources like seeds and labour. for example, it is seen that community seed banks maintained by such communities played an important role in this pandemic as these ensured local seeds, conserved biodiversity, and contributed to a diversified food system (de falcis, ) . the resiliency of such farms (measured by robustness and recovery of system productivity) was also observed during the great earthquake of when nepal was hit by -rector scale earthquake causing over , deaths and widespread damage of infrastructures (epstein et al., ) . resilience can also play a major role in the survival and expansion of many agricultural systems and great empires and strengthen the resilience of nations against future pandemics and other shocks (haldon et al., ) . in other countries (e.g. spain) too, family farms are seen to provide cushion against the pandemic (fao, ). on the other hand, the limitations of such subsistence farms were also realized when, despite potential, they could not fully engage these returnee migrants, and so a reverse migration has started to nepal"s cities and to india (see also ayer, ) . low productivity and inadequate ability to provide full livelihood security is a limitation of such farming systems despite the fact that they are somewhat resilient. moreover, these smallholder subsistence farms have also been neglected by government, and hence their potentials have not yet been realized. the land consolidation, use of fallow/barren land, irrigation, improvement in indigenous landraces, and promotion of market for niche products would have helped increased production. for example, meuwissen et al. ( ) j o u r n a l p r e -p r o o f journal pre-proof developed a conceptual framework to assess the resilience of farming systems and presented a methodology to operationalize the framework with a view to diverse farming systems of europe. such learning could have been useful in developing contextualized concept in case of nepal as well as in other countries of south asia. commercial or semi-commercial farms in nepal, which are generally located near the urban centres especially in downstream terai plains and produce mainly cash crops such as perishable fruits and vegetables, and eggs and milk, faced greater problems in this pandemic as they were neither able to sell their farm products to or purchase farm inputs (seeds, fertilizers, etc.) from markets on time due to lockdown and transport restrictions. situation of chitwan valley, a breadbasket for nepal and a centre of commercial and modern farming, clearly illustrates the plight of market-driven farming in such pandemic when marketing practices are not made resilient. its production of eggs and chicken has made the country more or less self-reliant in poultry production. in addition, it produces vegetables, fruits and milk to meet the significant market demand in cities like pokhara and kathmandu. it produced around . million litres of milk per day prior to covid- , but then due to lockdown and unavailability of feed (mostly imported from india), production declined and that too did not get the market (onlinekhabar, a) . immediately after the covid- , farmers had to throw their milk, eggs and vegetables and on the street, as they did not have any plans for such immediate breakdown in market channel (timilsina and ghimire, ) and to show wrath to government for not helping in the marketing of the products. banana did not sell and so were left rotten on the plants. lack of onfarm processing and cold storage facilities aggravated these problems for the commercial farmers. because of higher incomes, farmers even in high hill districts of province and province with accessibility to roads had slowly converted to commercial vegetable production prior to the pandemic. but these farms had to incur losses due to marketing problems triggered by covid- (adhikari, b; adhikari and hussain, ) . a survey of , households conducted in april -about a month after lockdown-revealed that covid- increased food insecurity by percentage points, pushing the proportion of food insecure households to % and deterioration of the dietary diversity by % affecting mainly children. the survey also showed that % households lost livelihood source altogether, and % faced a reduction in income (subedi, ) . vulnerability of karnali province, which had been suffering from food insecurity for a long time and was getting support from food-aid programmes, was most affected. by september , the vulnerability to food security had deepened, especially in karnali. for example, there were reports that all the food depots responsible for the distribution of food to people in mugu district in karnali had become empty of food stocks, and people could not buy food at all (shahi and gautam, ) . a second large survey conducted in august revealed that there is slight decrease in food insecurity overall in the country because of resumption of some supply networks. there was slight increase in loss of income (by . %), but more households faced severe and moderate loss of income (by %). for more than % households increases in food price was a major concern during the covid- crisis. lost income and increase in food price created a precarious food security situation (reliefweb, ) . covid- also exposed nepal"s vulnerability to dependency on other countries for inputs required in production of crops, livestock and poultry. as nepal has started modern farming methods, demand of these inputs is met through imports. however, this year, there was a serious shortage of chemical fertilizer for rice because of transportation restrictions and lack of preparedness from the government (prasain and giri, ) . the annual demand of chemical fertilizer is about . million tonnes and in most years the government imports about half of this. but this year, supply was delayed due to trade restrictions. as a result, farmers were distributed with only kg of urea per household during the j o u r n a l p r e -p r o o f journal pre-proof peak season of fertilizer use in rice, which will result in lower productivity. in the same line, productions of other crops and livestock and poultry are also expected to decline. as the prolonged lockdown started to impact food production and distribution, government allowed people to carry out their farming activities like harvesting of wheat and planting of maize and rice, respecting its covid- related precautionary health guidelines. nevertheless, the lockdown has continued to adversely impact food availability through production as well as trade/distribution as the supply chains of inputs and farm products were disrupted. on the other hand, the pandemic has now made the country and the people realize the problem when a country depends on others for food. this has now triggered a policy debate on the necessity to become self-sufficient in food production (adhikari, a) . covid- has also revealed the importance of federal political and administrative governance structure, which was created only in . the federal ministry of agriculture and livestock development created "rapid response teams" at different administrative levels (moald, a) to provide services to farmers to tackle their immediate problems in marketing and input supply, though they have not been as effective as planned because of lack of vertical and horizontal coordination with other related ministries, especially the ministry of health and population and the ministry of home affairs. the devolvement of power and resources at sub-national governments has however made it easier to make quick decisions to solve contextualized problems. for example, in the karnali province, a perennially food insecure region, the federal government responded by providing nrs . billion ( us$= nrs . ) for the agricultural sector including production of off-season potato and the local governments in the province responded by announcing minimum support price for wheat and timely supply of threshers for wheat harvest. likewise, a few best practices have also emerged from the actions of local governments across the country during this pandemic. these include, as observed by authors while working in the field, free threshers for wheat harvesting (e.g., saptari district in eastern terai); a system of buying vegetables from farmers and distributing them free to the affected people (e.g., khotang district in eastern hills); a program to pay four months" interest for loan taken by the affected people (e.g., province government); "agriculture ambulance service" for transport of farmers" products (e.g., province government), and cash grant to farmers if they use existing fallow lands for farming (e.g., gulmi district in western hills). now, the questions have arisen as to how these best practices are to be institutionalized and scaled-up, which could support farmers and produce more food locally in future. this pandemic and food insecurity caused thereby led to the realization that indigenous/local food systems are also important. in the past, these indigenous foods and local farming systems were overlooked and, in many cases, discarded, which in fact adversely affected indigenous populations. this has also been emphasized in a wider context in a recent article in lancet (zavaleta-cortijo et al., ) . support to increase production of food from such systems strengthen resiliency in food security with other positive consequences like self-reliance and mitigation of micronutrient deficiency and overall malnutrition especially among children and women. this would also help to conserve local agricultural biodiversity and a local food-culture. initiatives launched by government of sikkim, india to make the whole state "organic" through the promotion of organic farming based on indigenous farming systems could also be an alternative in the hills and mountain environments . as a silver lining of the covid- crisis, there is, thus, an opportunity to promote local foods and increase food availability locally (iied, ) . realizing this, provincial and j o u r n a l p r e -p r o o f journal pre-proof local governments in nepal are now more focused to increase availability of food locally, and so have placed priority in bringing fallow land (estimated to be %) under cultivation by engaging the returnee migrants from both within the country and overseas. for example, gandaki province has announced that it would provide nrs , per ropani ( ha = ropani) of fallow land, if the same is brought into cultivation. besides, covid- has also forced people to engage in backyard, balcony, and rooftop farming, which could increase food production, and government has initiated a policy of giving free seed and fertilizer to people interested in such farming. other measures of the government that came after the incidence of covid- include: policy intervention to support insurance of selected crops and livestock; minimum support prices of major crops; providing extension and advisory services; providing easy and cheap loans; and providing subsidy on improved/hybrid seed, fertilizers, and machines (moald, b). in terms of technology, it is now felt necessary to introduce labour saving technologies because of shortage of labour, especially male labour, because of their out-migration and to reduce work burden on women and elderly, who now carry the farm work. further participatory research is needed to find out context specific and scaleappropriate mechanization and other labour-saving techniques such as zero or reduced tillage, and direct seeding of rice (basnyat, ; paudel et al., ) . in the same line, key informants which were government officials identified measures that are essential to increase food availability, which include: establishment of agro-processing industries, agri-businesses and post-harvest facilities, development of cold storage and grain storage facilities, and expansion of irrigation facilities especially in the currently rainfed lands in hills. impact on access to food covid- reduced people"s access to food through the loss of livelihoods and income. according to a survey conducted in april , access to food and vulnerability to shocks has further deteriorated among daily wage laborers and female-headed households. about % non-agriculture daily wage laborer and % farm related daily wage earners were reported to have lost their jobs because of the covid- , and % of wage laborers experienced reduced income. income reduction was most common among traders ( %) and remittance receivers ( %) (subedi, ) . however, wage labourers were most vulnerable to food insecurity as they had no food stocks and reserve funds as there was no social safety-net as such, except for a temporary distribution of food that would last only for a few days. lack of this safety net was a major reason why there was exodus of wage workers from cities like kathmandu, who walked for weeks to reach home despite the restrictions to move out during lockdown. most of these migrant workers in cities (almost %) were involved in informal sector (spotlight, ) , which faced major loss in jobs. a study has revealed that % job losses in small and medium enterprises and % in informal daily wage job markets made many people unable to sustain their lives smoothly (spotlight, ) . for many families, remittances had been propping up the food security. at the national level, nepal received usd . billion remittances, equivalent of . % of gdp, in (world bank, c). covid- has two major consequencesreturn of migrants leading to further demand in food, and reduction in income. remittance in nepal is estimated to decline by % in highest decline in asia (adb, ). between , and , migrant nepalis entered nepal from india via land borders, and this migration had been the main coping mechanism, especially for the food-deficit and food-insecure households in karnali and sudur pacchim province. nepal government estimated that of about . million nepalis working in gulf and malaysia, about . million migrants are estimated to return due to covid- (acaps, ) . by september, however many migrants who had returned from india started going back to india again despite the increasing threat of covid- there (ayer, ) . these migrants, which were mainly from karnali and sudur pacchim province, reported j o u r n a l p r e -p r o o f that they could not sustain their livelihoods in their villages. this clearly showed that poorer people are more worried about food and livelihood than the covid- infection itself. gender dimension has emerged as a crucial issue in the analysis of vulnerability and safety net. this pandemic brought to light various unseen dimensions of the gender issues that made women further vulnerable in such crisis, for instance increase in women"s workload at home and decline in their income from wage work or sale of vegetables and milk. digital illiteracy and lack of driving skills also made them more vulnerable (barooah et al., ; ghale, ) . in quarantine/isolation too, women were not given food that is nutritious to their specific requirements, suffering badly the health of pregnant and lactating women and weaning children. domestic violence against women has increased rapidly (by %) since this pandemic started (ghale, ) . in dang district in province , women reported higher income losses leading to more often having insufficient food, eating less, skipping meals and going hungrier than their male counterparts during the pandemic (barooah et al., ) . the main coping mechanisms for income losses were the reliance on savings ( % of respondents) and borrowing funds ( %). another issue regarding the access to food was related to its distribution. whatever small relief the government provided was confined mainly in cities, and was marred by lack of information as to who is vulnerable and who is entitled or not. as a result, conflicts were witnessed among the people and between poorer people and relief agencies. a lesson was learned that it is wise to support everyone who comes to line for taking the minimum basic food. during the pandemic, a few issues about the sanitation of food, and contamination and decaying of food emerged. for example, people were confused about how to sanitize the food that was obtained from the market or touched by many people. availability of and access to vegetables, fruits and other nutrient-dense foods were limited, and whatever came to the market, it was sold without cleaning following safety and sanitization standards. harris et. al. ( ) report similar situation in india. foods distributed as relief package consisted only rice and pulse, and, as reported by authors working at the grassroots, it was often found to be contaminated, decayed, or of sub-standard quality. the chronic problem of malnutrition among children and women was exacerbated by covid- . children"s immunization and safe birth in hospital was compromised, leading to health problems in these groups (singh et al., ) , impacting food utilization. the pandemic has given a lesson to the policy makers that preparations are to be made for the unexpected events of vulnerabilities, especially about the need to keep higher amount of food stock. the immediate action of the government has, of course, been focused on supporting the people and in increasing food production in the next cropping season. a major issue that emerged from discussions and key informants in this regard was the small amount of buffer "food stock" that government maintained, and whatever was there was just meant for regular food-aid to some food insecure regions, mainly the karnali province. j o u r n a l p r e -p r o o f aside from undp ( ), there is still no systematic impact assessment of covid- on poverty, food security, and wellbeing in the country. our study pointed to some important directions as to what should be the policy choices and institutional mechanisms to deal with such problems based on the panel discussions, field observation, and information obtained from key informants and secondary sources. nepal has several active policies for agriculture and food security that emphasize right to food. key informants and discussants emphasized that these policies have not anticipated disasters like covid- pandemic, and so there were no preparations to deal with such crisis. the right to food and food sovereignty act and zero hunger policy provide strong support for the achievement of sdgs - , but they lack concrete action plans to improve food availability, access and utilization, and strategies to deal with crises like epidemics or pandemics. apart from strengthening safety net, nepal needs to increase food production in the smallholders through provision of appropriate inputs and build marketing networks that work even during such crisis. lack of this support mechanism had led to abandonment of cultivation from about % of the cultivated land. key informants indicated that some of these lands are already being utilized by returnee migrants in the recent rice season. with appropriate policies and support, remaining fallow lands could be brought back into cultivation, which would also help in conserving traditional and indigenous food system with positive consequences on food diversity, biodiversity and maintenance of food culture. immediately after the lock down, there was a shortage of food in the market. government did not have enough food-stock for food distribution to so many people in urban areas, especially to daily wageworkers. in addition, food had to be supplied to food dependent regions like karnali. as a policy option, the panel discussions, especially the last one, emphasized a much larger amount of food to be kept as "buffer stock" for the emergencies like this. nepal food corporation that maintains the buffer stock for public distribution and for emergencies has been keeping around thousand tons of food against a minimum required thousand tons. but emergencies like a drought and pandemic would mean such stock should be around to thousand tons (himalayan news service, ). moreover, a diversified mixture of food has to be kept in food reserve. as of now, it is only rice that is being kept as reserve with a small amount of lentil. as a result, food obtained from public distribution, as was the case in this pandemic, is generally of low nutritional value. a large stock would also make the food price more stable, and safety net wider and strong. it is also one of main indicators highlighted for monitoring food system disruption caused by covid- in bangladesh (amjath-babu et al. ). the covid- pandemic also revealed that it is important to identify, collect, conserve and research the indigenous species of crops, animals and other useful plants and promote the resilience aspects of subsistence farming especially in the hills and mountains to achieve resiliency at the time of future shocks due to climate or pandemics while also promoting commercial or semi-commercial farming to achieve food sufficiency. among the innovations made during the pandemic for increasing production, it is helpful to continue three innovations, which were found to be effective. the first innovation is providing support for mechanization that is suitable to the terrainlike larger machines (tractors and harvesters) in terai and small machines for seeding, plowing and threshing in the hills (paudel et al., ) . because of migration of young people, there is labour shortage in farming, and such mechanization helps in coping with such shortages, and makes farming less drudgery, especially taking into women"s heavy involvement in farming. the second innovation of cash support for bringing fallow lands into cultivation was found to be promising, which called for more funds j o u r n a l p r e -p r o o f allocation to local governments for this purpose. as a matter of fact these two polices would help in bringing abandoned farmland into cultivation. if the currently abandoned land is brought under cultivation and the rest of the farmland is intensively cultivated, nepal"s desire to become selfsufficient in food could be achieved. the third innovation in relation to digital marketing that connects local producers and consumers as implemented in few sites deserve further developments and up-scaling (see kumar et al., in case of india). sincere implementation of these policies is also equally important, as many good policies have not been implemented in the past. accordingly, good institutional infrastructures and governance structures are to be set-up so that these policies are effectively implemented and would enable nepal to achieve sdgs and by maintaining all four pillars of food security even during crisis times like covid- pandemic. migrant vulnerability in bangladesh, india and nepal. covid- and labour migration a future in farming. the record nepal vegetables worth millions rotting in farms amid lockdown in dhading covid- : why nepal"s farmers should have sustained cereal production key indicators for monitoring food system disruptions caused by the covid- pandemic: insights from bangladesh towards effective response nepali migrant workers start returning to india amid covid- threat in lack of job at home covid- challenges to equity: insights from rural nepal and senegal what is the role of community seed banks: lessons from the covid- epidemic coping strategies of smallholder farming communities after the nepal earthquake: insights into post-disaster resilience and social-ecological change national sample census of agriculture the economic lives of smallholder farmers: an analysis based on household data from nine countries the resilience of valencia"s "l"horta" in times of covid- child malnutrition and covid- : the time to act is now . i am saving vegetables in kitchen fifteenth plan nepal sustainable development goals: status and roadmap lessons from the past, policies for the future: resilience and sustainability in past crises food system disruption: initial livelihood and dietary effects of covid- on vegetable producers in india diversify food buffer stock to tame inflation will a hunger pandemic follow in the mountains? curbing-impacts-covid- -nepals-small-scale-farmers-seizing-oportunities-for-foodsystem-reform how indian agriculture should change after covid a framework to assess the resilience of farming systems formation of rapid response team food security policy ministry of agriculture and livestock development state of food security and nutrition in the world report: rising hunger and covid- present formidable challenges lockdown leaves chitawan dairy farmers lamenting scale-appropriate mechanization impacts on productivity among smallholders: evidence from rice systems in the midhills of nepal impact of covid- pandemic on socioeconomic and mental health aspects in nepal nepal"s fertiliser conundrum-governments ponder over it every paddy season and then forget after harvest. the kathmandu post the impact of covid- on households in nepal: second round of mvam household livelihoods, food security and vulnerability survey nepali farmers fight to save indigenous seeds food shortage looming large in mugu, dolpa districts of karnali province nepal covid- : food security and vulnerability update the perils of covid- in nepal: implications for population health and nutritional status covid- -nepal-where-are-we-after- -weeks-lockdown editorial: impacts of covid- on agricultural and food systems worldwide and on progress to the sustainable development goals food insecurity increased to percent; karnali most vulnerable how does transnational labour migration shape food security and food sovereignty? evidence from nepal impact of covid- lockdown on agriculture education in nepal: an online survey impact-of-covid- -on-nepal"s-agriculture-the-road-ahead envision : goals to transform the world for persons with disabilities rapid assessment of socioeconomic impact of covid- in nepal covid- : number of children living in household poverty to soar by up to million by end of year young country, fallow lands. the kathmandu post against-all-odds-what-driving-poverty-reduction-nepal covid- will double number of people facing food crises unless swift action is taken covid- coronavirus pandemic berrang-ford, l., the indigenous health climate change and covid- : reinforcing indigenous food systems we acknowledge nepalese association of agriculture, forestry and environment in australia (nepafe) for hosting the panel discussions and the institute for study and development worldwide (ifsd), sydney for in-kind support in literature review, virtual discussions, and interviews. we thank all participants from various countries for their participation and contribution in the discussions. we especially thank hom pant for his substantive inputs during and after the panel discussions. key: cord- -ipzntrm authors: dutta, anwesha; fischer, harry w. title: the local governance of covid- : disease prevention and social security in rural india date: - - journal: world dev doi: . /j.worlddev. . sha: doc_id: cord_uid: ipzntrm countries around the world have undertaken a wide range of strategies to halt the spread of covid- and control the economic fallout left in its wake. rural areas of developing countries pose particular difficulties for developing and implementing effective responses owing to underdeveloped health infrastructure, uneven state capacity for infection control, and endemic poverty. this paper makes the case for the critical role of local governance in coordinating pandemic response by examining how state authorities are attempting to bridge the gap between the need for rapid, vigorous response to the pandemic and local realities in three indian states -- rajasthan, odisha, and kerala. through a combination of interviews with mid and low-level bureaucrats and a review of policy documents, we show how the urgency of covid- response has galvanized new kinds of cross-sectoral and multi-scalar interaction between administrative units involved in coordinating responses, as local governments have assumed central responsibility in the implementation of disease control and social security mechanisms. evidence from kerala in particular suggests that the state’s long term investment in democratic local government and arrangements for incorporating women within grassroots state functions (through its kudumbashree program) has built a high degree of public trust and cooperation with state actors, while local authorities embrace an ethic of care in the implementation of state responses. these observations, from the early months of the pandemic in south asia, can serve as a foundation for future studies of how existing institutional arrangements and their histories pattern the long-term success of disease control and livelihood support as the pandemic proceeds. governance, we argue, will be as important to understanding the trajectory of covid- impacts and recovery as biology, demography, and economy. covid- has upended life around the globe. at the time of writing -may of -cases have been identified in over countries around the world, while the global infection rate continues to grow at exponential rates. as countries race to put in measures to confront the current crisis, there remains much uncertainty in how the situation will progress in the coming months. alongside direct effects of disease on health and mortality, widespread social and economic disruptions will have far reaching impacts on human well-being (bavel et al. , summer et al. , sibley et al. . while much public attention has focused on international and national policy responses (pena et al. ) , these efforts will ultimately need to be carried out by local-level institutions. as such, it is the character of local institutions, and their relationship with a broader set of governance arrangements across scales, that is likely to play a central role in determining the outcomes of different interventions, with significant implications for the trajectory of infection as well as longerterm outcomes for human well-being. this article provides preliminary analysis of how local level institutions are being operationalised for both disease control and social welfare mechanisms in rural india. as a country with over , local governmental units (gram panchayats), india has undertaken what is arguably the largest and most expansive mobilization of local governments around the world to the current crisis. there are several fundamental challenges to coordinating covid- response, for which local governance is likely to be particularly important. to begin with, there is a high level of uncertainty inherent in crafting responses to a crisis for which substantial existing policy experience does not yet exist. there is clearly a great deal of uncertainty concerning epidemiological aspects of the virus itself, with fundamental issues relating to transmission, treatment, and infection trajectories not yet well understood (who ). yet the ways that the virus and different control measures will interact with different societies -and different populations within them -is equally unclear. as anthropologist veena notes, "one issue that this pandemic has brought to the fore is that the experiences of governance vary enormously across different regions of the world -indeed, that the same policies such as the lockdowns will play out very differently for the middle classes and for the poor." economist jishnu has pointed out the uncertainties associated with feeding data on complex human behavior into epidemiological models, especially in the indian context; lack of basic knowledge of both the disease and human response to different policy measures raises critical questions about the validity of assumptions being used to guide planning efforts. it is indeed notable that these diverse disciplinary backgrounds -biomedical sciences, economists, and anthropologists -can all agree, at least on one thing: there is a lot we do not know, and need to know, to effectively address the present pandemic. this uncertainty highlights a critical challenge for implementing real-world responses in many administrative contexts. what kinds of subnational institutional arrangements will be responsive enough to match the standardized policy actions crafted at higher scales of government with complex, variable, and changing conditions on the ground? indeed, simply reaching the public to coordinate responses is likely to be a monumental task in many contexts, particularly in rural areas of the developing world. while public attention to date has focused on infection hotspots, largely in densely populated urban centres, rural areas pose particular challenges for conceiving and implementing policies for covid- . inadequate health facilities, poor water sanitation and hygiene infrastructures, high rates of wage labour migration, close living quarters, and low levels of public health awareness are just some of the difficulties that public authorities face for controlling infection (ranscombe ) . high rates of endemic poverty, weak food distribution networks, significant dependence on migratory wage labour, and more also suggest that economic dislocation resulting from infection control measures holds significant risk of hunger or worse (zetzsche , khanna et al. , barnett-howell and mobarak . there is an acute challenge of operating in many rural areas, where state presence is often highly variable, and low-level bureaucrats often struggle to bridge the gap between the highly formalized work of state institutions and the informal and syncretic worlds in which policy is expected to operate (corbridge et al. , gupta ). in settings where access to basic, well-defined social services remains uneven at best, effectively tracing, testing, isolating, and monitoring quickly developing infections is likely to be a monumental undertaking indeed. under such conditions, local governance is likely to be especially important in bridging the gap between policy measures and local realities for the coordination of responses to . a focus on local institutions is, of course, not new. from the s onward, scores of countries around the world have undertaken reforms for decentralization based on the belief that local governments are better able to carry many government functions than more distant bureaucratic institutions (manor , faguet . a large and growing body of research affirms that, while outcomes are uneven, vesting power and resources with local authorities can lead to gains in a wide variety of state functions relating to public service delivery, rural development, and the delivery of social security mechanisms (rondinelli et al. , heller et al. , faguet . local governments have also been observed to play a key role in coordinating responses to extreme climate events and other disasters (engle and lemos , agarwal et al. , tselois and tompkins . additionally, decentralized health systems have been shown to empower communities in health decision-making and thus making basic health care more responsive to local needs (munoz et al. ). there are many theoretical explanations for why local government preforms better for a variety of grassroot state functions. we highlight three key reasons that local governance is likely to play an essential role in covid- response. first, local governments are, quite simply, more closely connected to public and better able to navigate context-specific local conditions (manor ) . in contrast to more distant state bureaucrats, local authorities are often far more knowledgeable about local needs, more able to mobilize key local actors, are better positioned to monitor activities at the grassroots, and are better able to anticipate and resolve site-specific challenges that arise (agrawal , singh and sharma ) . second, local authorities are themselves embedded within the societies that they serve and likely to be more responsive to the public's urgent needs. not only are they often more accessible to the general public than more distant bureaucrats (kruks-wisner ), local authorities are embedded within an incentive structure that is likely to make them more accountable to local needs -both as a result of formal sanctions such as elections as well as the more general threat of public judgement and diminished personal reputation (agrawal and ribot , faguet , joshi & schultze-kraft . third, local government is often perceived as more legitimate than other external actors for carrying out different kinds of state regulatory functions. in electoral institutions, local authorities are directly selected by the public and thus may reflect citizens' values and aspirations, and often sense of identify (fischer , witsoe . citizens' perceived ability to engage directly with their leaders may likewise increase the perceived legitimacy of their actions (vogel and henstra ) . as previous experience reveals, trust in local governance can be an important factor in effective communication management in times of disasters (long staff and yanh ) , and conversely, distrust in government institutions often stands in the way of cooperation with public health recommendations especially in crisis times, observed during the h n pandemic in (quinn et al. ). these three characteristics -local governments' ability to negotiate context-specific local conditions, responsiveness toward the public, and perceived legitimacy to carry out state functions -are all likely to be important for the current crisis. in short, they suggest that local government may be better able to reach the public with various disease control and social security functions, with a higher degree of local cooperation as well as responsiveness to the public in delivering social security mechanisms at a time of unprecedented distress. yet the present situation also poses particular challenges compared to other local governance activities. while local governments have been called upon to address a variety of state functions over the years, responding to covid- requires a coupling of public health response with basic social security at an unprecedented scale -and this in a very short time frame. the challenges of social regulation in the context of covid- may also generate tensions between different local government functions. for example, local authorities' role in working with police to enforce strict lockdowns could run counter to political pressures embedded in elected structures. yet, local government is still likely to be better able than other administrative institutions to navigate such contradictory pressures inherent in a necessarily complex and unprecedented response in the face of covid- . perhaps never have local governments had such great and immediate importance; and quite arguably, never have their core functions been so dramatically extended in such rapid speed. how local institutions take on these new roles is likely to have significant bearing on the longterm trajectory of covid- response, with implications on disease control and infection rate, as well as the success of public support to protect the welfare at a time of severe social and economic dislocation. it is for this reasons that the present paper examines how local-level institutions are being operationalized in the present moment. while it is far too early to know how the situation will play out from our vantage point of the early days of covid- in south asia, our paper provides a record of how low level authorities are responding to the present challenge, which may serve as a foundation for future studies into how local governance conditions shape longterm trajectories of infection response and recovery in the years to come. india imposed a nationwide lockdown, considered one of the strictest in the world on th march . initial news reports revealed unprecedented social and economic disruption, on a scale not seen since the beginning of the post-colonial era. with millions of migrants returning home from urban localities to rural areas, a sudden and drastic decline in off-farm employment opportunities, and widespread disruption of social services, the authors quickly mobilized to understand how the pandemic was being experienced at the local level -and the governance structures that were being called upon to manage this situation. since we were unable to carry out our own field research, we reached out to a wide range of existing contacts across india in order to interview persons at the frontline of implementation of pandemic control and response measures. despite clear methodological limitations on who we could contact remotely and the information we were able to acquire, we felt that the emerging story was much too important to not be told, and that even imperfect information was better than none at all in the quickly developing pandemic situation. our sample is comprised of interviews with lower level bureaucrats, panchayat presidents, and kudumbashree leaders and heads of villages in the states of kerala, rajasthan and odisha. we interviewed three respondents from each state, who were the individuals that we could get in touch with remotely, and amidst a great increase in administrative functions that left many key actors with limited spare time for conversations. contacts with informants was made through our existing network in the three states and subsequent referrals to bureaucrats through these associations. the interviews were conducted remotely on the phone with additional follow up questions through whatsapp messages as needed. we panchayat is the lowest system of rural local administrative government in india. ii) the operationalization of subnational and local institutions for pandemic response in practice. in order to understand the ways bureaucratic departments were engaging with local institutions, we enquired about processes of implementing orders on the ground, ways of monitoring by state governments, follow up mechanisms available to local governments, the availability of financial support to carry out key functions, and the role of various local institutions and civil society actors in managing different responses. we also asked questions on the tensions between the different levels of government in negotiating the new and unprecedented responses they were required to undertake. iii) actions of local governments and their decision-making processes. we sought to better understand the level of local discretion in carrying out actions mandated at higher scales as well as the extent of local governments' compliance. we also tried to gather information related to local governments' ability to adapt responses -including existing policy support mechanisms such as india's employment guarantee schemes (mgnrega), provisions for subsidized food (through the public distribution system), and other social security mechanisms (emergency cash transfers) to the fast-evolving situation on the ground. iv) finally, we focused on interviewee's self-perceptions and reflections of the pandemic situation more specific to challenges encountered, as well as perceived successes and scope for improvement. these themes and questions were adapted to fit individual interviews within the scope of time available afforded by phone interviews with individuals in facing immense pressures on their own time to manage emerging tasks. we recognized, also, that bureaucrats would be inclined to show their "best face"; we have thus been careful not to assume responses are a fully accurate description, but a partial and suggestive account of some things happening on the ground. still, one of the things that really struck us throughout the course of interviews was just how much, many bureaucrats wanted to talk about the situation that was clearly both extraordinarily stressful and personally frightening for many in charge. a few of the bureaucrats repeatedly asked us to not quote them when they felt they might have divulged sensitive information on the pandemic management situation, including personal accounts about being unhappy with the coordination between the state government and the district administration, the unavailability of budget to make cash transfers for the poor, and the potential risk of being exposed to the virus itself in line of duty, without the availability of personal protective equipment such as face masks. (we do not identify the specific districts in our sample to ensure anonymity of key bureaucrats interviewed in these districts.) based on our relatively small sample and the lack of detailed data on infection rates or socioeconomic outcomes at the time of writing, we refrain from making both broad assessments of overall governance "effectiveness" based on such accounts. to the extent possible, we tried to corroborate our interview findings from bureaucrats through informal interviews over whatsapp calls and messages with a handful of additional civil society actors within our personal networks (three in each state); these actors came from a diverse mix of backgrounds including actors employed in ngos, social science researchers, and journalists. throughout this period, we were also in close contact with local government and bureaucrats in other indian states not including in this paper, especially assam, chhattisgarh and himachal pradesh where we have long-term research engagements, thus affording us a broader view of state responses in other parts of india. the formal rank of our respondents and their roles and functions are summarised in table . under whose provisions the lockdown was imposed. during the early days of the lockdown, major notifications and guidelines relating to covid- were primarily being issued by the union ministry of home affairs (mha) and not the ministry of health and family welfare (epw ). since the language used was mostly related to "law and order", we searched the mha website using keywords such as "lockdowns," "curfews," "fines" and "surveillance." in addition, we carefully scoured the government of india's websites of, the ministry of health extremely useful. all of these sources helped to complement our primary data, providing at least some means to triangulate our findings and contextualize them within broader processes happening across india during the period of our research. the indian government's decision to impose a -day lockdown, on th of march , came after being urged by the world health organization (who) to take aggressive action to contain the spread of covid- (lancet ). the lockdown was imposed with a four hours' notice and went into effect from the midnight of th of march. these sudden and drastic measures came at great shock to citizens across the country, however we learned through interviews that some administrators had prior notification that the lockdown would be imposed. as in other parts of the world, social distancing along with restrictive mass restrictions on movement is being used as the most widely adopted strategy for mitigation and spread of infection. this nation-wide lockdown has been imposed through the disaster management however, the rd amendment left significant discretion to india's states for its implementation, leading to very different character of local governance across the countryvariation which has been the topic of significant and ongoing analysis (singh and sharma , manor , maiorano et al. ). there is reason to believe that these variations will also shape covid- response. we have selected our study sites to encompasses some of the wide variation across india. rajasthan and odisha are somewhat poorer states, and despite social movements to promote more responsive governance -including activism leading up to india's right to information (rti) act ( ) -that emerged from rajasthan, both states have had variable success in improving the overall quality of governance as well as uneven development achievements overall (dreze and sen ). kerala in contrast is relatively prosperous, with a very robust civil society, a history of vibrant electoral competition at the state level and is generally celebrated for its significant social development achievements, which are at or near the top of india's states in areas such as literacy, health, and nutrition (heller ) . importantly, it also has a history of very strong state support for panchayats, especially through the state's "people's campaign for decentralized planning", which has been described as "the most ambitious effort to build local institutions of participatory democratic governance ever undertaken in the subcontinent" (heller et al. ). finally, the state's heralded kudumbashree program, a women-focused anti-poverty program that has given women a particularly strong and institutionalized presence in local government across the state (williams et al. ) . kerala and odisha have also had experience in dealing with health and natural disasters which has influenced current local institutional response to covid- . the covid- crisis has led the district magistrate (dm) to play a key role in both disease control and social protection in close coordination with panchayats. specifically, based on the ndma guidelines, district administrations across india have constituted district-level "task forces" to coordinate administration and containment efforts through the lockdown period. ( ) mitigating the spread of infection from urban centers to rural areas and ( ) helping to deal with widespread economic fallout from loss of cash income and consequent food insecurity for a large proportion of the population that already lives close to the margin to begin with. consequently, district authorities have issued guidelines to panchayats to undertake a wide variety of functions, as summarized in the table . importantly, instructions issued by the dm in order to implement policies related to disease control and social protection are ultimately the following sections further explore how local institutions have been operationalized to fulfill these activities as well as their implications -both for the structure and functions of panchayats in india as well as for the covid- response and recovery. in the initial days of the lockdown, there was an urgent need to control pandemic while also ensuring basic welfare and food security for citizens. under ndma, the central government issued guidelines to the states and district administrations for concrete actions undertaken by panchayats and other local actors, such as health care and community workers. of paramount urgency was to control the spread of infection from returning migrant laborers. to do so, panchayats have been instructed to work together with frontline health workers like the accredited social health activist (asha), auxiliary nurse midwives (anm), women shgs, local community members like teachers, and others. this is done through the formation of a committee at the panchayat or village level known as control rooms (in rajasthan), rapid response teams (in odisha) and panchayat jagruta sammittee (in kerala) . named differently across indian states, the committees perform similar functions. panchayats are also in charge of distributing cooked food to quarantine centers and households without income through community run kitchens. since agriculture has been recognized as an essential service by the national government, the dm has also instructions to panchayats for overlooking allocation of work through the mgnrega, providing access to agricultural inputs for farmers and also working with district administration to ensure linkages to storage facilities for crops and transportation for distribution. the range of functions being given to panchayats is impressive, however it is important to note that india's existing experience with decentralization suggests that the extent to which they are able to follow through with these tasks is likely vary significant in different parts of the country. together, these tasks -and in particular of monitoring the public to halt the spread of the virus --represent a great increase in state directives being coordinated at local and district levels. many actors in charge of these efforts did not feel prepared to assume these tasks. as a local bureaucrat (tehsildar ) from odisha described, "all of a sudden the government asked us to initiate cash transfers and also distribute food and cash…we did not have hard cash initially and banks were also not operating at full capacity due to the lockdown. we also had to figure out which local institutional machineries and actors we shall use and how in order for benefits to reach maximum number of people. it took us a about ten days just to figure out the logistics." underscoring the perception of urgency in response to the current situation, war metaphors have become common. 'at the state level we have a war room with senior bureaucrats in charge and responsible for coordinating covid- response in the state', recounted the additional magistrate of a district in rajasthan. the bureaucrat from odisha noted that "the government machinery is working * , with military like discipline." the kudambashree leader mentioned how they are using a 'volunteer army' of , across panchayats in kerala to respond to the covid- crisis. a tehsildar also known as an executive magistrate is a tax officer with the district revenue department in india, pakistan and bangladesh. yet, while coping with the sudden great expansion of new responsibilities, other more routine activities have been overshadowed such as health treatment of chronic diseases like tuberculosis, and routine immunization programs. the village head in rajasthan and tehsildar in odisha recounted that almost all development projects under india's employment guarantee scheme (mgnrega) had temporarily stopped, while agriculture suffered since this is the harvest season and lockdown has led to breaks in agricultural supply chains. other village development works also had to be discontinued. the village head summed it up by saying, "all development have come to a standstill". the central government's response to the covid- crisis, through the ndma, redefined existing institutional roles with a multipronged approach that has led to an integration of several institutional actors across state with district and local administrations. we already mentioned the key role that is being played by the dms who have been put in a position to make key binding decisions in operationalizing state guidelines. the table below highlights the functions of district level task forces set up in odisha, rajasthan and kerala. the dm is in a position to issue orders to several line departments and local level institutions and make decisions regarding sealing of district borders and to restrict movement within the districts, which the dm achieves through regular patrols by lower level bureaucrats. as the additional dm from rajasthan recounted to us, that district administration had never faced a situation so big and it has led to the entire district level machinery to work on one platform as well as with districts in other states for inter-state movement of migrants. he also added that the success or failure in implementation depended solely on the discretion and vision of the dm given his powers under the ndma. at the same time, dm's have faced new institutional imperatives for their actions, described as forms of 'deterrence' that, according to the additional dm of rajasthan, worked as a 'pushing force'. this included suspension from job if bureaucrats were not able to maintain lockdown regulations in their areas of jurisdiction. there have also been strict monitoring mechanisms imposed by dms; in odisha the bureaucrats we interviewed said they were required to report at least twice daily to the dm. at the level of the panchayats, panchayat level committees have been constituted. in both rajasthan and odisha, these have been constituted at the village level, knows as control rooms and rapid response forces (rrf), respectively. in kerala, the panchayats have more autonomy in both formulating and implementing responses related to covid- . in rajasthan and odisha, the core members constitute elected members of the panchayat, head of the village, schoolteachers, heads of self-help groups (shgs), asha and anm workers. they are responsible for coordinating activities on the ground as well as reporting to district administration of any emerging issues. the core members, who also belong to various departments like panchayat, health, education then mobilize other members from these institutions along with the public more generally as well as, at times, civic associations such as youth, women, and farmers groups. this has led to both leveraging and convergence of panchayats working together with local health, education and sanitation departments. in other words, the 'panchayat committees' link the elected authority of panchayats with other kinds of skilled individuals within the state as a linchpin to coordinate local responses. in despite these new collaborations, the indian bureaucracy runs on issuing directives and notifications which is also how things have been set in motion in the current crisis mode. the district administration with the dm at the top issues' orders percolating to the panchayats. this arrangement is sustained not just through perceived urgency; bureaucrats themselves could be penalized, issued show cause notices, arrested and fined if they fail to effectively implement government issues implementation procedures for lockdown. the fright of punishment percolates down to the bureaucrats and officers working below the dm, who are also compulsorily required to report to the dm twice a day, as mentioned above. there has been a proliferation of orders or government communications, notifications and guidelines aimed directly at citizens as well as for internal communication to bureaucrats. these are also long and phrased in ways that are difficult for either panchayat leaders or many field-level officers to comprehend. the national and state governments till rd of may had issued over government communications ranging from, specifying what one could buy or sell, determining the number of people who could attend a marriage or a funeral, or even whether one is allowed to leave the house to feed a stray dog. to give an example, the lockdown necessitated the closure of public spaces like village markets, places of worship and industries and enterprises, ensuring that essential enterprises and services remain open. but what constituted essential was also revised over the course of the lockdown. while alcohol was considered a non-essential commodity initially, it was deemed essential for a few days in the states of assam and kerala, and then classified as unessential once again. these standardized procedures often present their own complications. in our conversation with a village headman in rajasthan, for example, we learned that although the village was allocated a budget to procure a certain number of masks by the district administration, the headmen would have to place a requisition with the district administration to procure these masks from the district headquarters; on its own the panchayat was not allowed to procure the masks. in odisha, although the tehsildar we interviewed was legally permitted to impose fines on those violating lockdown, but he would have to pass an ordinance in order to impose and collect these fines. the top-down nature of bureaucratic institutions notwithstanding, local governments have a significant role in the current and fast evolving crisis. panchayats are clearly doing more than just providing relief measures; they are leveraging their positions as an institution of legitimacy with elected representatives to converge with other local institutions in addressing issues spanning from disease control, to monitoring of mobility, providing agricultural support, managing of quarantine centers and more. strikingly, our interviews showed a pervading sense of fear about the spread of the disease and increasingly so with the returning of migrants to villages. as a local bureaucrat in odisha described to us, when the district administration ordered the panchayats to set up quarantine centers in villages for returning migrants, several villagers protested out of fear of infection spread and wanted to seal off entry. only after the panchayat called meetings with local community and explained the situation, then they were given consent by the villagers. this illustrates not just how important inter-personal relationships in the community have been for making public health measures work, but also the very intimate ways in which local governments are often able to navigate social realities at a time of great fear and uncertainty. panchayats have also played a critical role assessing needs for the delivery of relief measures which was carried out by panchayat level committees. in kerala, rajasthan and odisha, the panchayats helped identify individuals and households who were outside of the government welfare schemes and in need of social support. in kerala, the panchayat president described to us how households in the village who are facing financial distress have approached elected panchayat leaders directly, who could then identify sources of public funding or social support mechanisms to help the household. at the same time, panchayats have been called upon to help implement various measures for social control which was done in close coordination with the police department. across india, the police have a central role in enforcing lockdown restrictions through activities ranging from asking violators to go home, using the threat of force to vacate public spaces, drawing lines to space people out in front of shops in markets, standing at the naka (barricade) to check cars at the state and even district borders, and arresting offenders. at times this has been accompanied by excessive force and even brutality such as beatings, as documented in the national media. our interviews with village heads across show that panchayats have the dual role of providing social security while implementing social regulations which sometimes put them in an awkward position, when police had to be called upon to report both violations of lockdown and/or isolation of suspected covid- cases. our interviews also show that in some villages police personnel also joined the local covid- management committee in patrols to enforce lockdown. one of the most striking things that we found in course of our interviews was the extent to which the present moment has spurred people at the district and grassroots level into action, expressed through a sentiment of social responsibility to confront present challenges. we found most of the bureaucrats we spoke with to be genuinely concerned about their districts and the general wellbeing of people. bureaucrats said to us that they themselves were scared due to the lack of protective gear and daily exposure in course of their duty, yet they still prioritized disease control. village headman and panchayat presidents also expressed a sense of fear and yet lauded the efforts of thousands of volunteers and grassroots health workers who went door to door. this was particularly true in the case of the kudambashree in kerala, which has been explicitly recognized as a part of kerala's response strategy. the kudumbashree is a poverty eradication program modeled through formation of women self help groups (shgs). it is built on an extensive network with participation from nearly four million economically women who implement programs and projects aimed at livelihood security and wellbeing. one of the key themes in the development of kudumbashree as an institution has been its convergence with panchayats across the state for planning, implementation, and sharing of resources. in short, the kudumbashree works together with the panchayats and is not a subordinate to it, which has served as a key channel for many women to gain prominences in local governance activities throughout the state. across its statewide membership, the kudumbashree comprises over , people. we interviewed a kudumbashree leader named lalitha , who explained to us their close relationship with those in, home isolation and also in quarantine facilities. they make phone calls to individuals in quarantine to monitor their health status and follow up for seven days post quarantine period. she also noted that it was not difficult to find volunteers; indeed, people have been ready and willing to work without remuneration simply for the good of their communities. she explained how daily calls to check up on quarantined individuals often led to friendship. she told us, with laughter in her voice, that even after the completion of quarantine, "they still call me and say, 'how are you doing lalitha, we have not heard from you in a while?'" although the imagery of the state in india is often considered to be distant, apathetic and anonymous, our interviews indicate that the mobilization of volunteer groups, frequent home visits, close planning and monitoring with the community has been underscored by an ethics of care. these examples are perhaps one of the strongest reasons that local governance is needed at the moment: it provides an avenue to harness the interests and concern of committed individuals toward public needs. the kerala case in particular highlights how sustained commitment toward supporting institutions can create a favorable relationship that are especially conducive to channeling these kinds of positive outcomes. working through the kudumbashree has, as an effect, brought an intimate ethic of care channeled through interpersonal relationships into disease prevention and control. the aforementioned case material shows some of the ways in which responses to have been coordinated through a combination of low-level administrative authorities, elected village governments, and other state and civil society groups. in aggregate, these activities represent a mammoth undertaking that has, at least for the time being, not only greatly expanded the roles and functions of local governments but also led to new forms of institutional interaction with administrative authorities across scales. the evidence presented here has several key implications for understanding institutional dimensions of policy response efforts in the present moment. to begin with, the material illustrates just how important local governance has been for carrying out response to covid- . while administrative authorities like the dm are ultimately in charge, they rely heavily on local level institutions for many different aspects of response. there are many actions that only local institutions have the knowledge, legitimacy, and coordinating capacity to do. accordingly, disease response is not simply the straightforward application of predefined biomedical guidelines; the character of governance -the nature of institutions, their capacities, and legitimacy -shapes how state responses will unfold over the long-term. as we have argued, such factors deserve at least as much attention in the trajectory of covid- as biology, demography, economy, or other factors in understanding the spread of virus and its impacts upon society. second, the effectiveness of local governments in carrying out responses to covid- are rooted in broader histories of policy interventions. india's rd constitutional amendment and subsequent interventions that have expanded the roles and capacities of local governments have all provided an important foundation for the efforts observed above. in the case of kerala in particular, especially robust, long-term support for local governments as a key arena for empowered local governance has made these institutions into a formidable force for confronting the present pandemic (isaac and sadananda ) , exemplified by a strong degree of trust and collaboration between state actors and citizens present in our data. these histories of institutional support over the past two decades may be as important for covid- responses as any of the policies quickly designed since the emergence of the virus. third, the experience of coordinating responses to covid- shows how large shocks can serve as a key force to propel institutional change. this is particularly notable in contexts such as india, which has a notoriously inflexible bureaucratic machinery. in the present context, the urgent need for rapid responses in conjunction with central directives to coordinate actions through integrative governance arrangements have led to new kinds cross-sectoral and multi-scalar collaborations for the implementing of response actions down the village level. such emergent forms of collaboration across established institutional divides seem likely to afford greater flexibility to negotiate actions on the ground. whether and to what extent these novel forms of coordination may leave a lasting imprint on local institutional practice remains to be seen. our case material -drawn from three states representing a diversity of social, economic, and political contexts -shows just how central local government has been to the story of covid- in india. as the local institutional foundation to carry out response measures, they are likely to play a critical role in confronting covid- in many other parts of the world as well. the future, of course, remains highly uncertain. as disease trajectories and recovery continues to be analyzed for years to come, analysis of local institutions will be important not just for understanding why different kinds of policy responses were adopted, but also the mechanics through which they have been brought into being at the local level. the present case provides some evidence of how local governments have been operationalized in the early days of covid- in india, which can serve as a foundation for future studies of how local institutional dynamics, their histories, and the government policies they are called upon to carry out influence the long-term success of disease control and livelihood support as the pandemic proceeds. forests, governance, and sustainability: common property theory and its contributions accountability in decentralization: a framework with south asian and west african cases environmentality: technologies of government and the making of subjects climate policy processes, local institutions, and adaptation actions: mechanisms of translation and influence the benefits and costs of social distancing in rich and poor countries health surveillance during covid- pandemic what difference does a constitutional amendment 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results of a national survey rural areas at risk during covid- pandemic. the lancet infectious diseases introduction: institutional choice and recognition in the formation and consolidation of local democracy decentralization in developing countries when people and governments come together. economic & political weekly effects of the covid- pandemic and nationwide lockdown on trust, attitudes toward government, and well-being decentralization: institutions and politics in rural india estimates of the impact of covid- on global poverty local government, political decentralisation and resilience to natural hazard-associated disasters using social and behavioural science to support covid- pandemic response studying local climate adaptation: a heuristic research framework for comparative policy analysis evaluating women entrepreneurs in the informal sector: some evidence from india everyday corruption and the political mediation of the indian state report of the who-china joint mission on coronavirus disease one million or one hundred million casualties?-the impact of the covid- crisis on low-and middle-income countries-. available at ssrn countries around the world have undertaken a wide range of strategies to halt the spread of covid- and control the economic fallout left in its wake. rural areas of developing countries pose particular difficulties for developing and implementing effective responses owing to underdeveloped health infrastructure, uneven state capacity for infection control, and endemic poverty. this paper makes the case for the critical role of local governance in coordinating pandemic response by examining how state authorities are attempting to bridge the gap between the need for rapid, vigorous response to the pandemic and local realities in three indian states --rajasthan, odisha, and kerala. through a combination of interviews with mid and low-level bureaucrats and a review of policy documents, we show how the urgency of covid- response has galvanized new kinds of cross-sectoral and multi-scalar interaction between administrative units involved in coordinating responses, as local governments have assumed central responsibility in the implementation of disease control and social security mechanisms. evidence from kerala in particular suggests that the state's long term investment in democratic local government and arrangements for incorporating women within grassroots state functions (through its kudumbashree program) has built a high degree of public trust and cooperation with state actors, while local authorities embrace an ethic of care in the implementation of state responses. these observations, from the early months of the pandemic in south asia, can serve as a foundation for future studies of how existing institutional arrangements and their histories pattern the long-term success of disease control and livelihood support as the pandemic proceeds. governance, we argue, will be as important to understanding the trajectory of covid- impacts and recovery as biology, demography, and economy.keywords: covid- , governance, local institutions, social protection, panchayats, india evidence from kerala illustrates how long-term support for local governments improves public trust and effectiveness of response.governance is as important to understanding covid- impacts and recovery as biology, demography, and economy. key: cord- -not z q authors: kumar, ankush title: modeling geographical spread of covid- in india using network-based approach date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: not z q covid- pandemic is a global concern, due to its high spreading and alarming fatality rate. mathematical models can play a decisive role in mitigating the spread and predicting the growth of the epidemic. india is a large country, with a highly variable inter-state mobility, and dynamically varying infection cases in different locations; thus, the existing models, based solely on the aspects of growth rates, or generalized network concepts, may not provide desired predictions. the internal mobility of a country must be considered, for accurate prediction. herein, we propose a framework for predicting the geographical spread of covid- , using reported covid- cases, census migration data, and monthly airline data of passengers. we discover that spreading depends on the spatial distribution of existing cases, human mobility patterns, and administrative decisions. in india, the mobility towards professional sites can surge incoming cases at maharastra and karnataka, while migration towards the native places can risk uttar pradesh and bihar. we anticipate that the state kerala, with one of the highest cases of covid- , may not receive significant incoming cases, while karnataka and haryana may receive the challenge of high incoming cases, with medium cases so far. using airline passenger's data, we also estimate the number of potential incoming cases at various airports. the study predicts that the airports located in the region of north india are vulnerable, whereas in northeast india and in some south india are relatively safe. the detailed analysis in this direction will guide policymakers for prior planning of transport, and minimize the spread of covid- . covid- is an actively spreading pandemic in the whole globe and is an unprecedented challenge for the healthcare, economy, and lifestyle of the community. [ ] [ ] [ ] countries are striving hard to mitigate the spread of covid- by various strategies: banning gathering, closing schools, stopping transports, locking down cities, imposing curfews, and sealing locations, and still not able to effectively contain it. the need of the hour is to get location by location risk assessment so that timely preventive measures can be taken. researchers have systematically studied various aspects related to covid- , such as the role of isolation of cases and their contacts, [ ] impact of non-pharmaceutical interventions, [ ] obtaining infected population from the death counts, [ , ] ,and calculating optimum duration [ ] and effectiveness of lockdown period [ , , ] . the available research in this area is primarily on analyzing growth in the number of infectious cases in the local community. [ , , ] these models mainly use non-linear fittings on time series of reported cases in a particular region to estimate the time evolution of epidemics in that region. human mobility and transport also play critical roles in the spread of covid- , adding seeds of diseasetransmission. however, there is a limited effort in the literature to model the impact of human mobility on the * ankush.science@gmail.com spread of covid- , particularly within a country. chinazzi et al. and wells et al. studied the importance of the travel ban of china and important border policies. [ , ] paster et al. used a long short-term memory (lstm) based neural network to predict the risk category of a country. pujari et al. attempted multicity model and assumed the fraction of population reaching a neighbor is inversely proportional to its degree connections. [ ] covid- currently affects almost all developed and developing countries; india is one of the countries with significant covid- cases. india is currently in stage of epidemics, and strict plans and steps are required to prevent it from entering stage or higher. india is a large country, with diverse cultures, languages, jobs, and educational opportunities, resulting into distinct and complex connection patterns between different locations. thus, a generic mathematical network approach [ ] [ ] [ ] such as a small world and scale-free model can not be employed for disease-spread analyzing for india; important geographical aspects of human-mobility should also be incorporated in a model. to tackle it, herein, we propose a network-based framework for modeling covid- risk at different geographical locations by using migration and airflow based real data. the proposed model can be used for policymaking, regulating transport, and predicting future hotspots. the model consists of dividing the space (say country) into various components, which can be states, districts or cities depending on the available data. consider there are n components with the population of individual components p i and infected numbers i i . the probability, p i of an infected person in the population p i can be written as now, let, t ij is the number of transported individuals from i to j component, then, a certain number of infected individuals would also be transferred from location i to j as follows: thus, the total number of incoming cases at destination (j) from all connected components(i) can be written as to model covid- spread in india, here we use the states and union territories as components and their reported positive cases as the number of people infected. mobility between two states relies on the intermixed community; migration may be a strong indicator of this. thus, to analyze the potential inter-state mobility, interstate migration data is obtained from the census . [ ] to obtain native to professional (work or education) place-based migration, only the data of male entries are considered to avoid significant marriage-related migration. figure (a) represents the migration map between different states with arrow-profile; here, the arrow width represents the migration number and the arrow direction is from native to the professional place. as seen from the arrow widths, the migration nature is unsymmetrical with high variability. the highest migration takes place between uttar pradesh to maharashtra, uttar pradesh to delhi, bihar to delhi and karnataka to maharashtra. in reference to covid- , different scenarios of mobility may arise: the mobility can be (a )towards the native site, (b) towards the professional place or (c) nearly equal in both the directions. as an example, few days before the declaration of lockdown, the migrants might prefer to move towards their native places; on the closing of the lockdown period, the migrants may flow back to their professional sites and . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint on the usual days the transport can be nearly equal in both the directions. the color map of figures b and c are depicting the total number of reported cases normalized with per million population. throughout this article, we have considered the cases reported on april , , and one can easily replace it with current data before the analysis and migration factor can also be reduced based on the situation. the case density (in per million population) is highly diverse, with a maximum at delhi ( ), andaman and nicobar islands( ), chandigarh ( ) , jammu, kashmir and ladakh ( ) , kerala( ), tamil nadu( )and maharashtra ( ) . figure b represents the flow of people towards their native places (case a), which is a question of national concern as tweeted by environment and tourism minister aaditya thackeray" right from the day the trains have been shut down, the state had requested trains to run for hours more so that migrant labor could go back home. cm uddhav thackeray ji raised this issue in the pm-cm video conf as well as requesting a roadmap for migrant labor to reach home." however, the preliminary calculations (figure b and d) reveal that this transport may transfer a significant number of infected individuals to uttar pradesh and bihar and can multiply further in the packed trains. it may be noted that, if the same scenario would occur in any other state having lower cases, instead of maharashtra, then the problem might not be that much challenging. now, we study case (b), i.e. the flow of people is from native to professional sites, which usually occurs at the ending of lockdown. figure c and e show that maharastra, karnataka, haryana, uttar pradesh could receive maximum infected individuals. strikingly, karnataka, haryana and uttar pradesh were not having high existing cases, yet could receive significant cases during the ending of lockdown. further, haryana and uttar pradesh may receive high cases from the hotspot delhi, while karnataka may receive infected cases from andhra pradesh, telangana, kerala, and tamil nadu. on the other hand, kerala, which emerged as one of the first hotspots, with several international cases, may not receive significant national cases due to fewer migrants. now we study case(c), importantly, it represents the natural connectedness between two locations, and in turn, decides the regular human mobility.. after a certain interval from lockdown, the flow would become equal from both sides due to regular movements; the transport, in this case, is the average of both side migrant flow (figure a) . the analysis of regular flow shows that uttar pradesh, bihar, maharastra, and karnataka can be at more risk, once the transport is resumed. by the above discussion, we conclude that the spreading depends on existing cases, connectivity between locations and social scenario, and is somewhat predictable by the proposed model. next, we examine the spread of covid- via transport through the airline's network. to obtain the mobility of passengers via airflow, we use monthly airline data provided by the ministry of civil aviation.[ ] figure a represents the pairwise passenger flow among different airports. the predicted flow of infected passengers is calculated and shown in figure b. it is clear from figure b, the cities with passengers from hotspots like delhi, mumbai can receive significant cases. figure c shows the predicted number of incoming infected passengers at busiest airports. mumbai, delhi, and bangalore would be receiving maximum incoming infected individuals, which is expected because of their high traffic. to normalize this effect, the total number of infected passengers is divided by the total number of passengers. the airports amritsar, dehradun, srinagar, jodhpur, lucknow, jammu, patna, varanasi can significantly receive a higher number of normalized infected individuals; it may be noted that all of these airports are situated in north india. also, it is interesting to know that most of the north-east airports (imphal, agartala, and guwhati) and a few south indian airports (vishakhapatnam and madurai) are relatively at the lower level of danger, due to less connection with hotspots like delhi and mumbai. the work can help in identifying which airports could be shut down, which could remain operational and estimating the required number of quarantine and medical facilities. through the above discussion, we infer that the incoming cases based on national migration cases are not going well with the current cases. the passenger's air-transport analysis and regular transport based on migration map (case(c)), both predict that uttar pradesh, bihar, and karnataka could receive a significantly higher number of cases. maharashtra with higher current cases already can receive additional incoming cases. several unpredictable local factors and strictness of administration may affect the active cases dynamically, thus the analysis should be performed on a day to day basis, once the transport is resumed. note that the airport traffic flow is an indicator of connectedness between two locations, thus results by analyzing train or road network may also provide similar inferences. the developed model and platform can effectively be used for real-time risk monitoring of different locations. therefore, future research will give optimal techniques for managing airflow, with minimum casespread and maximum airflow. the model can also be used for border policy purposes, in an international situation that differs dynamically. for instance, hotspots shifted dramatically within the first four months of , hotspots began from china in january, impacted iran in february, italy and europe in march, and the us in april. not that, india's foreign mobility is very complex from one state to another. as a result, higher cases of covid- in uae can have a greater impact on kerala, whereas the higher cases in canada can have a greater impact on punjab. the model may provide a systematic approach for controlling international flights in a rapidly evolving covid chart. the model is generic and has the potential to study more magnified regions such as state or districts; mobile location data, bus, or train passenger's network data can be used for the purpose. future work . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted april , . . https://doi.org/ . / . . . doi: medrxiv preprint can investigate the time evolution aspect of covid- in different locations. the present work proposes a network-based model for predicting the spread of covid- , incorporating human mobility through knowledge on migration and air-transport. we found that migration towards native places may result in higher incoming cases in uttar pradesh and bihar, while migration to the professional sites can surge incoming cases in karnataka, maharashtra, and haryana, and daily flows are likely to endanger both sets of sites. airports situated in north india are relatively at higher risks as compared to northeast and south. the model could be utilized to estimate the number of quarantine and medical facilities for incoming cases. additionally, it will help to control the spread of covid- by closing specific routes with a higher risk of pandemic spread. the lancet key: cord- -m tkgf x authors: ravi, kumar satish title: dead body management in times of covid‐ and its potential impact on the availability of cadavers for medical education in india date: - - journal: anat sci educ doi: . /ase. sha: doc_id: cord_uid: m tkgf x technology integration in teaching is an evolving concept in modern medical education like other study disciplines in india. the domain of medical science education is presently deficient of deploying technology-based practices. currently, majority of medical schools and colleges continue to choose traditional wet laboratory dissections over new virtual dissections which are being followed in institutions such as all india institute of medical sciences (aiims) and handful of other governmental as well as private medical schools of india like aiims rishikesh, aiims jodhpur, government medical college vimsar, burla, odisha, gsl medical college rajahmundry, andhra pradesh, yennapoya university mangalore, dutta megha medical college, gmc chindwara madhya pradesh, symbiosis institute pune and apollo medical college chitoor. not to mention, as the current push for technology integration increases, it is likely that a large number of indian academic scholars will begin seeing virtual dissections as beneficial to their classroom. to the editor of anatomical sciences education: technology integration in teaching is an evolving concept in modern medical education like other study disciplines in india. the domain of medical science education is presently deficient of deploying technology-based practices. currently, the majority of medical schools and colleges continue to choose traditional wet laboratory dissections over new virtual dissections which are being followed in institutions such as all india institute of medical sciences (aiims rishikesh) and handful of other governmental as well as private medical schools of india like aiims jodhpur, government medical college vimsar, burla, odisha, gsl medical college rajahmundry, andhra pradesh, yennapoya university mangalore, dutta megha medical college, gmc chhindwara, madhya pradesh, symbiosis institute pune, and apollo medical college chitoor. not to mention, as the current push for technology integration increases, it is likely that a large number of indian academic scholars will begin seeing virtual dissections as beneficial to their classroom. obviously, it is difficult to reach any consensus and conclusion as of now and only time will tell whether this new wave of change will be incorporated within our anatomy teaching and replace the traditional methods. in times of covid- , to maintain social distancing when the whole country is locked down, the ministry of health and family welfare, government of india, and board of governors of medical council of india have issued directives to all the medical institutions to suspend classes for courses such as m.b.b.s., b.sc., nursing, and other paramedical and allied health sciences to maintain social distancing (government of india, ) . keeping this in view, most of the medical institutions are conducting online classes for various undergraduate courses. theory classes of several subjects can easily be conducted by using video software like zoom, google classroom, google hangouts, google meet, and moodle to name a few. however, anatomy dissection classes remain challenging to conduct online. anatomy lays the foundation of surgical disciplines and a logical understanding of various surgical equipment and techniques can be successfully attained through cadaveric dissection classes (sugand et al., ) . cadaveric dissection is one of the methods of training hands and fingers for future surgical procedures on living human beings (ajita and singh, ) . understanding the significance of dead body, government of india, ministry of health and family welfare, directorate general of health services (emr division) have issued guidelines of dead body management in view of covid- pandemic. the guidelines for dead body management have been released by central government on march (government of india, ) . guidelines were issued with regard to precautions, infection prevention and control measures, handling of the human body, and environmental disinfection. it is based on the current epidemiological knowledge about the covid- as there was some delay in the cremation of the second disease-related casualty of a -year-old woman in delhi (india today, ). the first covid- casualty in india was a -year-old man in karnataka who died on march , . he had recently returned from saudi arabia (india today, ) . considering the fact that novel coronavirus is a new disease and there is a knowledge gap on best practices such as how to dispose the dead body of a suspect or confirmed case of covid- , the necessary guidelines were issued. the main mode of transmission of covid- is through droplets, fomites, and close contact with possible spread through feces (who, ). hence, the augmented risk of covid- contamination from a dead body to healthcare professionals or relatives who follow standard precautions while handling the body is quite unlikely (government of india, ) . till date there is no evidence of individuals getting infected from exposure to the bodies of people who died from covid- (who, ) . it is advised that healthcare workers identified to handle dead bodies in the isolation area, mortuary, ambulance, and in the crematorium/burial ground should be trained with respect to best infection prevention and control practices. the healthcare worker attending to the dead body should practice hand hygiene and ensure proper use of personal protective equipment such as coveralls, head covers, shoe covers, n respirators, surgical masks, goggles/face shields, etc. if the exterior of the body is visibly contaminated with body fluids, excretions or secretions, it has to be ensured that the gown is waterproof. they should remove all tubes, drains and catheters from the dead body. all puncture holes or wounds should be properly disinfected with % hypochlorite solution and dressed with impermeable material. it is advisable to properly dispose and take precaution while handling intravenous catheter or any sharp devices. to avoid leakage of body fluids, all the orifices of dead body should be plugged. viewing of the dead body for the relatives to see the body for one last time may be allowed by unzipping the face end of the body bag by using standard precautions. guidelines also advise to keep the dead body in a leak-proof plastic body bag. the exterior of the bag can be decontaminated with % sodium hypochlorite (naocl) solution. mortuary personnel managing the dead body of covid- patients are advised to observe standard precautions like storing the dead body in coolers maintained at approximately degrees celsius ( °c), disinfecting environmental surfaces, instruments, transport trolleys and cleaning the doors, handles, and floor with sodium hypochlorite % solution after removing the body. as per the guidelines, embalming of such dead bodies should not be allowed (government of india, ) . similarly, autopsy may be avoided and in case if it is to be performed for special reasons, the recommended infection prevention and control practices should be followed. the government of india has directed to avoid huge congregation either at the crematorium or burial ground as a social distancing measure due to an obvious reason that close family members or relatives may be symptomatic of corona virus disease (government of india, ) . according to voluntary body donation program, the general population can will their bodies to serve the purpose of medical education and scientific research. a beautiful quote by famous indian academician, author, and psychologist dr. amit abraham makes sense here: "after i die if i am buried, i will rot. if i am burnt i will become ash but if my body is donated i will live to give life and happiness to many" (abraham, ) . body donation in india is followed as per the bombay anatomy act ( ): an act to provide for the supply of unclaimed bodies of deceased persons (or donated bodies or any part thereof of deceased persons) to hospitals and medical and teaching institutions for the purpose of anatomical examination and dissection and other similar purposes (mohan foundation, ). body donation not only is useful for understanding human body and for advancing medical science but also helps medical students in learning relations of human anatomic structures and development of psychomotor skills by cadaveric dissection (ajita and singh, ) . each human body is a new source of knowledge with anatomical variations and a medium for gaining medical knowledge, more effective than any textbook or computer. nowadays, cadaveric dissection is not only limited to medical graduates and post graduates but it also helps various surgical disciplines such as surgical oncologists, neurosurgeons, burns and plastic surgeons, radiotherapists, head and neck and orthopedic surgeons to experiment innovative surgical skills and procedures in the form of cadaver laboratories and cadaveric workshops, to explore human body in a realistic manner before performing any major and complex surgery on living patients (ajita and singh, ) . apart from these, there are other uses of body donations such as cadaver banks for brain, skin, vessel and bones for molecular research and cadaver grafting. with the growing concerns regarding the corona virus (covid- ) pandemic, many anatomists have questions about the impact on body donation. we should maximize all donation opportunities, while keeping our healthcare professionals, medical students, and community safe. the risk of a covid- infection from an infected donor is unknown at this time. factors that could impact the risk of similar coronavirus such as sars-cov- transmission include epidemiological risk factors, incubation period, degree of viremia, and viability of the virus within the blood and specific organ compartments (lai et al., ) . we should follow infection prevention guidelines which address covid- . these include the screening and testing of body donors or potential donors that could have contracted covid- . donors should be screened for potential covid- infection (ast, ) . screening for covid- includes three different methods such as ( ) epidemiologic screening for travel and potential exposures, ( ) history for symptoms suggestive of covid- , and ( ) laboratory screening like nasopharyngeal and oropharyngeal or bronchoalveolar lavage sample for testing . recent studies indicate that negative results of laboratory screening may not rule out covid- infection (winichakoon et al., ) . the optimal approach to donor screening may change over time as more data accumulate. in the present scenario, medical professionals including anatomists need to be vigilant about evolving covid- guidelines and adopt their standard operating procedures accordingly. the covid- pandemic is unpredictable; still we are hopeful for the success of social distancing as the country is locked down else it might have a severe impact not only on medical education but on healthcare infrastructure and capacity crisis as well. amit abraham > quotes > quotable quote body donation and its relevance in anatomy learning -a review faqs for organ donation and transplantation bombay act no. xi of [the bombay anatomy act covid- : guidelines on dead body management government of india, ministry of health and family welfare, directorate general of health services (emr division -year-old coronavirus victim cremated under medical supervision in delhi. india today severe acute respiratory syndrome coronavirus (sars-cov- ) and corona virus disease- (covid- ): the epidemic and the challenges asp?gclid =cj kc qjw _ vzbrc iaris aos z tsf fowo tzpz d qze wtln m wz ebopj-r eck wwu w fccb ihqaa o sea lw_wcb [accessed the anatomy of anatomy: a review for its modernization world health organization. infection prevention and control for the safe management of a dead body in the context of covid- : interim guidance negative nasopharyngeal and oropharyngeal swab does not rule out covid- key: cord- -wvsc qv authors: davalbhakta, s.; sharma, s.; gupta, s.; agarwal, v.; pandey, g.; misra, d. p.; naik, b. n.; goel, a.; gupta, l. title: private health sector in india: ready and willing, yet underutilized in the covid- pandemic. date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: wvsc qv background: the private medical sector is a resource that must be estimated for efficient inclusion into public healthcare during pandemics. methods: a survey was conducted among private healthcare workers to ascertain their views on the potential resources that can be accessed from the private sector and methods to do the same. results: there were respondents, % of them being doctors. nearly half ( . %) felt that the contribution from the private medical sector has been suboptimal. areas suggested for improved contributions by the private sector related to patient care ( . %) and provision of equipment ( . %), with fewer expectations ( . %) on the research front. another area of deemed support was maintaining continuity of care for non-covid patients using virtual consultation services ( . %), tele-consultation being the preferred option ( %). . % felt that the government had not involved the private sector adequately; and . % felt they should be part of policy-making. conclusion: a streamlined pathway to facilitate the private sector to join hands with the public sector for a national cause is the need of the hour. through our study, we have identified gaps in the current contribution by the private sector and identified areas in which they could contribute, by their own admission. the novel coronavirus disease (covid- ) has consumed and exhausted widespread national health resources with unprecedented speed, and is expected to leave lasting consequences on global health, economy and growth. the massive losses call for the amalgamation of rapid innovations alongside bold public health measures led by a courageous political will to tackle this unique "war sans weapon" situation. as of may th , india has reported , covid- cases, a number that is rapidly rising, consuming the public healthcare system, which has been at the fore of this pandemic, despite deficient infrastructure, manpower and poor resources. , amongst other countries, india currently ranks fourth with regards to daily increase in the cases. with an availability of . public-hospital beds to population , it is not unreasonable to expect that the public sector may not be able to provide effective, sustained and uninterrupted healthcare in the face of the rising numbers. not surprisingly, countries ahead of us on the pandemic curve have recognized the need to utilize all available healthcare resources, forging partnerships between public and private healthcare sectors. in india, the healthcare scenario has transformed over the last few decades, , and almost % services are provided in the private sector, making it a major stakeholder. the first decade of this century saw a growth in private sector beds by almost %, bringing their total share to nearly %. although healthcare professionals in private enterprises are best suited to provide insights into potential areas of access from the private sector and methods to do so, yet there voices are seldom heard in the scientific world. improvements in outcomes and health indicators have been reported after private-public partnerships (ppp) in previous reports. the national health policy (nhp) not only advocates for exploring role of ppp in achieving universal health coverage (uhc), but ppp has also been proposed as an efficient model for disaster risk reduction. , the present survey was conducted to explore the opinions and preparedness of healthcare workers (hcws) in the private sector, on public-private partnerships (ppp) to provide a sustained, uninterrupted healthcare response in the face of the current pandemic. an online survey was conducted in april , and a pre-tested, content validated questionnaire was circulated over whatsapp® groups of healthcare professionals (doctors, nurses, technicians, students and administrators amounting to nearly individuals) in the private hospitals across india. the participants were requested to provide an informed consent at the beginning of the survey. we did not offer incentives for participation. the questionnaire featured questions, of which five identified respondent characteristics. fourteen items were multiple choice, with one being open-ended. the average time to complete the survey was five minutes. the respondents could change the answers before submission but not after it. internet protocol addresses were checked to avoid duplication of responses. content validity of the survey questionnaire was performed using lawshe's method and confirmed by three professors and one undergraduate medical student. the validated survey questionnaire was pre-tested among five hcws, and the identified errors in wording, grammar or syntax were rectified. the 'logics' feature available on survey monkey® allowed respondents to skip to a specific question on a later page based on their answer to a previous close-ended question. descriptive statistics were performed, and the results were expressed as numbers (percentages). the data/figures were downloaded from surveymonkey.com®. ethics approval exemption from review was obtained from the institute ethics committee [ - -ip-exp] as per local guidelines. we adhered to the checklist for reporting results of internet e-surveys to report the data. the participants included doctors ( % of the respondents) (age years + . ), and nurses or medical students ( %). nearly half ( . %) felt that the contribution from the private medical sector has been suboptimal. suggestions for improved contributions included patient care ( . %) and provision of equipment ( . %), and research ( . %). (figure ) participants suggested increased involvement in screening ( . %), testing ( . %), intensive care ( . %) and non-intensive-care ( . %) beds. some ( . %) felt that effective home outreach services could also be provided. participants believed that the private healthcare sector could provide insights into new testing methods ( . %), vaccines ( . %) and new or repurposed drugs ( . %). most participants ( . %) preferred use of their financial contribution for subsidized treatment of patients while only % favored donation to public agencies. most respondents felt that they could play a significant role in educating healthcare workers, medical students, and the community. another area of deemed support was maintaining continuity all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint of care for non-covid- patients, using virtual consultation services ( . %), teleconsultation being the preferred option ( %). more than half ( . %) felt a need for greater involvement of the private sector in the pandemic response including policy making. nearly half of the participants had made monetary donations for the pandemic from their personal funds ( . %). teleconsultations were being offered by doctors. more than a third ( . %) felt that they wanted to contribute more towards the pandemic response, and as many as % were keen to donate blood. in our e-survey assessing the opinions and readiness of hcws in the private healthcare sector, we found that participants felt that they had not contributed enough and were positively inclined to participate in the pandemic response. they expressed readiness to participate in screening, testing, patient care, support for equipment and clinical trials of newer drugs as well as repurposed medicines, vaccines or newer diagnostic tests. while testing and tracing contacts remains the primary public health response to an infectious disease pandemic, over million samples have been tested in india since january . although we have attained testing capacity of lac samples per day, it would still take more than three and a half years to test % of the population. this appears to be an optimistically conservative but inadequate strategy in a country with more than . billion susceptible individuals. , collaborations between government and private healthcare centers can decentralize screening and testing facilities, offloading central agencies while increasing the capacity and outreach. while the public sector has been holding forte in the past few months, the need for additional resources is being increasingly felt. the private healthcare sector has significant potential, [ ] [ ] [ ] with % of the hospitals, % of the beds and % of doctors. under severe strain, similar collaborations have been forged in italy, spain and several other countries. a similar exercise in india would be a prudent way ahead in these times. a large number of blood banks are in the private healthcare sector in india, and it might be worthwhile to explore the conversion of private blood banks into specialized units for the promising convalescent plasma donation therapy, if efficacy is proven in ongoing clinical trials. this will not only tide over the ongoing acute shortage of blood products but also be a sustainable source of convalescent plasma for therapy in severe covid- . in fact, a vast majority of respondents expressed their willingness to donate blood to tide over the acute shortage of blood products in present times. while most public facilities are busy in covid- care, patient with non-covid ailments have faced neglect and apathy. private healthcare respondents are willing and prepared to participate. additionally, a forward triage protocol using tele-medicine services may in-fact hearald a revolution for a large number of technology-enabled non-covid patients. in the western world too, teleconsultations are being increasingly preferred as means of avoiding congestion in public spaces. although lower literacy levels and traditional patterns of doctor-patient interactions are a challenge in providing effective home-based outreach care in india, yet the scope of mobile networks and empowerment by these hand-held computers cannot be underestimated. nearly two-thirds of the respondents felt that the private sector could leverage its financial resources by providing free or subsidized treatment to patients. while the government makes efforts to meet the requirement of ventilators, stuttering from the onslaught of paused supply from europe and china, it is prudent to recognize and utilize the dormant resources lying in the private hospital intensive care. [ ] [ ] [ ] further, private laboratories and research facilities, encouraged to develop new cost-effective and rapid high through-put testing methods, should start showing results soon. in unusual times such as this, lessons could be learnt from past experiences. during the influenza pandemic of , all dealings in india were restricted to the public sector to keep track of cases all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint while ensuring affordable healthcare. this eventually led to an infrastructural deficit, and the consequent need to amend policies to include support from the private sector. such experiences from previous epidemics have probably contributed to our hcws believing that the private sector in india can participate in a more significant manner. this is the first survey including a wide set of stakeholders in the private healthcare sector and in our opinion, it is an important move in the right direction to ascertain willingness and preparedness. the results, subject to opinionated biases of a small set of young technology-empowered respondents, largely doctors are nevertheless enlightening and encouraging. further, since this survey was electronically distributed, it has the advantage of a diverse representation of voices across the country, and yet opinions may be influenced by differential approach determined by local state policy. in the face of an unprecedented disease, with mystical transmissibility and unprecedented ability to devastate the human population, it is not surprising that the public healthcare sector is under more stress than it can handle alone. we have a large private healthcare sector in our country which is not only equipped but also willing, to share the burden of disease. thus, a pragmatic approach to facilitate the private-public partnership will go a long way in mitigating the community impact and reduce mortality in current times. an open, healthy and swift discussion between the public and private sector should be the first step towards sorting grey areas. table : : survey respondent's suggestions on how private practitioners can contribute on a professional front. all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . other (please specify) ( . %) all rights reserved. no reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . (which was not certified by peer review) is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted june , . . https://doi.org/ . / . . . doi: medrxiv preprint the socio-economic implications of the coronavirus pandemic (covid- ): a review covid- to trigger roughly million job losses: ilo. accessed the three steps needed to end the covid- pandemic: bold public health leadership, rapid innovations, and courageous political will the challenges confronting public hospitals in india, their origins, and possible solutions in the dark even after a decade! a -year analysis of india's national rural health mission: is family medicine the answer to the shortage of specialist doctor in india? india now ranks fourth globally on daily increase in covid- cases. the wire covid- | is india's health infrastructure equipped to handle an epidemic? accessed capacity building of private sector workforce for public health services in india: scope and challenges the private health sector in india private sector contributions and their effect on physician emigration in the developing world the indian health care system | health care | public health. international healthcare system profiles india -lessons for universal health coverage. dangal g, ed. plos one ministry of health and family welfare, government of india. national health policy public and private partnership in disaster risk management public-private partnerships (ppp) in disaster management in developing countries: a conceptual framework perception about social media use by rheumatology journals: survey among the attendees of iracon improving the quality of web surveys: the checklist for reporting results of internet e-surveys (cherries) coronavirus update (live): , , cases and , deaths from covid- virus pandemic -worldometer. accessed population, total -india | data we need strong public health care to contain the global corona pandemic india turns to private sector to boost health coverage. devex what can be done about the private health sector in low-income countries? how technology is changing health care in india the italian health system and the covid- challenge spain nationalises all private hospitals, uk rents hospital beds current and future applications of telemedicine to optimize the delivery of care in chronic liver disease census of india: literacy and level of education health needs, access to healthcare, and perceptions of ageing in an urbanizing community in india: a qualitative study local ventilators need of the hour to prepare for covid- . livemint lockdown . : over migrant workers reach lucknow from nashik by special train -the economic times video | et now covid- risks and response in south asia existing health inequalities in india: informing preparedness planning for an influenza pandemic key: cord- - mpob nx authors: varshney, mohit; parel, jithin thomas; raizada, neeraj; sarin, shiv kumar title: initial psychological impact of covid- and its correlates in indian community: an online (feel-covid) survey date: - - journal: plos one doi: . /journal.pone. sha: doc_id: cord_uid: mpob nx background: the pandemic of corona virus (covid- ) hit india recently; and the associated uncertainty is increasingly testing psychological resilience of the masses. when the global focus has mostly been on testing, finding a cure and preventing transmission; people are going through a myriad of psychological problems in adjusting to the current lifestyles and fear of the disease. since there is a severe dearth of researches on this issue, we decided to conduct an online survey to evaluate its psychological impact. methods: from (th) to (th) march an online survey (feel-covid) was conducted using principles of snowballing, and by invitation through text messages to participate. the survey collected data on socio-demographic and clinical variables related to covid- (based on the current knowledge); along with measuring psychological impact with the help of impact of event–revised (ies-r) scale. results: there were a total of responses from around cities in the country. out of these responses had at least one item missing; and were excluded from the analysis. the mean age of the respondents was around years with a male female ratio of : and around % respondents were health care professionals. overall approximately one third of respondents had significant psychological impact (ies-r score > ). higher psychological impact was predicted with younger age, female gender and comorbid physical illness. presence of physical symptoms and contact history predicted higher psychological impact, but did not reach statistical significance. conclusion: during the initial stages of covid- in india, almost one-third respondents had a significant psychological impact. this indicates a need for more systematic and longitudinal assessment of psychological needs of the population, which can help the government in formulating holistic interventions for affected individuals. from th to th march an online survey (feel-covid) was conducted using principles of snowballing, and by invitation through text messages to participate. the survey collected data on socio-demographic and clinical variables related to covid- (based on the current knowledge); along with measuring psychological impact with the help of impact of eventrevised (ies-r) scale. there were a total of responses from around cities in the country. out of these responses had at least one item missing; and were excluded from the analysis. the mean age of the respondents was around years with a male female ratio of : and around % respondents were health care professionals. overall approximately one third of respondents had significant psychological impact (ies-r score > ). higher psychological impact was predicted with younger age, female gender and comorbid physical illness. presence of physical symptoms and contact history predicted higher psychological impact, but did not reach statistical significance. corona is a single stranded rna virus that had its roots into the world from almost years since its discovery in late s. corona viruses belong to the corona viridae family in the nidovirales order. the nomenclature of the corona virus is named after the crown-like spikes on the outer surface of the virus structure. [ ] the virus has been infecting animals like chickens and pigs but there was no major human contraction to humans. [ ] earlier, the allied viruses of the same family like the severe acute respiratory syndrome coronavirus sars-cov in , human corona virus hcov nl in [ ] , hku in [ ] , middle east respiratory (mers) in , have shown their outbreaks and now the novel version of this virus has presented a threat of unmatched severity. according to the classification of international taxonomy of viruses (ictv) has referred this novel pathogen as sars-cov- (formerly known as -ncov) in . [ , ] the first case was identified in the city of wuhan, a chinese seafood market and since then it has been exponentially increasing with an evident human to human contact via respiratory droplets while sneezing and coughing. [ ] the mode and transmission and other related details about the virus continue to be updated in every few weeks, leading to enhanced uncertainty. [ ] during this period most of the research has been focused on understanding and preventing transmission; exploring treatment options and issues with global governance. however we think that the psychological impact of this pandemic like stress and anxiety among the general population is also a grave concern. [ ] a study from china suggesting that more than half of the participants had a significant psychological impact of the covid- pandemic. another recent study from denmark reported psychological well-being as negatively affected. in the united states nearly half were found to be anxious as per the survey conducted by the american psychiatric association. [ ] [ ] [ ] [ ] the same has not been studied in indian population systematically; except anecdotal discussions and case reports. [ ] in indian subcontinent, as of march , according to the ministry of health & family welfare (mohfw), a total of covid- positive cases (including foreign nationals) were reported in states/union territories. these include cases that were cured / discharged, one person who has migrated and deaths. [ ] hospital isolation of all confirmed cases, tracing and home quarantine of the contacts is on-going. in india, spread of the initial disease could be traced mainly to the foreign nationals who visited the country as tourists from the disease affected countries and secondly due to the mass immigration of indian nationals from abroad; due to the fear of infection. as the pandemic outbreak in india was on-going, the government of india took stringent measures to limit the cases by far in that stage only, by initiating a major lockdown pan-india and also by shifting the immigrants to the special quarantine facilities prepared by the indian military directly from the airports and seaports for a minimum of days. community health teams were also launched to spread awareness about the chances of spread and precautionary measures that one can use to protect themselves and others. [ ] during the early stages of the pandemic in india, this study was focused mainly to assess its psychological impact. the lives of people were drastically affected with lock-down and fear related to the disease's potential effects and transmission [ ] . the fear due to the contraction of covid - is on the rise because of the death tolls and global spread. [ , ] . hence, this study attempted to find the initial psychological impact of covid- among general public; and understand its relationship with physical symptoms. this can potentially help policy makers in formulating comprehensive interventions. the study has been approved by the institutional ethics committee at institute of liver and biliary sciences, new delhi (letter no: iec/ / /ma ). a cross sectional survey design was decided to assess the initial psychological impact of covid- , (fears worries and impairment in sleep). we collected data using an online (anonymous) survey platform (survey monkey) as per indian government's recommendations to minimise face-to-face or physical interaction as citizens continue to isolate themselves at home. potential respondents were invited through a text message, which lead them to a survey monkey page (designed by it team at ilbs, new delhi). all people who have registered at ilbs ( to present) since the inception were sent the sms for participation in the feel-covid survey. additionally, using the principles of snowballing, the link was circulated by the investigators through social media for capturing data from english speaking general population (who have some access to internet). an effort was made to capture healthcare workers who have handled patients / potential patients. additionally, family member of patients suffering from liver disease, being screened in institute of liver and biliary sciences, were requested to take the survey while waiting for their consultation. during offline requests all standard social distancing protocols were maintained as directed by indian government. we collected data anonymously, without collecting information that could identify the respondents. the period of data collection was between th and th march . once the user clicked on the link they were given information about the nature and purpose of survey on the first page. subsequently, if they consented to participate, they were taken to the next page (first section) of the survey. the first part of the study questionnaire collected sociodemographic information (age, gender, occupational status, city of residence, type of family) and information regarding physical symptoms like presence of cough, cold, head ache breathing difficulty, fever and fatigue related to coronavirus disease. contact history variables included close contact with an individual with confirmed covid- , indirect contact with an individual with confirmed covid- , and contact with an individual with suspected covid- or infected material; and any foreign travel in the last days. participants were also asked about being a healthcare worker and if they had a known pre-existing medical or psychiatric illness. the second part of the survey was adopted from impact of event scale-revised (ies-r). this tool comprised of -items questionnaire which measure the effect of routine life stress, everyday traumas and acute stress. for all questions, scores could range from through . categorization of the score ranges from to , to and more than which signify mild, moderate and severe psychological impact respectively. [ , ] . among this scale, the intrusion subscale is mean item response of items , , , , , , , . the avoidance subscale is the mean item response of items , , , , , , , . the hyperarousal subscale is the mean item response of items , , , , , . separately, the data on actual number of confirmed cases of covid- and deaths in the country was accessed through government of india website for general public which was available in the website url address "https://www.mygov.in/covid- ". for the purpose of this study we accessed the above website till st march . descriptive statistics were conducted for the socio-demographic variable and clinical parameters (like physical symptoms and contact history). normality of data was assessed using shapiro-wilk test. the scores of the ies-r and subscales were expressed as mean and standard deviation. we used linear regression to calculate the univariate associations between sociodemographic characteristics, physical symptom contact history variables, additional health information variables and ies-r score. all tests were two-tailed, with a significance level of p < . . statistical analysis was performed using spss statistic . (ibm spss statistics, new york, united states). during the very early period, fig depicts the progression of number of cases of covid- from st february to th march in india. the figure also has a timeline of events (first case, first recovered case, first death and curfew announced) to get a perspective of results during the initial period of covid- in india. the first case of covid- was reported on st february in india. thereafter there was a significant increase in the number of the confirmed, recovered and deceased individuals due to coronavirus outbreak up to th march . ("https://www.mygov.in/covid- ). at the time of conducting the survey, the number of cases was building up. a total of responses were obtained in the study duration through the survey monkey platform. out of these had at least one item missing in the psychological impact related responses and were excluded from analysis. the final analysis was done on rest of the respondents. the mean age of the respondents were . years (sd = . ; range = - ) with a male preponderance [ ( . %)]; among which participants ( . %) were health professionals. most of the respondents ( . %) belong to nuclear families and ( . %) respondents had reported a history of physical illness; including ( . %) with a history of known liver disease. the psychological impact of covid- outbreak, as measured by ies-r scale, revealed a mean score of mean of . ((sd) = . ) and median of . . as it can be seen from the table , most of the respondents ( . %) had minimal psychological impact ( . %) in reaction to covid- outbreak. around ( . %) had mild psychological impact (ies-r score of - ) and ( . %) had moderate psychological impact (ies-r score of - ) however, ( . %) reported severe psychological impact (ies-r score of > ). (table ) (table ) . linear regression showed that there was a statistically significant association found between male counter parts and minimal psychological impact which ranges from to on ies-r scale; and between age and psychological impact with higher age associated with lesser psychological impact. moreover, there was a significant association between history of any physical illness and psychological impact. however, there were no statistically significant association between any other demographic or clinical variables. as far as physical symptoms were concerned ( . %) respondents had reported the presence of cough. ( . %) respondents reported presence of cold. however, diarrhoea was the least reported physical symptoms which accounts for merely in two ( . %) respondents whereas headache was among ( . %) which was more frequently reported compared to other physical symptoms. interestingly, sore throat and myalgia were present in ( . %) and ( . %) respectively. only a few respondents had the symptoms of fever ( . %) and breathing difficulty ( . %). univariate linear regression revealed that there was a statistically significant association with presence of diarrhoea and the impact on their psychological health (p = . ). there was no statistically significant association between the physical symptoms such as cough, cold, headache, sore throat, myalgia, fever and breathing difficulty. only nine ( . %) respondents had travelled during past fortnight, ( . %) had visited covid- infected areas. ( . %) had direct contact with the covid-positive persons. there was no statistically significant association between contact history of the respondents and their impact on psychological health. the current study investigated the initial psychological impact of covid- outbreak in indian population. as the disease progressed, concerns regarding health, economy, and livelihood increased day-to-day. the findings of the pandemic's impact on mental health could help inform health officials and the public to provide mental health interventions to those who are in need. this can guide researchers to plan prospective longitudinal studies for assessing treatment need. [ ] there are mental health concerns like anxiety, worries and insomnia especially after the declaration of lockdown in india on th march, . government of india has launched helpline numbers to provide guidance and counselling, in collaboration with different institutes of national importance. [ ] world health organization has urged to take the necessary precautions to tackle the negative impact of the spread of coronavirus on psychological health and well-being. [ ] overall, among the respondents . % had significant (mild / moderate /severe) psychological impact regarding covid- . this finding was different from the study conducted in china by wang et al which reported . % of respondents suffered a psychological impact from the outbreak, ranging from moderate to severe among respondents. [ ] since these findings were during the early phase of covid- outbreak in the country, chances are they could have changed over time and hence, should be interpreted accordingly. in the past, during outbreaks such as 'ebola virus', individual and community at national and international had a major and wide spectrum of psychosocial impacts due to the sudden outbreak of the disease. it is likely that people are relating contracting the virus with a fear of falling sick, helplessness, hopelessness, stigma and even death. [ ] providing psychological first-aid & counselling are quintessential during an epidemic. it helps in reducing the psychological distress and promoting adaptive coping strategies to deal with the situation. [ ] despite the efforts of who and other public health authorities to contain the covid- outbreak, this time of crisis is generating stress throughout the country [ ] , much alike its impact on the global counterparts [ ] . constant support for mental and psychosocial well-being in different groups during the outbreak should be of highest priority. [ , ] demographic variables showcase that males had lesser psychological impact of covid- outbreak as compared to their female counterpart. the impact on females was found to be statistically significant. these findings were similar in the chinese community where females suffered a greater psychological impact of due to the coronavirus outbreak. [ , ] this also corresponds to previously available extensive epidemiological literature which shows that women are at a higher risk. [ ] in our survey, physical co-morbidities were a predictor for higher psychological impact in response to the outbreak, similar to the finds in existing research. [ ] an unexpected finding was the non-statistically significance of impact of being a health care worker on psychological impact. this is contrary to existing literature [ ] about them being more prone to unfavourable mental health outcomes. this could have been due to low sample size of healthcare professionals representation in the study; thus limiting generalizability of the findings. however, there are some more limitations to be considered while analysing the study results. first is the inherent design of the study like sampling technique being only restricted to people with internet access and having understanding of english; could also limit generalizability of the study. second are the concerns of social desirability while responding to questions on mental health issues. thirdly the study was conducted during a period of lockdown, which can have its own psychological impact and this confounder could not be addressed through the questionnaire used in the study. these issues could have caused under or over reporting in the rate of psychological impact found in the study. since approximately % of the study participants had history of some liver disease, there could be a sampling bias in the study. moreover, the questionnaire used has not been validated in indian population earlier. but we felt the timely need of conducting this survey in order to enhance the understanding of psychological concerns and hence a separate validation was not attempted before the study. despite the limitations, this study provides the first cross-sectional data on actual level of psychological impact among indian community; and how mental health of people is affected during a pandemic of this nature. online surveys (or self-administered questionnaires) have been found as an effective way of assessing problems related to mental health [ , ] and this becomes a prudent method of conducting research in the period of lockdown. since these findings pertain to the initial period of pandemic in india, a larger longitudinal study should be conducted in the current time to guide policy makers in understanding the psychological impact. covid- pandemic has caused a lot of uncertainty in the lives of indian public, just like their global counterparts. our survey is one of the first mental health related data from india, during the initial phase of covid- pandemic and indicated that a significant proportion of them have had a psychological impact during the crisis. the factors that predicted higher impact were younger age, being female and having a known physical comorbidity. there is a need for considering mental health issues by the policy makers; while planning interventions to fight the pandemic. covid- infection: origin, transmission, and characteristics of human coronaviruses coronavirus disease (covid- ) coronavirus nl -induced adult respiratory distress syndrome human coronavirus-hku infection among adults in cleveland, ohio. open forum infect dis evaluation and treatment coronavirus (covid- ) timely mental health care for the novel coronavirus outbreak is urgently needed clinical features of patients infected with novel coronavirus in wuhan centre for disease prevention and control. novel coronavirus disease (covid- ) pandemic: increased transmission in the eu/eea and the uk-sixth update- mental health and psychosocial considerations during covid- outbreak. world health organization immediate psychological responses and associated factors during the initial stage of the coronavirus disease (covid- ) epidemic among the general population in china covid- and mental health: a review of the existing literature the depressive state of denmark during the covid- pandemic especially for loved ones; older adults are less anxious how covid- is overwhelming our mental health focus on mental health during the coronavirus (covid- ) pandemic: applying learnings from the past outbreaks early release-public mental health crisis during covid- pandemic fear of covid : first suicidal case in india! the impact of event scale-revised: psychometric properties in a sample of motor vehicle accident survivors the impact of event scale-revised: psychometric properties of the lithuanian version in a sample of employees exposed to workplace bullying the covid- outbreak: crucial role the psychiatrists can play coronavirus: government launches helpline for mental health issues during lockdown. deccan herald rethinking online mental health services in china during the covid- epidemic the kikwit ebola outbreak: lessons hospitals and physicians can apply to future viral epidemics initial public health response and interim clinical guidance for the novel coronavirus outbreak-united states covid- , coronavirus and mental health rehabilitation at times of crisis patients with mental health disorders in the covid- epidemic depression after exposure to stressful events: lessons learned from the severe acute respiratory syndrome epidemic prevalence of depression in the community from countries between comorbidity and its impact on patients with covid- in china: a nationwide analysis factors associated with mental health outcomes among health care workers exposed to coronavirus disease responses to mental health stigma questions: the importance of social desirability and data collection method measuring mental illness stigma with diminished social desirability effects we are grateful to the it team of ilbs-ms jyoti agarwal, lt. col. rajnish kishore (general manager, it); mr sandip kumar for all the support during launch of the survey and compiling results. we also acknowledge ms garema khurana (deputy editor at xmedia) for her valuable and free of cost english language editing. key: cord- - v tpi n authors: gupta, m.; mohanta, s. s.; rao, a.; parameswaran, g. g.; agarwal, m.; arora, m.; mazumder, a.; lohiya, a.; behera, p.; bansal, a.; kumar, r.; meena, v. p.; tiwari, p.; mohan, a.; bhatnagar, s. title: transmission dynamics of the covid- epidemic in india, and evaluating the impact of asymptomatic carriers and role of expanded testing in the lockdown exit strategy: a modelling approach date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: v tpi n background: the coronavirus disease (covid- ) has caused over cases and deaths as on may , and has quickly become an unprecedented global health threat. india, with its unique challenges in fighting this pandemic, imposed one of the worlds strictest and largest population-wide lockdown on march . here, we estimated key epidemiological parameters and evaluated the effect of control measures on the covid- epidemic in india and its states. through a modeling approach that accounted for asymptomatics, we assessed the impact of lockdown relaxation and increased testing. methods: we estimated the basic reproduction number and effective reproduction number at a national and state level in india after adjusting for imported cases and reporting lag using established statistical methods, using time-series data from march to april . using a dynamic seir-qdpa model fitted to data from india, we forecasted the size and temporality of the ongoing first wave while accounting for the interventions in place. we used the model to simulate lockdown relaxation under various scenarios to evaluate its effect on the size and temporality of the second wave. we also evaluated the feasibility of increased testing as a containment strategy after restrictions are relaxed and its impact on the epidemic size and resumption of socio-economic activities, while taking into account the changes in transmission dynamics brought about by asymptomatic carriers. findings: the median delay from symptom onset to detection (reporting lag) was estimated to be {middle dot} days ( % ci {middle dot} - {middle dot} ) with an iqr of {middle dot} days ( % ci {middle dot} - {middle dot} ). the r for india was estimated to be {middle dot} ( % ci {middle dot} - {middle dot} ; r = {middle dot} ), while the rt gradually down trended from {middle dot} ( %ci {middle dot} - {middle dot} ) on march to {middle dot} ( % ci {middle dot} - {middle dot} ) on april. {middle dot} % of confirmed covid- cases in our sample were found to be asymptomatic. we observed that delaying the lockdown relaxation increases the time to new rise in active cases after the relaxation in a linear fashion. if lockdown was reintroduced after a fixed relaxation period, the magnitude of the second peak could be reduced by delaying the relaxation and decreasing the duration of relaxation. these benefits were greater in case of a gradual relaxation as compared to a sudden lifting of lockdown. we found that detecting a higher proportion of cases through testing significantly decreases the total infections. this positive impact of testing progressively increased at higher transmission rates when restrictions were relaxed. we found that similar containment targets could be achieved by both, a combination of high testing and less social restrictions, and a combination of lower testing with intensive social distancing. interpretation: the nationwide social distancing interventions in india since march have reduced the effective transmission levels, though sub-threshold rt remains to be achieved. if lockdown is to be extended, additional benefits for mitigating the second wave can be achieved if it is extended farther after the peak of active cases has passed. intensive social distancing is inherently enough to contain the epidemic, however, testing will play a pivotal role in the lockdown exit strategy by impeding the epidemic growth enough to allow for a greater resumption of socio-economic activities, thus minimizing the social and economic fallout resulting from severe restrictions. considering that asymptomatics play an undeniable role in the transmission of covid- , dependence on presence of symptoms for control strategies, behavioural changes and testing should be reduced. no funding was received for this study. evidence before this study a nationwide lockdown was imposed in india on march , about three weeks after the first locally transmitted case of novel coronavirus disease (covid ) was detected. the lockdown effectively confined . billion people to their homes, wherein all nonessential activities including offices and schools were shut down, mass gatherings banned, interstate travel highly restricted, and all international borders sealed. we searched pubmed and preprint archives for articles published up to may , , using the terms "coronavirus", " ncov", "covid ", and "reproduction number", "transmission", "lockdown", "interventions", and "india". we found two studies that reported the timevarying reproduction number (r t ) of covid based on timeseries data from india till earlyapril, but none accounted for imported cases and reporting lag in the estimation and none analysed the effect of interventions on the reproduction number. we could not identify any study which modelled the role of asymptomatic carriers and the impact of increased testing as a lockdown exit strategy. our study provides reliable estimates of r and r t for india and states after correcting for importations and delay to detection. the trend of r t upto march indicates that control measures implemented across india have been effective in reducing the transmission of covid , though subthreshold rt remains to be achieved. through a modelling approach which accounts for asymptomatic transmission, we evaluated various lockdown exit strategies, including the effect of onset and duration of lockdown relaxation on the second wave, and the impact of increased testing on epidemic size and resumption of socioeconomic activities. we found that extending lockdown farther beyond the first peak has additional benefits in mitigating the second wave. expanded testing significantly reduced transmission, and we found that this impact was greater at higher transmission rates which will be seen once restrictions are relaxed. to avoid a resurgence in cases, a flexible relaxation approach guided by regional monitoring of effective reproduction numbers is recommended, and this relaxation should be farther beyond the peak of the first wave as feasible. as restrictions are relaxed, increased detection through expanded testing will be essential in limiting the resurgence of cases and will allow greater resumption of socioeconomic activities, thus authorities should consider scaling up testing capacity preemptively before lifting restrictions. considering that asymptomatics play an undeniable role in transmission of covid , dependence on presence of symptoms for control strategies, behavioral changes and testing should be reduced. further research to determine the asymptomatic proportion and quantify their transmission potential is needed to better inform future control strategies. originating out of wuhan, china in december , the coronavirus disease (covid ) was declared a pandemic by the who on march . as of may , there have been more than cases and deaths worldwide, and close to cases and deaths in india. india reported its first covid case on january , although actual epidemic growth started from early march. for any novel infectious disease, the scale of its public health impact is determined by the basic reproduction number 'r ' which is the average number of secondary infections generated by an infectious index case in a wholly susceptible population. the r of an infection determines its potential to start an outbreak, the severity of control measures needed to contain the spread, and the fraction of the population that will be infected in the absence of interventions. however, once an outbreak is underway, the timevarying effective reproduction number 'r t ' is more relevant as it tracks the subsequent changes in transmission, and can thus be used to monitor the efficacy of control measures and adjust them accordingly. [ ] [ ] [ ] however, any given transmission event is reflected in the data only after a delay, which must be accounted for in the estimation of such indicators for accurate interpretation. previous studies have shown that a severe epidemic with r ~ • can be contained by combining effective quarantine, behavioral change to reduce social mixing, targeted antiviral prophylaxis, and prevaccination. however, in the absence of targeted therapeutics and vaccination for covid , an unprecedented onethird of the world's population is currently under lockdowns -with the primary target of reducing the r t below the threshold of . , india responded to the covid pandemic rapidly and decisively by imposing a nationwide lockdown on march , when there were cases and deaths. , this 'suppression strategy', though effective, has its limitations the social and economic cost of such populationwide social distancing is huge, which limits the long term implementation of these measures. , additionally, containing covid in india is a unique challenge due to its high population density, underprepared healthcare system, and wide socioeconomic disparity. a large proportion of india's labour force works as dailywage laborers or migrant workers, and are especially affected during such times, making lockdowns untenable without parallel social support. there could be yet unseen adverse effects in the form of noncovid morbidity and mortality due to aggravation of malnutrition, chronic diseases and lack of access to healthcare during this time. at the same time, premature withdrawal of lockdowns without adequately planned interventions for the postlockdown phase may lead to reemergence later, or the second wave. , thus there arises a need to create a balance to ensure that the disease is contained and the healthcare system remains well prepared while minimizing the collateral damage from intensive blanket interventions. comprehensive lockdown exit strategies will be central to the future course of the pandemic. in such scenarios with limited primary information, dynamic mathematical models can provide actionable insights for researchers and policymakers. , , evidence suggests that covid has a wide clinical spectrum which ranges from asymptomatic to fatal infections, which coupled with high infectivity can lead to a large number of infections and deaths. it may be possible that covid transmission is driven significantly by undetected asymptomatics while fatality is driven by severe cases a devastating combination. , some have deemed asymptomatic transmission as the "achilles' heel" of the current control strategies against covid . in this study, we estimate the key transmission parameters for covid in india and its states, and analyse how interventions affected transmission levels across time. considering that blanket lockdowns are an initial rather than a final step in controlling this pandemic, we model the effect of relaxing public health interventions at various timepoints. we evaluate the efficacy of increased detection of asymptomatics through wider testing as a viable lockdown exit strategy, through a modelling approach. for estimating the basic reproduction number (r ) and effective reproduction number (r t ) for india and various states, we used the publicly available dataset from covid india from march to april . for estimating the proportion of asymptomatic cases and the delay from symptom onset to confirmation, we obtained data for covid patients admitted to a tertiary care hospital near delhi, which included duration from symptom onset to date of admission for symptomatic patients (appendix p ). we used data from johns hopkins university (jhu) covid database on daily cumulative cases, daily cumulative deaths, and daily cumulative recoveries in india from march to april for model fitting and parameter estimation. we used the world bank population database for population data for india. a laboratory confirmed case irrespective of symptoms is counted as a confirmed covid case in india. testing criteria are provided in appendix p . the bestfit r was calculated for the national and state level incidence data using the r package in r • • using two independent methods: maximum likelihood (ml) method and the exponential growth (eg) method after adjusting the incidence data for imported cases. [ ] [ ] [ ] we assumed the serial interval to be gamma distributed with a mean of • days ( % ci • - • ) and a sd of • days ( % ci • - • ). we analysed the sensitivity of the estimated r to the choice of the time period over which the r was estimated and the serial interval (appendix p ). a variable delay occurs from symptom onset to covid confirmation (henceforth referred to as the reporting lag) which is attributed to multiple factors including time taken to seek care (patient dependent) and time taken to detect and test the case (healthcaresystem dependent). since all included patients were tested and confirmed positive within a day of admission, the time from symptom onset to admission obtained from data approximates the reporting lag of these cases. we fitted appropriate distributions to the data and the best fit distribution was chosen. due to lack of data, we assume that the reporting lag for india and for each state is statistically the same as the estimated reporting lag for the patients from delhi whose onset date was known. for each reported case, onset dates were sampled to generate lagadjusted datasets for incidence by onset (appendix p ). using the reporting lag adjusted incidence, the timevarying r t was calculated using epiestim package in r • • which uses the time dependent maximum likelihood approach. , the same serial interval distribution was used as for r estimation. cases in the dataset not explicitly labeled as 'imported' were considered to be locally transmitted. we determined both the imported cases adjusted rt and unadjusted rt for india. the rt trends were overlaid with major epidemic events in the country and mobility information from google community mobility reports to analyse the correlation between social mobility and transmission rate, if any. modelling the pandemic using dynamical compartmental models in order to model the spread of sarscov in the population, we generalize the extensively used seir model for epidemics, which can fit the early dynamics of the covid pandemic well it but lacks important social and biological factors that play a critical role in determining the disease's progression. for introducing the required complexities, we build a model as shown in figure . model parameters are defined in table . compartments include s(susceptible), e(infected but not yet infectious), ia(undetected asymptomatic; infectious), is(undetected symptomatic; infectious), qa(detected and quarantined asymptomatic), qs(detected and quarantined symptomatic), ru(undetected recovered asymptomatic), ra(recovered detected asymptomatic), rs(recovered detected symptomatic), d(dead), and p(protected; nonsusceptible). compartments in red are fitted to data; q=qa+qs to active cases, r=ra+rs to total recovered cases, and d to total deaths. transition rates in red are inputs to the model, while others are estimated (table ) . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) tested sensitivity analysis to the choice of assumed parameters ai, fa, and pa was performed for the fitted parameters α, β, δs , κ and λ in appendix p . confidence intervals for incubation period and asymptomatic infectious period have not been included since these parameters are fixed and not sampled. through a positive protection rate (α), the susceptible population gradually decreases to account for the effect of increasingly intensive social distancing policies and improved public behaviour in reaction to the epidemic. we introduce a deprotection rate (σ) which increases the susceptible pool once social distancing policies are relaxed. we set the probability of infected case being asymptomatic (p a ) to • , • , • , • , as reported estimates for the percent of infections that are asymptomatic range widely from % %. , , [ ] [ ] [ ] we consider that asymptomatic cases do not exhibit coughing, sneezing or sputum production and are thus expected to show lower infectivity than symptomatics. we conservatively assume an asymptomatic patient is % as infective as a symptomatic patient (a i = • ). we set the fraction of detected asymptomatics (f a ) at baseline to • , the incubation period (γ ) to • days, and the infectious period for asymptomatics (δ a ) to days based on virologic and epidemiologic studies. , we assume that all symptomatics are detected, and that no asymptomatic dies from the disease. further details regarding the construction of the model, including the governing equations are available in appendix p . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint we fitted for the values of transmission rate (β), protection rate (α), reporting lag (δ s ), recovery rate (λ), mortality rate (κ), and the initial values of exposed (e ) and infected (i ) individuals in the population. we estimated the unknown parameters of the model by fitting time series data for active cases (given by cumulative confirmed casescumulative recoveriescumulative deaths), cumulative recoveries and cumulative deaths to the q(t) = q s (t) + q a (t), r(t) = r s (t) + r a (t), and d(t) compartments respectively. we then simulate the model with the estimated parameters to predict the key time points and the number of expected cases in the ongoing first wave. we define and predict three key time points which are inherent to epidemic progression time at peak of daily new reported cases (t ), time at peak of active cases (t ), and time when recovered cases > active cases (t ). note that these predictions do not take into account the change in transmission dynamics due to relaxation of lockdown. sensitivity of our results to assumptions of p a , f a and a i was analysed. in the article, we have used the following operational definitions obtained by combining values of various compartments: 'symptomatic cases' cumulative detected symptomatic cases; 'detected cases' cumulative detected cases including symptomatic and asymptomatic cases; 'total infections' cumulative infections including detected cases and undetected asymptomatic infections. to model complete lifting of the nationwide lockdown, α is set to zero and σ is set to a large value such that the entire protected population is emptied into the susceptible population in a short interval (t ½~ • day). we trigger this change on may (tentative date of lockdown relaxation in india) and day intervals thereafter, to compare outcomes if lockdown is lifted at different dates. we also consider the scenario where the lockdown is reenforced after a fixed relaxation period which we model by setting σ to zero and reenforcing the same α as before lockdown relaxation. alternatively, we model a comparatively gradual lockdown relaxation by setting σ=α. to model the effect of increased testing capacity and subsequent improved detection, we assume that it will increase the asymptomatic detection rate f a from • in lockdown, to • , • , • , • , • , and • after lockdown relaxation starting may . to model the effect of varying levels of reduced social mixing and positive behavior change after the lockdown is lifted, we change the effective transmission rate to %, %, %, %, % and % of the original β, starting may . varying levels of social mixing influences the contact rate, while behaviour changes like wearing masks and hand washing decrease transmissibility given a contact the transmission rate β captures both these changes. we hypothesise that increased testing after lockdown relaxation will decrease the epidemic growth enough to allow for greater resumption of normal social mixing, thus minimising the social and economic fallout resulting from vigorous restrictions, and that this effect will be proportional to the amount of testing done. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . the funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the article. the corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. the exponential growth (eg) method had a better bestfit r over a larger time period and was less sensitive to the choice of the time period (appendix p ). the best fit r for india was found to be • ( % ci • - • ; r = • ). taking into consideration the uncertainty in reported serial intervals, the r ranged from - • for serial intervals ranging from - • days. , [ ] [ ] [ ] results were found to be sensitive to the serial interval (si) distribution, thus we provide r estimates based on the most reliable serial interval from infectorinfectee pairs in china, and also consider a range of possible serial intervals based on other studies. figure a ). incidence by onset and timevarying r t could be ascertained upto april since some cases with onset after this date may not have been reported yet in the data, due to the reporting lag. the r t trends for india showed visible fluctuations over time ( figure b ). the first uptick in unadjusted r t (blue band) starting around march was presumed to be an artifact due to imported cases, since it coincided with increasing imported case onsets, and was not accompanied by a concurrent uptick in import adjusted r t (pink band is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint on march, except for a rise in residential neighbourhood mobility ( figure c ). the daily r t values for india, and r t trends for states of india are provided in appendix p . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint april in india stratified as imported (red) and local (light blue), along with the instantaneous effective reproduction number rt adjusted for importations (pink) and without adjusting for importations (blue). dark bands indicate % confidence interval and light bands indicate % confidence interval for estimated rt. similar graphs for states of india are provided in appendix. [c] mobility trends in india, compared to a baseline median value for the corresponding day of the week, during the week period jan -feb , . holiday due to the holi festival on march caused a dip in mobility. a sharp dip in mobility is noted at the voluntary public curfew on march and after the nationwide lockdown was enforced on march, except for a rise in residential neighbourhood mobility. the weekly rise in workplace mobility appears to be an artifact due to comparison with normal weekends at the baseline. source google community mobility reports. major interventions are shown, the effects of which are best correlated with rt trend and mobility changes, since these changes occur in realtime. rt= timevarying effective reproduction number estimated model parameters from data the model was able to fit the data well for the early exponential phase of the growth and also captured the recent slowdown in epidemic growth through the protection rate. table shows the bestfit parameter estimates for the base assumptions of p a = • (chosen based upon the asymptomatic proportion estimated from primary patient data), a i = • , and f a = • . the reporting lag estimated from model fit was • days ( % ci • - • ), which was in agreement with the reporting lag of • days ( % ci • - • ) estimated from primary patient data. the sensitivity of the fit parameters to our assumptions was evaluated (appendix p ). initial symptomatic infected (i ) estimates are for base assumptions (ai= • , pa= • , fa= • ). . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . after comparing with recent data, we note that the model underpredicted the first wave because it did not consider a parallel leakage of protected compartment back into the susceptible compartment, which tends to happen in reality as lockdowns are not absolute. this also leads to a higher estimated transmission rate (to account for transmission otherwise caused by leakage of protected people), and thus our modeling results for lockdown relaxation and impact of testing should be considered as worstcase scenarios. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . on a complete removal of the lockdown irrespective of the date of relaxation, we observed that the number of active cases will start to rise exponentially after a variable delay ( figure a ). we varied the time when the lockdown relaxation was initiated from th may to th july at one week intervals and quantified the delay (from the relaxation date) after which the number of active cases started rising again. we observed that delaying the lockdown relaxation increases the time to new rise in a linear fashion, with pearson's r = • ( % ci • - • ; p< • ) ( figure b ). when we simulated limited time duration relaxation periods, we found that there is a rise in active cases observed in all simulations but the extent of the rise is highly dependent on when the relaxation was started and the duration of the relaxation period ( figure c and d). both delays in the lockdown relaxation and smaller relaxation periods reduced the number of active cases at the peak, suggesting that small relaxation periods enacted once the peak has been crossed may help reduce the number of active cases at any future point in time. is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint the mean lag for bootstrapped simulations, and bands represent % confidence intervals. in the case of a gradual lockdown release, we found that there was both a delay to new rise in active cases and the reduction in the second peak was more pronounced (appendix p ). the results shown in figure consider that the peak of active cases is expected to be on may . since our model underpredicted the first wave, the actual peak of active cases may occur later than may. the findings remain unaffected in essence, though these results will be better interpreted in the context of the actual peak. we observed that both increased testing and increasingly vigorous social distancing have a positive impact on reducing the number of total infections and symptomatic cases. with increased testing, the fraction of total infections that were detected increased, ie, the ascertainment rate improved ( figure a and b). although the number of detected cases may remain almost constant in some scenarios of increased testing, a lower proportion of the same are symptomatic, which highlights the significance of detecting more asymptomatic infections. we further found that the positive impact of increased testing becomes more prominent at progressively higher values of transmission rate β ( figure c ). in the baseline scenario with detection increased from % to % for days-for every extra asymptomatic detected by increased testing, the number of infections prevented are • at β, • at • β and • at • β, while the number of symptomatic cases prevented are at β, • at • β, • at • β. this benefit increases further with higher increases in testing. for an increase in detection from % to %, the symptomatic cases decreased by • % at β, by • % at • β, and by % at • β. for an increase in testing from % to %, the symptomatic cases decreased by • % at β, by • % at • β, and by • % at • β. after lockdown relaxation, lower levels of social restrictions (high β) when coupled with increased testing, can achieve similar results as a more restrictive social distancing regime where testing was not increased ( figure d ). that is, increased testing allowed greater resumption of normal social mixing after lockdown relaxation. an example of a feasible combination of testing and social restrictions is indicated by the area between two watershed lines (grey) in figure d . due to uncertainty in the percent of infections that are asymptomatic, we evaluated the effect of testing across the range of p a (appendix p ). . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . for a containment target of , , cases. similar heatmap for total infections is given in appendix p . the trend of effective reproduction number (r t ) of covid in india indicates that control measures have been effective in slowing down the spread of covid across the country. to achieve sustained suppression, monitoring of the time varying r t at district, state and national level should be done to reach and maintain an r t close to the threshold value of . if lockdown is to be extended, additional benefits can be achieved if it is extended farther after the peak of active cases has passed. as these restrictions are relaxed, increased detection through testing will be essential in limiting the resurgence of cases and thus testing capacity should be ramped up . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . preemptively before lifting restrictions. considering that asymptomatics play an undeniable role in transmission of covid , dependence on presence of symptoms for control strategies, behavioral changes and testing should be reduced. the range of r of sarscov in india was found to be - • , with • being the best fit. our results align with recent studies which estimate the r to be - • . - in comparison, the r was • - • for the influenza (h n ) pandemic, • - • for the sars epidemic, and • - • for the spanish flu pandemic, which reflects the seriousness of the current pandemic. [ ] [ ] [ ] the proportion of population that must become immune in order to halt the epidemic is given by - /r , the herd immunity threshold. for covid , our estimates imply that approximately - % of the population must be infected or vaccinated in order to attain longterm epidemic control. in reality, this threshold is usually higher due to nonhomogenous mixing in populations. in early stages of the epidemic in india, we found that restrictions on international travel were effective in limiting the number of imported cases in india, although this is of limited importance once local chains of transmission had been established. since testing of travelers was based on appearance of symptoms, asymptomatic imported infections that remained undetected may have played some role in the early spread of covid . a 'suppression' strategy (eg: lockdown) aims to arrest epidemic growth by reducing r t below . , after the nationwide lockdown was imposed on march , the mobility levels quickly dropped to low levels, but the r t continued to increase till march ( figure ) probably due to inflation of estimated transmission by the is of particular interest and it remains to be seen, as to whether the r t can reach subthreshold levels (below ) before the lockdown is relaxed. india is under one of the strictest lockdowns in the world for more than five weeks now, and a comprehensive lockdown exit strategy will be needed to consolidate and build upon the gains achieved this far. a sudden and complete lifting of the ongoing nationwide lockdown is not a feasible option since it will lead to a rapid exponential increase in cases due to absence of herd immunity. a lockdown of adequate length and efficacy eventually causes . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint the active cases to peak and then gradually decrease. once the peak of active cases is reached, extending lockdown farther beyond the peak may have additional benefits due to progressive exhaustion of the infectious pool in the population, which is practically comparable to a lower prerelaxation prevalence of covid . this has effects-first, the rebound epidemic growth is initially slower which delays the resurgent rise in cases after relaxation of lockdown. this seems to imply that though extending lockdown inherently buys time for preparation, it also adds progressively longer preparation time after the lockdown is relaxed. second, we find that if lockdown is to be reimposed after a fixed relaxation period, the magnitude of the second peak can be reduced by relaxing the lockdown farther from the first peak. this is of particular interest if an intermittent lockdown strategy is implemented in the future, where measures need to be imposed and relaxed repeatedly. the time gained should be used to strengthen surveillance systems, rampup testing capacity and increase healthsystem preparedness. it is optimal to prevent a second wave from occurring at all, by finetuning lockdown relaxation based on serial monitoring of r t to keep its value under . , in this scenario, a later relaxation will allow stabilisation of disease prevalence at a lower value, which can provide a buffer for response if and when a resurgent rise in cases is seen (maintaining r t = implies that the prevalence will remain constant at the prerelaxation level). these observations may increase the benefit of lockdowns above what is widely known, and can better inform the delicate balance of cost and benefits of such intensive policies. massive scaling up of testing has been proposed as a lockdown exit strategy. , in this study, we present quantitative evidence based on modelling for the same. extremely low transmission rates during intensive restrictions are inherently enough to contain the epidemic. however, as transmission rates increase with progressive restoration of normal socioeconomic activities post lockdown relaxation, testing assumes an increasingly substantial role in containment. the extent of relaxation that will be possible without causing an untenable rebound in infections, will highly depend on the amount of testing that is done, especially after lockdown relaxation. while having both intensive social distancing policies and very expansive testing may be nonviable, combining the effects of both to a feasible extent can effectively keep the epidemic under control. our findings align with results seen in countries with an aggressive testing approach, like south korea and taiwan where severe restrictions have been avoided. even if the amount of testing being done during lockdown is deemed to be sufficient, a rapid and massive scaling up of testing capacity is needed preferably before relaxing restrictions. the monetary cost of expanding testing even at a large scale, is expected to be smaller than the cost of implementing intensive social distancing for long periods. in addition to supporting the economy, this approach can ameliorate the humongous social and humanitarian implications of imposing populationwide lockdowns, especially in a country such as india. , blanket testing of hcws can be a judicious use of the expanded capacity, considering they are highly exposed personnel, and risk spreading the infection to patients, coworkers and family members if infected. this will limit . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . depletion of an already scarce workforce due to unnecessary quarantine, while also reducing spread from unrecognised asymptomatic infections in hcws. other essential workforce like law enforcement personnel, grocery vendors, sanitation workers, etc with high contact rates should also be considered. sarscov did not reach the scale of sarscov despite a comparable r due to low community transmissibility and onset of infectivity well after symptom onset which allowed optimal efficacy of traditional control measures like symptomtriggered isolation and contact tracing. , presymptomatic transmission occurs before the onset of symptoms in an eventually symptomatic patient, while asymptomatic transmission occurs through patients who never become symptomatic. presence of both these features in covid is a significant deterrent for control strategies. , , , in such a scenario and r ~ . , modeling studies indicate that controlling covid outbreaks through contact tracing and isolation alone is not possible. however, contact tracing systems should be strengthened since they are a prerequisite for expanded testing of contacts, and they may achieve significant containment at lower r t . based on our findings, it is possible that detecting more asymptomatics through testing impedes transmission to an extent where the total number of infections and thus the number of symptomatic cases decreases ( figure ), relieving burden upon the healthcare system and reducing mortality. this finding will increasingly approximate reality if asymptomatics play a larger role in transmission. a case in point is a blanket testing study done in a small town of italy which achieved almost complete outbreak control. although blanket testing is not practical for larger implementation, it further highlights the importance of detecting and isolating asymptomatics in controlling covid outbreaks. a symptombased monitoring approach during quarantine will miss asymptomatic infections, who will escape the quarantine net and go on to spread the disease. with emerging evidence of infectious asymptomatics, it is prudent to modify the public health response to address these concerns. thus, all contacts should ideally be tested at the end of quarantine irrespective of symptoms. in settings where testing all contacts is not yet possible, extended quarantine periods upto days may be considered, which have twofold benefits. first, almost all asymptomatics finish their infectious period before days, and second, more symptomatics can be detected by day (only out of symptomatic cases are missed by day , compared to cases by day ). such extended quarantines are already in place in certain parts of india and china. , currently, a day quarantine is recommended based on studies of incubation period of covid , , but studying the incubation period inherently assumes an onset of symptoms. it is encouraging to note that the need for expanded testing can be supported by highthroughput machines and by pooling of samples. pooling can also be used for community surveillance, and has the potential to drastically increase detection capabilities while saving costs and resources and should be used wherever possible, while also enhancing research to boost pool size and testing accuracy. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint while contact tracing, isolation and testing are important, the role of behaviour change in reducing transmission must not be underestimated. asymptomatic people are themselves less likely to take appropriate precautions, and people use less caution around other people who don't have symptoms. universal mask wearing in public spaces should be encouraged, and mandated by policy if required. since ensuring longterm compliance of citizens to health advisories and public restrictions will be another challenge, transparent and proactive communication by authorities along with continued social support for vulnerable groups will be essential. there is looming uncertainty regarding the burden of asymptomatics and the role they play in transmission. estimates for asymptomatics range from % to % of total infections. , , [ ] [ ] [ ] with india and china reporting asymptomatics in the higher ranges, it may be possible that young and developing countries have a high proportion of asymptomatic carriers. these estimates are crosssectional, and thus do not differentiate asymptomatics from presymptomatics. it is only retrospectively that the true burden of asymptomatics can be ascertained through serological studies, which will also help us to understand the true fatality rate of covid . epidemiologic and virologic studies have established that asymptomatics are infectious, and have similar upper respiratory viral loads as symptomatic patients. , , , this is in comparison to influenza, where asymptomatics have lower viral loads and thus are less infectious. studies to evaluate presymptomatic transmission of covid have shown that - % of total transmission occurred before the index case showed symptoms, , although quantitative evidence of asymptomatic transmission is lacking and deserves further research. there is an urgent need to identify these gaps in the understanding of sarscov in order to grasp the true size and severity of this pandemic and plan future strategies accordingly. blanket interventions have been effective to suppress the pandemic till now, but targeted interventions will be key as we move forward. various interventions need to be stratified based on how effectively they suppress viral transmission and the amount of disruption they cause. cost effectiveness analysis must be done, and bundles of interventions that together achieve high efficacy with least accompanying disruption should be deployed. highly effective and disruptive interventions should be targeted to areas with active hotspots and high community transmission. it will be essential to build robust disease surveillance systems to assess the relative impact of each intervention in realtime and reduce the time delay to response. expanded testing and strengthened contact tracing will enable this by reducing the reporting lag and rapidly detecting any surge in cases. instead of adopting an intermittent lockdown policy, where lockdowns are treated as either 'on' or 'off', some countries have adopted a staged alert system for responding to the covid pandemic, where a geographical area may move up and down alert levels, to reflect the level of suppression that the local outbreak situation demands. similarly, india has recently stratified its districts into red, orange and green zones based on surveillance trends, in preparation for a . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint staggered relaxation of lockdown. such social distancing policies which are dynamic with respect to geography and time are direly needed as we move into a time of relative uncertainty post lockdown relaxation. several limitations of our study should be noted. first, we assumed the delay from symptom onset to confirmation to be similar to the delay from symptom onset to isolation due to lack of data, and that this delay is uniform across india. though the latter approximates the former, further studies to ascertain the true reporting lag in india are needed since it is critical for identifying r t changes at correct points in time. second, our model does not factor in presymptomatic transmission, which along with a short estimated reporting lag may underestimate the transmission by symptomatic cases and thus inflate the effect of detecting asymptomatics. third, since our primary goal was to evaluate the effect of identifying asymptomatics, we assumed that increased testing increases the detection of asymptomatics only, while in reality it would detect more cases across the clinical spectrum. however, the interpretations regarding impact of increased testing are not sensitive to this assumption, which has been discussed through an alternate interpretation of the model (appendix p ). fourth, we assumed a constant death rate (κ), in contrast to reality where the death rate gradually decreases during an epidemic to ultimately converge at the nearactual death rate . thus, we refrained from forecasting deaths due to obvious bias in the prevailing death rate. notwithstanding the limitations, this study reports a reporting delay estimate from india for the first time, which can be used in future modeling studies. here, we built a mathematical model which can account for the dynamics of lockdown imposition and relaxation, varying levels of case detection, lag to symptom onset and case reporting, while simultaneously allowing to test the range of asymptomatic burden and transmissibility. since we have presented findings across the range of uncertainty regarding asymptomatics (appendix), our results are robust to emerging evidence. though our model is fitted to data from india, we expect the insights into lockdown relaxation and testing impact to be generalisable. in conclusion, though disruptive, the world's largest lockdown in india has been effective in reducing the transmission levels of covid . to avoid a resurgence in cases, a dynamic relaxation approach guided by regional monitoring of effective reproduction numbers is recommended, and this relaxation should be farther from the peak of active cases as feasible. asymptomatic infectives could be a considerable challenge to longterm containment efforts, and increased detection will play an increasingly pivotal role once restrictions start to be lifted. the amount of testing will dictate the extent of resumption of socioeconomic activities, and authorities should scaleup testing capacity as a priority. further, control measures should be appropriate in the social context of the population, as this pandemic brings a humanitarian crisis in addition to a public health one, especially in vulnerable populations across the world. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the code for the simulations and detailed results are available at the following github repository: https://github.com/technosap/seir_qdpa-covid_ . the primary data for calculation of reporting lag is available in the appendix. all other data is from publicly available datasets. we declare no competing interests. we thank all members of the india covid apex research team (icart) for sharing their expertise. we thank our professors at the all india institute of medical sciences (aiims), new delhi for their mentorship. ssm received a kvpy fellowship and support from iiser pune. we thank dr hemant deepak shewade from the international union against tuberculosis and lung disease (the union) for his valuable inputs. the views expressed in this publication are those of the authors and not necessarily those of their affiliated institutes. we express our gratitude to all personnel who are at the frontlines of this pandemic across the globe. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . table s . rt point estimates for national covid- incidence data (without import adjustment) . . table s . rt point estimates for national covid- incidence data (import adjusted . . figure s : incidence by onset and effective reproduction rates (rt) up to april for indian states of maharashtra, gujarat, kerala, delhi, rajasthan, and madhya pradesh. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . . figure s . rt for other indian states up to april . model fitting and fit sensitivity analysis . . fitting methods, initial conditions and uncertainty estimation . . figure s . best fit to data for base assumptions (ai = · , pa = · , fa = · ). . . assumption of constant recovery rate and mortality rate . . sensitivity of estimated parameters to assumptions of ai, pa, and fa . . figure s . sensitivity of fit parameters α, β, δs to assumptions of ai, pa, and fa. . . figure s . sensitivity of fit parameters λ and κ to assumptions of ai, pa, and fa. . . figure s . sensitivity of fit parameters δs to assumptions of ai, pa, and fa . prediction sensitivity . . figure s . sensitivity of predictions to assumptions of ai, pa, and fa. calculation of r from the model parameters . . calculating r from seir-qdpa model . . figure s . estimation and sensitivity of model r to assumptions. sensitivity analysis of the effect of testing rate and social distancing policies . . figure s . sensitivity of effect of testing rate and social distancing policies on total symptomatic cases to probability of asymptomaticity at days after lockdown relaxation. . . figure s . sensitivity of effect of testing rate and social distancing policies on total symptomatic cases to probability of asymptomaticity at days after lockdown relaxation. . . figure s . sensitivity of the number of symptomatic cases to probability of asymptomaticity over a -day period after lockdown relaxation if the testing rate and social distancing policies are not changed after relaxation. . . figure s . sensitivity of effect of testing rate and social distancing policies on total infections to probability of asymptomaticity at days after lockdown relaxation. . . figure s . sensitivity of effect of testing rate and social distancing policies on total infections to probability of asymptomaticity at days after lockdown relaxation. effect of gradual lockdown relaxation . . simulating gradual lockdown relaxation . . figure s . gradual complete lockdown relaxation at three different points of time. . . figure s . lag before new rise in active case after slow lockdown relaxation. . . figure s . gradual lockdown relaxation for days at two different points of time. lockdown relaxation and the healthcare system capacity . . estimating the indian healthcare system capacity . . estimating the time taken to reach the healthcare system capacity under lockdown relaxation scenarios. . . figure s . time taken to reach the healthcare system capacity under lockdown relaxation scenarios. google covid- mobility reports . . background information on how google's mobility reports are generated . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint in order to accurately describe the progression of the epidemic in the population, we generalize and redefine the compartments of a seir model ie. [s(t), e(t), i(t), r(t)]. we redefine the i(t) compartment as the number of undetected infective people and split it into two compartments signifying the undetected symptomatic infectives is(t) and undetected asymptomatic infectives ia(t). exposed patients go to either of the compartments at a fixed ratio of asymptomatics to symptomatics given by r = pa/( -pa) where pa is the probability of being asymptomatic. we set the rates of transition from e(t) to ia(t) and is(t) as rγ and γ respectively. this results in the distribution of exposed cases into the two infective compartments such that for each symptomatic case, there are r asymptomatic cases, causing a fixed fraction (pa) of the cases being asymptomatic. in our model, we further assume that a fixed fraction of asymptomatic infectious cases gets detected (fa) and go to the asymptomatic quarantine compartment qa(t) with detection rate atδa where at = fa/( -fa), and the rest go into an undetected recovery compartment ru(t) with recovery rate for asymptomatics δa. the choice of rates leads to the distribution of asymptomatics into detected quarantined and undetected recovered in the ratio of at, i.e. a fixed fraction (fa) of asymptomatics are detected. he et. al. determined that infectiousness declines significantly after a period of days by studying the distributions of incubation period and serial interval. wölfel et al found that live virus could not be isolated after day in spite of continuing high viral loads in young cases with mild symptoms. backed by both epidemiological and biological evidence, we set the time spent by an asymptomatic being infectious as days. the δa then becomes ⅛ days - . we assume that all symptomatic cases get detected with an average reporting lag δs - after which they go to the symptomatic quarantine compartment qs(t). we refer to the symptomatic and asymptomatic quarantine compartment together as the quarantine compartment q(t). we assume that transition of a case from ia(t) and is(t) to q(t) entails isolating, testing and reporting the case and that this isolation is % effective. from the symptomatic quarantine compartment, cases go to either the rs(t) or d(t) denoting symptomatic recovered cases and fatal cases with recovery rate λ and mortality rate κ respectively. we assume that the recovery of asymptomatic cases in quarantine occurs at the same rate as symptomatics. thus, from the asymptomatic quarantine compartment, cases go to ra(t) denoting detected asymptomatic recovered cases with the recovery rate λ. we assume here that no asymptomatic case dies due to the infection. we refer to the symptomatic and detected asymptomatic recovered compartment together as the recovered compartment r(t). finally, we introduce an extension previously described by peng et al where a new compartment p(t) is added to account for the combined effect of social-distancing by individuals and lockdown of infected regions within the country thus reducing the pool of susceptible individuals in the population at a protection rate α. further, to model the effect of the relaxation of such measures, we introduce a deprotection rate σ with which individuals can leave the p(t) compartment thus increasing the susceptible population s(t). the value of σ is set to zero till any preventive policies are withdrawn. the dynamics of the model are described by the following ordinary differential equations (odes): where n is the total population of the country and is assumed to be constant. the compartments [s(t), e(t), is(t), ia(t), qs(t), qa(t), rs(t), ra(t), d(t), ru(t), p(t)] denote the susceptible, exposed, undetected symptomatic, undetected asymptomatic, quarantined symptomatic, quarantined asymptomatic, recovered symptomatic, recovered asymptomatic, fatalities, undetected recovered, and protected individuals respectively at time t. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint an increase in testing criteria and capacity would naturally have the largest impact on increasing the detection of infections with no or mild symptoms, considering that most infections with moderate-severe symptoms are more likely to be detected even at baseline testing. since our primary goal in this study was to evaluate the effect of detecting more asymptomatics, we assumed that increased testing increases the detection of asymptomatics only, while in reality it would detect more cases across the clinical spectrum. however, the interpretations regarding impact of increased testing are not sensitive to this assumption, which has been discussed here through an alternate interpretation of the model. our -compartment model allows some flexibility in terms of interpretation. if instead of interpreting the is and ia compartment as the symptomatic and asymptomatic infected individuals, we consider them as the detectable and undetectable infections (irrespective of symptoms), our model parameter pa now represents -ascertainment proportion (ascertainment proportion is the proportion of total infections that are considered detectable at baseline) and increasing the fa now becomes equivalent to improving the testing by reducing the bias towards detectable cases and improves detection of all cases irrespective of symptoms. our model takes into account that undetected infected spend more time in an infective state in the population(δa - ) compared to the detected cases(δs - ), which reflects reality. thus, this alternate view allows us to generalize our results with respect to how the testing policies affect the epidemic after lockdown relaxations. one limitation of this interpretation is that we assume asymptomatic cases (here, undetectable cases) have lower infectivity than symptomatics (here, detectable cases) in a homogenous social mixing environment. although undetectable cases are more likely to be asymptomatic, this assumption does not necessarily hold true in this alternate interpretation. still, this limitation would result in an underestimation of the impact of testing rather than an overestimation. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . delay from onset to admission was available for out of symptomatic patients. gamma and exponential distributions were fit to the reporting lag data with maximum likelihood estimation using the fitdistrplus package in r · · . due to the small sample size and lack of reliable prior information about the distribution of reporting lag, the maximum likelihood method was chosen. since the data was found to have a heavy tail, we chose to fit gamma and exponential distributions. the goodness of fit was estimated using the akaike information criterion (aic) and bayesian information criterion (bic). the distribution with a better bic was selected as the appropriate descriptor of the reporting lag distribution. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . the distribution was found to have a heavy tail and was fit on a very small number of samples likely leading to high uncertainty observed in the fits. kolmogorov-smirnov statistic · · cramer-von mises statistic · · anderson-darling statistic · · akaike's information criterion · · bayesian information criterion · · δ bic > and δ aic > . the difference in fit is very strong suggesting the gamma distribution is a much better fit. from the estimated distribution of reporting lag, samples of the fitted distribution parameters (φi) were drawn taking into account the uncertainty in the distribution parameters ie. shape and scale for the gamma distribution and rate for the exponential distribution to serve as the posterior distribution of reporting lag. for each of the samples of fitted parameters, the reporting dates (ri) were transformed to give the symptom onset date (oi) by the formula: oi = ri -li where li ~ gamma(φi) or exp(φi) resulting in lag adjusted datasets. this process was applied to the reporting incidence data for the nation and the different states. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . r estimates with both eg and ml methods and r for states of india for the estimation of r , we use maximum likelihood (ml) method as described by white & pagano and the exponential growth (eg) method as described by wallinga & lipsitch in r · · using the r package. , the best fit time period was chosen for calculation of confidence intervals for r . as we had adjusted for imported cases, we reported the results of the method which gave a more reliable fit with a better r score as the r . we also analysed the sensitivity of r to the serial interval distribution chosen by keeping standard deviation fixed at and varying the mean from days to days. maximum likelihood best fit time-period days days the r could be estimated for the states of kerala, maharashtra, delhi, rajasthan, tamil nadu, uttar pradesh, telangana, andhra pradesh, karnataka, jammu & kashmir, haryana and punjab. the ml algorithm failed to converge for the states of gujarat, west bengal, madhya pradesh and bihar. the fits for the states had a very low r due to multiple factors such as a major impact of import of new cases from other states (significant for some states due to import of cases from the delhi cluster) in the estimation of r and policies implemented by the government to curb the spread. when calculating the r , we were unable to adjust for imported cases as state-wise imported case data was not available. thus, we used maximum likelihood approach for estimating r for the states as it is more robust for unaccounted import of cases. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . figure s . sensitivity of india r estimates to serial interval and time period. (a,b) sensitivity analysis of r estimates with respect to the choice of the time period over which the r was calculated for eg and ml methods. (c,d) goodness of fit across a choice of time periods over which the r was calculated for eg and ml methods. red represents the best fit. (e,f) sensitivity analysis of r estimates with respect to the distribution of serial intervals across which the r was calculated for eg and ml methods. all graphs were generated in r package with r · · . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint testing policies are updated with time to reflect the pandemic situation. newly added criteria are written in bold. mohfw = ministry of health and family welfare, government of india. *symptomatic refers to fever/cough/shortness of breath. # direct and high-risk contacts include those who live in the same household with a confirmed case and hcp who examined a confirmed case. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint when evaluating the rt in epiestim package in r · · with the method described by wallinga and teunis, we consider a gamma prior with mean · and sd , and -day sliding windows. the serial interval distribution was assumed to follow a gamma distribution with mean · days ( % ci · - · , sd = · ) and a standard deviation of · ( % ci · - · , sd = · ) days based on a study done in wuhan on infector-infectee pairs. correction for the imported cases was done for the national incidence data after adjusting for reporting lag. the estimates of the effective reproduction number for each day were combined for the lag adjusted datasets by calculating pooled mean and pooled standard deviation and a net estimate for % and % confidence intervals were calculated. all simulations were done in python · and plots were made in matplotlib · · . is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint the rt was evaluated for states with more than cases on th april other than odisha due to a lack of active cases until very recently. the method to estimate was the same as the method used for the national data. imported cases could not be adjusted due to lack of state-wise data of internationally imported cases and for interstate transport of covid- cases. the estimates of the effective reproduction number for each day were combined for the lag adjusted datasets by calculating pooled mean and pooled standard deviation and a net estimate for % and % confidence intervals were calculated. all bootstraps were done in python · and plots were made in matplotlib · · . we examined the rt curves of the states of maharashtra, gujarat, delhi, rajasthan and madhya pradesh which together accounted for % of total cases in india as on april . delhi, maharashtra, rajasthan and madhya pradesh showed the nizammudin clusterrelated rise in rt during late-march, with delhi being the origin of the cluster showing the highest rise. gujarat, in contrast, showed a rise later in early-april which was probably linked to increased local transmission in the state capital of ahmedabad. we also included kerala since it was the first state to reach rt= in early april and has sustained low transmission levels since then. all states except madhya pradesh showed a continuing downtrend on the last examined date. the composite of these trends roughly depicts the trend of rt of india. kerala's ability to maintain a low rt may be attributed to its high literacy rate, active community participation and decentralisation of power-village councils taking the initiative to contain cases locally, use of drones for cluster containment, and social welfare initiatives which provided isolation rooms for people with cramped homes which didn't allow social distancing from family. kerala's health-system response has been proven to be robust in earlier outbreaks like the nipah virus outbreak in . figure s : incidence by onset and effective reproduction rates (rt) up to april for indian states of maharashtra, gujarat, kerala, delhi, rajasthan, and madhya pradesh. the state name is green if the most recent % ci of rt is below as on april , otherwise red. state-level incidence by onset and effective reproductive number (rt) number calculated with timedependent maximum likelihood method with day sliding windows and lag adjusted datasets. all bootstraps were done in python · and plots were made in matplotlib · · . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint maximum likelihood method with day sliding windows and lag adjusted datasets. all bootstraps were done in python · and plots were made in matplotlib · · . fitting was done using least-square fitting with trust region reflective algorithm in scipy package (python · ). this method was chosen as it allows for a bound on the fitted parameters and was found to converge reliably. the data was fit from the date the number of active cases crossed individuals. due to lack of data for e(t) and is(t) compartment, we also fit for the initial conditions for these compartments. initial conditions for ia(t) and ru(t) were set in the ratio of asymptomatics to symptomatics with respect to the initial values of is(t) and r(t) compartments respectively. since the number of detected recovered cases was very small we assume all of them were asymptomatic and thus ra(t) was initially set to zero. all other compartments were set to zero with the exception of s(t) which was set to ensure the sum of all compartments was n. newer values were given higher weightage for the fitting by supplying the fitting algorithm with errors given by e = w ( -w) t where t is the index of the sample and w = · is an arbitrary error weightage parameter as described by chowell. in order to estimate the uncertainty in the parameter fit we adapt the bootstrap approach described by chowell using a poissonian error structure without overdispersion and determine the % confidence intervals of the parameters with bootstrap samples. all simulations were done in python · and plots were made in matplotlib · · . figure s . best fit to data for base assumptions (ai = · , pa = · , fa = · ). '+' represent data with which the model was trained, 'o' refers to data points for dates after the training limit. bands represent % confidence intervals for the mean prediction. all simulations were done in python · and plots were made in matplotlib · · . our model fails to predict the increased rise in recovery as it assumes a constant recovery rate (λ) but in reality, the recovery rate (λ) is often found to increase during the progress of an outbreak due to multiple factors. similarly, mortality (κ) is also found to reduce. due to lack of sufficient data about the nature of the increase in these rates, the model was assumed to have a constant value that fits well to early dynamics of epidemics. in reality, a more flexible form such as a sigmoid may be a better assumption. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . sensitivity of estimated parameters to assumptions of ai, pa, and fa the sensitivity of the fit parameters to our assumptions were evaluated and it was found that recovery rate (λ) and mortality rate (κ) is independent of the assumptions, which is expected as these parameters are directly dependent on the relation between quarantine, recovery and fatality data. on the other hand, while there was some variability in the values of protection rate (between · - · ) and reporting rate (between · - · ) many of which were within the confidence interval, a large variability was observed in the value of transmission rate ( · - · ) with higher transmission rates favoured when the ratio of asymptomatic was low and their relative infectivity is also low. figure s . sensitivity of fit parameters α and β to assumptions of ai, pa, and fa. all values are reported with % ci (empirical estimate) with bootstrapped fits to the dataset as described in chowell ( ) . all plots were made in matplotlib · · . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . figure s . sensitivity of fit parameters λ and κ to assumptions of ai, pa, and fa. all values are reported with % ci with bootstrapped fits to the dataset as described in chowell ( ) . all plots were made in matplotlib · · . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . figure s . sensitivity of fit parameters δs to assumptions of ai, pa, and fa. all values are reported with % ci with bootstrapped fits to the dataset as described in chowell ( ) . all plots were made in matplotlib · · . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . figure s . sensitivity of predictions to assumptions of ai, pa, and fa. all values are reported with % ci with bootstrapped fits to the dataset as described in chowell ( ) . cases counts are reported in thousands and dates are reported with respect to th april . all plots were made in matplotlib · · . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . the basic reproduction number (r ) can be calculated for the model using the next-generation matrix method as described by van den driessche ( ). when there is a non-zero probability of asymptomaticity (pa), the r is given by: r = (δaβ( +at) + δsaiβr)/(δaδs( +r)( +at)) when the probability of asymptomaticity is zero, the model reduces to an seir at the initial time point and the r is simply given by: a very important factor that should be taken into consideration when interpreting the value of r given by the model is that unlike other simpler models such as sir or seir models, r is not a descriptor of the dynamics at all points of time of the epidemic. this is because of the introduction of the "protected" compartment. the better descriptor of the dynamics is given by the effective r given by: which is a function of time that takes into account the reduction in the number of susceptibles in the population as they enter the "protected" compartment. the true effective reproductive number rt is given by: since our reduction in susceptible population necessarily decays exponentially from n and asymptotic to zero, our estimates of r from the model are artificially higher than r directly estimated from data in order to explain the dynamics of the epidemic where the spread is very fast in early stages but saturates before the spread to less than the growth limit of rt = . while our assumption of the constant protection rate with no leakage, may stand true for small ideal communities, for a country with non-homogenous responses to the crisis this assumption may not stand true. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . figure s . estimation and sensitivity of model r to assumptions. all values are reported with % ci with bootstrapped fits to the dataset as described in chowell ( ) . the r is found to be lowest in the scenarios of low asymptomatic infectivity, high probability of asymptomaticity and high detection rate and conversely the highest at high asymptomatic infectivity, low probability of asymptomaticity and low detection rate. all plots were made in matplotlib · · . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . sensitivity analysis of effect of testing rate and social distancing policies . figure s . sensitivity of effect of testing rate and social distancing policies on total symptomatic cases to the probability of asymptomaticity at days after lockdown relaxation. all values are reported in thousands of cases. all simulations were done in python · and plots were made in matplotlib · · . when the proportion of asymptomatics is %, and detection is increased from % to % for days-for every extra asymptomatic detected by increased testing, the number of infections prevented is . at β, . at · β and . at · β. when the proportion of asymptomatics is %, and detection is increased from % to % for days-for every extra asymptomatic detected by increased testing, the number of infections prevented is . at β, . at · β and . at · β. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . figure s . sensitivity of effect of testing rate and social distancing policies on total symptomatic cases to probability of asymptomaticity at days after lockdown relaxation. all values are reported in thousands of cases. all simulations were done in python · and plots were made in matplotlib · · . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . figure s . sensitivity of the number of symptomatic cases to the probability of asymptomaticity over a -day period after lockdown relaxation if the testing rate and social distancing policies are not changed after relaxation. it is observed that the order of the trends reverses over time. this can be explained by the fact that when the epidemic was under control due to a large fraction of the population being protected, lower values of pa reduced the total number of infections due to decreased asymptomatic spread. but when the lockdown was relaxed, the incidence of symptomatic cases reflected the probability of being symptomatic which is higher when pa is lower and vice versa. all simulations were done in python · and plots were made in matplotlib · · . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . figure s . sensitivity of effect of testing rate and social distancing policies on total infections to the probability of asymptomaticity at days after lockdown relaxation. all values are reported in thousands of cases. all simulations were done in python · and plots were made in matplotlib · · . figure s . sensitivity of effect of testing rate and social distancing policies on total infections to probability of asymptomaticity at days after lockdown relaxation. all values are reported in thousands of cases. all simulations were done in python · and plots were made in matplotlib · · . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint in order to simulate a slow lockdown release, instead of setting the value of deprotection rate (σ) as a large value, we set it equal to the value of protection rate (α) such that the lockdown reverts itself at the same rate as it occurred. all simulations were done in python · and plots were made in matplotlib · · . figure s . gradual complete lockdown relaxation at three different points of time. the delayed gradual relaxation of the lockdown buys more time before the number of active cases starts rising again as observed in the fast lockdown relaxation. bands represent % confidence intervals for the mean prediction. all simulations were done in python · and plots were made in matplotlib · · . figure s . lag before new rise in active case after slow lockdown relaxation. the time gained by delaying the relaxation is found to be linearly increasing (pearson's r: · ; % ci · - · ; p< · ). the gain in time in the case of a slow lockdown relaxation is found to be more than the case of a fast lockdown relaxation. all simulations were done in python · and plots were made in matplotlib · · . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint . figure s . gradual lockdown relaxation for days at two different points of time. the delayed gradual relaxation of the lockdown reduced the number of active cases in the second as observed in the fast lockdown relaxation. a slow relaxation reduced the effect of relaxation on the growth of the second peak compared to the fast lockdown relaxation. bands represent % confidence intervals for the mean prediction. all simulations were done in python · and plots were made in matplotlib · · . . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint previous studies have estimated the number of icu beds in india to be around , to , icu beds. we assume the number of icu beds in india to be around , to account for growth in the healthcare system. if we assume that % of these beds are equipped with ventilators and are allocated exclusively to covid- patients, that gives us , covid- ready icu beds. previous studies suggest that approximately % of symptomatic patients need icu support, that gives us an upper bound for the healthcare system capacity of , , active symptomatic cases. we simulate the model under the different (fast) lockdown relaxation scenarios we described earlier and determined the time taken to reach the healthcare system capacity of , , active symptomatic cases from the date of relaxation. we find that for all finite relaxation durations, there exists a delay in lockdown relaxation that prevents the scenario of the health capacity being overloaded. for smaller relaxation periods, this delay is found to be smaller. it should be noted that these assumptions assume fast and complete lockdown relaxations periods for the entire country at once. in reality, the lockdown relaxations will likely be introduced on a state-by-state basis and may be more of a slow staggered response. figure s . time taken to reach the healthcare system capacity under lockdown relaxation scenarios. blank blocks represent the scenario where the healthcare system capacity is never reached and the epidemic is under control. figure shows the heatmap for the mean time taken to hit the healthcare capacity under different lockdown durations and dates of start of lockdown relaxations. . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint the mobility scores are calculated by comparing visits and length of stay at different places change compared to a baseline value for the day of the week. the baseline values were calculated from the median values during the -week period jan -feb , . these values were calculated on the basis of anonymized data from users who have opted-in to location history for their google account. we acknowledge that this mobility data may be biased towards users of this service, and may or may not represent the exact behavior of a wider population. for the analysis of mobility, google has divided the mobility into categories relevant to social distancing policies and practices. they are: grocery & pharmacy (places like grocery markets, food warehouses, farmers markets, speciality food shops, drug stores, and pharmacies), parks (places like local parks, national parks, public beaches, marinas, dog parks, plazas, and public gardens), transit stations (places like public transport hubs such as subway, bus, and train stations), retail & recreation (places like restaurants, cafes, shopping centres, theme parks, museums, libraries, and movie theatres), residential (places of residence), workplaces (places of work such as offices). . cc-by-nc . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint a novel coronavirus from patients with pneumonia in china who directorgeneral's opening remarks at the media briefing on covid novel coronavirus covid data repository by johns hopkins csse covid india database api containing pandemic influenza at the source firstwave covid transmissibility and severity in china outside hubei after control measures, and secondwave scenario planning: a modelling impact assessment early dynamics of transmission and control of covid : a mathematical modelling study association of public health interventions with the epidemiology of the covid outbreak in wuhan, china impact of nonpharmaceutical interventions (npis) to reduce covid mortality and healthcare demand a third of the global population is on coronavirus lockdown extended lockdown to cause $ . billion economic loss social distancing is a luxury indians earning just rs a day cannot afford more than crore workers in india's unorganized sector may be affected due to the lockdown: ilo. gaonconnection your connect covid : collateral damage of lockdown in india | the bmj feasibility of controlling covid outbreaks by isolation of cases and contacts clinical characteristics of asymptomatic infections with covid screened among close contacts in nanjing suppression of covid outbreak in the municipality of vo spread of sarscov in the icelandic population asymptomatic transmission, the achilles' heel of current strategies to control covid world bank population database the r package: a toolbox to estimate reproduction numbers for epidemic outbreaks a likelihoodbased method for real time estimation of the serial interval and reproductive number of an epidemic how generation intervals shape the relationship between growth rates and reproductive numbers early release serial interval of covid among publicly reported confirmed cases volume a new framework and software to estimate timevarying reproduction numbers during epidemics different epidemic curves for severe acute respiratory syndrome reveal similar impacts of control measures google covid community mobility reports global analysis of an seir model with varying population size and vaccination the incubation period of coronavirus disease (covid ) from publicly reported confirmed cases: estimation and application federal testing recommendations provided by the indian council of medical research (icmr) date icmr testing criteria for covid- all contacts of laboratory confirmed positive cases if they become symptomatic (fever, cough, difficulty in breathing etc.) within days of home quarantine all people with history of international travel to covid- affected countries within the last days if they become symptomatic (fever, cough, difficulty in breathing etc.) within days of home quarantine all people with history of international travel if they become symptomatic (fever, cough, difficulty in breathing etc.) within days of home quarantine health care workers managing respiratory distress / severe acute respiratory illness should be tested when they are symptomatic all symptomatic* individuals who have undertaken international travel in the last days all symptomatic contacts of laboratory confirmed cases all symptomatic health care workers. . all hospitalized patients with severe acute respiratory illness (sari: fever and cough and/or shortness of breath) asymptomatic direct and high-risk contacts** of a confirmed case should be tested once between day and day of coming in his/her contact all symptomatic individuals who have undertaken international travel in the last days . all symptomatic contacts of laboratory confirmed cases . all symptomatic health care workers . all patients with severe acute respiratory illness (fever and cough and/or shortness of breath) asymptomatic direct and high-risk contacts # of a confirmed case should be tested once between day and day of coming in his/her contact . in hotspots/cluster (as per mohfw) and in large migration gatherings/ evacuees centres: all symptomatic influenza like illness (ili: fever, cough, sore throat, runny nose) a. within days of illness -rrt-pcr b rt point estimates for national covid- incidence data (without import adjustment) date rt estimate ( % ci) date rt estimate ( % ci) rt point estimates for national covid- incidence data date rt estimate ( % ci) date rt estimate ( % ci) temporal dynamics in viral shedding and transmissibility of covid- virological assessment of hospitalized patients with covid- epidemic analysis of covid- in china by dynamical modeling fitdistrplus: an r package for fitting distributions a likelihood-based method for real-time estimation of the serial interval and reproductive number of an epidemic how generation intervals shape the relationship between growth rates and reproductive numbers testing strategy updates for covid- in india nowcasting and forecasting the potential domestic and international spread of the -ncov outbreak originating in wuhan, china: a modelling study early release -serial interval of covid- among publicly reported confirmed cases covid india database api fitting dynamic models to epidemic outbreaks with quantified uncertainty: a primer for parameter uncertainty, identifiability, and forecasts reproduction numbers of infectious disease models cost of intensive care in india characteristics of and important lessons from the coronavirus disease (covid- ) outbreak in china: summary of a report of cases from the chinese center for disease control and prevention key: cord- -l cyzocv authors: aneja, ranjan; ahuja, vaishali title: an assessment of socioeconomic impact of covid‐ pandemic in india date: - - journal: j public aff doi: . /pa. sha: doc_id: cord_uid: l cyzocv coronavirus (covid‐ ) pandemic has created an unprecedented loss and disruptions over all across the world. from developed to developing, no country has been spared from its brunt. in this paper, we have analyzed the implications of covid‐ on the economy and society of india so far. an impact assessment on the basis of available lietrature is made on all the three sectors—primary, secondary and service sector along with the impact on migrants, health, poverty, job losses, informal sector, environment, and so forth. the all sectors of the economy has been disproportionately affected and even within a sector, there is a disproportionate loss. the societal impacts are dire too with job losses, mental illness, increased domestic violence, and so forth. some positive effects can be seen in terms of improved air quality, water quality, wildlife but the sustainability of such impact is conditional upon post‐covid and people's habits and future policies related to the environment. welfare, goi). most of the countries including even developed nations like united states, italy, and united kingdom are not prepared enough to deal with this pandemic. presently, the worry is not for just human well-being besides for the worldwide economy which is most noticeably awful hit in each viewpoint. economic disturbances are probably going to be more extreme and extended in developing and emerging countries with bigger domestic outbreaks and the more fragile and weak healthcare system; with larger exposure to international spillovers through various channels like trade, tourism, and commodity and financial markets; weaker macroeconomic frameworks; and more pervasive informality and poverty (global economic prospects, world bank, ) . it is not just a health crisis; it is the economic and humanitarian crisis and called a black swan by many economists. as a result of its infectious nature, almost all nations favored lockdown to limit its spread. following this, india initially proclaimed a one-day "janata curfew" on march , . from there on, a total lockdown was reported in india at first for days which was extended to an additional days, and thereafter it got broadened further with minor relaxations. after june , many relaxations are given to proceed with the economic activities but borders of some states are sealed even now depending on the severity of the health crisis in a particular state. all the economic activities however now been provided some relaxations after a complete halt on them but an unprecedented loss has already occurred and the economy is shaken badly. india is also amid a severe crisis. "this is the greatest emergency for the indian economy since independence," said raghuram rajan, former rbi governor. this is worse than the financial crisis of , which affected the demand side but workers/people could still go to work, the financial conditions of government of india was sound but it seems that everything is against the economy this year. almost all the countries due to covid- are affected similarly in terms of demand-supply shocks and disruptions but in india, there was already a downturn in the economy. in pre-covid era india was encountering with major macroeconomic issues such as nearly recession with the sluggish gdp growth rate of . % in which is lowest since (as indicated by the official statistics), high unemployment rate, decline in industrial output of core sectors-the worst in years, stagnancy in private sector investment, decline in consumption expenditure for the first time in several decades (dev & sengupta, ) . also, the informal sector of india which is the largest in the world employs nearly % of the total working population and contributes significantly in overall gdp (more than %) has been hit by two major shocks (or reforms) already due to demonetization in and gst in . the financial sector who has got the most important role to play in the crisis times has also been having huge problems in india like twin balance sheet (tbs), high levels of non-performing assets (npas) and an inadequately capitalized banking system. in the private corporate sector too, firms are financially weak and over-leveraged (sengupta & vardhan, ) . some more problems like il&fs crisis, decline in commercial credit of around % in fy (q ) etc. , with the emergence of such a deadly disease, a new set of challenges is ready for india for both the short-run and long-run. albeit the macroeconomic uncertainty cannot be gauged, the situation requires major policy interventions in terms of healthcare infrastructure, livelihood, vulnerable sections and various humanitarian issues. variant of helicopter money-"money financing of the fiscal programme" is a solution suggestion by (chakraborty & thomas, ) as an innovative method for financing deficit. in this article, an attempt is made to investigate the socioeconomic implications of the draconian coronavirus pandemic in india. the motivation behind this is to provide an overview of the loss that occurred to different sectors of the indian economy and society to have a better understanding of the issues to the government. in this article, we have reviewed many latest articles, authentic newspaper articles, discussions, and interviews of experts from different fields, and so forth. the article is organized in four sections including introduction. section reviews the various researches highlighting the economic impact on different sectors-primary, secondary, and tertiary sectors. there were relaxations to the agriculture sector during lockdown but transport constraints, mobility restrictions and lack of labor due to reverse-migration of labor to their native places were the major problems faced by the farmers. farmers in maharashtra called it a worse situation than that occurred during the demonetization in (saha & bhattacharya, ) . before this pandemic, the rural economy of india was witnessing a decline in incomes of mainly casual workers along with declining rural wages (real). some rays of hope were seen in january when food prices started rising but all hopes collapsed with this new crisis. (mukhopadhyay, ) agriculture and allied activities are not a homogenous group of activities, in fact, an umbrella of different activities having their different dynamics each. so, the impact of covid- on this sector varies according to the set of activities, that is, on crops, livestock, fisheries, and so forth. horticulture and foodgrains production is part of crops and is impacted differently. horticulture is likely to face the brunt more because of the nature of perishability whereas food grains are non-perishable and apart from problems in harvesting and labor shortage, this is not impacted much. rabi harvesting has gone well and msp hike has also been announced for the kharif crops which assures farmers a - % return on their production cost. with declining demand and reduction in exports of fruits and vegetables, horticulture is hit hard. similarly, floriculture has been affected because of less demands due to shut down of religious places, postponement of marriages, and so forth. in livestock (milk, meat, eggs), milk is the major contributor that has been impacted and fortunately, had stability during the lockdown. fishing and aquaculture are expected to have a high negative impact, food grains and livestock low, and horticulture medium, relatively. agriculture seems to be a bright spot in india amid the covid- crisis and crisil expects agriculture to grow at a rate of . % in fy . (crisil, ). the manufacturing sector is the major contributor of gdp and employment in the secondary sector and has been recognized as an engine for vibrant growth and creator of the nation's wealth (rele, ) . the manufacturing sector is important in the way that it has strong linkages with other sectors, both forward and backward linkages so any impact in this sector will affect other sectors as well. overall, the manufacturing sector is going to be affected badly by demand-supply disruptions and global value supply chain. the % contributor to the manufacturing sector, the automotive sector was suffering before covid- too due to low consumer demand, inadequate credit facilities, and more problems due to the nbfc crisis. there is a lot of pressure due to demand-supply disruptions on the health of the auto sector in india due to covid- . as per the latest assessment related to the impact of covid- done by siam, the auto sector is expected to have a decline between % and % in various industry segments conditioned with gdp growth of - % for fy . said rajan wadhera, president, siam. from decades, china has been the epicenter of manufacturing accounting for one-third of total manufacturing over the world. but after the outbreak of covid- , many countries are planning to shift focus from china and looking for countries like china where cheap labor is available. so, it is a golden opportunity for india to make "made in india" global. there is huge potential in india, if proper measures will be taken to boost the manufacturing sector, india will emerge as a new manufacturing hub surpassing china. the micro, small and medium enterprises (msmes) as a whole form a significant share of manufacturing in india and play a crucial role in providing employment opportunities and also in the country's exports. as indicated by recent reports msmes contribute % in india's gdp and % in the employment of industrial workers. but this sector has issues like the non-availability of adequate, timely, and affordable institutional credit. although all the businesses and sectors are affected due to the pandemic, this sector is badly hit due to reduced cash flows, supply chain disruptions, shortage of migrant workers due to reverse migration, less demand, and so forth. like china, india is also expected to have major destructions in this sector with more challenges to small firms as compared with upstream firms (dev & sengupta, ) . it is not easy to re-start msmes once they are shut down (chidambaram, ) . india's sherpa to the g also said that small industries are most vulnerable and it is difficult for them to survive without financial assistance because of their incapability to deal with such sudden disruptions. . | service sector the financial sector who has got the most important role to play in the crisis times has also been having huge problems in india like twin balance sheet (tbs), high levels of non-performing assets (npas) and an inadequately capitalized banking system. in the private corporate sector too, firms are financially weak and over-leveraged. (sengupta & vardhan, ) . some more problems like il&fs crisis, decline in commercial credit of around % in fy -first half, and a near-demise of a well-known and reputed private bank-yes bank, and so forth. to what extent the financial market will be affected depends on the severity and longevity of the crisis, effectiveness of the implementation of fiscal and monetary policies and central bank's reactions (beck, ) . there is no such impact on the banking sector, but because banks are at the forefront of public attention the indirect impact of several other sectors that are hit by the pandemic is likely to be on the banks and other financial institutions. banks are the major source of help in times of crisis, therefore when all other sectors are hit badly, banks will also face the brunt. the already existing problems in the financial sector are expected to multiply due to this draconian crisis. the stock market has also seen the worst in march, due to the lockdown and collapse of various business activities. subramanian and felman ( ) suggested that around one-third of industrial and service firms have applied for moratoria on their bank loans. the stock of non-performing assets (npas) may increase by rs. lakh crore even if only a quarter of these deferred loans go bad, eventually. and this is a conservative estimate. senior bank officials have been quoted as estimating that the stock of npas could increase by as much as rs lakh crore. in this case, we would be looking at npas of rs lakh crore, equivalent to around % of current loans outstanding. for planning purposes, it is worth considering who will pay for such losses, if they do materialize. other important dimensions of service sector like aviation, transport, travel, and tourism are worst hit not only in india, but globally. the loss to this sector too will be based on the severity and longevity of the crisis. a report by kpmg indicates that around million job losses are expected in india's travel, tourism and hospitality industry. | societal impacts of covid- it has been estimated that globally, women are more likely to be vulnerable to losing their jobs as compared to men due to the covid- pandemic. the drop in employment is found to be biased and not genderneutral in india which has one of the most unequal gender division of domestic work globally. the drop in absolute number is more for men compared with women because of the already existing large gender-gap in employment. by comparing the pre and post lockdown hours spent on domestic chores, a decline in gender gap is found in terms of hours devoted to domestic chores on an average during the first month of lockdown in most of the states. also, there is an increase of . to hours in men's proportion of housework post-lockdown. still, the male proportion/distribution continues to be skewed to the right (deshpande, ) . considering the disproportionate burden of the crisis on low skilled workers, poors, other vulnerable sections, many economists think that covid- is most likely expected to raise inequality within and among countries (initiative on global markets, ) and the results of study conducted by (furceri, loungani, ostry, & pizzuto, ) confirms that those having basic education (low skilled) are affected more than those with higher and advanced degrees, in terms of loss of income hence confirming increase in income inequality after during and after pandemics. due to the paucity of testing services, shortage of doctors, health equipment, beds even in the developed area of india, covid- is a major threat for india. with a subsequent rise in the no. of confirmed cases india's capacity to contain the further spread and to handle the current cases is questioned by many experts. as per the national health profile of india, , india's expenditure on healthcare as % of gdp was merely . % which is lower than poorer countries of the world (rakshit & basishtha, ) . coronavirus pandemic has disproportionately affected the rural and urban areas. presently, the brunt is faced more in urban areas because of the high density of people. but the risk is much more to the rural areas where around % of india's population resides. india's healthcare sector is still developing and there are large differences in the healthcare systems of rural and urban areas. the rural health care system which is a three-tier system is comprised of-• sub-centres with % shortfall in healthcare facilities, • primary health centres with % and • community health centres with % shortfall, as of july , . the healthcare system in the rural area is not adequate to handle this pandemic and the transmission especially in the northern states where population density is high because of doctors' shortage, healthcare facilities like very less availability of no. of beds per thousand people, equipment, and so forth. (kumar, nayar, & koya, ) according to the latest report by national commission for women (ncw), within days following lockdown, there was a % increase in the number of cases of domestic violence against women. domestic violence cases have seen an upsurge mainly in states of uttar pradesh, bihar, haryana and punjab with a near doubling of the cases as compared to pre-lockdown cases said ncw chief rekha sharma. the real situation, however, may be more dangerous because many women from rural areas especially do not file a case and raise their voice and are scared of their husbands and family (kundu & bhowmik, ) . for the overall crime rate, there has been good news since lockdown that the crime rate has decreased significantly in india and globally too but studies shows that the hunger, poverty and inequality which are the after results of any crisis and pandemic lead to increase in the crime rate (uppal, ) . after the partition in , it is the second biggest mass relocation that india is experiencing. more specifically, it is the "reverse migra- (ministry of health and family welfare, government of india). now, due to covid- there is mass reverse migration due to limited employment opportunities, fear of more destruction due to the uncertainty of future crisis, financial crisis, health crisis, and so forth. the extent of this reverse migration was such that the efforts of government through policies could not match this crisis. (mukhra, krishan, & kanchan, ) singh ( ) studied the impact of the coronavirus pandemic on the rural economy of india mainly about the plight of migrant workers and the short run-long run implications of covid- on the rural economy. he stated that covid- is going to affect the rural economy in both the short run and long run with reverse migration exerting excess pressure on the agriculture and rural economy that will significantly affect the poverty and will put a greater number of people into abject poverty. he also discusses that although the government is announcing schemes and helping in many ways. but mass corruption in the system is the biggest challenge in the effective implementation of plans. according to the world bank ( ) report, every fifth indian is poor with around % population residing in rural areas. at least million individuals all over the world are expected to dive into "extreme poverty" as a direct result of the destruction caused by the pandemic and according to world bank, india is estimated to have its million citizens pushed in extreme poverty (bloomberg, ) . according to the centre for monitoring indian economy (cmie), in india more than million people lost their jobs in april , out of them largely were the small traders and wage-laborers. according to a phone survey of , workers conducted by centre for sustainable employment, around % of urban workers in the sample lost jobs with a sharp decline in the earnings of farmers and those who were self-employed in sectors other than agriculture. pre-existing similarities in the formal and informal sectors in india are more likely to be increased because the informal or unorganized sector or workers do not have access to social security benefits and there is a lot of uncertainty in their work. the informal sector workers were already facing issues like low wages and income and in this pandemic, they are among the most affected people. around to million workers are seasonal migrant which are directly and harshly affected and moved back to their native places (reverse migration) due to lack of employment, income, shelter, and so forth (dev & sengupta, ) . apart from the health and economic crisis, this is the major challenge to every country hit by the pandemic. due to lockdown, mass unemployment, the collapse of various businesses, loss of income, increasing inequalities and poverty, deaths, less mobility, and so forth. there is a huge impact on the mental status of people. from older to younger, rich to poor, everyone is affected. this outbreak is resulting in additional health issues like anxiety, stress, depression, anger, fear, and so forth, globally. (torales, o'higgins, castaldelli-maia, & ventriglio, ) the psychological challenges can be severe to marginalized people like farmers who already have psychological burdens due to pre-existing problems in the agriculture sector. nearly , cases of farmers' suicide are reported every year due to their poor socioeconomic conditions and due to covid- such cases can be aggravated. (hossain et al., ) recent studies in psychological science and evidence show that similar pandemics like the current one increased mental health problems like post-traumatic stress disorder (ptsd), confusion, loneliness feeling, boredom during and after the quarantine too. (brooks et al., ) older people are battling with larger health risks as well as are likewise prone to be less fit for supporting themselves in isolation. with serious negative implications and destruction to the economy and people, covid- has got some positive implications too. one such is a gift to the river ganga. in just - days of lockdown due to covid- in india, the pollution in the river has decreased significantly which the two major plans, ganga action plan, , and namami gange, , with there is a positive impact on air quality, water quality, wildlife and vegetation due to less traffic, less pollution due to lockdown and less business activities etc. | conclusion covid- pandemic has incurred unprecedented loss globally but india being an emerging economy is likely to get more affected in every sector and that too disproportionately. agriculture and allied sector have been hit disproportionately with horticulture, poultry facing more brunt but overall agriculture sector is seen as a bright spot and is likely to get affected less as compared with loss occurred to other sectors. manufacturing sector especially automotive sector and msmes are suffering more loss and due to global suppy chain disruptions this sector is affected badly. service sector which is the key driver of economic growth and largest contributor of gdp has been hit hardly due to various restrictions on mobility, halt on tourism and hospitality for the time being, very less transport activities, shutdown of schools/colleges, and so forth. the overall loss to the economy and to different sectors depends on the severity and longevity of crisis. amid this coronavirus pandemic and an unprecedented crisis, apart from the monetary losses, the societal impact is harsh with major sociological and psychological challenges. already existing poverty and inequality is likely to increase with major negative impact on migrants, casual and informal worker with domestic violence and mental illness being another major challenge. although there are some positive impacts also but the sustainability of these impacts on air quality, water quality, wildlife is conditional to post-lockdown scenario and people's behavior and habits. various fiscal and monetary policy measures are undertaken and announced by the government and reserve bank of india but prominent economists are of the view that more spending is needed by the government regardless of the gdp numbers and fiscal deficit. in fact, more attention is needed toward the vulnerable sections of the society and sectors especially poor people, msmes and the non-essential commodities sector who is worst hit in this demand contraction due to pandemic. unique, inclusive and innovative measures are the need of the hour. there are around - million seasonal migrant workers in india ongoing research government of india ministry of health and family welfare statistics division rural health the world bank-ibrd-ida ongoing research finance in the times of coronavirus the psychological impact of quarantine and how to reduce it: a rapid review of the evidence covid- and macroeconomic uncertainty: fiscal and monetary policy response we will never know how many people died of starvation, because no state government will admit to starvation deaths. the indian express quickonomics: the one bright spot in the economy. crisil, an s&p global company the covid- lockdown in india: gender and caste dimensions of the first job losses, working papers id: , esocialsciences covid- : impact on the indian economy will covid- affect inequality? evidence from past pandemics suicide of a farmer amid covid- in india: perspectives on social determinants of suicidal behavior and prevention strategies covid- : challenges and its consequences for ruralhealth care in india societal impact of novel corona virus (covid pandemic) in india covid- and the indian farm sector: ensuring everyone's seat at the table covid- sets off mass migration in india. archives of medical research can india stay immune enough to combat covid- pandemic? an economic query emerging outbreaks and epidemic threats: the practicalityand limitations in the development and manufacturing oftreatments for coronavirus (covid- ) consequences of lockdown amid covid- pandemic on indian agriculture banking crisis is impeding india's economy impact of covid- on rural economy in india with covid- crisis dealing sharp blow to struggling financial sector, revival calls for new approach. the indian express india's poor may have lost rs lakh crore in the coronavirus lockdown. scroll the outbreak of covid- coronavirus and its impact on global mental health world's biggest lockdown to push million into extreme poverty in india covid- will lead to increased crime rates in india key: cord- - obj rs authors: srivastava, ravi title: growing precarity, circular migration, and the lockdown in india date: - - journal: indian j labour econ doi: . /s - - - sha: doc_id: cord_uid: obj rs the paper examines the nature of the migrant crisis in india after the country-wide lockdown in march and brings out the types of labour migrants who were severely adversely affected by the lockdown, leading to their exodus towards their native villages. it further assesses the government’s response and proposes some key policy imperatives. the covid- pandemic has made the position of international migrants even more vulnerable and has exposed the poor living conditions in which international emigrant workers work and live in countries across the globe. however, in the case of india, the lockdown imposed to slow the spread of the pandemic created an unprecedented humanitarian crisis for internal migrants, revealing the vast magnitude of invisible and vulnerable migrants in india's workforce across cities and states. in a public address to the nation on march , the indian prime minister announced a "janata (people's) curfew" on march , from morning to night, which was to be monitored by civil society organisations, and voluntarily observed. at that stage, india had experienced deaths and infections due to the covid- . several trains were cancelled and flights reduced for the janata curfew, but these cancellations continued after the "curfew". on march , at pm, the prime minster announced a country-wide lockdown effective from midnight, to last till april . the lockdown was introduced to ostensibly slowdown and break the transmission cycle of the virus, and people-except those engaged in essential serviceswere advised to stay indoors. the sudden lockdown left tens of millions of people stranded across india. these included students, travellers, pilgrims, and migrant workers. the government and the country were completely unprepared for what followed. within a couple of days of the lockdown, migrants started thronging highways and bus stands, prepared to go home anyhow. between march and , the government responded with a series of directives asking the migrants to return and stay indoors. when the numbers became unmanageable, some state governments stepped in with announcements to facilitate the interstate movement of the migrants. however, the central government came down heavily both on governments, which were seen to facilitate the movement of migrants, and on the migrants. the latter were forced into shelters and quarantines or pushed back to their shelters. on march , in response to a petition in the supreme court, the government of india claimed that "not a single migrant was on the roads". it further claimed that the attempted exodus of migrants was the result of a panic created by fake news that the lockdown would continue for three months. as is well known, the supreme court concurred with this view and expressed satisfaction at the steps taken by the government for relief and immobilisation of the migrants. in its submission to the supreme court on march , the government of india stated that india had . crore migrant workers. a perusal of the census of india shows that this is the figure of all migrants (internal as well as international) in india who gave "employment" as the initial reason for migration whenever they had changed their usual place of residence. it is clear that the government did not have any idea of the numbers or the kind of migrants who were facing distress and who were attempting to return to their homes. in the same year, the census showed that there were crore internal migrants in india, of whom . crores were workers. most migrants in india do not give employment as a reason for migration, but rather marriages and other associational reasons (moving with families). an analysis of all the migrants in india shows that they fall into different streams and segments. most migrants move short distances, within the same district, followed by movement to other districts within the state. only a small percentage ( %) of those recorded in the census move to other states. while the classic migration in development literature is rural-urban, most migrants in india ( %) are in rural areas. studies show that the migrants are more likely to be concentrated in higher consumption quintiles than non-migrants. furthermore, unlike the classical one-way rural-urban movement, a large percentage of rural-urban migrants retain their links with the rural hinterland, returning occasionally to it during spells of unemployment, for holidays, or when work in rural areas peaks. some of them may stay on permanently in urban areas, while others may eventually return to their rural homes. so who were the migrants who were impelled to move back to their homes in villages after the lockdown? these were clearly not the permanent rural-urban migrants who have severed links with their rural origin. they were quite prominently semi-permanent or long-term circular migrants who had retained links with their families homes in rural areas. even more prominently, they were seasonal and short-term circular migrants who do not figure in census and nss statistics and who have no worthwhile place they can call their home in the urban destination areas. delving a little more in the nature of short-term and long-term circular migration, studies have shown that the former are in temporary and seasonal precarious jobs, mostly in wage employment. the latter belong to various socio-economic strata but include a large chunk of precariously placed rural-urban migrants who are either self-employed or wage-employed. unlike the short-term circular migrants, they have acquired a tenuous foothold in urban areas, although acquiring this foothold may have taken a number of years. like the short-term circular migrant, this segment of long-term circular migrants also remains in precarious jobs, vulnerable to shocks. estimates of these three segments of migrant workers and precarious workers among short-term and long-term circular migrant workers are given in fig. and are based on the estimates prepared in srivastava ( b) . our analysis elsewhere shows the growing precarity of the indian workforce engaged in industry and services (srivastava ) . while this workforce has steadily grown, but only matching the decline in the agricultural workforce, or estimates show that between - and - , the percentage share of circular migrants in the precariously employed workforce outside agriculture grew by about ten per cent points-from about % to % (see fig. ). we have argued that precarity and circular migration have grown hand in hand, promoted by macroeconomic and labour policies in india (srivastava ) . the lockdown exposed the vulnerable circular migrants to a range of extreme vulnerabilities, which were felt within a short period of time, ranging from immediate to a few days. first, the lockdown was so severe that all circular migrants, except a handful engaged in essential permitted services, lost access to jobs and incomes. wage workers employed through contractors even lost access to wage and income sus sus & sus , and nso, sus - sus & sus - arrears, as contractors refused to settle dues. second, those circular migrants-and these included a majority of the short-term circular migrants-lost access to shelters which were nothing but their worksites. those who lived in squalid and congested rented accommodation were left with no means to pay rent and started to be pressurised by their landlords within the first few weeks. third, as we show below, government measures for social protection were least likely to reach these workers as few of them had valid registrations in the destination areas, and relief was both scarce and difficult to access. fourth, the distance from kin and family folk was acutely felt by the risk of disease, and government barriers on interstate movement made going back all the more urgent for interstate migrant workers and their families. the government of india announced a package of measures to support poor households and workers on march , immediately after the imposition of the lockdown. this package was called the prime minister garib kalyan yojana and it comprised of measures of cash transfer using the direct benefit transfer (dbt) route, kind support (through the public distribution system), and a set of directions to various statutory funds/welfare funds, and finally a set of directives whose legal backing, if any was derived from the powers that the government derived from the disaster management act, (dm act). the cash transfers comprised of (a) a fast forwarding of the first instalment of the income transfer scheme for farmers under the pm kisan yojana; (b) a cash transfer of rs. each per month for three months to woman account holders of jan dhan yojana bank accounts; and (c) an amount of rs. to each pension holder under the national social assistance programme. as kind assistance, the government offered extra free rations of kg. of cereals and one kg. pulses per person for three months and a provision of free gas cylinders under the ujjwala scheme. the government also involved the employee fund organisation (epfo) and the state welfare & , and nso, - & - funds under the building and construction workers' welfare fund by asking the former to give concessions to workers and employers, and the latter to make ex gratia payments to construction workers. finally, it also issued a directive to employers to pay wages to workers during the lockdown period and asked landlords to exempt workers from payment of rents during that period and increased the wages payable under mgnrega from rs. to rs. . although the total package carried a price tag of rs. . lakh crores, the additional cost to the government exchequer was rs. , crores, or only about . % of gdp. more important, while the meagre assistance amounts were targeted at existing beneficiaries, they could not touch the circular migrants who did not have access to the pds in destination areas, and many did not even have access to bank accounts, leave alone beneficiary accounts. similarly, the directions to pay wages during lockdown and rent remissions by landlords had no practical impact on the migrant workers engaged in informal jobs. in general, as surveys of migrant workers succeeded in bringing out, the limited package announced by the government bypassed most of the circular migrants, exacerbating their condition in the cities. despite the stiff conditions of the lockdown, large number of migrants made it to their homes just before or after the lockdown was announced, but these were mostly intra-state migrants. the government's strict measures stemmed the tide of the exodus which had started soon after the lockdown. but after the announcement of the second lockdown on april , the exodus turned into a tide, with workers and their family members attempting to walk back across thousands of kilometres, even in the face of harassment and worse by government forces. the government of india's policy response continued to treat the movement of the migrants simply as a violation of the lockdown procedures. there was very little acknowledgement of the difficult conditions of the migrant workers and their families. the policy measures that were announced were contradictory and aimed at continued restriction on coordinated interstate movement of migrants. initially, the central government announced (on april ) permission to deploy migrant workers within destination states where they were stranded. then, on april , it permitted interstate movement, subject to protocols but only by buses. on may , trains were permitted to be deployed but through a cumbersome administrative and interstate coordination procedure, and on may , the central government again issued a notification virtually disentitling temporary migrants from interstate movement. but since mid-april, for the next several weeks, the country saw the largest urban exodus ever in its history, with millions of migrants attempting to move back to their home villages on foot, bicycles, cycle carts, and hired vehicles. by the beginning of june, the government estimated that it had been able to facilitate the interstate movement of about a crore of migrants, but several times that number moved on their own under unimaginable conditions. migrants bore significant costs, financial and nonfinancial, both for their autonomous movement, but also the transportation arranged by the states and the railways, with them or their families incurring debts to make this possible. as is well known, several hundred people died in the process, including more than a hundred on trains. since may , the government of india has announced some follow-up measures to support the affected poor and the migrant workers. under the atma-nirbhar package that was elaborated by the finance minister between may and may , the government enhanced the mgnrega budget by rs. , crores. it announced a scheme worth rs , crores by which states could identify and provide free ration ( kg. per month of cereals and one kg. pulses per month for three months) to each migrant workers and her/his family member not covered under the national food security act (nfsa). it also announced concessions through the employees provident fund organisation to employers and workers in some categories. it declared a scheme to provide working capital to street vendors to provide support to a rental housing scheme with an initial outlay of rs. crores. on june , the prime minister announced the prime minister garib rojgar abhiyan in districts in six states, with more than , returnees migrant each as per the government data. under the scheme, the implementation of existing schemes/works, costing about rs. , crores (without any additional financial allocation), was to be frontloaded in these districts in order to provide employment. on june , the prime minister announced the extension of the free gas cylinder and pds ration schemes for another four months (till november ) at an estimated budgetary cost of rs. , crores. taken together with the earlier measures announced in march, the total budgetary outlay on the measures announced is only about % of gdp. in addition, the central several non-budgetary measures also include portability of pds by june . meanwhile, most states were highly ambivalent in their policies towards sending/ receiving migrants for different reasons. states initially responded with tightening the controls on migrant movement and arranging shelter/quarantines and food for them. kerala, by standards of destination states, does not account for a significant percentage of circular migrants, set up the largest proportion of shelters. a number of state governments announced ex gratia payments from the building & construction welfare funds for workers registered under these funds. however, in most states, interstate migrant workers are not registered and among those workers, are a high proportion of those who are not employed in the construction industry. we must note that kerala emerged as an outlier among states by announcing a comprehensive package of rs. , crore for protection of livelihoods of workers, including migrant workers, even before the lockdown. apart from these ex gratia payments, some states followed up with other ex gratia payments and made additional efforts to provide rations to workers, including migrant workers, not registered in the pds. telangana announced an ex gratia payment for migrant workers early on in the second phase of the lockdown, as did kerala. as the migrant crisis escalated, sending states announced measures to support stranded migrant workers. in the beginning, an initiative was taken by jharkhand, followed by bihar which announced an ex gratia payment of rs. per worker. with the return of the migrants, state governments have announced measures for preparing a database of migrants and their skills, and programme to absorb them in the local economies. the odisha government announced a rs. , package to provide support to the msme and rural sectors, and skill training, with the objective of enhancing employment opportunities to migrant returnees. these measures have provided a patchwork of support to migrant workers and their families. at the same time, several state governments have moved ahead to make drastic changes in labour laws, in some cases (as in uttar pradesh and gujarat) almost abolishing the entire framework of labour regulation and social security under the flawed assumption that this will help to revive investment and economic activity. the pandemic and the lockdown have brought to light the extent to which industrial and urban india has grown to depend on the labour of migrant workers. at the same time, it has also exposed the precarity and vulnerability of these workers, in terms of their jobs and employment relations, their living conditions, and lack of social protection. with the passage of time, and as the economy slowly begins to revive, the gap in wages and employment opportunities can be expected to draw many of the migrants back into migration circuits and urban destinations. the moot question is whether the lessons of the crisis during the pandemic are addressed by the state in the short and medium period. the pandemic has given several other clear lessons which are unaddressed in the policies taken by the indian state so far. first, it is undeniable that the migrants claim to constitution rights vis a vis articles , , , and of the constitution as citizens have not been respected, either in the destinations where they work or in their areas of origin. given the integral link between migration and development, there is a need to reflect and strengthen their full rights as citizens. second, the pandemic has again brought home the important fact that public health is an externality and that state and employers need to invest more in workers' health. this also means much higher investment in workers' housing and access to basic amenities. third, the grim situation of the migrant workers reinforces the need to institute an adequate social protection floor for all the workers. there has been an urgent immediate requirement for income transfer for a few months to compensate informal workers for their loss of income during the lockdown. on behalf of the indian society of labour economics (isle), a large number of economists and public figures had demanded a short-term quasi-universal income transfer of rs. to households. in the short to medium term, there is a need to institute universal social security for all workers, including the migrants who are informal workers. the code on social security presented to parliament in does not present a time bound road map for universal social security. fourth, in the interim, there is need to institute portability in existing social protection schemes, some of which have statutory backing and central funding (srivastava a). portability and a universal social security system will require a pan-india system of social security registration, which can guarantee privacy, security, and safety of the registrant's information. fifth, the devastating circumstances of the migrants remind us that the labour market needs to be re-unified with registration and formalisation of the workforce and greater job security being provided for informal workers, including the circular migrants. this would also mean a thorough review of the labour code on occupational safety, health, and working conditions which currently promotes informality, with inadequate provisions for occupational safety and health. this also demands a reversal of the direction of labour law changes which several states have undertaken in the name of increasing the ease of doing business. sixth, the situation requires an institution of an integrated rural-urban and regional planning framework, which can promote rural regeneration, especially in poorer states, on the one hand, and inclusive urbanisation, on the other. in conclusion, the pandemic should provide an opportunity to gear the economy towards more equitable and inclusive development rather than increased inequalities built on the higher precarity of informal workers in general, and circular migrants in particular. vulnerable internal migrants in india and portability of social security and entitlements. centre for employment studies working paper series understanding circular migration in india: its nature and dimensions, the crisis under lockdown and the response of the state. centre for employment studies working paper series. wp / , institute for human development emerging dynamics of labour market inequality in india: migration, informality, segmentation and social discrimination key: cord- -pkkh uy authors: rajhans, vidyut; memon, usman; patil, vidula; goyal, aditya title: impact of covid- on academic activities and way forward in indian optometry date: - - journal: j optom doi: . /j.optom. . . sha: doc_id: cord_uid: pkkh uy abstract purpose academia is experiencing massive reforms globally amid lockdown in covid- outbreak. this study is aimed to apprehend the enabling and impeding factors of these reforms, with a focus on optometry education. it brings together how the indian optometry educational system has responded to covid- disruptions with findings of the survey, in light of similar survey done in . methodology a cross-sectional survey was designed to find changes in optometry training and adaptations of indian optometry educators amid covid lockdown. in the last week of april , on the observation that the majority of optometry institutions have switched their teaching-learning activities on e-learning mode, an online survey was conducted using a validated questionnaire containing a mix of open and close-ended questions. results seventy-three out of optometry educators ( . %) have switched to e-learning mode in a very short time span with good confidence. most teaching-learning and assessment activities are carried out using multi-device supporting video conferencing tools, dedicated educational portals and social media apps. conclusion the covid- pandemic is proving to be constructive disruptor, giving an opportunity for restructuring the present conventional, classroom based educational system. the quick transitions to online mode assisted in keeping continuity of optometry education programs, effectively fitting in the purpose of completion of the current academic year. the rapid transition to online education has not only benefited optometry students but also has created a momentum of continued education for practicing optometrist in the country. as of may , covid- pandemic has gripped countries across the globe and many of these faced lockdown . academia was among the first few sectors that faced rapid shut down of all its activities . thousands of schools and higher education institutions and millions of students are affected by lockdown due to the covid- pandemic as the first response from the educational sector was to completely halt its operations . coronavirus pandemic has triggered the significant change, imposing many challenges in the higher education community globally . after about four months in the global crisis, we have started realizing that the covid- is here to stay and we need to find solutions to move on. this crisis can be looked upon as an opportunity to reconstruct our longstanding educational systems and establish better and updated practices in academia, suitable for the present generation of learners . we must prepare ourselves for the changing world when covid- pandemic is blown off. india is a demographically diverse large country with high population density. the nationwide lockdown was the only strategy in the fight against covid- pandemic, which started on th march and is continued in its fifth phase until th june with some relaxations in no infection areas . citizens across the country chose to sit in their homes abiding the guidelines issued by the government of india. academic activities in india were rapidly halted in the middle of the year, by individual institutions and states even before the countrywide lockdown began . as per the recent guidelines issued by university grant commission (ugc), the apex body for higher education in india, the educational institutes must strive to provide quality education, ensuring uniformity, equity and universal accessibility to all the learners . there is constant encouragement from hon. prime minister shri narendra modi, for innovative use and promotion of technology in ushering educational reforms to create a vibrant knowledge society . medical and healthcare education is also severely affected by this global crisis. moreover, it will continue to remain affected as healthcare systems as most teaching hospitals are completely occupied by covid- load . the challenge of clinical exposure to the medical and health profession students will aggravate even further . owing to the rapid transmission of covid- , face-to-face and small group tutorials are prohibited. this imposes greater challenge especially in the context of ophthalmic and optometric skills, which requires close contact between the eye care practitioner and the patient , . social distancing and telemedicine are set to be 'a new normal' hereafter, imposing a persistent challenge for global optometry educators, to teach various clinical skills to the students . the scenario is prompting an urgent need for transformation of optometry education, from traditional brick mortar system to e-learning environment, imparting updated competencies in our graduating optometry professionals. optometry educators in india have responded very quickly to this crisis situation, in the light of guidelines issued by the government of india and ugc. there is a sudden surge seen in the number of webinars and online learning sessions on social media platforms, on various topics of optometry, attended not only by students but also by a massive number of practitioners. this has generated never before momentum in optometry education and also in continuing education programs. the purpose of this study is to apprehend the enabling and impeding factors behind this momentum. this paper reports the findings of the observational study describing the rapid transition of optometry education in india amid covid disruptions. findings of nationwide online survey ascertaining the present practices of teaching-learning in optometry are discussed in light of similar survey done in by the same authors (vr and um). it not only informs the readers about what changed in reference to the past but also appraises how and why the quick adaptation was possible, along with the challenges that are faced during the transition from educator's perspectives. study design: a cross-sectional survey was designed to find changes in optometry training and adaptations of indian optometry educators amid covid lockdown. questionnaire development: a cross-sectional survey was conducted in using a questionnaire comprised of items (hereafter referred to as ' survey'). it was designed to know various teachinglearning methods used for subjects related to applied optics curriculum in optometry programs in india. this questionnaire collected factual data about teaching learning methods used in visual optics, optometric optics and dispensing optics curriculum. the survey also gave insights on teacher's perception about academic practices followed at that time. a follow-up survey was now necessary as significant modifications are witnessed in educational activities amidst this lockdown period. due to the drastic changeover of the situation, and to address the questions of the present study, we extensively revised the the survey recorded a total of respondents, with valid responses. one respondent was not an educator hence was omitted before analysis. of valid responses, were males ( . %) and were females ( . %). one respondent preferred not to disclose the gender identity. the survey reported representation pan india which was found consistent with the findings of the survey (table ). the responses were received from educators in all categories of optometry institutions of india. these demographic results add value to the reliability of the present study. the decision of switching to the online mode of teaching was taken after consultation with students by educators ( . %) while educators ( . %) did not get a chance to consult students as the transition was very rapid. student's training for using online platforms for learning was facilitated by educators overall perception about e-learning environment: overall satisfaction of educators on switching to online mode was . on the likert scale of (least satisfied) to (most satisfied), indicating that most of the educators are satisfied with it. positive perception is seen on being collaborative in adapting with this new normal, summarized in table below. the survey questionnaire also asked six open ended questions to the educators, based on their experiences, to narrate the facilitating and limiting factors in transiting to online education, which are analyzed using qualitative thematic analysis methods. these findings are deliberated in the discussion section. the table below relates the parallel findings from both the surveys, which will help us know the exact nature of the transition of the optometry education system in india. as the two surveys were done with different intentions and instruments, we do not intent to calculate statistical significance but the mere comparison will help us derive appropriate explanation for the research question under consideration. conduct of examination theory written examination; practical skills demonstration online examination for theory in the form of assignments /presentations. skills examination in the form of roleplays and oral examination. this study brings together how the indian optometry educational system has responded to covid- disruptions using findings of the survey, in light of findings of the survey , combined with authors' experiences and observations in academia. covid- pandemic is proving to be a creative disruption with tough challenges for all educational systems . at the same time, there is a strong opportunity for us to adopt newer techniques that are more suitable for the present generation of learners . lockdown is still continued in several states in india. while some other states are starting up with gradual and prioritized restoration of their activities. with norms of social distancing in place, and the guidelines issued by ugc, the academia is likely to continue with e-learning platform at least for few more months these factors kept the motivation of teachers high in adapting to e-education mode. . tech-savvy igeneration students: the present generation of learners has grown up with technology. greater use of online learning activities facilitate greater engagement of the learner. ability to learn and revise at one's own pace, being independent of place and time leads to better educational prospects . the forced transition to online mode is in-fact a sure go for igeneration learners. the students are more concerned about their education and completion of training on time . in this situation of uncertainty, the students are welcoming every single act which will ensure continuity of their academic activities. they are actively involved in, not merely attending the online sessions but are also actively searching and bringing the relevant online content to the session. . safe learning environment: students are allowed to ask their doubts using social or personal messaging apps that get addressed without disclosing their identity during the online class. this type of multi-channel communication between the students and teachers is helping to achieve better outcomes . . ease and comfort of attending online sessions from home without physically travelling anywhere save a lot of time and energy. further, students can choose and attend many online sessions other than regular online classes, either live or in deferred time, organized by various national and regional associations in optometry. they get to hear and interact with many faculties, the practitioners of national and international repute, which excites them to learn more. j o u r n a l p r e -p r o o f . institutional infrastructure: the use of technology, blended learning and e-learning is on the rise since about a decade . these are promising techniques to foster self-learning attitude in health professional students. an increasing number of institutions are encouraging the use of technology in day to day teaching as students find it enjoyable. purposeful and effective use of blended learning is absolutely necessary for managing student-centric learning system percentage of patients requiring critical care, higher recovery rate and lesser morbidity rate . this has brought a general sense of confidence which is helping in overcoming the challenges . a positive and hopeful environment definitely has contributed directly or indirectly towards the success of this transformation. this is evident by the fact that our survey recorded more inputs to advantages and facilitating factors and listed out very few challenges faced during the transition to e-learning. according to who, covid- is here to stay for long period. the health care practices are experiencing significant changes, establishing 'new normal' by using technology of next generation. the restrictions of physical contact with patients, reduction in face to face consultation, social distancing norms are some of the challenges identified in clinical skills training . these challenges will persist for a longer period of time as telemedicine, artificial intelligence and innovative technologies are ready to set in permanently into eye care systems , . experiential learning with direct patient exposure in already strained resources is now significantly challenged in optometry skill training. therefore, we must find an effective longlasting solution by incorporating blended learning in educational system. a good mix of online and face to face learning is suggested while addressing the challenges surfaced during this initial experience. the respondents of survey enlisted the challenges of execution of online teaching such as uninterrupted internet connectivity, technical disturbances in apps, student orientation, adjusting the pace to suit most learners, restriction on a number of online sessions per day, extension of working hours and working on weekends. few challenges related to communication, for example, no eye contact, face reading or body language reading to understand if students are following were also reported. the time and efforts required in the preparation of high quality customized, attractive and user-friendly educational material, suitable j o u r n a l p r e -p r o o f for digital delivery of optometry content was enormous. institutional support in terms of faculty development, student's training for efficient use the technology was also lacking. students of present generation are used to group learning and value peer opinion . optometry students in india are young, having just completed schooling, without much experience. most of them do not get in a job while pursuing their education and are financially and emotionally dependent on family, assuming very little self-responsibility. therefore, educators do not believe that the learners will engage themselves in self-directed learning. further, the lockdown has imposed the challenges of solo learning on them. hence, the total and long term transition to e-learning is challenged. the development of dedicated online modules specific to defined areas of competency along with detailed planning of blended learning activities is required. accessing telehealth interactions in compliment with e-learning modules can address the perceived gap in clinical skill teaching. we must move ahead from just taking online lectures to the development of more engaging and novel teaching-learning methods based on principles of adult learning . we must utilize this once in a lifetime opportunity where massive sudden transitions are taking place in all sectors of life. this accelerated change if continued in the direction of upcoming trends of optometry practice will fetch positive rewards in years to come. the study was focused more on optics related subjects while the survey addresses the entire curriculum taught by optometry faculties. in india, the optometry faculties are mostly engaged in teaching applied optics, contact lenses, binocular vision and low vision subjects . since the two surveys were addressing similar but not exactly the same research question, in different learning environments, with two different instruments, no direct statistical comparison was possible. but we felt that it was reasonable to see the results of the latest survey in the light of earlier one, in order to gain clarity about the journey so far from the traditional classroom system to the technology-aided competency-based educational system. the covid- pandemic and its disruptions have created an opportunity for the restructuring of the optometry educational system. the quick transitions to online mode assisted in keeping continuity of optometry education programs, effectively fitting in the purpose of completion of the current academic year. clearly, the journey from the tea steeping model of education to a competency-based learning program has commenced. online teaching, use of internet technology in optometry education are set to become a new normal. the transition can be quick and smooth if educators and technical staff show an adaptive and collaborative attitude. it is, however, very early to conclude the successful narrative of transition as the judgment of students' performance and quality of passing out professionals is yet to be realized. further studies may be directed to test student's performance and satisfaction on switching to the e-learning educational system. world health organization the socio-economic implications of the coronavirus and covid- pandemic: a review covid- : countries' higher education intra-period digital pedagogy responses influence of covid- confinement in students ' performance in higher education how can the covid- pandemic help higher education ? lockdown in india: lockdown till may can stall coronavirus pandemic, says study | india news -times of india covid outbreak: the disappointment in indian teachers ugc guidelines: ugc issues new calendar for universities; - session to begin from coronavirus: india's education minister aims to "save" academic year | times higher education (the) covid- and medical education pandemics and their impact on medical training: lessons from 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transform india into digital empowered society and knowledge economy covid- pandemic and the digital revolution in academia and higher education using technology , bioinformatics and health informatics approaches to improve learning experiences in optometry education the effectiveness of blended learning in health professions: systematic review and meta-analysis why india may do much better off with covid- sentiment analysis of nationwide lockdown due to covid outbreak: evidence from india optometry-facilitated teleophthalmology: an audit of the first year in western australia innovative approaches in the delivery of primary and secondary eye care. switzerland: springer nature ready for action listos para la acción pattern of optometry practice and range of services in india key: cord- - gwb b authors: sarkar, priyanka; debnath, nirmal; reang, demsai title: coupled human-environment system amid covid- crisis: a conceptual model to understand the nexus date: - - journal: sci total environ doi: . /j.scitotenv. . sha: doc_id: cord_uid: gwb b abstract the world today is dealing with a havoc crisis due to the pervasive outbreak of covid- . as a preventive measure against the pandemic, government authorities worldwide have implemented and adopted strict policy interventions such as lockdown, social distancing, and quarantine, to curtail the disease transmission. consequently, humans have been experiencing several ill impacts, while the natural environment has been reaping the benefits of the interventions. therefore, it is imperative to understand the interlinked relationship between human society and the natural environment amid the current crisis. herein, we performed a meta-analysis of existing literature reporting the various impacts of covid- on human society and the natural environment. a conceptual model was developed to portray and address how the interaction of the existing elements of both sub-components of the coupled human-environment system (ches) – human society and natural environment – are impacted by the government interventions. results revealed a suite of positive and negative impacts of covid- on both the sub-components. our model provides an explicit impression of the complex nexus of ches amid the current crisis. the proposed conceptual model could help in understanding the complex nexus by identifying the route of short-term impacts of covid- measures and thus may aid in identifying priority areas for discussion and planning in similar other crises as well. coupled human-environment system (ches) represents a complex, dynamic, interconnected, and integrated system in which humans and the natural environment interact with each other (turner et al. ; liu et al. ; galvani et al. ) . in recent centuries, humans have been remarkably intervening with the environment to fulfill the demands of the growing population and rapid economic development (myers and patz ) . such a plethora of anthropogenic interventions poses long-term repercussions i.e., extreme climatic events and other natural calamities, food, and water scarcity, increased exposure to infectious diseases, population displacement, etc. on the human society (myers and patz ; galvani et al. ). therefore, understanding the complex ches is important for recognizing and addressing the vulnerability of the situation on human society, and natural ecosystems amid any local or global crisis (turner et al. ) . the world today is dealing with a havoc crisis due to the pervasive outbreak of coronavirus disease . the vicious covid- is an infectious disease caused by a new ), and exhibits a higher human to human transmissibility (chan et al. ) . the pandemic has posed a great threat to the global-public health and economic recession and is still ongoing (bogoch et al. ; wu et al. ) . so far, no proven pharmaceutical treatment has been developed to combat the pandemic (singhal ). given its severe impact, the world health organization (who) has declared covid- as a public health emergency of international concern on january , . as a preventive measure against the pandemic, the government authorities worldwide have implemented and adopted strict policy interventions to maintain social (physical) distancing and curtail the transmission of covid- . almost one-quarter of the global population is now confined within their homes, experiencing several negative/ill impacts in terms of socioeconomic and psychological well-being. on the contrary, there are several hidden benefits of the interventions on the environment or natural world. therefore, it is imperative to understand and appreciate the mutually-affective relationship between human society and the natural environment amid the current crisis (kumar a ) and identify the priority areas for designing necessary action plans for a balanced state. although, few studies have highlighted the impacts of covid- and relevant policy actions on the environment, and social aspects like economic and health consequences (hevia and neumeyer ; lin et al. ; muhammad et al. ; sharma et al. ; zambrano-monserrate et al. ) , the complexity of ches amid the current crisis has not been well understood. unpredictability and vulnerability of ches require a case or situation-specific assessment to consider appropriate relationships of variables with a set of standardized methods (polsky et al. ; turner et al. ) . in this regard, our study attempted to understand the processes, responses, and feedbacks within the complex ches amid the crisis through a conceptual model. such models are valuable communication tools that represent the current knowledge of a system and illustrate its complex interactions in a simplified way (gross ; imgraben j o u r n a l p r e -p r o o f journal pre-proof et al. ) . conceptual models may thus assist in identifying the priority areas that require further research or monitoring and build a basis for discussion and planning (roman and barrett ) . the specific objectives of the study were to (i) perform a meta-analysis of existing literature reporting various impacts of covid- on human society and the natural environment, and (ii) develop a conceptual model to illustrate and understand the complex nexus of ches amid the pandemic. our conceptual model could be helpful in clearly portraying the complex and coupled nature of the system amid the current crisis. thus, aid in identifying the priority areas and intrigue the discussion for further planning towards mitigating the effects of the current-as well as similar crisis. we performed a systematic review of peer-reviewed scientific articles on the impact of covid- on human society and the natural environment worldwide written in english using the isi web of science (wos) -core collection database published until april , (with an open initial date). a literature search was conducted using a combined search string with two topic fields. search strings in the first topic field included different terms denoting covid- outbreak, restrictions and their impacts ("covid- ", 'coronavirus', the conceptual model was developed based on the information collected from the literature review, and the previous experience and expertise of the first author on model development -'expert-based models' approach (ferrier et al. ). this was followed by brainstorming amongst all the authors to improvise the model. during the entire process of model development, authors' practical experiences and in-depth understanding of the context of ecological and environmental studies, and associated socio-economic factors were advantageous. the literature review revealed a suite of impacts (positive and/or negative) of covid- and lockdown/restrictions on human society and the natural environment (table ) on both human society and the environment were also recorded (table ) . the proposed conceptual model comprises of two modules, (i) drivers of change: covid- (direct driver) and lockdown/restrictions (indirect driver), and (ii) our focal point: coupled human-environment system (ches) (fig. ) . drivers of change refer to the factors that directly or indirectly cause changes in nature and its components, anthropogenic assets, and good quality of life (ipbes, https://ipbes.net/glossary/driver). the conceptual model illustrates how the different elements of two sub-systems: human society and natural environment, interact with one another -directly and/or indirectly, through forming a network of associations. the relationships between the elements of the two sub-systems are depicted by arrows, which also shows the direction of impacts, positive and/or negative ( fig. ). for example, for the sub-system: human society, limited transportation had a positive impact in containing the disease, thus lowering infection & death. similarly, limited transportation due to lockdown resulted in reduced fuel consumption, generating positive impacts on the sub-system: natural environment, characterized by reduced-air pollution (lower conc. of co , co, nox, pm . , pm ) and environmental noise, leading to flourished biodiversity/wildlife. the conceptual model also displayed two feedbacks -(i) between the primary and secondary drivers -covid- and lockdown/restrictions, and, (ii) between covid- and the health workers. to illustrate, the spreading of the virus has mandated the implementation of lockdown inducing grief to human society worldwide, which on the other hand, had a positive impact on suppressing the pandemic. covid- crisis is considered one of the worst pandemics in history which has further complicated the entire coupled human-environmental system. lower adaptability of human society to various socio-environmental crises arises mainly due to the poor understanding of the complex and interconnected nature of the human-environment system (dearing et al. ). hence, understanding the complexity of any system is pressing to avoid any environmental ensue on a regional or global scale (roberts et al. ) . conceptual models assist in envisioning the complex interactions in a simplified manner and recognize priority areas for the implementation of necessary management strategies. our conceptual model explicitly illustrates the impacts of covid- and lockdown/restriction -directly or indirectlyagainst the pandemic on the various elements of the intricate and coupled humanenvironment system and/or the feedbacks amongst them as described below: as depicted in the model, covid- has a direct negative impact on human health owing to its high risk of infection and death. the fatal impact of covid- on global human health has surpassed the number of infections and deaths caused by its ancestors and is still accelerating (bogoch et al. ; chan et al. ; lin et al. ; wu et al. ) . grech ( ) suggested that the pandemic may lead to half a billion deaths i.e., ~ % of the global population or more; likely due to the absence of a concrete approved treatment to combat the pandemic (singhal ). the pandemic has led to the increased generation of tons of medical/healthcare wastes several folds when compared to before the disease outbreak (adb j o u r n a l p r e -p r o o f journal pre-proof calma ; isdm ; saddat et al. ) . as highlighted in the model, increased generation of medical wastes, in turn, led to unmanageable medical waste triggering other human health risks (alverson ; jiangtao and zheng ; zambrano-monserrate ). for example, health-& sanitation workers, rag pickers, trash cleaners, etc. are at high risk of infection due to close contact with the patients and/or unmarked medical wastes such as discarded masks, gloves, etc. (mallapur ; saddat et al. ). in addition, the model also depicts the existence of feedback between covid- and health workers. for instance, while the health workers are at the front line of the pandemic outbreak, their exposure to the virus has put them at the risk of infection and death, coupled with other health risks such as fatigue, occupational burnout, psychological distress, etc. making them vulnerable to the current crisis. as of april , , the who reported that the pandemic has already hit over , health workers across countries (the economies times a). on the contrary, health workers stand as an important potential barrier to minimize the risk of covid- infections and death as feedback and contribute largely to the wellbeing of the global public. the pandemic has plunged the entire world into a looming global economic recession (corlett et al. ; giles et al. ; ozili and arun ) . as depicted in the model, the the model depicts a direct negative impact of lockdown on human society in terms of inducing poverty and food insecurity/crisis. however, the impact of lockdown on the poor and wealthy sections of society has been disparate. for instance, while the period of total lockdown has been easier for the rich and middle-class society to pull through with assured incomes, health insurance, adequate spaces at home to maintain physical distancing & running water supplies, daily sustenance of the weaker section of the society has been very miserable. insecure sources of income for billions of the poor people worldwide due to loss of jobs amid lockdown as discussed in section . . have severely affected their livelihoods pushing them towards extreme poverty. in addition to the instability of food availability due our model highlights both positive and negative impacts of lockdown due to the limitedtransportation and movement. the model depicts the positive impact of lockdown through limiting movement/transportation, thus ceasing all events -social, political, sports, academic, and other gatherings (breeding grounds of the virus) to maintain social distancing and curtail the disease transmission as mandated by government authorities worldwide (financial express ). more than . billion people or half of the world's population are currently under containment (sandford ) . consequently, the lockdown has posed a negative impact on the psychological resilience of people (homes et al. ; li et al. ; qiu et al. ; wang et al. ) . however, it is worth mentioning that homestay due to limited movement may likely bring a positive impact in terms of enhancing the family bonding. as shown in the model, paralyzed transportation due to lockdown has negatively impacted the global economic recession. for instance, lockdown against covid- has caused the shutdown of national borders in nearly countries which have dropped air travel by % j o u r n a l p r e -p r o o f journal pre-proof (wallace ) , causing a loss of us$ billion to the air travel industry (appleton ). the tourism industry has also come to halt, causing % global economic contraction as reported by the un (the statesman ). similarly, the lockdown has also hit the railway industry in terms of financial loss as reported by western railways, govt. of india (the economic times ). limited transportation has also caused unemployment and job insecurity for people involved in the private transport sector, which would ultimately affect their psychological resilience. . esa also reported the changing density of harmful gases emitted due to fossil fuel burning (child ) . in addition, the carbon emissions in china, the epicenter of the covid- pandemic, has dropped by ~ % over four weeks at the beginning of (child ) . in northern india, the residents now could view the himalayan mountain range due to increased visibility, which otherwise has been concealed by pollution for ~ years (child ) . the air quality index (aqi) in delhi and ncr's, india, has reduced to , which otherwise scores an aqi of during the smoggy winter months (the economic times ). while in venice, italy, restrained tourism industries have improved the water quality of winding canals (child ) . moreover, paralyzed transportation has also plummeted environmental noise due to the slowdown of traffic (gibney , schuster ). all these factors are likely to contribute to the flourishing and liberation of biodiversity and wildlife. our model also shows an indirect positive impact of improved air quality in containing the disease transmission and death. air pollution is known to have a strong association with a high incidence of various respiratory infections (cipolla et al. ; silva et al. ; zhang et al. ) , and higher mortality rates (lelieveld et al. ) . evidence shows high cases of covid- in highly polluted areas of china, italy, and the united states, the countries with higher cases (pansini and fornacca ) . in addition to the impact of covid- in terms of infection and death as discussed in section . , extended lockdown and stay-at-home regulations against the pandemic has associated human health risks such as weight gains due to sedentary lifestyle, psychological/behavioral changes, etc. (lippi et al. ) parivaar, govt. of india, https://www.gangaaction.org/actions/issues/solid-waste/). all these activities are very likely to contribute to flourishing biodiversity/wildlife. the shutdown of offices, business centers, industries, and other workplaces due to the pandemic (muhammad et al. , richards and rickard ) has both negative and positive impacts on the ches as identified in the model. nickle ( ) suggested that % of industry members such as the growers, shippers, retailers have been reported to be affected due to the lockdown. this instigated a high negative impact through a looming global economic recession, leading to unemployment/job insecurity and lower psychological resilience. on the contrary, the model also identifies the positive impact of the shutdown of workplaces on the natural environment. for example, reduced generation of industrial and commercial wastes contributed to the improvement of air quality, creating a similar situation like halted transportation as discussed in section . . in addition, the shutdown of the industrial sector that releases a huge quantity of pollutants has contributed to improving the air and water quality as identified in the model. for some years now, the river ganga and yamuna of india were considered amongst the most polluted water bodies. however, due to the lockdown, the rivers have been reported to appear cleaner and brighter owing to the temporary shutdown of the chemical industries; the major source of river pollution in india (times of india ; the economic times c). all these factors are likely to contribute to enhancing the overall environmental quality and flourishing biodiversity/wildlife. benefits for the wildlife in terms of higher reproductive success, less migration, and lower mortality rates (ro ) . seismologists suggest that such noise reductions have resulted in less seismic noise, or vibrations in the earth's crust by ~ one-third compared to pre-lockdown levels (ro ) . moreover, decreased noise in oceans due to halted cruises is likely to decrease the production of stress hormones in sea fauna (koren ) . as shown in the model, humans are also likely to be beneficial given the harmful physical effect of chronic noise such as high stress, disrupted sleep, high blood pressure, cognitive impairment in children, hearing loss, heart disease, etc. (ro ). owing to the indirect positive impact of lockdown on the natural environment as discussed above, nature is reviving, thereby contributing to flourished wildlife and biodiversity as depicted in the model. due to the improved water quality in rivers, many of the rare animals have been spotted in the places not seen earlier. for example, the indian gangetic dolphins (one of the four freshwater dolphin species in the world; an iucn endangered species) could be spotted more in vikramshila gangetic dolphin sanctuary, bihar, india, as a result of limited human activity along the river ganga due to lockdown (khan ) . the presence of dolphins is a bio-indicator of a healthy river ecosystem (khan ) and hence, the lockdown in human society has turned to be a 'blessing in disguise' for the dolphins. elsewise, degradation of water quality in indian rivers due to dumping of municipal and industrial wastes is known to have a negative impact on human health and other aquatic fauna (ganga action plan, govt. of india, https://www.gangaaction.org/actions/issues/solid-waste/). das ( ) reported mass nesting of the endangered olive ridley sea turtles at rushikulya rookery in odisha, india due to the shutdown of touristic activities. in thailand, restriction of fishing and touristic activities has favored the increased spawning of rare leatherback sea turtles (a vulnerable iucn species) (the guardian ). basu ( ) reported that restricted j o u r n a l p r e -p r o o f journal pre-proof transportation due to nationwide lockdown has led to flourishing bird diversity in kolkata, india. our model identified the negative impacts of lockdown on education. for instance, government authorities worldwide have mandated shutdown of academic sectors including schools, colleges, and universities in countries to maintain social distancing to curtail the transmission (corlett et al. ) . as a result, more than . billion students, and nearly . million teachers are no longer in the classroom (un ), postponing and/or canceling of examinations and subsequent delay in graduating. nevertheless, the lockdown of academic institutions has provided an opportunity and platform for digital education and online/elearning. yet, the negative impacts of lockdown on education is more overpowering on its positive aspect. on the other hand, we identified both positive and negative impacts of lockdown on research. for instance, the lockdown has frozen many laboratories, and field-based research, thus halting the ongoing research and instigation of new research as well (corlett et al. ). moreover, travel restrictions have canceled and/or postponed many national and international conferences, meetings, and research stays. yet, the lockdown has also provided ample time for research and innovations (paital et al. ) , and to collaborate among the experts globally. given the complexity of ches, the emergence of unprecedented uncertainties is inevitable for a pandemic like covid- which was not evidenced in the last century (who ). uncertainties mainly arise due to limited current knowledge about the virus and how people j o u r n a l p r e -p r o o f journal pre-proof across the globe modify their behaviors in response to the pandemic (chater ) . hence, uncertainty can accelerate fear, stress, panic, anxiousness, loss of trust amongst human society, making us powerless over the direction of life (robinson and smith ; who ) . in absence of the covid- vaccine, it is uncertain if the virus will flare up as restriction gets relaxed; or, whether the lockdown & personal safety measures in addition to contact-tracing and testing, might be able to stamp it out. over time, the ongoing restrictions due to the current crisis are likely to surge the uncertainty over the various elements of human society such as the economy, health, psychological well-being, etc. as discussed in section . . , governmental intervention such as strict lockdown has potentially impeded the spreading of the virus saving billions of lives worldwide. however, this has come at the cost of doomed economy and income loss due to the shutdown of industry and transportation sectors, etc. as discussed in section . . , creating a 'health-wealth trade-off'. in the opposite scenario, the relaxation of lockdown would involve a reverse trade-off where the economy recovers at the expense of an increased threat of mass contamination and death. it is therefore uncertain or unclear to decide the best policy measure yet as covid- would take a toll either way. this scenario is likely to be worse especially in the developing countries due to the differences in population structure, fiscal capacity, healthcare capacity, higher prevalence of "hand-to-mouth'' households, and the size of the informal sector (alon et al. ) . herein, the quantification of trade-offs for a better understanding of the current crisis is urgent for the decision-makers to develop effective policy measures that account for different resource allocation strategies (daher and mohtar ) . such quantitative analyses may also assist in understanding how the different policy response priorities to the current pandemic should differ in the developed and developing nations (alon et al. ) . another important instance worth mentioning amid the current crisis is the differential scenario of water security in the developed and developing world. until the discovery of j o u r n a l p r e -p r o o f journal pre-proof medicine or vaccine to control the disease, the who has recommended basic protection measures such as the frequent washing of hands and the use of face masks and hand gloves to curtail/spread the virus infection, in addition to maintaining social (physical) distancing. while frequent hand washing is well-practiced in the rich/developed societies/countries having better availability of safe water, millions of people especially in the poor countries/societies are highly susceptible to the virus due to the lack of safe water supply (ndaw ). however, in a world with the frequent outbreak of similar pandemics, it is uncertain if only the countries/communities with low/no access to safe water would be affected more. there is a high chance of water scarcity due to water overuse for domestic and hygiene-related practices to prevent or suppress the potential pandemics throughout the world irrespective of its economic stability (kumar b; rohila ) . the abatement of air pollution due to lockdown is another instance with high uncertainty. although the emission of co has reduced due to the lockdown/restrictions as discussed in section . . , such short-term drops in gas emissions are likely to have very little impact on the overall co concentration in the atmosphere given its relentless pile-up and longer residence in the atmosphere. as mentioned in section . . , flourished biodiversity due to governmental interventions has been one of the bright sides of the current crisis for the natural environment. however, it is uncertain if such liberation would be favorable for the wildlife in the long run. as wild animals venture into settlement areas and human-modified landscapes in search of food and resources, unexpected threats such as human-animal conflicts might arise. this may favor the poachers and opportunistic delinquents as the lockdown prevails, ultimately leading to conservation threats. in addition, the toll on the global economies might also reflect in reduced funding for wildlife conservation and management. illegal encroachment of forested lands is also likely to arise when the forest officials split their time between regular duties and j o u r n a l p r e -p r o o f journal pre-proof helping out with the covid- situation. another instance could be the risk for biodiversity and natural habitat by forcing poor people to adopt hunting and illicit lopping of trees for daily livelihood sustenance as a result of the loss of employment as mentioned in section . . . in-depth and country-tailored assessment & quantification of such uncertainties through developing multiple scenarios for both the developed and developing nations is therefore important to better understand the long-term impacts of such crises on ches. future studies may consider quantifying the trade-offs and uncertainties of the current crisis on ches to assist the decision-makers for better policy-making process. overall, our study demonstrates how the different policy actions i.e., lockdown, socialdistancing, quarantine, etc. against covid- has changed the way ches interacts and influences each other. although the crisis has instigated severe ill impacts on human society, it has proved to be a 'blessing in disguise' for the natural environment as discussed in sections . . , . . , . . . restricted/regulated anthropogenic interventions against covid- have given rise to a better natural environment for which governments and scientists worldwide have been investing time and money for decades. on the contrary, the current situation urges for the adoption of preventive measures to mitigate ill effects faced by human society as discussed in sections . . - . . , . . , & . . . however, the recent situation does not reflect sustainable earth, given the overpowering negative impact of the current crisis on human society. thus, even if the natural environment is benefited due to the ongoing crisis, several uncertainties persist as discussed in section . . the situation is likely to reverse once the lockdown is withdrawn, and both the sub-systems would be affected -the worst-case scenario. over the centuries, humans have imposed dazzled pressure on nature and experienced its repercussions from time to time. thus, in both cases, the benefits are shortterm, which is likely to lead to a pessimistic future where both the sub-system of ches is negatively affected. thus, with a prolonged crisis, it is likely that the aspects of ches would j o u r n a l p r e -p r o o f give rise to several trade-offs and many more uncertainties as discussed in section . . our study, therefore recommends that new policies should aim to convert the short-term gains into long-term benefits, creating an optimistic post-coronavirus world, beneficial for both the sub-systems. given the fact that the human sub-component of ches is experiencing the worst impacts of the crisis, policy actions should primarily focus on mitigating the ill impacts faced by human society. in this regard, our model could help identify the priority areas to understand the vulnerability of the current situation. however, incorporating the perspective of the local stakeholders and policymakers is important while developing a conceptual model. this allows covering the gaps and variations in external political and economic forces on the regional and local environment, which is a limitation of the present study given the sensitivity of the current crisis. the covid- crisis might be an 'eye-opener' for humanity. the current predicament reflects that nature has the potential to revive itself given that the anthropogenic interventions are checked. therefore, it is high time to understand and appreciate the complexity of ches and adopt appropriate measures towards tackling the current crisis while maintaining harmony with nature. the main purpose of the study was to propose a conceptual model to portray and address how the interaction of the existing elements of both sub-components of ches -human society and natural environment -are impacted by the various governmental interventions i.e., lockdown, social distancing, quarantine, etc. towards combating the crisis. the merit of our model is that it comprises all possible elements of ches and provides an explicit impression of complex ches amid the crisis. the proposed conceptual model provides an insight into the intricate linkage of ches and helps in understanding the j o u r n a l p r e -p r o o f journal pre-proof complex nexus by identifying the route of short-term impacts of covid- measures. thus, our model may be considered as a baseline for further studies and may serve as a precursor towards building quantitative modeling. the model thus may aid in policymaking by identifying the priority areas for discussion and planning in similar other crises as well. future studies may focus on forecasting the long-term impacts of the current crisis through developing scenarios considering the different components of the ches identified in the present study. the first author would like to acknowledge the ipbes and bpbes experts from the 'são dutheil, f., baker, j.s., navel, v., . covid- as a factor influencing air pollution?. j o u r n a l p r e -p r o o f how should policy responses to the covid- pandemic differ in the developing world? 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- journal: j public aff doi: . /pa. sha: doc_id: cord_uid: epmcognh this study is an attempt to find and analyze the correlation between covid‐ pandemic and weather conditions in indian context. secondary data analysis of surveillance data of covid‐ is taken from wikipedia (updating information from world health organization) & statista.com and weather data through power data access viewer (dav) (power.iarc.nasa.gov) from nasa after mentioning latitude and longitude of india. the minimum temperature (°c) at metre, maximum temperature (°c) at metre, temperature (°c) at metre and relative humidity (%) are taken as component of weather. to find the association, spearman's rank correlation test was applied. the minimum, maximum temperature (°c) at m, temperatures (°c) at m and humidity at m are significantly correlated with covid‐ pandemic cases (r = . , . , . , and . ) at % two‐tailed significance level. the findings serve as an initial evidence to reduce the incidence rate of covid‐ in india and useful in policy making. a novel human coronavirus, named as severe respiratory syndrome coronavirus subsequently named as sars-cov- was first reported in wuhan, china, in december (holshue et al., ; sohrabi et al., ) holshue et al., ; sohrabi et al., ; van doremalen et al., ) . on march , when the number of covid- cases outside china has increased times and the number of countries involved has tripled with more than , cases in countries and over , deaths, who declared the covid- outbreak as a pandemic. this has resulted in lockdown in many nations worldwide. the first case of covid- was reported in india on january , with origin from china (pib, ) . it spreads to the maximum districts of the country. on march , the government of india ordered a nationwide lockdown for days, limiting movement of the entire . billion population of india as a preventive measure against the coronavirus pandemic in india. it was ordered after a hr voluntary public curfew on march , followed by enforcement of a series of regulations in the country's covid- -affected regions. the lockdown was placed when the number of confirmed positive coronavirus cases in india was approximately . this lockdown enforces restrictions and self-quarantine measures. lockdown was extended nationwide till may , with a conditional relaxation promised after april for the regions where the spread has been contained by then. as on april , , the total cases reported in india were , with , recoveries and deaths (covid- in ). hospital isolation of all confirmed cases, tracing and home quarantine of the contacts is ongoing. however, the rate of infection in india is fewer as compared with other countries. common signs and symptoms of covid- infection include symptoms of severe respiratory disorders such as fever, coughing, and shortness of breath. the virus that causes covid- is mainly transmitted through droplets generated when an infected person coughs, sneezes, or exhales. these droplets are too heavy to hang in the air, and quickly fall on floors or surfaces. the average incubation period is - days with the longest incubation period of days. in severe cases, covid- can cause pneumonia, acute respiratory syndrome, kidney failure, and even death. the clinical signs and symptoms reported in the majority of cases are fever, with some cases having difficulty breathing, and x-rays show extensive pneumonia infiltrates in both lungs (holshue et al., ; perlman, ) . the clinical symptoms of severe and critical patients with covid- are likely similar with the clinical symptoms of sars and mers (wang, tang, feng, & lv, ; wang, wang, chen, & qin, ) . preventive measures for covid- include maintaining physical and social distancing, washing hands frequently, avoid touching the mouth, nose, and face (who, ). interesting point of discussion among the researchers gupta, raghuwanshi, & chanda, ; ma et al., ; poole, ; sajadi et al., ; tomar & gupta, ) . in case of west nile virus in the united states and europe (epstein, ) , yuan et al. ( ) study the relationship between climate conditions and sars-cov, and suggested that climate variable can also be the cause of biological interactions between sars-cov and humans. bull ( ) also suggested that weather is very significantly correlated with change in mortality rates due to pneumonia. several factors such as clouding, temperature, humidity, and population density are influenced the transmission of the viruses (dalziel et al., ) . tosepu et al. ( ) the computerized datasets of daily confirmed cases, recovered cases, and death of covid- pandemic in india were obtained from who through wikipedia and statista.com for the period of january , to april , . while weather data which include minimum, temperature ( c) at m, maximum temperature ( c) at m, temperature ( c) at m, specific humidity at m, and relative humidity at m were obtained through power data access viewer (dav) (power.iarc. nasa.gov) from nasa after putting the longitude and latitude of india for the same time period. we found that datasets do not fulfill the assumptions of pearson product moment correlation, therefore, spearman's rank correlation test was used to examine the relationship between weather and daily confirmed cases of covid- pandemic. the maximum temperature ( c), minimum temperature ( c), temperature ( c), and relative humidity are plotted against the days from january to april , along with the confirmed cases, recovered cases, and death in figure . figure shows that the first case of covid- appeared on january , and rapidly increasing till april from march . the figure also depicts that growth of covid- cases is very high as compare with the temperatures ( c). the descriptive statistics of the components of weather are presented in table . table describes the average minimum temperature ( c), average maximum temperature ( c), temperature ( c), and average specific humidity along with standard deviation and skewness for each components of weather. this table depicts the idea about the distribution of weather data. if we compare the mean and standard deviation of temperatures ( c), we see that the standard deviation is almost same around . for each temperature ( c), whereas standard deviation of confirmed cases of covid- pandemic is , . . these findings are oblivious because temperature is homogenous as compare with cases of covid- . for the period of study, temperatures ( c) are negatively skewed which means data points below the mean are larger comparatively. the spearman's rank correlation coefficient calculated between confirmed case of covid- and components of weather and summarized in table . table shows that there is high positive correlation in the confirmed cases of covid- and temperatures ( c), whereas low positive correlation is present between confirmed cases of covid- and specific humidity. all these coefficients are statistically significant at . level of significance for two-tailed correlation test. with the help of table and figure , we can see that the pattern of climate change helps to provide a picture of occurrence of covid- in india. this result is in line with the earlier research done in the case of sars (tan et al., ) , syncytial virus respiration (rsv) (vandini et al., ) , and (shi et al., ; who said, temperature is also the environment driver of covid- outbreak in china). the result is showing positive correlation between temperature and covid- (as shown by tosepu et al., ) but degree of correlation is comparatively high. in spite of weather condition, india is a country of young population (approx. % are below years, mospi) who interact daily with other people for their studies, job, and daily needs. since, covid- is a contagious disease; population density may be another reason for the spread of covid- in india. though our findings are significant for the considered time period, the present study of correlation between weather and covid- dose not implies causality, that is, through this study, we cannot conclude that weather is a cause of spreading the virus in india. there was a myth in the society that the increase in temperature will reduce the cases of covid- . our study opposes this myth and support the fact that temperature increase cannot reduce the cases of covid- . this study supports the fact that despite of the good degree of correlation between weather and covid- and significant finding, the study has few limitations. first, since the disease is contagious, many factors need to be examined such as population, population density, education, spiritual belief, medical facility, and mobility. second, specific health of a person, personal hygiene, washing habits, immunity of a person, and use of mask and sanitizers may be the other factors, which can influence the spread of covid- in india. the effect of policies and measures on covid- transmissions was not assessed in our study. covid- battle during the toughest sanctions against iran the weather and deaths from pneumonia roles of meteorological conditions in covid- transmission on a worldwide scale urbanization and humidity shape the intensity of influenza epidemics in u west nile virus and the climate effect of weather on covid- spread in the us: a prediction model for india in first case of novel coronavirus in the united states effects of temperature variation and humidity on the death of covid- in wuhan, china. science of the total environment another decade, another coronavirus seasonal influences on the spread of sars-cov- (covid ), causality, and forecastabililty temperature and latitude analysis to predict potential spread and seasonality for covid- the impact of temperature and absolute humidity on the coronavirus disease (covid- ) outbreak-evidence from china world health organization declares global emergency: a review of the novel coronavirus (covid- ) an initial investigation of the association between the sars outbreak and weather: with the view of the environmental temperature and its variation prediction for the spread of covid- in india and effectiveness of preventive measures correlation between weather and covid- pandemic in jakarta aerosol and surface stability of sars-cov- as compared with sars-cov- respiratory syncytial virus infection in infants and correlation with meteorological factors and air pollutants high temperature and high humidity reduce the transmission of covid- unique epidemiological and clinical features of the emerging novel coronavirus pneumonia (covid- ) implicate special control measures a climatologic investigation of the sars-cov outbreak in beijing he has contributed number of research papers and articles in various national and international journals indexed in scopus her area of research is design of experiments. she has years of teaching and research experience anukriti has published research papers in reputed indexed journals. how to cite this article: sharma p, singh ak, agrawal b, sharma a. correlation between weather and covid- pandemic in india: an empirical investigation we are very thankful to the anonymous reviewers and editor-in-chief professor phil harris for their careful reading of manuscript and many insightful comments and suggestions, which improved the overall quality of this paper. https://orcid.org/ - - - key: cord- -v lrg p authors: iyengar, karthikeyan; mabrouk, ahmed; jain, vijay kumar; venkatesan, aakaash; vaishya, raju title: learning opportunities from covid- and future effects on health care system date: - - journal: diabetes metab syndr doi: . /j.dsx. . . sha: doc_id: cord_uid: v lrg p background and aims: covid- has had a crippling effect on the health care systems around the world with cancellation of elective medical services and disruption of daily life. we would like to highlight the learning opportunities offered by the current pandemic and their implication for a better future health care system. methods: we have undertaken a comprehensive review of the current literature to analyse the consequences of covid- on health care system. using suitable keywords like ‘covid- ’, ‘telemedicine’, ‘health care’ and ‘remote consultations’ on the search engines of pubmed, scopus, google scholar and research gate in the first week of may we gathered information on various aspects of effect of covid- . results: there has been a shared drive worldwide to devise strategies to protect people against viral transmission with reinforcement of hand hygiene and infection control principles but also to provide continuity of health care. virtual and remote technologies have been increasingly used in health care management. conclusion: covid- has offered unique learning opportunities for the health care sector. rationalizing and optimizing available resources with resilience shown on the coronavirus frontline during the crisis are some of most important lessons learnt during the crisis. importance of personal hygiene and re-enforcement of infection control measures have been acknowledged. telemedicine revolution will be a vital factor in delivering health care in the future. covid- has had a crippling effect on the health care systems around the world with cancellation of elective medical services and disruption of daily life. we would like to highlight the learning opportunities offered by the current pandemic and their implication for a better future health care system. we have undertaken a comprehensive review of the current literature to analyse the there has been a shared drive worldwide to devise strategies to protect people against viral transmission with reinforcement of hand hygiene and infection control principles but also to provide continuity of health care. virtual and remote technologies have been increasingly used in health care management. december and spread worldwide [ ] . it has now spread to over countries and the latest world health organisation (who) reports there are over million confirmed cases of covid- with more than , deaths ( may ). [ ] predominantly a respiratory illness, the novel coronavirus respiratory spreads predominantly by droplets and is highly contagious [ ] . serious illness requires hospital admission [ ] . to prevent the spread of this contagious virus, national governments have introduced 'lockdown' measures with infection control strategies including 'social distancing' and 'self-isolation' guidelines which severely restricts the movement of people and affects their daily life [ , ] . lockdown and strategies to prevent covid- viral transmission has caused significant economic, geopolitical and health consequences all over the world [ ] . covid- has had significant effect in normal working of health care organisations. ( figure ) it has made patients staying away from accident and emergency departments and reaching out for urgent medical conditions such as heart, cancer illnesses. [ ] . this has shown the versatility and the spirit of support and unity of all community sectors to help out during a disaster. . . government initiatives -covid has exposed health care system of many countries including india. in india public health-care system in grossly under-funded and patchy while private health-care sector is unregulated. the indian government's expenditure on health as a percentage of gdp is around · %. there are several gaps in india's preparedness for covid- pandemic [ ] . this pandemic could be the much-needed wake-up call to the necessity of long-term changes to india's health [ ] . recently taking in account during pandemic the indian government has increased expenditure in the public health system to reboot healthcare. the government has launched an ambitious project 'aatmanirbharbharat' to become more self-reliant with investment in acquiring and building lifesaving equipment's like ppe, ventilators, building hospital infrastructure, icu beds, oxygen supply in hospitals, strengthening of laboratories, hiring of additional human resources which were scarce before pandemic [ , ] . all this will improve the health care system and facilities in india. . . in covid- , organisations have accepted that telemedicine has a key role, developed their departments to facilitate telemedicine [ ] . current and evolving telecommunication technologies play a key role in exchange of valid information for diagnosis and management of diseases and injuries. the main modalities for remote consultations include telephone consultations, virtual fracture clinics and video consultations [ , , ] . these innovations are going to be main-stay in how we deliver health care in the future. . . face to face consultation is common in india and has and has its own drawback. recently telemedicine or delivery of health care services using information or the indian medical association has adopted the necessary regulatory frameworks for supporting wide adoption of telemedicine and issued an advisory for its use in few situations. when the pandemic will end, doctors will prefer to see patients directly, but at the same time due to increased experience in tele-medicine will help them to see patient if they skip the doctors' visits. there is a myriad of medical conditions that are self-limiting. e.g. traditionally orthopaedic doctors have been receiving referrals before the pandemic and had to counsel patients regarding these conditions (e.g. patellar tendinitis, ganglion swellings) [ ] . during the pandemic, patients with those conditions were given advices over the phone and guided to online resources by which they were satisfied. we believe patients with those conditions would benefit from the education and positive message that can be provided by accessing designated online websites and online physiotherapy services. this saves plenty of consultation time and help offload our health care systems and outpatient services teaching is a mandatory part of medical training in all specialities. different online applications have been used to continue delivering teaching sessions to trainees at variable levels. this has proven to be more convenient, flexible and bringing education. also, this has given us the chance to meeting international interesting people and gain real world skills at our homes. smartphone technology allows conferences, seminars, workshops, and other forms of online teachings [ , , ] . webcams captured hospital rounds; d images replaced cadavers, zoom classes, virtual simulators, webcasting, online chatrooms, virtual dissection, e-anatomy with virtual reality [ , , ] . the global lockdown during this pandemic has given a unique opportunity to the researchers and clinicians to complete their pending paper publications and research works. there have been an unprecedented number of publications during the peak of the covid- pandemic across all the medical journals of the world [ ]. this positive trend might continue in future and help the healthcare industry to benefit from these research and innovations, including finding effective means of dealing with the future epidemics and pandemics. human crisis like covid- pandemic has also offered some unique opportunities for the healthcare sector. it has allowed us to revisit the healthcare delivery. rationalizing and optimizing the available resources during such crisis are some of the most import lessons learnt from this crisis. although, there has been severe disruption in the healthcare delivery during this time globally, but several positives have also come out of it viz., the effective use of telemedicine, importance of personal hygiene, and the importance of infection control. the virtual means of teaching, educating, and sharing knowledge has now become popular and acceptable. the research and publications have also seen a significant rise during these difficult times. clinical features of patients infected with novel coronavirus in wuhan, china. lancet clinical course and outcomes of critically ill patients with sars-cov- pneumonia in wuhan, china: a single-centered, retrospective, observational study world health organization. coronavirus disease (covid- ) advice for the public effects of covid pandemic in daily life world economic forum. the economic, geopolitical and health impacts of covid- the bmj today: the versatility of medical careers guidance on supply and use of ppe health workers are the frontline soldiers against covid- . let's protect them | africa renewal attend anywhere covid- and remote consulting strategies in managing trauma and orthopaedics telemedicine for diabetes care in india during covid pandemic and national lockdown period: guidelines for physicians roadblock in application of telemedicine for diabetes management in india during covid pandemic covid- and applications of smartphone technology in the current pandemic augmenting critical care capacity in a disaster challenges and solutions in meeting up the urgent requirement of ventilators for covid- patients gaps in india's preparedness for covid- control india under covid- lockdown government of india. transforming india a brief guide to telephone medical consultation adopting and sustaining a virtual fracture clinic model in the district hospital setting: a quality improvement approach government of india. esanjeevani. an integrated telemedicine solution jumping off the merry-go-round twelve tips for rapidly migrating to online learning during the covid- pandemic do not neglect the children: considerations integrated virtual and cadaveric dissection laboratories enhance first year medical students' anatomy experience: a pilot study key: cord- -pd r cp authors: singh, omvir; bhardwaj, pankaj; kumar, dinesh title: association between climatic variables and covid- pandemic in national capital territory of delhi, india date: - - journal: environ dev sustain doi: . /s - - - sha: doc_id: cord_uid: pd r cp globally, since the end of december , coronavirus disease (covid- ) has been recognized as a severe infectious disease. therefore, this study has been attempted to examine the linkage between climatic variables and covid- particularly in national capital territory of delhi (nct of delhi), india. for this, daily data of covid- has been used for the period march to june , , ( days). eight climatic variables such as maximum, minimum and mean temperature (°c), relative humidity (%), bright sunshine hours, wind speed (km/h), evaporation (mm), and rainfall (mm) have been analyzed in relation to covid- . to study the relationship among different climatic variables and covid- spread, karl pearson’s correlation analysis has been performed. the mann–kendall method and sen’s slope estimator have been used to detect the direction and magnitude of covid- trends, respectively. the results have shown that out of eight selected climatic variables, six variables, viz. maximum temperature, minimum temperature, mean temperature, relative humidity, evaporation, and wind speed are positively associated with coronavirus disease cases (statistically significant at and % confidence levels). no association of coronavirus disease has been found with bright sunshine hours and rainfall. besides, covid- cases and deaths have shown increasing trends, significant at % confidence level. the results of this study suggest that climatic conditions in nct of delhi are favorable for covid- and the disease may spread further with the increasing temperature, relative humidity, evaporation and wind speed. this is the only study which has presented the analysis of covid- spread in relation to several climatic variables for the most densely populated and rapidly growing city of india. thus, considering the results obtained, effective policies and actions are necessary especially by identifying the areas where the spread rate is increasing rapidly in this megacity. the prevention and protection measures should be adopted aiming at to reduce the further transmission of disease in the city. ; wu et al. ) . overall, the scientific community and people have a belief that an increase in temperature and humidity will reduce the number of covid- cases. india with its . billion population is highly overpopulated and is constantly at high risk due to covid- pandemic outbreaks (minhas ) . as of july , , india, after usa, and brazil have the maximum covid- pandemic confirmed cases in the world in the wake of striking its first case on january , (who ). according to ministry of health and family welfare, india have confirmed a total of , , cases, , , recoveries, and , deaths all over india till july , , with an increase of over , confirmed new cases per day. besides, suicides among people on account of unwarranted panic of contacting and touching with coronavirus-infected patients have been recorded (goyal et al. ). till july , , maharashtra has the largest number of confirmed cases ( , , ) accompanied by tamil nadu ( , , ) and national capital territory of delhi (nct of delhi) ( , ) . further, the disease has been reported in majority of districts in the country, though initially the degree of spread is small than other nations but currently showing the signs of community spread at several locations. apart from the above, several researchers have focused on covid- pandemic in relation to climatic variables in india (das et al. ; dimri et al. ; ghosh et al. ; gupta and pradhan ; gupta et al. a, b; meraj et al. ; roy ; vinoj et al. ) . however, most of the studies have used short period of data and provided the association of covid- with two variables, i.e., temperature and humidity. in india, so far, no comprehensive academic study has been reported, which can guide researchers and policy makers about the influences of climatic conditions on the extension of covid- pandemic in the megacities. therefore, to fill this research gap, this study has been attempted to provide scientific evidences regarding the spread of covid- -infected cases in relation to various climatic variables over nct of delhi, a megacity in india. the present study has utilized the -month-long period data from march to june , ( days) . this is the only study which has presented the analysis of covid- pandemic in relation to several climatic variables for the most densely populated and rapidly growing city of india. the study will provide a holistic insight to researchers, academicians and health policy makers to study the relationship of covid- in relation to several climatic variables. the findings of this study will also provide a base for future studies regarding climatic variables and covid- pandemic transmission over other megacities of india located in tropical and sub-tropical zones. the study area, nct of delhi, extends between ° ′ e to ° ′ e longitudes and ° ′ n to ° ′ n latitudes and covers an area of approximately km (fig. ) . being the national capital territory, it is among the vital centers for business, industries and commerce in north india. it is also known as the legislative and second economic metropolis of the country. it is the largest urban agglomeration of the country with a population of about . million. according to the census of india , the density of population of nct of delhi is , persons/km , which is highest in the country. the decadal growth rate of population has been found about %. delhi has been growing by approximately persons every day for a number of years. further, migration is approximately . times of the natural growth in nct of delhi (singh and shukla ) . the urban population is approximately . % of the total population. the average annual growth rate of urban population is about . % (goi ). overall, its growth is higher than growth rate of other cities in india. apart from this, the nct of delhi is characterized by continental climate with warm and dry summers, and cold and dry winters. during summers, the maximum temperature reaches up to °c, whereas during winters, it drops to about °c (kumar et al. ) . monsoon season (june-september) accounts approximately % of total annual rainfall in the city (perrino et al. ) . for this study, daily data between march to june , , ( days) with respect to prevalence of covid- pandemic corresponding to nct of delhi has been retrieved from a source openly accessible through the https ://www.covid ind ia.org/link, as this dataset provides the detailed information of covid- without any gap for the study period. in this study, the initial date, i.e., march , , has been chosen because nct of delhi has been identified for its first confirmed covid- pandemic case on this day. the covid- pandemic data on the website are preserved and maintained by a group of volunteers and can be downloaded free of cost. the volunteers have extracted and homogenized the covid- pandemic statistics from various internet references associated both with government and independent organizations. the dataset has comprised of the diurnal occurrence of covid- pandemic confirmed cases, active cases, deceased and test conducted. however, in this study, total confirmed cases and deceased data has been considered as the values of these two variables have been found consistent throughout the study period. apart from the covid- pandemic transmission data, the daily climatic data with respect to eight selected climatic variables for the same period (march to june , ) have been procured from the bona fide internet site of icar-indian agricultural research institute, new delhi (www.iari.res.in). in the present study, the selected climatic variables have consisted of maximum, minimum and mean temperature (°c), relative humidity (%), bright sunshine hours, wind speed (km/h), evaporation (mm) and rainfall (mm). the climatic variables data has been found consistent without any gap during the study period. the collected data have been analyzed by using microsoft excel spreadsheet and presented in tabular form and graphs. the values of various covid- confirmed cases and deceased have been found highly dynamic and changed rapidly every day. thus, the data has also been analyzed separately for days intervals. the monthly averages of different climatic variables have been computed by using their daily values from march to june , . recently, correlation analysis has been extensively used to associate covid- pandemic confirmed cases with climatic variables (bashir et al. ; ma et al. ; prata et al. ) . therefore, to study the relationship among different climatic variables and covid- pandemic confirmed cases, karl pearson's correlation analysis has been performed by employing the statistical package for the social sciences. the nonparametric mann-kendall test (mann ; kendall ) has been applied to detect the trends in the daily data of covid- . the magnitude of trends has been estimated by sen's slope estimator (sen ). the presence of statistically significance has been considered at and % level of confidence. figure exhibits the daily count of covid- pandemic confirmed victims and deceased persons along with their cumulative numbers. the figure displays that the covid- pandemic cases has been very less up to march in nct of delhi. however, from march , , a sharp rise in the count of covid- pandemic patients has been witnessed. to represent a comprehensive picture of covid- pandemic spread, the -day study period (march -june , ) has been divided into periods of days each. during march - , march to april , april - , april to may , may - , and may to june , a total of , , , , , and , covid- pandemic cases (total , ) have been reported in the city, respectively. only during may to june , , approximately % confirmed cases and % deceased cases have been reported. also, the cumulative number of deceased persons has been increasing rapidly in the nct of delhi. the results of trend test have shown significant increasing trends in the covid- cases and deaths, significant at % confidence level. moreover, fig. exhibits the daily pattern of climatic variables during days period from march to june , , over nct of delhi. a rise in temperature (maximum, minimum, and mean), relative humidity, and evaporation has been observed from march to june , , in nct of delhi. also, wind speed has shown slight increase with large fluctuations. bright sunshine hours have shown almost constant pattern, whereas almost negligible rainfall has been experienced during this period. during -day period, the mean temperature has been recorded as . °c (lowest mean temperature . °c and highest mean temperature . °c), mean maximum temperature has been . °c (lowest maximum temperature °c and highest maximum temperature . °c) and mean minimum temperature has been experienced as . °c (lowest minimum temperature . °c and highest minimum temperature . °c). the mean relative humidity has been observed to be . % (maximum . % and minimum . %). the mean bright sunshine has been recorded as . h (maximum . h and minimum, . h), whereas the mean evaporation has been . mm (highest . mm and lowest . mm). the mean wind speed has been measured as . km/h (maximum . km/h and minimum . km/h). similarly, the mean rainfall has been gauged to the tune of . mm (maximum . mm and minimum mm). the association among selected climatic variables and covid- pandemic cases has been demonstrated in fig. and table . a strong positive relationship of maximum temperature, minimum temperature and mean temperature with the count of covid- pandemic confirmed victims and deceased persons (significant at % confidence level) has been witnessed. it indicates that the count of covid- pandemic confirmed patients and deaths have increased with increasing temperature in nct of delhi. these results are in agreement with gupta and pradhan ( ) , who have observed that the covid- cases are likely to increase with increasing air temperature in india; however, the role of humidity is not clear. gupta et al. ( b) have examined the climatic records of air temperature, rainfall, actual evapotranspiration, solar radiation, specific humidity, wind speed with topographic altitude and population density and suggests that comparatively hot and dry regions in lower altitude of the indian territory are more prone to the infection by covid- transmission. tosepu et al. ( ) have also shown a significant positive association among covid- pandemic victims and mean temperature in jakarta, indonesia. bashir et al. ( ) have observed a noteworthy positive correlation of mean and minimum temperature with covid- pandemic cases in new york city of usa. interestingly, the results of present study have been found consistent with tosepu et al. ( ) and bashir et al. ( ) . benedetti et al. ( ) have not found a significant correlation between average monthly high temperatures and number of deaths per million people in the month of march. however, a statistically significant inverse correlation has been observed in the month of april between average monthly high temperatures (p = . ) and latitude (p = . ) with number of deaths per million people. they have also observed a statistically significant correlation between population density and number of deaths per million people. prata et al. ( ) have shown a negative association among the temperature and covid- pandemic confirmed victims in tropical cities of brazil. several other studies have also shown a negative link within covid- cases and temperature for different parts in the world (sahin ; núñez-delgado ; zhu and xie ). apart from the above, a positive correlation has been observed between relative humidity and covid- pandemic confirmed cases and deceased (table ) . these results are not consistent with gupta et al. ( a) , who have witnessed the maximum transmission of confirmed covid- pandemic cases within the states having wet and extremely wet climatic conditions. however, oliveiros et al. ( ) have discovered a significant affirmative relation between covid- pandemic spread and temperature, although a negative relationship has been identified with humidity in china. in addition, sahin ( ) has shown an inconsistent negative relationship among humidity and covid- pandemic transmission in turkey. bashir et al. ( ) have shown a non-significant negative correlation among humidity and covid- pandemic confirmed cases for new york city of usa. ma et al. ( ) have reported a negative relation among humidity and covid- pandemic victims in wuhan region of china. also, a positive correlation among the evaporation and count of covid- pandemic confirmed victims and deceased has been observed over nct of delhi. further, a positive correlation has been witnessed among covid- pandemic confirmed and deceased cases with wind speed. however, the value of correlation has been found weak (table ) . similarly, sahin ( ) has shown that the count of covid- pandemic victims surges with an increase in wind speed in turkey. islam et al. ( ) have shown inverse relationship of covid- incidences with the temperature, humidity and wind speed world over. adhikari and yin ( ) have found that cloud cover, precipitation, and wind data are significantly associated with one-day lagged covid- confirmed cases in queens, new york. contrastingly, bashir et al. ( ) and oliveiros et al. ( ) have not observed any correlation of covid- pandemic spread with wind speed in china. abdollahi and rahbaralam ( ) have also witnessed a weak correlation of wind speed with covid- in spain. again, rainfall has not been found associated with covid- pandemic spread in nct of delhi (table ) , which has been found consistent with the results reported by tosepu et al. ( ) . raina et al. ( ) have shown that the countries with higher number of cases have cold weather. these are also the countries with low humidity which could be favoring the transmission and survival of covid- . the bright sunshine hours have not shown any association with the covid- pandemic spread in nct of delhi. likewise, asyary and veruswati ( ) have not observed any noticeable trend of sunlight exposure with the transmission rate, but reported a significant recovery rate under sunlight exposure in indonesia. gupta et al. ( b) have shown a significant positive correlation between high solar radiations during daytime and covid- transmission in india. interestingly, wang et al. ( b) and araujo and naimi ( ) have reported a lower survival rate of covid- at higher temperatures and humidity. middle east respiratory syndrome-related coronavirus cases have also shown an increase with high temperatures, coupled with high ultraviolet index, low wind speeds, and low relative humidity (altamimi et al. ). harmooshi et al. ( ) have observed that the covid- can survive for up to days at °c, and if this temperature rises to °c, its lifespan will be shorter. likewise, the covid- is sensitive to humidity, and lifespan of viruses in % humidity is longer than that of %. bu et al. ( ) have concluded that a temperature range of - °c and humidity of - % are suitable for the survival and transmission of covid- . yuan et al. ( ) have presented a comprehensive review on the impact of temperature and humidity on the transmission of covid- . ujiie et al. ( ) have observed higher infectivity of covid- pandemic patients during the winter season in japan. iqbal et al. ( ) have shown that most of the countries located in the relatively lower temperature region have shown a rapid increase in the covid- cases than the countries located in the warmer climatic regions despite their better socioeconomic conditions. they identified that the regional meteorological parameters (aerosols, maximum and minimum temperature, day length, etc.) are among the contributors to the fast spread of coronavirus over most countries of the world. shahzad et al. ( ) have witnessed that the increase in average temperature and bad air quality have significantly enhanced the covid- new cases in all regions of spain. interestingly, yao et al. ( ) have not shown any relationship between transmission of covid- pandemic cases and temperature in chinese cities. ahmadi et al. ( ) have performed the sensitivity analysis and shown a direct relationship with the infection outbreak with population density, intraprovincial movement, whereas the areas with low values of wind speed, humidity, and solar radiation exposure to a high rate of infection that support the virus's survival. the correlation has disapproved their initial hypothesis that the extensive spread of covid- may be limited by temperature and humidity. additionally, xie and li ( ) have found a positive correlation of population density and old-age people ( +) with both the infection and mortality rates of covid- in usa. moreover, the counties that are percentage of rural, farm-dependent, or miningdependent population have high mortality rate of covid- , which may be attributed to the poor preparedness and medical systems in rural areas for the covid- infection. this finding should be alarming since rural areas have limited medical resources to respond to this pandemic and treat covid- patients. vardavas and nikitara ( ) and liu et al. a, b have found a negative association between percentage of smokers with the infection rate of covid- . however, other studies showed that smoking could worsen the health outcomes of covid- patients (vardavas and nikitara ; liu et al. a, b) . sarmadi et al. ( ) have shown the higher covid- cases and deaths rate per lakh population over the northern areas of the globe, including some parts of north america and approximately the entire asia and europe which are located in higher latitudes and have a colder climate and better socioeconomic conditions. the higher rates of covid- cases and deaths over these areas could be related to the availability of diagnostics kits and health care facilities (bi et al. ). in addition, both colder climate and more densely populated areas could contribute to the spread of the disease in european and asian megacities (xie and zhu ; sajadi et al. ) . sannigrahi et al. ( ) have found a heterogeneous distribution of the covid- confirmed cases and deaths across europe. this uneven distribution could be attributed to many corresponding factors, including demography, climatic, cultural, or socio-economic differences among the countries. for both covid- cases and deaths, the maximum records (actual values) have documented in the western european region (spain, italy, france, germany, uk, belgium, the netherlands). the cases and deaths have been found lower (actual values) in the eastern (romania, bulgaria, greece, estonia, latvia, lithuania) and northern european region (norway, finland, sweden) . this can be attributed to the sociodemographic composition of these countries as italy has the second oldest population ( %) in the world and the oldest in europe (population ages and above). a study on covid- patients from china and other countries showed that the older age group (above years) had significantly higher death rate than the younger age group (below years) (verity et al. ). mahajan and kaushal ( ) have noticed that among all confirmed cases, about % cases are of - age (median age of indian covid- patients is ) which is working age in india and % cases are reported for men. ghosh et al. ( ) have observed that the major covid- outbreak clusters are located in western and northern india and they are associated with major cities. besides, approximately % people sustain their life in slum area in india, and they have no option to maintain social distancing rule due to their unhygienic and congested ambience. manzak and manzak ( ) have observed that the counties having high percentage of african american black populations show a high infection rate and high mortality in usa. remarkably, the temperature, hours of sunshine, and white population percentage has a non-significant negative correlation with covid- . das et al. ( ) have highlighted that the risks of covid- tend to be higher in areas with low socioeconomic status over the northeastern part of chennai megacity. bhopal and bhopal ( ) have examined the sex differential in the covid- mortality and found that the male to female mortality sex ratio is . per , , population over northwestern europe, however, ratio is not equal at all ages. in the present study, an attempt has been made to examine the association between climatic conditions and covid- pandemic transmission victims over nct of delhi. the daily data of covid- and eight climatic variables such as maximum, minimum and mean temperature, relative humidity, bright sunshine hours, wind speed, evaporation, and rainfall have been analyzed for the period march to june , ( days). to study the relationship among different climatic variables and covid- , karl pearson's correlation analysis has been performed. the mann-kendall method and sen's slope estimator have been used to detect the direction and magnitude of covid- trends, respectively. the analyses have shown that the covid- is significantly associated with the climatic variables over the nct of delhi. the covid- pandemic spread is positively related with the maximum temperature, minimum temperature and mean temperature, relative humidity, evaporation and wind speed. no link amid bright sunshine hours and rainfall has been witnessed with the covid- pandemic spread in nct of delhi. apart from this, covid- cases and deaths have shown increasing trends, significant at % confidence level. the finding of this study may represent the impact of climatic variables on the highdensity cities located in a warmer tropical climate. this study will also provide a base for other studies regarding climatic variables and covid- pandemic transmission over other megacities of india located in subtropical zone. these results may be useful for researchers and health policy-makers. despite this, the current study may have some limitations. for example, these results are based on only one city. also, a sharp increase in count of covid- pandemic confirmed patients may be anomalously due to an increase in number of tests conducted during the last days of this study than the initial outbreak of pandemic in nct of delhi (fig. ) . also, this study has not considered the non-climatic factors such as density of population, population by age-group, sociocultural factors, movement of people, urban-rural settings, gender, education and economic level, lifestyles and the size of household. these factors can help to transmit this disease. therefore, further studies are needed on these shortcomings. effect of temperature on the transmission of covid- : a machine learning case study in spain short-term effects of ambient ozone, pm . , and meteorological factors on covid- confirmed cases and deaths in queens investigation of effective climatology parameters on covid- outbreak in iran spread of sars-cov- coronavirus likely to be constrained by climate sunlight exposure increased covid- recovery rates: a study in the central pandemic area of indonesia preliminary evidence that higher temperatures are associated with lower incidence of covid- , for cases reported globally up to th correlation between climate indicators and covid- pandemic inverse correlation between average monthly high temperatures and covid- -related death rates in different geographical areas sex differential in covid- mortality varies markedly by age. the lancet epidemiology and transmission of covid- in cases and of their close contacts in shenzhen, china: a retrospective cohort study. the lancet infectious diseases a spatio-temporal analysis for exploring the effect of temperature on covid- early evolution in spain analysis of meteorological conditions and prediction of epidemic trend of -ncov infection in urbanization and humidity shape the intensity of influenza epidemics in u.s cities modeling the effect of area deprivation on covid- incidences: a study of chennai megacity understanding trend of the covid- fatalities in india inter-state transmission potential and vulnerability of covid- in india the great lockdown: worst economic downturn since the great depression fear of covid : first suicide case in india significance of geographical factors to the covid- outbreak in india. modeling earth system and environment impact of daily weather on covid- outbreak in india effect of weather on covid- spread in the us: a prediction model for india in environmental concern regarding the effect of humidity and temperature on -ncov survival: fact or fiction. environmental science and pollution research the effects of regional climatic condition on the spread of covid- at global scale temperature, humidity, and wind speed are associated with lower covid- incidence rank correlation methods the influence of odd-even car trial on fine and coarse particles in delhi analysis of factors associated with disease outcomes in hospitalized patients with novel coronavirus disease impact of meteorological factors on the covid- transmission: a multi-city study in china effects of temperature variation and humidity on the death of covid- in wuhan epidemic trend of covid- transmission in india during lockdown- phase nonparametric tests against trend analysis of environmental, economic, and demographic factors affecting covid- transmission and associated deaths in the usa coronavirus pandemic versus temperature in the context of indian subcontinent: a preliminary statistical analysis. environment, development and sustainability could india be the origin of next covid- like epidemic? what do we know about the sars-cov- coronavirus in the environment? role of temperature and humidity in the modulation of the doubling time of covid- cases chemical characterization of atmospheric pm in delhi, india, during different periods of the year including diwali festival temperature significantly changes covid- transmission in (sub) tropical cities of brazil does temperature and humidity influence the spread of covid- ? a preliminary report temperature and covid- : india impact of weather on covid- pandemic in turkey temperature and latitude analysis to predict potential spread and seasonality for covid- examining the association between socio-demographic composition and covid- fatalities in the european region using spatial regression approach association of covid- global distribution and environmental and demographic factors a proposal for isotherm world maps to forecast the seasonal evolution of the sars-cov- pandemic estimates of the regression coefficient based on kendall's tau effects of climatological parameters on the outbreak spread of covid- in highly affected regions of spain impact of temperature on the dynamics of the covid- outbreak in china profiling "informal city" of delhi. policies, norms, institutions & scope of intervention. wateraid india and delhi slum dwellers federation correlation between weather and covid- pandemic in jakarta effect of temperature on the infectivity of covid- covid- and smoking: a systematic review of the evidence estimates of the severity of coronavirus disease : a model-based analysis the covid- spread in india and its dependence on temperature and relative humidity temperature significant change covid- transmission in cities high temperature and high humidity reduce the transmission of covid- coronavirus disease: what you need to know? effects of temperature and humidity on the daily new cases and new deaths of covid- in countries health and demographic impact on covid- infection and mortality in us counties association between ambient temperature and covid- infection in cities from china no association of covid- transmission with temperature or uv radiation in chinese cities do humidity and temperature impact the spread of the novel coronavirus? frontiers in public health a novel coronavirus from patients with pneumonia in china the authors sincerely thank both the data sources for giving access to relevant data which has been used in this research. the authors sincerely thank the anonymous reviewers for critical comments and constructive suggestions, which improved the overall quality of the manuscript. conflict of interest we have no conflicts of interest to disclose. key: cord- -jowb kfc authors: ganesh, ragul; singh, swarndeep; mishra, rajan; sagar, rajesh title: the quality of online media reporting of celebrity suicide in india and its association with subsequent online suicide-related search behaviour among general population: an infodemiology study date: - - journal: asian j psychiatr doi: . /j.ajp. . sha: doc_id: cord_uid: jowb kfc the literature reports increased suicide rates among general population in the weeks following the celebrity suicide, known as the werther effect. the world health organization (who) has developed guidelines for responsible media reporting of suicide. the present study aimed to assess the quality of online media reporting of a recent celebrity suicide in india and its impact on the online suicide related search behaviour of the population. a total of online media reports about sushant singh rajput’s suicide published between (th) to (th) june, were assessed for quality of reporting following the checklist prepared using the who guidelines. further, we examined the change in online suicide-seeking and help-seeking search behaviour of the population following celebrity suicide for the month of june using selected keywords. in terms of potentially harmful media reportage, . % of online reports violated at least one who media reporting guideline. in terms of potentially helpful media reportage, only % articles provided information about where to seek help for suicidal thoughts or ideation. there was a significant increase in online suicide-seeking (u = . , p < . ) and help-seeking (u = . , p < . ) behaviour after the reference event, when compared to baseline. however, the online peak search interest for suicide-seeking was greater than help-seeking. this provides support for a strong werther effect, possibly associated with poor quality of media reporting of celebrity suicide. there is an urgent need for taking steps to improve the quality of media reporting of suicide in india. suicide is a major public health problem, and is one of the leading causes of mortality globally (naghavi, ) . the reported deaths due to suicide in india is highest among countries worldwide (dandona et al., ) . studies have reported that media reports of celebrity suicide stimulate imitation acts in vulnerable population (gould et al., ) . also, repeated insensible media coverage may act as a source of misinformation that suicide is an acceptable solution to ongoing difficulties in life. this has been supported by the bulk of available literature, with a recent meta-analysis reporting a % increased risk of suicide ( % confidence interval of - %; median follow-up duration of days) in the period following the media report of celebrity suicide death (niederkrotenthaler et al., ) . media reporting of suicide is a double-edged sword, with inappropriate and sensational reporting of suicide news leading to copycat phenomenon or werther effect. whereas, sensible media reporting of suicide along with media involvement in spreading preventive information shown to minimise copycat eff ects, and has been shown to be eff ective in reducing suicide deaths (cheng et al., ) . thus, researchers have advocated for a more responsible descriptive reporting of suicide news, with emphasis on sharing preventive information related to suicide. this includes reporting upon how people could adopt alternative coping strategies to deal with life stresses or depressed mood along with sharing links of educative websites or suicide helplines; and has been shown to be associated with decreased suicide suicidal behaviour and ideation in vulnerable population (niederkrotenthaler et al., ; till et al., ) . therefore, media reporting of suicide-related preventive information has been associated with positive effects on subsequent suicide rates and ideation. this is described as the papageno effect, and acts as a counterforce to the werther effect responsible media reporting of suicide is considered as the best available strategy to counter the harmful effects of media reportage (niederkrotenthaler et al., ) . in recent years, internet is being increasingly used by the public for seeking health-related information; and information related to mental health related disorders or problems also being widely available online (amante et al., ) . it is understandable, that several researchers have expressed concerns about vulnerable individuals either using internet to access pro-suicide information (e.g. methods of suicide) or inadvertently being exposed to online news or information which negatively affects their thoughts or mood and promote suicidal behaviours in them (arendt and scherr, ; till and niederkrotenthaler, ) . however, internet also provides a host of suicide prevention related information and resources which could in turn decrease the risk of suicide (biddle et al., ) . further, news over internet and social media is able to reach to a large number of vulnerable and difficult to reach youth population; and has been shown to potentially influence the public opinion, attitudes, and behaviours over wide range of topics (kaplan and haenlein, ) . thus, it is important to explore the quality of online media reporting of celebrity suicide in india. this would in turn help in better understanding the role played by this new electronic medium in either predisposing or protecting people with suicidal ideas or death wishes. there has been limited literature available assessing the quality of media reporting of suicide in india. most of the studies assessed media reporting of suicide in general population, and only one study had focused on celebrity suicide specifically (harshe et al., ) . however, that study took death of robin williams (hollywood movie actor of us origin) as the reference event and was done about four years back. further, all the available studies have assessed newspapers in a particular region and were conducted prior to press council of india (pci) issuing media reporting guidelines on suicide and mental illness in india. the pci has adopted the guidelines of world health organization (who) report on preventing suicide (press council of india, ). it forbids undue repetition of stories, placing stories in prominent positions, explicit description of the suicide method, providing details about the suicide location, using sensational headlines and reporting photographs of the person. there might be some change in the quality of media reporting of suicide in recent years, more specifically after the pci guidelines. further, the who guidelines for responsible reporting are valid for all types of media, and it is important to explore the role played by the online media in current digital world. moreover, to the best of our knowledge there has been no study from indian context yet exploring the association between media reporting of death of celebrity by suicide and subsequent suicidal behaviour in the general population. the official figures for deaths due to suicide in india is released by the national crimes record bureau (ncrb) in india. however, the ncrb has stopped releasing this data since and the official suicide statistics have not been made public till now. further, it is usually available at the end of the year and does not provide data on a weekly basis. moreover, any other system of directly recording suicide statistics in india will face the challenges associated with collecting vital statistics through sub-optimal existing vital registration system, misclassification, and under-reporting of suicide deaths due to associated legal complications and social stigma around suicide death in the family . additionally, the restrictions imposed on movement of people and social distancing guidelines to be followed during the current covid- pandemic, makes it even more difficult to access the study population in a systematic manner for assessment of suicide risk using traditional research methods (bidarbakhtnia, ) . the above described limitations could be addressed by employing research methods and techniques involving the study of internet-based search behaviours and social media content. infodemiology has been defined as "the science of distribution and determinants of information in an electronic medium, specifically the internet, or in a population, with the ultimate aim to inform public health and public policy" (eysenbach, ) . google trends is an analytical tool available for tracking the online search interests of the population. the evidence supporting correlation between increased online search interest for particular suicide-related search queries using google search engine and the actual number of suicides in that region during that particular time-period has been increasing over the past two decades (lee, ) . moreover, recent studies have shown that data obtained using google trends for suicide-seeking keywords could be used for predicting actual monthly suicide numbers at the country level (kristoufek et al., ) . thus, in the present study we monitored the changes in internet search volumes for keywords representing suicide-seeking and help-seeking behaviours using the google trends platform as a proxy marker to assess the impact of recent celebrity suicide in india. sushant singh rajput (ssr) was a much-loved indian actor who died by suicide on june , . this was reported by various national and international media, and was considered as the reference event in this study. thus, the present study aimed to assess the quality of online media reporting of a celebrity suicide in india, and evaluate its adherence with the who guidelines for responsible media reporting of suicide. further, we aimed to examine the change in internet search volumes for keywords representing suicide-seeking and help-seeking behaviours of the population immediately following the celebrity suicide. this would provide indirect evidence for either existence or absence of the werther and the papageno effect at the population level in india. the online media reports related to the theme of death of ssr by suicide on th june were retrieved using the google news online platform (https://news.google.com). the search was conducted on th june, in the tor browser, using search terms "sushant", "singh", "rajput", "died", "death" and "suicide". the search period was restricted between to june, . this corresponded to first week immediately after the reference event. a total of reports published on various international, national, and regional online news and entertainment media portals were retrieved. fourteen of them contained either only videos or were not related to theme of the present study, and were excluded. thus, a total of articles were selected for further analysis. the news headlines were analysed to generate a word cloud (using a word cloud generator available at https://www.wordclouds.com) representing the commonly used terms in the online media reports covering ssr death. two authors independently reviewed and extracted information related to different news report characteristics using a pre-designed format in microsoft excel. it included information pertaining to descriptive characteristics of the news report such as the date of publishing, name of the news publisher, type media agency, and primary focus of the article being descriptive or commentary. the quality of articles was evaluated using a checklist prepared on the basis of who j o u r n a l p r e -p r o o f responsible media reporting of suicide guidelines (see supplementary table ) , and is similar to that used in previous studies . the items were coded as " " if the guideline was violated and " " if the guideline was adhered to in the report. two trained researchers independently reviewed and extracted information following the above described procedure. any discrepancy or disagreement between the two researchers was resolved by consensus. the third author was consulted if needed. the data were analysed using spss version . (ibm corp, armonk, ny). the descriptive (frequency and percentage) and inferential statistics (chi-square and fishers' exact test) were conducted. a p-value of less than . was considered significant for all tests. the google trends utilizes an algorithm to give normalized relative search volume (rsv) for the keyword(s) searched for a specified geographical region and time period. the rsv represents how frequently a given search query has been searched on the google search engine, compared to the total number/volume of google searches conducted in the same geographical region over the selected time period. the rsv values range from zero (representing very low search volumes) to (peak search volume for that query). google trend analysis was conducted to evaluate the online search interest for keywords representing suicide-seeking and help-seeking behaviours of the population for the month of june . the initial list was made based on the review of available literature, which was finalized by the process of consensus building between two authors r.g. and s.s (qualified psychiatrists with clinical and research experience of working with people with mental illness and suicidal ideas/attempts) based on the face validity of search terms. the examples of suicide-seeking keywords included in the study were 'commit suicide', 'suicide method', and 'kill myself'. whereas, the helpseeking keywords such as 'suicide help', 'suicide treatment', and 'psychiatrist' were used. the four google trends options of region, time, category, and search type were specified as india, from june to june , all categories, and web search in the present study. the "plus" (+) function from google trends was used to integrate the search volume (rsv) of all suicide-seeking terms and help-seeking keywords. a graph showing daily variation in rsv for suicide-seeking and helpseeking keywords was constructed. the change in mean rsv value for the suicide-seeking and helpseeking keywords after the reference event, when compared to baseline was analysed by applying the mann whitney-u test. the complete list of keywords used in this study along with other details pertaining to the google trends methodology are described in supplementary table . the information used in this study involved published online media reports and data related to the volume of anonymized web searches made during a given time period, both of which were freely available in the public domain. further, no patient or participant was approached directly in this study. thus, no written ethical permission was required from the ethics committee. the frequency of different words used in the headlines of the media reports analysed in the present study were depicted as a word cloud, with the size of font used being representative of its frequency (figure ) . apart from the words in the name of ssr, the most commonly used words were "suicide", "death", "actor", "police", "bollywood", "mumbai", "rhea", and "kapoor" in decreasing order of frequency. this suggested that a significant proportion of headlines used words like suicide, police or bollywood to sensationalize or glamourize the headlines, with no significant difference between news media ( . %; / ) and entertainment media ( . %; / ) headlines (χ = . , p= . ). the term "suicide" was used with similar frequency in both news media (n= ; . %) and entertainment media (n= ; %) headlines. only two news media reports (n= ; . %) mentioned 'hanging' term in the headlines. the location of suicide was mentioned in two news media ( . %) and two ( . %) entertainment media headlines. the selected media reports were published from various media platforms: international news group, % (n= ); national news group, . % (n= ); regional news group, . % (n= ); and entertainment blogs, % (n= ). seventeen news media platforms had reported the story four or more times in the immediate one-week period following the ssr suicide, with hindustan times ( ), ndtv ( ), republic world ( ), times of india ( ), dna ( ), india tv ( ), the indian express ( ) and times now ( ) contributing to . % (n= / ) of the articles. around % (n= ) articles were published on th june, , while . % of articles (n= ) were published on th june, . about . % (n= / ) articles were focussed at direct descriptive reporting of suicide. the descriptive analysis of media reports for different potentially harmful and helpful media report characteristics are described in table and respectively. about . % of reports violated the recommendation provided in the guideline, by including at least one potentially harmful information. there was significant association between the type of news media and the use of sensational language [χ ( )= . (p< . )]. regional and entertainment media used more sensational language compared to national and international media. there was significant association between the type of news media and provision of information about where to seek help [χ ( )= . (p< . )]. mainstream news media provided such information more than entertainment media. final social media posts were shared more by national media compared to international, regional and entertainment media [χ ( )= . (p< . )]. the median and inter-quartile range (iqr) values of rsv for suicide-seeking keywords in the twoweeks before and after the death of ssr on june were (iqr: . - . ) and (iqr: - ) respectively. whereas, the median and iqr values of rsv for suicide-seeking keywords in the two-weeks before and after the death of ssr were ( - . ) and ( - ) respectively. there was a significant increase in rsv for suicide-seeking (u= . ; z= - . ; p< . ) and help-seeking (u= . ; z=- . ; p< . ) keywords after the reference event, when compared to baseline. however, the online peak search volume and search interest for suicide-seeking was greater than help-seeking as shown in figure . the present study analysed the online media reports related to the theme of a popular bollywood movie actor's suicide, and compared it against the who media reporting guidelines for suicide. the story of this recent celebrity suicide received widespread coverage across different online news platforms, including national and international news agencies. overall, majority of articles showed poor adherence with the who guidelines while reporting the celebrity suicide. the reports had minimal focus on educating the public the regarding suicide. further, the change in online search interest for different keywords related to "suicide-seeking" and "help-seeking" behaviours after this event were analysed to explore for possible werther and papageno effects. a substantial proportion of articles did not follow most of the recommendations. about % articles used sensational language, . % articles mentioned suicide site, % articles suggested possible cause for suicide which was not related to poor mental health. a study assessing the quality of suicide reporting in indian print media found increase in prominence of suicide reports after the celebrity suicide (harshe et al., ) . it speculated that the most likely reason for sensationalism in media reporting of suicide might be to enhance the readership. further, only % articles provided information about where to seek help for suicidal thoughts. a previous study evaluating the newspaper coverage of celebrity suicide in united states against 'mindset' recommendations for reporting suicide, found % articles provided details about suicide method and only % provided information about help-seeking (carmichael and whitley, ) . previous studies from india found minimal adherence to media reporting recommendations for suicide in the print media. menon et al found that the method of suicide was reported in . % articles and locations of suicide was reported in . % articles (menon et al., ) . chandra et al showed that % articles reported suicide location and % suggested monocausality for suicide (chandra et al., ) . the high frequency of harmful reporting characteristics observed in the present study is consistent with the low adherence to who guidelines reported in other neighbouring asian countries as well (s.m. yasir . studies from bangladesh (s. m. yasir , indonesia (nisa et al., ) and sri lanka (brandt sørensen et al., ) have also reported non-adherence to who recommendations in print media such as reporting of suicide method, description of suicide note and inclusion of personal identification characteristics in reports. the headlines of the online reports included in the current study used the term 'suicide' in % articles. previous studies on print media from india reported "suicide" mentioned in headlines of . % articles (chandra et al., ) and . % articles (harshe et al., ) . refreshingly, in the present study . % articles did not use the word 'commit' or related terms while reporting suicide, and . % articles did not mention the suicide method in the reports. this is a welcome improvement in media reportage of suicide, which might be due to the positive effect of pci adopting guidelines on media reporting of suicide in september based on the who guidelines (vijayakumar, ) . however, photograph of the celebrity was provided by . % of news media reports and % of entertainment media reports. publication of photograph of a person with mental illness without the individual's or his/her next of kin's consent in case of suicide violates section ( ) of the mental health care act, in india ("mental healthcare act," ). further, sensational language was used to report celebrity suicide by majority of news media and entertainment media reports. among the news media, regional media used sensational language more frequently than national and international media. final social media posts were reported by . % news media and . % entertainment media. among the different media platforms, national media shared final social media posts more frequently than international, regional and entertainment media. mainstream news media provided information about where to seek help more frequently than entertainment media. this is in line with a study on print media from india, that reported vernacular newspapers to be more compliant with who suicide reporting guidelines compared to english language newspapers (menon et al., ) . moreover, in terms of providing potentially helpful information, only one article provided research findings and population level statistics regarding suicide. only two percent articles included expert opinion from health professionals while reporting suicide. also, . % articles tried to address the link between suicide and poor mental health in the present study. this highlights the need to emphasize the importance of including such information in media reports of suicide among journalists and news editors. it helps in increasing the awareness about mental health problems among the general population and encourage them to seek treatment for the same. a previous study assessing south indian newspapers found that a few articles recognised the link between suicide and psychiatric disorders or substance use disorders (menon et al., ) . similarly, previous studies from india evaluating the reporting of suicides in newspapers found that only few articles tried to educate public about the issue of suicide by including opinion from health professionals, research findings or information about suicide prevention programmes (chandra et al., ; harshe et al., ; menon et al., ) . one possible solution is to have a uniform national suicide reporting guideline for the media of the entire country. a similar approach has been shown to be beneficial in improving the overall quality of media reporting of suicide in australia (pirkis et al., ) . however, as prior researchers have pointed out (vijayakumar, ) , merely framing of guidelines may not help in improving the quality of media reporting of suicide. a continuous collaborative approach involving both mental health experts and media professionals should be adopted to sensitize them about the available research evidence backing these media reporting guidelines has been shown to successful in improving adherence to media reporting guidelines (bohanna and wang, ) . also, there should be regular workshops held for media professionals to provide them with adequate training and support in covering mental health and suicide-related topics. the findings from google trend analysis showed a significant increase in online search interest for terms representing both suicide-seeking and help-seeking behaviours after the ssr death. the surge in internet search volume for suicide-seeking keywords along with media reports of copycat suicides from different parts of india provides evidence of the werther effect (hindustantimes, ; news , , p. ; timesofindia, ) . there are several possible mechanisms described in the literature to explain the observed increase in suicidal behaviour among the general population associated with media reporting of celebrity suicide (niederkrotenthaler et al., ) . first, people may identify with the deceased celebrities, which is usually more common in case of entertainment celebrities due to their strong public identity and following. second, repeated insensible media reporting might lead to normalization of suicide as an acceptable way out of their problems by the vulnerable population. third, media reporting about the method of celebrity suicide might increase the cognitive availability of that method and remove ambivalence about which method to choose for suicide in vulnerable individuals, leading to an increase in suicide by the same method among the vulnerable population. interestingly, there was also smaller but significant increase in the internet search volume for helpseeking keywords. the peak search volume for help-seeking and suicide-seeking keywords was observed on the day of ssr's death, with a lower peak rsv and subsequently lower daily rsvs for help-seeking terms as compared to suicide-seeking terms among the general population. this suggests a weaker papageno effect as compared to the werther effect, possibly due to poor adherence to the who suicide reporting guidelines by the online and other types of media in india while covering the celebrity suicide (newslaundry, ) . there only a few studies that have assessed the fidelity of suicide reporting in india, with almost of the studies having evaluated the quality of media reporting of suicide in general population and included only few print media newspapers. thus, our study provides valuable addition to bridge these gaps in the existing literature on media reporting of celebrity suicide from india. further, a wide range of online media reports were analysed in this study for the first time in indian settings to the best of our knowledge. further, the use of a novel google trends analysis to show an increased online search interest for suicide-seeking keywords immediately after the reference celebrity suicide provided support for the existence of werther effect in the indian context. however, there are certain limitations as well which should be kept in mind while interpreting the findings of this study. the study focussed only on english language media reports. we did not assess print media without online version, television, radio and social media. this might be an important area for future research, since studies from western countries suggest television coverage or social media (e.g. twitter) to be associated with increased suicide rates (jashinsky et al., ) . further, the relationship between people searching for suicide-seeking keywords might not be as clear as that observed for people with certain infectious disease like the influenza, with google trends analysis of data about searching for disease symptoms or other disease-related information being used to predict their incidences or outbreaks prior to the traditional methods of reporting an outbreak (cao et al., ; ginsberg et al., ; zhang et al., ) . this is likely due to the fact that that someone who searched about suicide might not be actually suicidal, and may or may not kill themselves during the specified study period. further, the keywords representing suicide-seeking and help-seeking behaviours were derived from review of literature from western countries mostly followed by consensus amongst the authors based on their face validity. however, the search methodology used for doing the google trends analysis in the present study is in accordance with the guidelines for conducting a robust google trends research (nuti et al., ) . the quality of media reporting of celebrity suicide on online media in india is poor when compared to adherence with the who guidelines or the pci guidelines. in terms of including potentially harmful information, about . % of reports violated at least one recommendation provided in the guideline. further, compliance with recommendations of including potentially helpful information about creating awareness about suicide and possible ways of seeking help for suicidal thoughts was very low, with only few articles % articles providing information about where to seek help for suicidal thoughts or ideation. there was a significantly greater increase in the online search interest for suicide-seeking keywords after the recent celebrity suicide. this in turn provides support for a strong werther effect, possibly associated with poor quality of media reporting of celebrity suicide. the results emphasize the need for an increased collaboration, promotion, and advocacy by experts for uptake of existing media reporting guidelines on suicide by journalists and other stakeholders. there is an urgent need for research on understanding the effects of media reporting of suicide at general population's suicidal acts and thoughts. funding sources: no financial support was received for this study. the authors declare no conflict of interest. j o u r n a l p r e -p r o o f access to care and use of the internet to search for health information: results from the us national health interview survey quality of media reporting of suicidal behaviors in south-east asia 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educate the public about suicide? content analysis from a high suicide union territory in india global, regional, and national burden of suicide mortality to : systematic analysis for the global burden of disease study andaman's minor girl hangs herself after she went into depression over sushant singh rajput's suicide [www document are top indian newspapers complying with guidelines on suicide reporting? association between suicide reporting in the media and suicide: systematic review and meta-analysis media and suicide : international perspectives on research, theory, and policy role of media reports in completed and prevented suicide: werther v. papageno effects indonesian online newspaper reporting of suicidal behavior: compliance with world health organization media guidelines the use of google trends in health care research: a systematic review changes in media reporting of suicide in australia between / and / guidelines adopted by the pci on mental illness/reporting of suicide cases surfing for suicide methods and help: content analysis of websites retrieved with search engines in austria and the united states beneficial and harmful effects of educative suicide prevention websites: randomised controlled trial exploring papageno v. werther effects patna: girl hangs self after watching sushant singh rajput's suicide news | patna news -times of india media matters in suicide -indian guidelines on suicide reporting using internet search data to predict new hiv diagnoses in china: a modelling study j o u r n a l p r e -p r o o f key: cord- -cbejbm v authors: roy mukherjee, tapasi; chanda, shampa; mullick, satarupa; de, papiya; dey‐sarkar, malay; chawla‐sarkar, mamta title: spectrum of respiratory viruses circulating in eastern india: prospective surveillance among patients with influenza‐like illness during – date: - - journal: j med virol doi: . /jmv. sha: doc_id: cord_uid: cbejbm v in developing countries, viruses causing respiratory disease are a major concern of public health. during january –december , , patients with acute respiratory infection from the outpatient departments as well as patients admitted to hospitals were screened for different respiratory viruses. nasal and or throat swabs were collected and transported to the laboratory where initial screening of influenza a and influenza b viruses was performed. the samples were tested further for influenza c virus, parainfluenza viruses – , human rhinovirus, metapneumovirus and respiratory syncytial virus by conventional rt‐ pcr. the study revealed that the majority of the patients were under years of age; both due to their higher susceptibility to respiratory infections and presentation to hospitals. out of , patients enrolled in this study, % were found positive for one or more respiratory viruses. influenza b infection was detected in % of patients followed by influenza a ( . %), respiratory syncytial virus ( . %), parainfluenza virus‐ ( %), metapneumovirus ( %), parainfluenza virus‐ ( %), parainfluenza virus‐ ( . %), parainfluenza virus‐ ( . %), influenza c ( . %) and human rhinovirus ( . %). distinct seasonal infection was observed only for influenza a and influenza b viruses. j. med. virol. : – , . © wiley periodicals, inc. acute respiratory infections are a leading cause of morbidity and mortality in infants and children, especially in developing countries. according to the world health organization (who), acute respiratory infections account for approximately % of all deaths among children under years [who, ] , and % of these deaths occur in africa and southeast asia [williams et al., ] . viruses are a leading cause of acute respiratory infections with epidemiological variability that depends on the climate [armstrong et al., ] . to date, most of the known data are based on studies with children and infants only [choi et al., ; costa et al., ; kusel et al., ; ma et al., ; ordás et al., ; pierangeli et al., ] whereas the etiology remains largely undetermined for infections in the elderly [fine et al., ; garbino et al., ; file, ] . in children, respiratory syncytial virus and influenza viruses induce bronchiolitis, asthma exacerbation and pneumonia, leading to high rates of hospital admission [el-hajje et al., ; di carlo et al., ] . human rhinovirus, believed previously to cause only mild upper respiratory illnesses, has also been found in association with acute and chronic lower respiratory tract infections, including asthma exacerbations and chronic obstructive pulmonary disease (copd); although the role of human rhinovirus as a cause has only been established for asthma [papadopoulos et al., ; friedlander and busse, ; xatzipsalti et al., ; pierangeli et al., ; singh and busse, ; matthew et al., ] . it was reported that metapneumovirus accounted for approximately - % of all acute respiratory infections in children and adults [van den hoogen et al., ] whereas adenoviruses were responsible for - % of acute respiratory infections only in children [chen et al., ] . in addition, infections caused by other respiratory viruses such as parainfluenza viruses and coronaviruses occur worldwide. furthermore, coronavirus nl [van der hoek et al., ] , coronavirus hku [fouchier et al., ; woo et al., ] and bocavirus [allander et al., ] are also responsible for acute respiratory infections in pediatric, elderly and immunosuppressed patients. most studies based on laboratory diagnosis in hospitals are still restricted to influenza and respiratory syncytial virus. on the other hand, emerging respiratory viruses have been a subject of concern because of the risk of rapid spread and high fatality rates due to lack of both diagnosis and effective antiviral therapy. in developing countries where diagnosis of viruses causing respiratory disease is restricted to a few laboratories, the etiology is undefined in a significant proportion (> %); which undermines the impact of acute respiratory infections on health and economic burden [monto, ; henrickson et al., ] . in eastern india, frequency and genetic diversity of influenza viruses during [ ] [ ] [ ] [ ] [ ] have been reported , but no information is available from the indian subcontinent regarding other respiratory viruses. the present study aimed to identify common circulating respiratory viruses in addition to influenza during january through december in the eastern region of india. nasal and/or throat swabs were collected from patients with influenza like illness attending the outpatients departments of hospitals in kolkata, west bengal, as described previously [agrawal et al., a] . in addition, swabs from patients with severe respiratory illness admitted to different hospitals in west bengal were also referred to the laboratory for diagnosis. [mukherjee et al., ] . informed consent forms and detailed case histories were recorded before the collection of a specimen. the study was approved by the institutional ethical committees. viral rna was extracted by using commercially available qiaamp viral rna mini kit (qiagen, hilden, germany) as per manufacturer's instructions. real-time pcr for initial detection of influenza viruses, amplification of the matrix (m) gene of influenza a and influenza b viruses were carried out by real-time rt-pcr as described previously [agrawal et al., a] . respiratory viruses other than influenza were detected using a multiplex rt-pcr technique. firststrand cdna synthesis was achieved using random primers and reverse transcription system (invitrogen, carlsbad, ca). the resulting cdna was then subjected to multiplex pcr to enable simultaneous detection of multiple viruses. primer sequences used in the study are described in table i . the amplified products were then separated by agarose gel electrophoresis and visualized under uv after ethidium bromide staining. all samples were tested independently three times, using negative and positive controls to exclude cross-contamination of samples. distribution frequencies of respiratory viruses were compared using pearson's chi square test and fisher's exact test. continuous variables for population parameters such as age, laboratory investigations and other parameters were compared using one-way analysis of variance. from january through december , , swab samples from patients with respiratory infections were obtained; , ( . %) of the patients were out of , samples, , ( %) were positive for one or more respiratory viruses; of which . % were positive for influenza a; which comprised both influenza a(h n )pdm ( . %) and influenza a(h n ) ( %), influenza b was detected in % cases, influenza c ( . %), parainfluenza virus- ( . %), parainfluenza virus- ( %), parainfluenza virus- ( . %), and parainfluenza virus- ( . %), respiratory syncytial virus ( . %), metapneumovirus ( . %) and human rhinovirus were found in . % cases (fig. ) . during the study period, samples were found to be co-infected with respiratory syncytial virus and influenza b viruses. metapneumovirus was found together with respiratory syncytial virus (n ¼ ), influenza a (n ¼ ), and influenza b (n ¼ ) viruses. mixed infection with influenza a and influenza b was detected in cases. the prevalence of viral infection in different age groups has been shown in figure . infections due to influenza a(h n ), influenza b, metapneumovirus and respiratory syncytial virus was high in children under years of age followed by - years and - years; whereas, adults ( - years) and the elderly people were infected mainly with influenza a (h n )pdm virus. influenza c virus infection predominantly occurred in children under the age of years; although the frequency is very low. similarly higher percentage of parainfluenza virus- infection was observed among children (under years of age) followed by - years of age. in other age groups parainfluenza virus- was not observed in this study. elderly persons (> years of age) were at high risk for infection with parainfluenza virus- and - , followed by the patients of - and patients under years of age; whereas the infection rate for parainfluenza virus- was high among the patients under years of age. for human rhinovirus infection, the risk group was - years followed by - years. during this study, all mixed infections were observed only in children aged less than years. the correlation of meteorological variations with the prevalence of respiratory viruses in eastern india is shown in figure . due to the pandemic in , only influenza a(h n )pdm strain was found in , however influenza a(h n ) emerged again in . influenza b was found mainly after the monsoon season (october-december). seasonal fluctuations for influenza c virus, parainfluenza virus - , metapneumovirus and respiratory syncytial virus infection have not been observed during this study. in , surveillance for influenza viruses was expanded to india, as part of the global influenza surveillance network. however specific diagnosis which requires laboratory tests, were not widely available in eastern india. hence the information on epidemiology and clinical features of respiratory virus infection in india is based entirely on research studies and the disease burden or seasonal prevalence of respiratory viruses remains largely undefined. this study initiated to complete the information on circulating respiratory viruses among patients attending the outpatients departments of different hospitals with acute respiratory infections in the eastern region of india during through . during this surveillance, influenza b infection was found to be most prevalent followed by influenza a. in , only influenza a(h n )pdm virus circulated whereas in , only influenza a/h n was found. this was in contrast with the previous report from eastern india, where higher prevalence of influenza a was observed compared to influenza b . increased frequency of influenza b infection could be due to the post-pandemic effect of influenza a(h n )pdm following which seasonal influenza a/h n and influenza a/h n viruses disappeared during - . this is consistent with studies from vietnam [do et al., ] and other asian countries [mathisen et al., ] . metapneumovirus has been associated with both upper and lower respiratory tract infections in children ( - %) [van den hoogen et al., ; bosis et al., ; gerna et al., ; choi et al., ; sarasini et al., ; boivin et al., ] . during this study period, metapneumovirus was found in only % samples. this finding corroborates with reports from canada, england and the usa, where the infection rate due to metapneumovirus varies from % to . % [stockton et al., ; falsey et al., ; boivin et al., ] , but is significantly less compared to the prevalence in netherlands ( %), australia ( . %), and chile ( . %) [van den hoogen et al., ; luchsinger et al., ; mackay et al., ] . respiratory syncytial virus which is the most common etiological agent of viral lower respiratory tract infections in infants and young children in the world caused . million new episodes in children < years of age [nair et al., ] and is also associated with hospital admission of - per , children below year [pancer et al., ] . in thailand alone, . / , incidences of pneumonia per year are attributed to respiratory syncytial virus [olsen et al., ] . worldwide, respiratory syncytial virus has been identified as the cause of . million cases of acute lower respiratory infections requiring hospital admission. among all age groups, . % cases were found positive for respiratory syncytial virus during - in this study. following respiratory syncytial virus, parainfluenza virus- was the most predominant virus ( %) compared to parainfluenza virus- , - or - . consistent with surveillance results during - , in eastern india roy et al., ] and in bangladesh [zaman et al., ] children under years old were found to be most vulnerable to infections due to influenza b and influenza a (h n ) viruses. whereas, influenza a (h n )pdm affected adults and the elderly which is consistent with findings from other studies [cauchemez et al., ; john and moorthy, ; mukherjee et al., ] . similar to influenza viruses, metapneumovirus infection was also detected mainly in children (under year of age), suggesting early acquisition of infection [van den hoogen et al., ; lu et al., ; zappa et al., ] . during - , only . % of respiratory syncytial virus infection was found among children [agrawal et al., b] ; whereas in the same geographical region, . % samples were found to be positive for respiratory syncytial virus in children (under years) during this study period ( ) ( ) . the higher prevalence of respiratory syncytial virus during this study period could be due to lower activity of influenza a viruses compared to the activity of influenza a viruses in - [agrawal et al., b] . among children with acute respiratory infections, co-infection with one or more respiratory viruses has been observed [bonzel et al., ; canducci et al., ] which correlates with results of present study, where predominant mixed infections were observed only in children. unlike temperate countries where the prevalence of seasonal influenza may reach epidemic proportions during the winter months [john and moorthy, ] , in tropical countries like india, year round circulation of strains has been reported, though the infection peaks during rainy season (june-september) [agrawal et al., a . there could be several factors such as socio-economic, environmental, education, overcrowding and other factors, which could affect the seasonal incidence and distribution of viral infections. in eastern india, influenza b was found to be prevalent after the monsoon season as well as in the winter months [roy et al., ] , and influenza a viruses predominated during the monsoon (june-july) [agrawal et al., a; mukherjee et al., ] . during - seasonal infection due to influenza a [influenza a(h n )pdm or influenza a/h n ] correlated with previous reports. however the seasonal pattern of infection with respiratory syncytial virus during - was found to be different from the previous reports from kolkata, india [agrawal et al., a,b] and bangladesh [huq et al., ] , where respiratory syncytial virus infection was found more commonly in the winter months or the dry seasons. such variations in seasonal incidence are difficult to explain, as virus infection could be affected by a large number of different factors [weber et al., ]. previous studies in temperate climates showed that parainfluenza virus- and - infection occurs annually [laurichesse et al., ; karron and collins, ] , parainfluenza virus- infection occurs twice-yearly during the late fall and winter [aguilar et al., ; vachon et al., ; lau et al., ] and parainfluenza virus- infection occurs mainly during late spring and summer [laurichesse et al., ] . these differences may be attributed to different geographical regions and study years. however, as the numbers of positive cases were very low in the present study, the seasonal prevalence of influenza c, parainfluenza viruses and human rhinovirus could not be determined. hence large-scale studies over a broader geographical range and longer time period are required to understand the seasonal infection pattern of respiratory viruses in india. comparative evaluation of real-time pcr and conventional rt-pcr during year surveillance for influenza and respiratory syncytial virus among children with acute respiratory infections in kolkata, india, reveals a distinct seasonality of infection prevalence of respiratory syncytial virus group b genotype ba-iv strains among children with acute respiratory tract infection in kolkata, eastern india genetic characterization of circulating seasonal influenza a viruses ( - ) revealed 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deaths from acute respiratory infections characterization and complete genome sequence of a novel coronavirus, coronavirus hku , from patients with pneumonia rhinovirus viremia in children with respiratory infections influenza in outpatient ili case-patients in national hospital-based surveillance co-circulation of genetically distinct human metapneumovirus and human bocavirus strains in young children with respiratory tract infections in italy key: cord- - x nxgx authors: kumar, s. title: will covid- pandemic diminish by summer-monsoon in india? lesson from the first lockdown date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: x nxgx the novel coronavirus ( -ncov) was identified in wuhan, hubei province, china, in december and has created a medical emergency worldwide. it has spread rapidly to multiple countries and has been declared a pandemic by the world health organization. in india, it is already reported more than thousand cases and more than deaths due to coronavirus disease (covid- ) till april , . previous studies on various viral infections like influenza have supported an epidemiological hypothesis that the cold and dry (low absolute humidity) environments favor the survival and spread of droplet-mediated viral diseases. these viral transmissions found attenuated in warm and humid (high absolute humidity) environments. however, the role of temperature, humidity, and absolute humidity in the transmission of covid- has not yet been well established. therefore the study to investigate the meteorological condition for incidence and spread of covid- infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease is required for india. in this work, we analyze the local weather patterns of the indian region affected by the covid- virus for march and april months, . we have investigated the effect of meteorological parameters like temperature, relative humidity, and absolute humidity on the rate of spread of covid- using daily confirm cases in india. we have used daily averaged meteorological data for the last three years ( - ) for march and april month and the same for the year for march to april . we found a positive association (pearsons r= . ) between temperature and daily covid- cases over india. we found a negative association of humidity (rh and ah) with daily covid- cases (persons r=- . , - . ). we have also investigated the role of aerosol in spreading the pandemic across india because its possible airborne nature. for this, we have investigated the association of aerosols (aod) and other pollutions (no ) with covid- cases during the study period and also during the first lockdown period ( march- april) in india. we found a negative association in march when there were few cases, but in april, it shows positive association when the number of cases is more (for aod it was r=- . and r= . respectively). during the lockdown period, aerosols (aod) and other pollutants (no ; an indicator of pm . ) reduced sharply with a percentage drop of about and , respectively. this reduction may have reduced the risk for covid- through air transmission due to the unavailability of aerosol particles as a base. hysplit forward trajectory model also shows that surface aerosols may travel up to km according to wind and direction within three h of its generation. if coronavirus becomes airborne as suggested by many studies, then it may have a higher risk of transmission by aerosols particles. so relaxing in the lockdown and environmental rules in terms of pollutant emissions from power plants, factories, and other facilities would be a wrong choice and could result in more covid- incidences and deaths in india. therefore the current study, although limited, suggests that it is doubtful that the spread of covid- would slow down in india due to meteorological factors, like high temperature and high humidity. because a large number of cases have already been reported in the range of high tem, high relative, and high absolute humidity regions of india. thus our results in no way suggest that covid- would not spread in warm, humid regions or during summer/monsoon. so effective public health interventions should be implemented across india to slow down the transmission of covid- . if covid- is indeed sensitive to environmental factors, it could be tested in the coming summer-monsoon for india. so the only summer is not going to help india until monsoon is coming. only government mitigations strategies would be helpful, whether its lockdown, aggressive and strategic testing, medical facilities, imposing social distancing, encouraging to use face mask or monitoring by a mobile application (aarogya setu). r= . ) between temperature and daily covid- cases over india. we found a negative association of humidity (rh and ah) with daily covid- cases (person's r=- . , - . ). we have also investigated the role of aerosol in spreading the pandemic across india because it's possible airborne nature. for this, we have investigated the association of aerosols (aod) and other pollutions (no ) with covid- cases during the study period and also during the first lockdown period ( march- april) in india. we found a negative association in march when there were few cases, but in april, it shows positive association when the number of cases is more (for aod it was r=- . and r= . respectively). during the lockdown period, aerosols (aod) and other pollutants (no ; an indicator of pm . ) reduced sharply with a percentage drop of about and , respectively. this reduction may have reduced the risk for covid- through air transmission due to the unavailability of aerosol particles as a base. hysplit forward trajectory model also shows that surface aerosols may travel up to km according to wind and direction within three h of its generation. if coronavirus becomes airborne as suggested by many studies, then it may have a higher risk of transmission by aerosols particles. so relaxing in the lockdown and environmental rules in terms of pollutant emissions from power plants, factories, and other facilities would be a wrong choice and could result in more covid- incidences and deaths in india. therefore the current study, although limited, suggests that it is doubtful that the spread of covid- would slow down in india due to meteorological factors, like high temperature and high humidity. because a large number of cases have already been reported in the range of high tem, high relative, and high absolute humidity regions of india. thus our results in no way suggest that covid- would not spread in warm, humid regions or during summer/monsoon. so effective public health interventions should be implemented across india to slow down the transmission of covid- . if covid- is indeed sensitive to environmental factors, it could be tested in the coming summer-monsoon for india. so the only summer is not going to help india until monsoon is coming. only government mitigations strategies would be helpful, whether its lockdown, aggressive and strategic testing, medical facilities, imposing social distancing, encouraging to use face mask or monitoring by a mobile application (aarogya setu). keyword: novel coronavirus; india; summer; covid- ; pandemic; absolute humidity; -ncov . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . highlights:  first study on the effects of meteorological factors on covid- cases in india.  a positive association between daily new cases of covid- with temperature.  rh and ah are negatively associated with daily new cases of covid- .  early lockdown in india slows down the spread of contagious disease covid- .  more than a % fall was found in aod and no values during the lockdown period. the novel coronavirus ( -ncov) was identified in wuhan, hubei province, china, in december (bukhari and jameel, ) and caused over . million cases and over thousand deaths worldwide till date ( april ) (worldometer) . it has spread rapidly to multiple countries and has been declared a pandemic by the world health organization on march , (who). in india, it is already reported more than thousand cases and more than deaths due to coronavirus disease (covid- ) (covid/tracker). previous studies have supported an epidemiological hypothesis that cold and dry (low absolute humidity) environments facilitate the survival and spread of droplet-mediated viral diseases. warm and humid (high absolute humidity) environments see attenuated viral transmission like influenza and sars (schoeman and fielding, ) . as this coronavirus appeared for the first time and was highly contagious, it poses a great challenge to diagnosis and prevention and control. human coronaviruses have been associated with a wide spectrum of respiratory diseases in different studies and belong to the coronaviridae family (bukhari and jameel, ; weiss and navas-martin, ) . it has been suggested that flu viruses are not easily transmitted in hot and humid conditions. similar comments about the covid- have repeatedly been made by health officials as well as world leaders that the outbreak will slow down by summer, due to decreased transmissivity (bukhari and jameel, ) . also found a similar result in his model study. they suggested that during the coming summer in the northern hemisphere, the spread of coronavirus will be reduced in tropical regions. it is also important to note that sars-cov, which is a type of coronavirus, loses its ability to survive in higher temperatures, which may be due to the breakdown of their lipid layer at higher temperatures (schoeman and fielding, ) . however, no seasonality has been established for covid- . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted april , . . https://doi.org/ . bukhari and jameel ( ) reported that in the beginning none of the asian, middle eastern and south american countries had implemented drastic quarantine measures such as those in china, europe, and some us states, however, their overall growth rate was lower, but now the rate is much similar to the europe and usa. he suggested that it could be due to a lower number of testing, such as in india, pakistan, indonesia, and african countries. many countries such as singapore, uae, saudi arabia, australia, qatar, taiwan, and hong kong have performed more -ncov tests per million people than the usa, italy, and several european countries. it was suggested that non-testing was not an issue, at least for the tropical countries. at the beginning of april, thousands of new cases have been documented in regions with tem > c, suggesting that the role of warmer temperature in slowing the spread of the covid- , as suggested earlier, might only be observed, at much higher temperatures. unlike temperature, most of the covid- cases were reported in the range of ah has consistently been between and g/m (bukhari and jameel, ) . bukhari and jameel, ( ) also suggested that if, new cases in april and may continue to cluster within the observed range of ah, i.e., to g/m , then the countries experiencing monsoon, i.e., having high absolute humidity (> g/m ) may see a slowdown in transmissions, due to climatic factors. but for india, it is not true as many states having high temperate and high humidity are still leading in covid- cases in india like maharashtra and tamil nadu ( fig. ) as for india, the average ah, is between to g/m during march and april month. a higher number of cases also reported for kerala and uttar pradesh at the beginning of april, but government early mitigation strategies controlled the daily new covid- cases. since january , after the first case was reported in india, the increasing number of cases caused by covid- had been identified until february. up to the second week of march, only cases which were coming from foreign or in contact with them were reported, but after th march, new daily cases appeared with no foreign travel cases. the number shoots up after th march when a community of "tablighi jamat" in delhi was reported that they might have covid positive cases with at least people. after this event increasing number of daily cases continues with new and with those who have contact with these peoples. presently this community has % cases of covid- on total indian cases across the india. on march , , india, the residence of more than . billion humans, was forced to shut down both outbound and inbound traffic to contain the covid- outbreak. in addition to population mobility and human-to-human contact, environmental factors can impact droplet transmission and survival of viruses (e.g., influenza) but have not yet been . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . examined for this novel pathogen for indian cases. absolute humidity, defined as the water content in ambient air, is a strong environmental determinant of other viral transmissions (barreca and shimshack, ; luo et al., ) . for example, influenza viruses survive longer on surfaces or in droplets in cold and dry air -increasing the likelihood of subsequent transmission. thus, it is key to understand the effects of environmental factors on the ongoing outbreak to support decision-making about disease control, especially in locations where the risk of transmission may have been underestimated, such as in humid and warmer locations. we examine variability in temperature (tem), relative humidity (rh), and absolute humidity (ah) and transmission of covid- across india. we show that the observed patterns of covid- are not completely consistent with the hypothesis that high ah may limit the survival and transmission of this new virus. bu et al., ( ) found from a global perspective, cities with a mean temperature below °c are all high-risk cities for -ncov transmission before june. in our case, it is not true as in india; the temperature was always high when the covid- growth rate is high. few studies supporting the hypothesis that high temp and high humidity will reduce the case like, wang et al., ( ) find in their study, under a linear regression framework, high temperature and high humidity significantly reduces the transmission of covid- . they reported that a onedegree celsius increase in temperature and a one percent increase in relative humidity lower r by . and . , respectively. the transmission of coronaviruses can be affected by several factors, including climate conditions (such as temperature and humidity), population density, and medical care quality . therefore, understanding the relationship between weather and the transmission of covid- is the key to forecast the intensity and end time of this pandemic. the number of -ncov cases detected in a country/state depends on multiple factors, including testing, population (density), community structure, social dynamics, governmental policies, global connectivity, air and surface life, reproduction number, and serial interval of the virus. many of this information regarding -ncov are still emerging, such as the virus being airborne for more than hours and having very different survival times on metals, cardboards and plastics (van doremalen et al., ) . the behavior of -ncov with meteorological parameters and with aerosols is still under investigation and also the subject of this paper over the indian region during its spread and during the first lockdown period ( march- april ). the analysis presented in this paper provides a direct comparison between the spread of covid- virus and local environmental conditions over india region and study the growth rate of covid- among different states of india (fig. ). . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . in our study, we have used covid- data of daily conformed cases, surface temperature and surface humidity, aerosol optical depth (aod), and no with daily averages time series data for the indian region. following data were used, the daily number of confirmed cases of patients infected with covid- were taken from the who website and other public sources like worldometer (worldometer) and covid- tracker/india (https://www.covid india.org/) (covid/tracker) for march and april . the meteorological parameters during the outbreak of the novel coronavirus in india for and three year past data were collected and analyzed. air temperature and relative humidity data were taken from atmospheric infrared sounder (airs) onboard eos aqua. daily data were taken for the surface temperature and surface relative humidity for the indian region with resolution degree for days march to april , , and for - from march to april. we have calculated the absolute humidity using these two parameters using the clausius clapeyron equation (bolton, ) as follows: where ah is the absolute humidity, and t is the temperature in degrees c. aerosols optical depth (aod) and no data were taken from giovanni nasa (https://giovanni.gsfc.nasa.gov/giovanni/) sites from modis and omi satellites. modis provides daily aod data with the -degree resolution, which we used for the indian region, and omi also provides daily data with resolution . degrees. more details about modis data can be found elsewhere (kumar et al., ) . we have used data for - from march to april and from march to april. hysplit (noaa) forward trajectories model was used to find out the surface air movement for the spread of aerosol. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . . results and discussion: we look into the relation between daily temperature (tem), relative humidity (rh), and absolute humidity (ah) with the daily number of confirmed cases of corona patients in india. we have used daily averaged meteorological data for the last three years ( - similarly, we have plotted the rh value and daily confirmed cases of covid- for average ( - ) and for for march and april. we found a slowly decreasing trend in average rh varying from ( %- %), and for we found overestimating rh from average with range % to % in india. rh values show the negative association with the daily confirm cases (fig. ) . we found a positive correlation (pearson's r= . ) between temperature and daily covid- cases over india and found negative correlations of humidity (rh and ah) with daily covid- cases (person's r=- . , - . ) (graphical abstract). absolute humidity, the mass of water vapor per cubic meter of air, relates to both temperature and relative humidity. we have also investigated the relation of confirmed cases with ah. the ah vales vary from - . g/m during march and april months of . we found that the new cases are low when ah vales are greater than . g/m and high cases and high death when ah vales are going low from . g/m (fig. ) cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . similarities to the other studies done earlier on covid- cases in china, europe, and the usa. studying wuhan, guangzhou, and beijing covid- cased bu et al., ( ) found a meteorological condition with the temperature between - °c and humidity between % and % was suitable for the survival and transmission of the coronavirus. they also speculated that from february to the end of may , the areas ranging the temperature ( ℃ - ℃) are all key areas for disease prevention, especially densely populated cities; from june and after that, the disease in regions with a mean temperature over °c will begin to subside. they suggested before june , cities with a global average temperature below °c are all under high-risk of the transmission of new coronaviruses. after june, the risk of disease transmission will be significantly reduced in the cities with a mean temperature reaching °c or higher. our results for the indian case did not match with the hypothesis said above as average temperature for the indian region for march and april is above °c, even the covid- cases are increasing rapidly in india even though restrict lockdown is there. based on their study of the spread of -ncov, bukhari and jameel ( ) hypothesize that the lower number of cases in tropical countries might be due to warm-humid conditions, under which the spread of the virus might be slower as has been observed for other viruses. they found that the relation between the number of -ncov cases and temperature and absolute humidity observed is strong; however, the underlying reasoning behind this relationship is still not clear. similarly, they do not make clear that which environmental factor is more important. it could be that either temperature or absolute humidity is more important, or both may be equally or not important at all in the transmission of -ncov. the humidity dependency may be due to the less effective airborne nature of the viruses at higher absolute humidity, thus reducing the overall indirect transmission of -ncov at higher levels of humidity. although higher humidity may increase the amount of virus deposited on surfaces, and virus survival time in droplets on surfaces, the reduction of the virus spread by indirect (through air) transmission may be the factor behind the reduced -ncov spread in the humid climate. these explanations are speculative and based on patterns observed for other coronaviruses. urgent study/experiments on the association between coronavirus transmission against temperature and humidity in laboratories are needed to understand these associations. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . many studies suggested that covid- may be stable up to hours on aerosols (van doremalen et al., ) and may be transmitted to long distances in a closed environment (santarpia et al., ) as well as the open environment (wang and du, ) . these studies suggest that covid- may be airborne and can give a high risk of transmission through aerosols. aerosols are particles formed by solid or liquid particles dispersed and suspended in the air. they contain soil particles, industrial dust particles, particulates emitted by automobiles, bacteria, microorganisms, plant spore powders, and other components. when a person who was infected with the virus, coughs, sneezes, breathes vigorously, or speaks loudly, the virus will be excreted from the body. it may dissolve with the aerosol and become the bio-aerosols. bio-aerosols ranging in size from . to . μm generally remain in the air, whereas larger particles are deposited on surfaces. droplets spread in the space of about to m from the source of infection. however, aerosol can travel hundreds of meters or more. wang and du ( ) , in his many case studies of covid- , speculated that the spread of the virus might be due to the aerosols because new patients in inner mongolia and wuhan were never in direct contact with the confirmed cases. they found that covid- may transmit through aerosol directly, but it needs to be further verified by experiments. if the aerosols can spread covid- , prevention and control will be much more difficult. many of the information regarding -ncov are still emerging, such as the virus being airborne for more than hours and having very different survival times on metals, cardboards and plastics (van doremalen et al., ) . doremalen et al., ( ) found in his experiment that the covid- virus can remain viable in aerosols throughout his experiment ( hours), similar to that observed with sars-cov- . santarpia et al., ( ) in their clinical study found that sars-cov- is shed during respiration, toileting, and fomite contact, indicating that infection may occur in both direct and indirect (through aerosols) contact. although this study did not employ any size-fractionation techniques to determine the size range of sars-cov- droplets and particles, the data was suggestive that viral aerosol particles are produced by individuals that have the covid- disease, even in the absence of cough. therefore the covid- may spread through the aerosols if the sufficient amount of aerosols is present in the environment. also, the reduction in aerosol concentration during the lockdown may reduce the risk of transmission of covid- through aerosols. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . to prevent further spread of covid- , india has started the world's biggest lockdown of history on th march , where the whole country was locked, and more than . billion people were forced to remain in their homes. this lockdown surely has positive feedback by less daily new covid cases compared to europe and the usa and also affect the environment. due to the strict lockdown in india, all public transport, industries, and individual activities were shut, which was reflected in air quality and aerosols over india. the aerosols decrease sharply over india in comparison with the average value of aod of the last three years (fig. ) . we have found a clear decrease in aod value from the first day of lockdown with little increase in value in the coming days due to some relaxation in lockdown. also, april month is harvest month so, aerosols are increased due to harvesting and crop residue burning in the april month, which can also be seen in averaged data. now the first days lockdown ( march- april) period is over, and the second lockdown ( april- may) is going on but with some relaxation in few important activities, so it may increase the aerosol concentration. if a lockdown is followed strictly till may , , then a big reduction in aod may be observed, which may restrict the risk of further new covid- cases by its transmission through aerosols. no is a marker of the particulate matter (pm . ) for the study of pollutions. strict lockdown in india reduces the tropospheric column no also, which again lowers the risk of covid transmission through pm . for the indian region (fig. ). it's very clear from the plot that the concentration of no is reduced after the lockdown in comparison to the threeyear average value of no . figure shows the percentage dropdown in the values of aod and no in comparison to the average value of the last three years over india. we found maximum dropdown during the lockdown period of up to % for aod and % for no in comparison to the average value of - . we have also investigated the correlation of aod with the daily new confirmed case in india for march and april. we found the negative correlation during march when there were fewer cases of covid- , but in april, the correlation turned in to positive (fig. ) when daily . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . cases are more and which again indicating that possible covid- transmission through the aerosols if it is airborne. we have used the hysplit trajectory model for calculation of the forward trajectory (not shown here) of surface aerosols. as van doremalen et al., ( ) found in his study that covid- virus can be stable at aerosols surface for about hours. so if a coronavirus is attached to the aerosols, then it may travel for longer distances and become airborne, this may be a reason for the high number of cases in the usa and other european countries as in earlystage they did consider covid- may not transmit through the air and not using the face mask. so when we run hysplit forward trajectory model for the surface level air for hours period, we found that in normal condition in april month in india, a surface level aerosol can travel up to km distance in hours according to the wind speed and direction. so there is a great risk of transmission of covd- through aerosols if their concentration is high and viruses have plenty of bases to stick it. therefore our study suggests that there must be strict lockdown for all factors affecting the concentration of aerosols; otherwise, it may be an invitation to a disaster to give relax in lockdown in india like a country with high aerosols in coming months. before in march , many studies speculated that the places with higher temperatures are in less risk, and it appeared that temperature might play an important role in the spread of the virus. however, more new cases were recorded in regions with a temperature between and o c in march even more up to o c in india during march and april , which is now challenging the hypothesis that a rise in temperature would minimize the spread of the -ncov. nonetheless, the observation of more than , cases in the last ten days in india makes it clear that the effect of rising summer temperature, if any, would not be observed in the current hotspot of india, as the mean temperature for most of the major cities in india is above o c for most of april and may. indeed, laboratory experiments performed between - o c at a relative humidity of %, showed that the virus survived for several days on plastics and metals (van doremalen et al., ) . therefore temperature may affect similar to the relationship observed between sars-cov and temperature (bukhari and jameel, ) . still, we can't say at what temperature and to what extent it would help in reducing the spread of -ncov. under any circumstances, we believe that large gatherings (both indoor and outdoor) should be avoided across india. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . based on currently available data, -ncov is spreading easily in regions with absolute humidity < g/m (bukhari and jameel, ) , this has serious implications on the assumption that the -ncov spread would slow down during summer in the current hotspot of india as in many regions the absolute humidity might be above g/m (fig. ) . on the other hand, if, new cases in april and may continue to cluster within the current observed range of ah, i.e., to g/m , then the states experiencing monsoon having a high absolute humidity (> g/m ) may see a slowdown in transmissions, due to climatic factors. if it is then for india, it has long waiting time up to june , when the monsoon will come, and up to then, only government mitigation policies are going to reduce the covid- spread over india. the novel coronavirus pneumonia is caused by -ncov, which is a new pathogen for the human being. due to its outbreak during the spring and summer, it is spreading very fast in a short period. faced with this new disease, we lack reliable epidemiological information for effective treatment and prevention. however, any infectious disease origins and spread occur only when affected by certain natural and social factors through acting on the source of infection, the mode of transmission, and the susceptibility of the population. the weather and meteorological factors also may play a part in the coronavirus outbreak besides the social factors. also, aerosols may play a crucial role during the spread of covid- . following conclusions and suggestion may be drawn from the current study; . we have studied the effect of environmental factors and aerosols on the spread of covid- during march and april in india. we have studies the total number of daily confirmed cases of covid- and its association with the temperature, relative humidity, and absolute humidity over india for march and april . we found a positive association between daily new cases of covid- with temperature for india. relative humidity and absolute humidity is negatively associated with daily cases of covid- in india. we found a positive correlation (pearson's r = . ) between temperature and daily covid- cases over india. we found a negative correlation of humidity (rh and ah) with daily covid- cases (person's r =- . , - . ). . to reducing the covid- effect, summer alone is not going to help majorly, as high absolute humidity regions like maharashtra and tamil nadu are getting the maximum number of confirmed daily covid- cases (fig. ) . so only the government's strict . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . mitigation strategies would be helpful, whether their totals lockdown or strictly imposing the social distancing for the community. two coastal states of india (kerala and maharashtra) are the example for rest of the india who has an almost same meteorological environment and had same numbers of covid- patient on th march, but during first lockdown period, their governments' strategies made a big difference as now kerala is on th position, and maharashtra is at the top in the total number of covid- patient in india (fig. ). . there is a thin hope that increasing temperature in coming months in india may reduce the number of new covid- cases, because in india during summer, crop residue burning and major dust storms occur (kumar et al., ) , which further will degrade the air quality especially in the north indian region and will create the health emergency by producing respiratory diesis due to increased particulate matter, ultimately which may enhance the number of death of patient suffering from the covid- , also will increase the chance of spreading through aerosols. . we also investigated the aerosols and pollutants behavior with the total number of cases during the covid- outbreak. the concentration in aerosols (aod) and other pollutants (no ) was sharply reduced during the first lockdown period ( march- april) in india, which may have a negative effect and lowered the risk of covid- to be airborne because less available aerosols as the base for the virus to stick on it. . since many earlier studies and our findings are suggesting that covid- may be airborne, so to slow down its spread, governments should impose strict lockdown and motivate the society to follow the social distancing, thermal scanning, and wearing a face mask when going outside. health workers and those are working at the front line must take precautions as it may be airborne. also, the mild infected and the severely infected patient should be kept in a separate medical facility. . the structures of social contact critically determine the spread of the infection and, in the absence of vaccines, the control of these structures through large-scale social distancing measures appears to be the most effective means of mitigation. as in the previous study by singh and adhikari, ( ) suggested that the three-week lockdown will be insufficient, and it's found true for india, our suggestion is for complete lockdown with minimal relaxation with strict social distancing for more weeks. . we found that early lockdown in india reduces the possible number of infections/death due to the coronavirus. in india, most of the cases identified during the lockdown period, which shows less effect of weather to slow it down, as it is already summer in the indian . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . region. the number of cases per million populations is least for india in comparison to the usa and europe, which shows the government mitigations working well as it was a historic move by the indian government to lockdown . billion people with the different social and economic background when there were only cases of the corona. . after april, the temperature will be very high as summer approaching its maximum and in india during june also humidity will be high in coastal states. it will increase slowly over the northern parts of india in late june month. then this hypothesis may be tested for the indian region that high temp and high humidity will reduce the number of cases due to the coronavirus. that time will tell, but before that, at least up to may , there must be strict lockdown by the government (the second lockdown announced for april- may) over india and community should strictly follow the social distancing to reduce the number of covid- cases. relaxing in the lockdown and environmental rules in terms of pollutant emissions from power plants, factories, and other facilities would be the wrong choice. it could increase pollutants like pm . , which may result in more covid- incidences and deaths in india. there is a need for a more appropriate study of the rate of outdoor transmission versus indoor and direct versus indirect transmission as they are not well understood, and environmental-related impacts are mostly applicable to outdoor transmissions. we are thankful to giovanni nasa for providing the satellite data for aod, no , temperature, and relative humidity. we are thankful to the volunteers of covid- tracker/india (https://www.covid india.org/) for providing all the data of india related to covid- . we thank noaa for providing the hysplit trajectories through their online models. finally, the author is profoundly grateful to the vice-chancellor of v.b.s. purvanchal university prof. (dr.) raja ram yadav for providing funding and encouraging to engage in research with teaching. . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted april , . . https://doi.org/ . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted april , . . https://doi.org/ . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted april , . . https://doi.org/ . absolute humidity, temperature, and influenza mortality: years of county-level evidence from the united states the computation of equivalent potential temperature analysis of meteorological conditions and prediction of epidemic trend of -ncov infection in will coronavirus pandemic diminish by summer? ssrn electron meteorological, atmospheric and climatic perturbations during major dust storms over indo-gangetic basin the role of absolute humidity on transmission rates of the covid- outbreak transmission potential of sars-cov- in viral shedding observed at the university of nebraska medical center coronavirus envelope protein: current knowledge age-structured impact of social distancing on the covid- epidemic in india international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity covid- may transmit through aerosol high temperature and high humidity reduce the transmission of covid- . ssrn electron coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. microbiol temperature, relative humidity, and absolute humidity from march - april for the indian region.. cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review)the copyright holder for this preprint this version posted april , . . https://doi.org/ . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . . cc-by-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted april , . . https://doi.org/ . key: cord- -of qgl authors: singh, ramesh p.; chauhan, akshansha title: impact of lockdown on air quality in india during covid- pandemic date: - - journal: air qual atmos health doi: . /s - - - sha: doc_id: cord_uid: of qgl first time in india, total lockdown was announced on march to stop the spread of covid- and the lockdown was extended for days on march in the first phase. during the total lockdown, most of the sources for poor air quality were stopped in india. in this paper, we present an analysis of air quality (particulate matter-pm( . ), air quality index, and tropospheric no( )) over india using ground and satellite observations. a pronounced decline in pm( . ) and aqi (air quality index) is observed over delhi, mumbai, hyderabad, kolkata, and chennai and also a declining trend was observed in tropospheric no( ) concentration during the lockdown period in compared with the same period in the year . during the total lockdown period, the air quality has improved significantly which provides an important information to the cities’ administration to develop rules and regulations on how they can improve air quality. covid- is considered as one of the major disasters, which has impacted the whole world. wuhan city, capital of hubei province of china, faced the first outbreak of this covid- during december and all nations of the world are affected by covid- in a gradual manner (raibhandari et al. ; wang et al. a, b) . after china, most south asian countries like japan, south korea, and others are affected by the cross-border travels. the return of chinese workers spread covid- in italy. the government of india issued an advisory for travelers from china during early january and also started screening the travelers from china (https://www. mygov.in/covid- /?cbps= ). in response to the global covid- pandemic, the indian prime minister announced janata (people's) curfew on march from am until pm (https://economictimes.indiatimes.com/news/politicsand-nation/after-janata-curfew-india-gets-ready-for-long-haul/articleshow/ .cms). soon after, the government of india announced a complete nationwide lockdown, from march for days ( april ) (https://www.bbc. com/news/world-asia-india- ), all the domestic and international flights, trains, and vehicular transport except for non-essential purposes were stopped and banned. such lockdown was unique in india; total lockdown was not seen in any other countries. this sudden decision impacted poor people and migrant workers in major cities, delhi, and mumbai. these migrant workers were daily wages and without any job, it was difficult for them to survive. migrant workers in delhi and mumbai even started walking to their hometown from far distant places since there was no means of transportation available. in general, the northern parts of india are subjected to poor air quality and atmospheric pollution, mainly due to emissions from vehicles, industry, brick kilns, coal-based power plants, and crop residue burning (singh et al. , prasad et al. , venkataraman et al. . for instance, new delhi, capital of india, suffers with sustained poor air quality where pollution levels are higher compared with beijing (zheng et al. ) . the air quality and atmospheric pollution in china has improved in recent years, whereas in india, the poor air quality has persistently increased over the last several decades associated with growing anthropogenic activities (chauhan and singh . in recent past, the delhi government conducted experiments of permitting odd or even licensed vehicles on the road to curb the pollution level (like beijing). however, such experiments have generally not helped or improved the air quality of delhi (chandra et al. ) . recently, wang et al. ( a, b) carried out an analysis of pm . data in a number of chinese cities, beijing, shanghai, guangzhou, and wuhan during covid- , and found a pronounced reduction in air pollution attributed to the reduction of emissions in transportation and industrial sectors. muhammad et al. ( ) found - % reduction in emission of no in china, spain, france, italy, and the usa due to lockdown. chauhan and singh ( ) observed a decline in pm . in major cities of the world. during complete lockdown in india, roads were deserted without any vehicle except the emergency vehicles. the month of april every year is the peak time of winter crop harvesting (wheat) and planting of vegetables in india, so the government relaxed the movement of farmers from lockdown in the second phase during april- may . the government of india has further extended lockdown in some parts in a relaxed manner; now they have opened vehicular transport, domestic flights, and few trains; as a result the air quality is getting poor. also, farmers at many places have started burning crop residue, and long-term transport of dusts during the pre-monsoon season are also being observed, which affects the air quality of delhi and major cities located in the indo-gangetic plains (igp). recently, sharma et al. ( ) considered the central pollution control board dataset and studied the impact of lockdown on air quality for the period march to april . the aim of this paper is to study the impact of a complete lockdown in india on air quality (pm . , aqi, and no ) during covid- by comparing air quality parameters during march and . our results show a pronounced decline in pm . , aqi, and no over major cities where us embassies are located during t he c omplete lo ckdown period ( - march ). we have considered air quality parameters (pm . and aqi) from the us embassy located in five indian cities, and no is considered from the satellite data. in india, wheat crop is harvested during april and may and that affects the air quality due to emission of various pollutants. for our study, we have considered major cities, delhi, kolkata, mumbai, chennai, and hyderabad, where us embassies are located. the details of us embassies are given in table . the us embassies are located in five major metropolitan cities in india, new delhi ( million), mumbai ( million), hyderabad ( . million), kolkata ( . million), and chennai ( . million) (fig. ) ; in the bracket, the populations are given as per the latest census. we have studied two primary air quality parameters (pm . particulate matter with a particle size of . -micron diameter and air quality index-aqi) which are monitored by each respective us embassies at five locations. data are taken from the us environmental protection agency (epa) through airnow portal (https:// www.airnow.gov/index.cfm?action=airnow.global_ summary). the epa claims to provide better quality of data. we have considered tropospheric no , one of the major pollutants which is highly dependent on the local sources because of its short residential time in the atmosphere. we have considered tropospheric no data from the ozone monitoring instrument (omi). omi is part of the nasa a-train satellite missions, which measures the concentration of various trace gases in the atmosphere. we have used omi version data which has a -day temporal and . °× . °spatial resolutions. the details of the data are discussed by krotkov et al. ( ) . the data are downloaded through nasa giovanni portal (https://giovanni.gsfc.nasa.gov/). we have selected a °× °square box (table ) over the five us embassies in india to study the temporal variation of tropospheric no . we have carried out the trajectory analysis over delhi, mumbai, hyderabad, chennai, and kolkata using the noaa hysplit model (https://ready.arl.noaa.gov/ hysplit.php) to study the sources of air mass reaching at five locations. the back trajectories were analyzed for h to track the air mass reaching at the measuring site; after every h, these trajectories are overlapped on the world map. the details of the hysplit model are discussed by stein et al. ( ) . results and discussion figure shows the impact of complete lockdown in india, average pm . concentrations during march , and after lockdown period ( - march ) along with the average pm . concentration during march . the average concentration of pm . before lockdown was higher in comparison with the concentration after lockdown. the pm . concentration in kolkata is reduced by . %, and . % in delhi, capital of india. in general, pm . is much higher throughout the year in the northern parts of india especially in the indo-gangetic plains (igp). during pre-monsoon (march-june), winter season (december-january), and crop residue burning seasons (mid-october to mid-november), pm . varies in a range of - μgm/m (sarkar et al. , . in mumbai, chennai, and hyderabad, pm . was reduced by . %, . %, and . %, respectively. the dominance of westerly wind from arid and semi arid region and lower temperature along the indo-gangetic plains in the month of march, the average concentration of pm . remains higher in comparison to other cities. the proximity of mumbai and chennai to the sea, the air mass mostly reaches from the sea surface during march and the pm . , is lower in comparison with delhi and kolkata. similar changes are also observed in the air quality index (aqi) which is a function of pm . and other emissions. the improvement in air quality is clearly observed mainly due to lockdown during - march . this lockdown is now extended until may with little relaxation in some of the localities in cities where no case of covid- was found. in india, complete lockdown was observed in a phased manner. we have considered data only for the phase to avoid influence of crop harvesting, long range transport of dusts, and crop residue burning on the air quality in the month of april and later months. we have carried out an analysis of air mass trajectory for four different time periods. in fig. , we have shown air mass back trajectories at five locations of us embassies during - march and - march for the years and . the back trajectories provide details about the sources of air mass reaching to five measurement locations. we have observed that delhi is mostly influenced by western and northwestern air mass during march and march . over mumbai, the air mass is reaching from northern india and also from the arabian peninsula during , whereas in march , first half, air mass is coming from the arabian sea and surrounding regions, and during - march , air mass is coming from gujarat, rajasthan and also from the arabian peninsula. in hyderabad, during and , the sources of air mass are different; during , air mass is coming from the southern coastal region and western parts of india. but during , air mass is coming from the bay of bengal before lockdown, and during lockdown, the air mass is coming from the indo-gangetic plains and the bay of bengal (fig. ) . over chennai, the air mass is reaching from the bay of bengal in the month of march and , and during - march , air mass is coming from the eastern parts of india and from the northern parts (igp). kolkata city is located in the eastern part of the indo-gangetic plains and is mostly influenced by westerly air mass except - march ; in this period, air mass is coming from hyderabad and the odisha region. the hysplit analysis clearly shows the influence of long-range transport of air mass over five different locations. the westerly air mass brings dust that affect the air quality (pm . and aqi) of delhi, and further, the dust is transported in the eastern parts of the indo- gangetic plains affecting air quality of kolkata city. although this does not happen always, the transport of dust at kolkata city depends on the wind velocity; during - march , the westerly air mass from igp and long-range transport of air mass from southern india influence this city. at hyderabad, the sources were different during and . in mumbai, mostly the air mass was northerly and westerly except - march when dominant air mass comes from the seaside. chennai is mostly influenced by oceanic air mass. in chennai, due to change in source of air mass, the average pm . was lower during march compared with march and also during the lockdown period (as of march ). the long-range transport of the air pollutants influences pm . concentrations in chennai during ; thus, a high value of pm . was observed during march . in fig. , we have shown tropospheric no over india during march and for the periods - and - march. over delhi, mumbai, and kolkata cities, the main sources of the no emissions are anthropogenic during the month of march. generally, in this month, biomass burning influences the southern parts of india; as a result, high no concentration over chennai and hyderabad are observed ; the fossil fuel consumption also adds to the pollution level. in central indian states, jharkhand and march , the effect of lockdown is clearly observed in the average tropospheric no concentrations in most parts of india. in figs. a, b , and c, the national capital region (ncr, delhi areas) is the hotspot for no concentrations (high values) in the northern parts, but during the lockdown period in the month of march (complete lockdown and closure of power plants, factories, vehicles, etc.), the no hotspot is not seen (fig. d) . in the month of march , major no hotspots (high values) are observed in jharkhand, odisha, and eastern states. higher values of tropospheric no concentration is attributed to the dense coal-based power plants and forest fires in jharkhand and odisha, and in the eastern states (prasad et al. ). in the eastern states, crops' residue is burnt to prepare farms for new crops every year during march (chauhan and singh, . but we also observed a decline in no concentrations during the lockdown period in these parts of india. during the lockdown period starting from march , a sudden drop in tropospheric no concentrations over igp is observed during - march (fig. ) . such results clearly show that tropospheric no concentrations are directly related to decline in fossil fuel use and other anthropogenic activities due to complete lockdown in india. further, we have carried out a detailed analysis of no concentration and plotted the temporal variations of tropospheric no over five major cities (fig. ) for the month of march (blue bar) and (red bar). in delhi, an increasing trend of tropospheric no is seen in , whereas during , a decline in tropospheric no is observed. soon after the total lockdown after march, a sharp decline in no concentration is observed. in kolkata, tropospheric no concentration was almost the same (blue trend line) as in the month of march , but in the month of march (red trend line), a decline in concentration was observed. in mumbai, in both years, and , a decline in no tropospheric concentration during march to april was observed, but due to lockdown, low tropospheric no concentration was observed in the year compared with . in hyderabad, tropospheric no concentration was also affected by lockdown; in march , high values were observed compared with march ; a negative slope (red color line) in the month of march shows a decline in tropospheric no concentration due to lockdown. in general, in the month of , concentration of tropospheric no was lower during compared with march . chennai also shows a decline in tropospheric no values during march . our results show lower values in tropospheric no due to the lockdown over five us embassies located in major cities in india. in delhi, kolkata, and chennai, a big contrast was observed during the lockdown periods compared with the same periods in , whereas in mumbai and hyderabad, decline was not appreciable. the lockdown appears to show pronounced improvement in air quality over these large densely populated metropolitan footprints of india where us embassies are located, but the lives of hundreds of millions of indian people have been disrupted due to the lockdown in response to the covid- pandemic. our results show a pronounced decline in air pollutants during lockdown especially in delhi and kolkata; these two cities are known to be highly polluted cities in india and in the world. the results will attract the attention of the indian government to ponder on how to strictly minimize vehicular and industrial pollution to improve air quality which will help to sustain better public health in india. oddeven traffic rule implementation during winter in delhi did not reduce traffic emissions of vocs, carbon dioxide, methane and carbon monoxide poor air quality and dense haze/smog during in the indo-gangetic plains associated with the crop residue burning and diwali festival decline in pm . concentrations over major cities around the world associated with covid- omi/aura no cloud-screened total and tropospheric column l global gridded . °x . °v , nasa goddard space flight center covid- pandemic and environmental pollution: a blessing in disguise? influence of coal based thermal power plants on aerosol optical properties in the indo-gangetic basin air medical evacuation of nepalese citizen during epidemic of covid- from wuhan to nepal crop residue burning in northern india: increasing threat to greater india ) on air quality, meteorological, and atmospheric parameters over the northern parts of india effect of restricted emissions during covid- on air quality in india variability of aerosol parameters over kanpur, northern india noaa's hysplit atmospheric transport and dispersion modeling system source influence on emission pathways and ambient pm . pollution over india severe air pollution events not avoided by reduced anthropogenic activities during covid- outbreak a novel coronavirus outbreak of global health concern a comparison of trace gases and particulate matter over beijing (china) and delhi (india) publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations acknowledgments the authors are grateful to environmental protection agency (epa) for providing pm . and aqi data for five us embassy in india. the authors also thank nasa giovanni team for facilitating use of tropospheric no satellite data. we are grateful to the two anonymous referees for their useful comments and suggestions that have helped us to improve earlier version of the manuscript.author contributions rps and ac created the original study plan. rps and ac designed and executed the study, ac carried out the analysis. rps and ac wrote the original manuscript and both edited the final manuscripts. both the authors read and approved the manuscript.data availability statement all the data used in the present study are freely available; if needed, we will provide the data used in the present study to anyone. key: cord- - lp i v authors: rishi, praveen; thakur, khemraj; vij, shania; rishi, lavanya; singh, aagamjit; kaur, indu pal; patel, sanjay k. s.; lee, jung-kul; kalia, vipin c. title: diet, gut microbiota and covid- date: - - journal: indian j microbiol doi: . /s - - - sha: doc_id: cord_uid: lp i v worldwide, millions of individuals have been affected by the prevailing sars-cov- . therefore, a robust immune system remains indispensable, as an immunocompromised host status has proven to be fatal. in the absence of any specific antiviral drug/vaccine, covid- related drug repurposing along with various other non-pharmacological measures coupled with lockdown have been employed to combat this infection. in this context, a plant based rich fiber diet, which happens to be consumed by a majority of the indian population, appears to be advantageous, as it replenishes the host gut microbiota with beneficial microbes thereby leading to a symbiotic association conferring various health benefits to the host including enhanced immunity. further, implementation of the lockdown which has proven to be a good non-pharmacological measure, seems to have resulted in consumption of home cooked healthy diet, thereby enriching the beneficial microflora in the gut, which might have resulted in better prognosis of covid- patients in india in comparison to that observed in the western countries. ever since the outbreak of covid- occurred in wuhan, china in december , it has rapidly spread throughout the globe. in view of the scourge of this disease world over, the world health organization (who) declared it as a pandemic on march , [ ] . by now, it has affected approximately . million people worldwide (as on th july, ) and the number continues to increase. thus, the entire human population is being threatened to get exposed to this highly contagious virus sooner or later [ ] . infection with covid- has been associated with significant mortality, particularly in the high-risk group such as health care providers and elderly people, with or without comorbidities [ , ] . very recently, it has been proposed that people with an underlying chronic inflammation of the gut are more predisposed to a heightened cytokine storm when infected with this virus [ ] . cytokine storm has been defined as the over-production of early response cytokines leading to an increased risk of vascular hyper-permeability, multi-organ failure and eventually death, as a result of high cytokine concentrations which are not found to reduce over time [ ] . further, chronic gut inflammation has been suggested to result from a specific constitution of gut microbiome, with the latter being regulated by diet. for example, plant-based foods are likely to support a gut microbiome capable of inducing an appropriate level of anti-inflammatory response in the host in contrast to a pro-inflammatory immune response elicited by the gut microbiome of individuals consuming food products such as wheat, red meat and alcohol, thereby resulting in chronic gut inflammation [ ] . simultaneously, since many people had to undergo forced fasting during the covid- pandemic, it might have affected their microbiota. the main hypothesis underlying the study is that, can this lead to susceptibility to infections? and can vegetarian diet help to boost immunity and help human beings to fight the pathogens? believing the notion: ' we are, what we eat', this manuscript provides an opportunity to the researchers in the field of microbiology and medical health to carry out studies on the effect of forced fasting on gut microbiota and means to counter any potential ill effects. in this context, the present review envisages the possible association of diet and microbiota with the incidence/severity/recovery of covid- cases during the lockdown period (from th march to st may ) in india. dietary habits and amount of food consumed has been reported to shape the microbiome [ ] . predominant microbial phyla of the human gastrointestinal tract include bacteriodetes, firmicutes, actinobacteria, fusobacteria, proteobacteria and verrucomicrobium [ ] . of these, bacteriodetes (bacteroides, prevotella) and firmicutes (eubacterium, lactobacillus) constitute more than % of the bacterial population inhabiting the colon. in early s, É lie metchnikoff reported that bulgarians have very high life expectancy, which was attributed to the consumption of yoghurt, thereby meeting the requirement of harboring a good microbiota to maintain homeostasis [ ] . ever since then, several reports reflecting changes in the diet as well as the gut microbiota have made this hypothesis worth exploring. it is now a well-established fact, that modern western diet consisting of food, which is processed and kept in cold storage, has less fiber content in comparison to the diets consumed by developing countries [ ] . it has been shown experimentally that there was an increase in abundance of bacteria belonging to firmicutes phylum with a simultaneous decrease in the bacteria of bacteroidetes phylum in the gut of people residing in western countries. generally, bacteriodetes are found to be dominant in people with vegetarian diet whereas firmicutes are dominant in people having animal-based diet [ ] . for example, it has been reported that children from africa were enriched with bacteroidetes due to high fiber content in their diet. moreover, they possessed higher counts of bacteria, such as prevotella and xylanibacter, which have been reported to possess genes coding for molecules involved in hydrolysis of such complex plantbased polysaccharides (which are otherwise indigestible). they were also found to possess lower number of firmicutes and demonstrated increased amount of short chain fatty acids (scfas) in their faeces as compared to the microbiota of the children of european origin [ ] . the concentration of scfas is important at local (colon) or systemic (blood) levels for immunoregulation [ ] . even immigration to the us has been reported to westernize the human gut microbiome [ ] . migration, specially from a non-western nation such as india to western countries, has been reported to present with a decreased abundance of plant fibre degrading enzyme as a direct implication of decrease in the gut bacterial diversity. in these immigrants, bacteroides strain has been found to displace prevotella strains subject to the duration of stay in the usa. moreover, loss in gut-microbial diversity has also been shown to increase with obesity and the problem stands exacerbated in future generations [ ] . bacterial genera such as prevotella, lactobacillus, and carnobacterium were found to be more abundant in indian population as compared to the chinese population. also, prevotella and bifidobacteria were the dominant genera in indian population owing to the vegetarian diet followed by most inhabitants in contrast to chinese inhabitants where bifidobacteria and blautia were found to be most abundant which can be attributed to the increased consumption of animal based diet therein [ ] . recently, pareek et al. [ ] compared the gut microbiota of indian and japanese population and have also indicated the diet dependent interaction between bacteria and fungi residing in the gut. it has been observed that presence of more plant polysaccharides in indian diet as compared to that of japanese leads to increased numbers of prevotella and candida in the gut of indians. moreover, candida species were found to promote the proliferation of prevotella when provided with arabinoxylan rich diet [ ] . india records the second largest population along with being the seventh largest country in the world and exhibits diverse dietary habits, ethnicity, and lifestyle. various studies have highlighted the link between the diet and gut microbiota profile of indians [ , ] . core microbiota analysis of indians revealed the distinctive predominance of genus prevotella in % of the population while almost % of the population harbored bacteroides, prevotella, megasphaera, and roseburia in their gut [ ] . one comparative study also indicated that prevotella are the dominant species in the gut of most north-central indians, who mostly consume plant-based carbohydrate rich diet whereas bacteria such as bacteroides, fecalibacteria and ruminococci make a significant part of gut microbiota of south indians who mostly consume an omnivorous diet [ ] . another comparative study revealed that the gut bacterial profile of indian tribal population is like that of the mongolian population because of similar dietary habits [ ] . the effect of urbanization on the gut microflora of humans in india has shown a clear difference between the gut microbiota profiles of the rural and urban counterparts [ ] . it was observed that bacteroides species were found to be abundant in indians residing in urban areas whereas prevotella species were dominant in rural population. dietary habits have been reported as one of the driving factors for these differences. further, the amount of dietary nutrients including micronutrients (polyphenols and vitamins), macronutrients (carbohydrates, fats and proteins) as well as minerals and trace metals (magnesium, iron, selenium, zinc) have been reported to exhibit substantial effect on the gut microbiota [ ] . in vitro studies have suggested that polyphenols such as phenols, flavonoids, and lignans present abundantly in raw vegetables and fruits along with cereals and drinks such as coffee, tea and wine could greatly modulate the gut flora favouring the growth of potentially beneficial organisms such as lactobacillus, bifidobacteria, akkermansia and fecalibacteria, simultaneously inhibiting the growth of potentially pathogenic bacteria such as helicobacter pylori and staphylococcus species [ ] . preclinical studies and clinical trials have shown that polyphenols affect the ratio of firmicutes to bacteroides (f/b) [ ] . this could be attributed to the prebiotic like activity of the polyphenols (for example, inulin has been reported as a prebiotic for lactobacillus plantarum [ ] and their biotransformation to produce scfas, along with other bacterial metabolites, that contribute to the growth of beneficial bacteria resulting in a significant reduction in inflammation and thereby improving the systemic state of disease [ ] . likewise, vitamins c (lemon, spinach, broccoli), d (eggs, fish) and e (almonds, spinach, broccoli, olive oil) supplementation have been found to modulate health-beneficial microbiota (bifidobacteria, lactobacillus, and microbes of the genus roseburia) and reduce the f/b ratio [ ] . however, modulation of the gut microbial profile depends on the level of vitamins in the host. therefore, clinical trial pertaining to concerns regarding excess vitamin supplementation are required to address these issues. out of the minerals, zinc supplementation (milk products, nuts, read meat) has been reported to reduce the deleterious microbes and increase the beneficial ones in various preclinical studies [ ] . carbohydrates also play a pivotal role in influencing the gut flora. plant derived carbohydrate based high-fiber diet was found to increase the abundance of bifidobacterium and reduce the f/b ratio [ ] . most of the carbohydrates such as galacto-oligosaccharides, arabinoxylan, oligofructose institutes the growth of bacteria such as bifidobacteria, lactobacillus, roseburia, etc., which have been known to confer health benefits and has been found to influence the f/b ratio [ ] . certain carbohydrates have been reported to possess restorative activity in reversing the state of dysbiosis, thereby indicating their potential as a possible therapeutic intervention for management of various metabolic diseases. in case of fats, both the quantity as well as their type plays a major role in modulating the gut microbiota [ ] . for example, saturated fat reduces beneficial microbes such as bifidobacterium and fecalibacterium, thereby increasing the f/b ratio. on the contrary, unsaturated fat has been found to reduce detrimental microbes such as escherichia and streptococcus species and simultaneously increasing the beneficial bacteria such as bifidobacteria and akkermansia, hence lowering the f/b ratio. moreover, studies have also reported that high fat deteriorates the density of beneficial microbes whereas following it with a low-fat diet reverses this effect. similarly, based on their quality and quantity, proteins have also been reported to affect the heterogeneity and the constitution of gut flora [ ] . for example, whey protein increases bifidobacteria at low concentrations but decreases the same at higher concentrations. furthermore, animal-based proteins (eggs, fish, meat) have been reported to increase deleterious gut microbiota, thereby increasing the susceptibility of an individual to intestinal inflammation. however, preclinical, and clinical trials are still being carried out to confirm these effects on gut microbiota. in view of the above-mentioned information, it is suggested that a healthy diet leads to symbiosis and contributes immensely in maintaining homeostasis. on the other hand, dysbiosis is linked to various kinds of gut inflammation which eventually culminate in gut-associated co-morbidities [ ] . interdependence between the host and gut microbiota has been found to be indispensable [ ] . various studies have reported that mutualistic association between the two holds immense significance in maintaining an equipoise as the former provides the latter with a nutrient rich milieu and the latter in turn aids in various key functions necessary for host sustenance [ ] . in this regard, the impact of gut microbiota can broadly be classified into structural, metabolic, and protective functions. the gut microflora has been known to strengthen the gut barrier by enhancing expression of tight junction proteins and simultaneously inducing iga production and prominent bacteria that aid in both include bacteroides spp., f. prausnitzii, akkermansia muciniphila, roseburia spp.; probiotic bacteria including bifidobacterium and lactobacillus spp. [ ] . the metabolic functions include their ability to produce essential vitamins and simultaneously metabolize iron, other dietary carcinogens along with fermentation of non-digestible carbohydrates. the indigenous microflora also protects the host by preventing establishment of gut pathogens due to enhanced competitive binding by competing for nutrients, space, and host cell receptors along with production of various anti-microbial factors thereby resulting in pathogen displacement [ ] . the fermentation of dietary fiber by gut microbes, resulting in formation of short chain fatty acids, has been further known to regulate immune functioning via various receptors and pathways involving molecules such as g-protein coupled receptors (gpcrs). gpcrs such as gpcr and gpcr have been reported to regulate anti-inflammatory pathways such as enhanced reactive oxygen species (ros) mediated killing coupled with enhanced phagocytosis, induction of apoptosis, recruitment of specific proteins and cytokine production thereby contributing immensely to immune regulation [ ] . all these findings substantiate the role of gut flora, its composition and its role in immune system regulation owing to its ability in producing molecules such as scfa, peptidoglycans and polysaccharide a from a fibre rich diet, which significantly contributes to the maintenance of homeostasis. in addition to the regular diet intake, fasting is an integral part of many cultures worldwide and is considered auspicious traditionally. this concept has been getting scientific validations for its role in maintaining gut and immune homeostasis. intermittent fasting (if) (which includes alternate day fasting or time restricted feeding) has been reported to favorably influence the gut microbiota [ ] by increasing the abundance of beneficial akkermansia muciniphila and bacteroides fragilis [ ] . in fact, various animal trials and some human intervention studies have clearly demonstrated health benefits associated with if in people with underlying diabetes, obesity, and cardiovascular ailments [ ] . it has been established that plant food-based diet promotes the microbes that ensue anti-inflammatory response and is thus, known to maintain a more diverse and stable microbiota [ ] . in other words, a vegetarian diet seems to be more beneficial for human health due to its ability to maintain a state of symbiosis i.e., balanced microflora within the host. in contrast to this, certain food items such as gluten in wheat, red meat and alcohol can promote the growth of dysbiotic microorganisms which trigger a heightened pro-inflammatory response, thereby culminating in chronic inflammation [ ] . this chronic inflammation has been reported to cause gut leakiness due to degradation of tight junctions by various proteases [ ] , thus allowing the dissemination of cells, pathogenic bacteria, and viruses into the blood circulation and transforming the existing state of gut inflammation into chronic systemic inflammation [ ] . this chronic inflammation may remain undetected for years altogether, serving as a predisposing risk factor which may, at any time soon, aggravate into ailments and other serious manifestations, and therefore can be considered as a comorbidity. the term 'comorbidity' refers to any added illness in patients already suffering from a disease. in the recent decade, occurrence of psychiatric comorbidity in chronic disease has been widely observed and has been emphasized as an important aspect of disease management [ ] . various studies have reported the association of dysbiosis with the pathogenesis of various intestinal or extraintestinal disorders such as coeliac disease, cardiovascular disease, diabetes, and obesity [ , ] . similarly, kedia et al. [ ] have reported comparable changes in the gut microbiome of patients suffering from autoimmune (inflammatory bowel disease, ibd) as well as infectious diseases, suggesting the role of inflammation in the altered status of the gut microbiome. hence, it can also be inferred that comorbidity can arise because of dysbiotic inflammatory condition. the prevailing covid- pandemic situation arising from the spread of highly contagious virus led to a lockdown in various countries. indian government also announced the lockdown on march , , further followed by three more lockdowns. based on the interim guidelines of who, most of the countries opted for several non-pharmacological measures such as social distancing and masking along with lockdown of varying time intervals. though a huge global economic loss was incurred due to enforcement of restriction on outdoor activities [ ] , but lockdown was propounded to be the most effective way to mitigate this dreadful situation in the absence of any treatment procedures or therapeutic/prophylactic agents. lockdown implementation proved to be a reasonably effective strategy even in india (despite being one of the most populous country in the world), as by the end of th lockdown ( st may ), total number of confirmed infection cases in india were , (fig. a) with deceased cases [ ] . thus, on an average, only infected cases per lakh people were seen during the lockdown period (fig. b) . the fatality rate ( . ) of india was also observed to be the lowest as compared to the worst affected western countries (fig. b) and basic reproduction unit (r o ) was significantly reduced during the course of lockdown from r = . to r = . till the end of th lockdown ( st may ). r o or basic reproduction unit is the ratio of transmission rate to recovery rate calculated by sir modelling study [ ] conducted in our lab (data not reported here). a positive impact of lockdown up to the second lockdown period is clearly visible in fig. c , after which a rapid upsurge in the cases was observed which can be mainly attributed to considerable relaxations made by the government of india. it may be argued that the number of confirmed cases represented may not be correct because of insufficient testing of the indian population as only symptomatic people with a travel history to affected countries or people in close contact with the covid- positive case were being tested [ ] . in this case, it is also worth noting that in india, an enough percentage of infected individuals have been reported to be asymptomatic (approximately %) [ ] . therefore, it can be presumed that even if infected cases are there, these are probably asymptomatic due to the healthy dietary habits and symbiosis. however, being asymptomatic is always a risk of transmission of infection to others and that is where measures like social distancing, masking and respiratory etiquettes prove to be of immense benefit. here, it may be inferred that plant based, home cooked, rich fiber diet consumed by the indian population during lockdown, might have resulted in generation of symbiotic microflora, thereby eliciting anti-inflammatory responses. indian diet is also rich in whole grains, which are a rich source of dietary fiber, carbohydrates, resistant starch and oligosaccharides. these are fermented in the colon after escaping digestion in the small intestine and result in production of scfas, which act as an energy source for the colonocytes, lower the colonic ph as well as alter the blood lipids, hence eliciting an immune response beyond the gut [ ] . whole grains are also rich in antioxidants such as phenolic compounds which have been shown to result in disease prevention [ ] . moreover, whole grains also possess certain compounds which may reduce the risk of chronic diseases such as diabetes, obesity, and cancer. furthermore, state wise data distribution within india presented that the states where millet is the staple food, less prevalence of the disease was observed along with a higher recovery rate and a lower fatality rate. simultaneously, a shift from animal-based diet to plantbased, fiber rich diet, has been reported to be associated with a change in microbiota (which changes within days to weeks) [ ] . this shift was expected during the lockdown in the indian population. this might have downregulated any pre-existing chronic inflammation, thereby reducing the occurrence of cytokine storm. due to an almost total shutdown, it can be presumed that the public had limited access to animal based or ready to eat processed food, which is generally rich in refined carbohydrates and fats. the lockdown very successfully steered the public to consciously consuming homemade healthy diet, which probably resulted in reduced incidence/severity of disease during this period due to an improved microbiota or symbiosis. it was also observed that besides having many cases, india was spared from the fatality caused by sars-cov- as compared to other countries, especially western countries, such as usa (fig. b) . usa ( , , ) and brazil ( , ) have maximum number of cases followed by european countries [ ] . both the regions consume meat rich diet and saturated fatty acids. pro-inflammatory responses triggered due to such a diet may lead to fatal complications in patients infected with covid- , where lung epithelial cell inflammation might have detrimental consequences. moreover, it was also observed that due to lockdown restrictions in the western countries, access to fresh vegetables or fruits were also restricted to the population, unlike india, where daily grocery items such as fresh fruits, vegetables, and milk were accessible to the public daily. the former situation might have resulted in increased consumption of processed food, leading to dysbiosis and simultaneously resulting in addition of more cytokines to the pro-inflammatory milieu. increased consumption of processed foods which are mostly rich in fats, sugars, and salts, not only increases the risk of lifestyle diseases such as obesity and cardiovascular problems in patients suffering from chronic inflammation, but has also been found to have grave implications in enhancing covid- related complications [ ] . most of the covid- related deaths reported in india so far, might be attributed to the immunocompromised status of the individual as most of them were found to be suffering from some comorbidity such as hypertension, diabetes or other cardiovascular diseases [ ] . therefore, early implementation of lockdown by indian government was a great step towards preventing a catastrophe as there are over crore hypertension patients and about million diabetic patients in india [ ] . a tool developed by the oxford university, oxford covid- government response tracker (ofcgrt), also applauded the indian government for having done exceptionally well in curtailing the coronavirus outbreak [ ]. an italian survey carried out by di renzo et al. [ ] , has also highlighted some of the positive effects of the lockdown, such as, a higher indulgence in physical activity and adoption of healthier lifestyles by quitting smoking. moreover, an increased adherence to the mediterranean diet was seen in the age group of - , which might have reduced the risk of oxidative damage and in turn, the susceptibility to covid- infection. this survey also emphasized the protective potential of healthy plant-based diet as compared to the processed food or animal-based diet. further during the lockdown period several of the daily wagers including migrant workers faced adversity and underwent phases of forced starvation. similarly, people working in corporates away from their homes and taking their meals outside may also have faced situations where they underwent phases of no or little food during the lockdown. this situation is comparable to an intermittent fasting condition. in this context, it can be speculated that if might have given the advantage to some by enriching their beneficial gut microbiota and thus the former nonpharmacological interventions can have special implication amidst the covid- crisis, assisting the microbiomeimmune axis. it may be noted that perhaps, deaths which occurred amongst migrants were due to road accidents or starvation but not due to sars-cov- infection! on the other hand, quarantine has also been reported to induce stress which leads to 'stress eating' wherein individuals tend to increasingly consume food with high fat and sugar content thereby leading to obesity. an obese individual has been reported to possess a decreased immune function demonstrated by a deficit in cd ? t cells responses used to combat viral infections. this leads to higher mortality due to increased viral load in lungs and is also coupled with lung pathology [ ] . furthermore, in western countries it was observed that a diet poor in fresh fruits and vegetables was more frequently ingested, thereby reducing the daily required intake of antioxidants and vitamins, which have been reported as potential weapons against the covid- . therefore, strategies which encourage healthy diet and increased home-based physical activities should be implemented to reduce the risk of above-mentioned conditions. in addition to a decline in the physical health of individuals due to ingestion of improper food, the effect of quarantine in deteriorating the mental health, especially in children, was also observed [ ] . herein, we would like to point out that such a condition may be avoided if the person is accustomed to healthy diet or diet supplemented with healthy microbes such as probiotics [ , ] . disturbances at the gut-brain axis, occurring due to various gastro-intestinal conditions, have been implicated in various mental health abnormalities as well such as anxiety, mood disorders and depression [ ] . probiotics have been reported to restore this balance and act as 'psychobiotics', thereby serving as an alternate treatment option. in this context, we recently studied the effect of a potential probiotic strain, lactiplantibacillus plantarum (rta ), on psychological, histological and physiological status of diseased host and its role in ameliorating host health by modulating various aspects of the gut-brain axis [ ] . the schematic representation of the possible association as mentioned above has been shown in fig. . given the purported association of microbiota with covid- cases, studies on analysis of gut microbiome using faecal samples of these cases are warranted to validate this hypothesis. briefly, it can be concluded that the high fatality rate in western countries as compared to india, during the lockdown, can be attributed to ( ) their animal based diet which increases dysbiosis, hence increasing the pro-inflammatory cytokines resulting in cytokine storm in contrast to the sattvic diet of the indian culture including plant based diet and use of traditional medicine as recommended by the ministry of ayush (ayurveda, yoga and naturopathy, unani, siddha and homeopathy), government of india [ ] ; ( ) the unhealthy dietary habits during lockdown, especially attributed to limited access to fresh grocery shopping, thus resulting in an increase in underlying conditions; ( ) the late implementation of lockdown in contrast to the timely implementation of lockdown by the government of india; ( ) the possibility of a more virulent variant of covid- strain prevalent in western countries in comparison to that prevalent in india due to high mutation rate in the genome of sars-cov- virus [ , ] and; ( ) india, being a developing country, is more exposed to infections as compared to the developed nations, thereby resulting in priming of their immune response against a wide variety of microbes leading to a better immune status than that observed in the western population. there has been a growing appreciation of the role played by commensal microbiota in human health. here, diet has been found to play a crucial role in modulating the gut microbiota, thereby resulting in symbiosis or dysbiosis. in this context, people should be enlightened about the importance of daily intake of a balanced diet which can be better defined and prescribed through the help of nutritional biologists and food industries. a balanced diet, like the ones prepared by the dieticians in hospitals and hostels of educational institutions, can also be defined for public. the same can also be supplied to the migrants and the economically weaker sections of the society to prevent malnutrition. furthermore, the importance of intermittent fasting or following a fasting-mimicking diet can be an indian j microbiol important advisory to the population, for not only restoring beneficial gut microbiota but promoting overall health as well. rapid advancements in the molecular techniques for assessment of human gut microbiome has helped in defining the diversity and metabolic properties of the gut microbiota. intestinal microbiota of the host can be modulated through administration of synbiotics (probiotics and prebiotics), thereby conferring holistic health benefits. developing such a combination of probiotics and prebiotics may ultimately prove to be more cost effective than developing new drugs. gut microbiota can be modulated by enriching it with beneficial ones and eliminating the pathogenic microbes using antipathogens as an alternative to antibiotics [ ] [ ] [ ] [ ] [ ] [ ] [ ] . the acceptance of scientific community/physicians for their application, specific to the control of infection, beyond the accepted source of health promoting effects is important. in addition to the regulatory and scientific constraints, public acceptance may be another hurdle which needs to be surmounted by educating and enhancing awareness to increase intake of probiotics/ prebiotics along with plant-based fiber rich diet to the recommended level. as per the experience gathered during the lockdown period, a significant increase in the cleanliness quotient has been observed in the environment which is crucial for decreasing the incidence of infections along with contributing to robust health status of individuals. as environment is directly related to health, therefore, even post this covid- pandemic, lockdown for a specific period once in every year may be practiced enriching the environment as well as health [ ] . this would also give opportunity, particularly to the next generation, in inculcating good habits of healthy diet to strengthen their immune system. in this regard, the concept 'let food be thy medicine', proposed by hippocrates way back in bc, needs to be revisited, particularly during such situation as the present one, when there is no therapeutic or protective agent available and for now, cure lies only in prevention. covid- pandemic in india: what lies ahead cumulative active and recovery rates based criterion for gradual lockdown exit: a global 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of rapidly evolving sars cov- viruses reveal mosaic pattern of phylogeographical distribution quenching the quorum sensing system: potential antibacterial drug targets genomic analysis reveals versatile organisms for quorum quenching enzymes: acyl-homoserine lactone-acylase and-lactonase quorum sensing inhibitors: an overview extending the limits of bacillus for novel biotechnological applications evolution of resistance to quorum-sensing inhibitors quorum sensing inhibitors as antipathogens: biotechnological applications inhibition of microbial quorum sensing mediated virulence factors by pestalotiopsis sydowiana reconciling hygiene and cleanliness: a new perspective from human microbiome key: cord- -bj pp d authors: bhattacharyya, a.; bhattacharyya, d.; mukherjee, j. title: the connection of growth and medication of covid- affected people after days of lock down in india date: - - journal: nan doi: . / . . . sha: doc_id: cord_uid: bj pp d the covid- pandemic has already consumed few months of indolence all over the world. almost every part of the world from which the victim of covid are, have not yet been able to find out a strong way to combat corona virus. therefore, the main aim is to minimize the spreading of the covid- by detecting most of the affected people during lockdown. hence, it is necessary to understand what the nature of growth is of spreading of this corona virus with time after almost one month ( days) of lockdown. in this paper we have developed a very simple mathematical model to describe the growth of spreading of corona virus in human being. this model is based on realistic fact and the statistics we have so far. for controlling the spread of the covid- , minimization of the growth with minimum number of days of lockdown is necessary. we have established a relation between the long-term recovery coefficient and the long-term infected coefficient. the growth can be minimized if such condition satisfies. we have also discussed how the different age of the people can be cured by applying different types of medicine. we have presented the data of new cases, recovery and deaths per day to visualize the different coefficient for india and establish our theory. we have also explained how the medicine could be effective to sustain and improve such condition for country having large population like india. the declaration of pandemic situation due to covid on th march by who [ ] has made almost all the world to lockdown several countries, either partially or fully to control the spreading the virus. the invisible manifestation o f a respiratory infection with symptoms ranging from mild common cold to a severe viral pneumonia leading to acute respiratory distress, is potentially fatal for the people having copd and other lung deceases. the outbreak of such virus was earlier predicted in china [ ] . the present time motivation is to find out as much possible number of such infected cases to slow down the contamination chain of the virus. hence more and more testing were done during the lockdown period to identify the victims of covid . at the same time, it is also an important that we can identify the maximum number of cases with minimum lockdown days, since the lockdown hampers the economical growth. there are lots of societal impact of lockdown which has already been reported [ ] . hence the question is how to minimize the spreading of covid- ? scientists are trying to develop many statistical and mathematical model [ ] [ ] . recently a few mathematical models have come across to describe this spread of corona virus to estimate the minimum number of lockdown days to reach base line of the contamination [ ] [ ] [ ] [ ] . almost every natural phenomenon follows an exponential law and hence to saturate the graph we must maintain a long lockdown period. at the contemporary time, we see that the number of corona virus infected people are increasing day by day even after days of constant lockdown. hence to minimize the effect we must need a vaccine to stop the increase of spreading, or we must involve in r&d that which medicine is applicable for faster recovery of patients. no such strong evidence has yet been published so far, that connects the medicine to mathematics. here in our paper we propose a simplistic model to visualize the control the covid- growth. is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint to build the growth equation with time. the minimization of the growth equation shows a relation between the coefficients. we have explained this and corelate the effect of medication. to construct a growth equation of corona virus affected people, we have taken into consideration of four numbers. the number of corona virus affected people at ant point of time will be denoted by n(t). n be the number of preexisting active case. the number of daily upcoming case will be denoted by n (t). there are a huge number of people who are recovering daily and let's say those number is n (t) and finally, n (t) is the number of people dying with time. now at any instant, we can write an equation which can balance between all the parameters. the negative sign of n (t) and n (t) are negative because it reduces the number of covid- patient at any point of time. if any change in the number of covid - patient will be given by the rate of change of n(t), i.e. dn(t)/dt which can be obtained by having derivative of the equation ( ). the derivative of n is put to zero since it is a constant number. now currently we introduce a new concept. we know that the growth of natural phenomena increases exponentially with time. let us assume that the growth of daily reported case, recovered people increases cubic polynomial of time, whereas the number of people who died varies with linear in time (since the mortality rate in india is very less compared to the other countries). then the n (t), n (t) and n (t) can be written as follows. n (t) = n + a t +b t + c t , n (t) = n + a t +b t + c t , n (t) = n + a t where a i , b i , c i are the co-efficient of different polynomial term which has different physical significance and 't' is the number of days spent after lockdown announcement. these assumptions are based on completely realistic point of view. the coefficient plays important roles in controlling the spread of corona virus. if the coefficient of t i.e. a in new cases data, is greater than the coefficient of t , i.e. b than that of c (a >>b >>c ) then with a smaller number of days we have to spend as lockdown to reduce the number. again, if the coefficient of t i.e. b is less than c then we have to spend more days in lockdown to minimize the number. the same can also applicable for n (t) and n (t) also. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint suppose t = , then t = and t = , we can stay in lockdown for days but not the days. hence the coefficient of t must be very less. hence our approximation can be a valid and good approximation. now to understand the minimization of growth to control the spreading of covid - we have to find the minima of the dynamical equation ( ) . to do that let us first put the polynomial expansion of n (t), n (t) and n (t) in the equation ( ). the equation ( ) is actual dynamical equation of covid spreading in terms of new cases, recovery and death parameters. zeroing the first order derivative of the equation ( ) gives the no of days to reach extrema. the equation ( ) . now to equation ( ) to be minimum (c -c ) > , or c > c . as we have already discussed above that the coefficients c i are related to long term case detection and recovery. this in equality suggest us that if the cubic power recovery coefficient is greater than the cubic power infected coefficient, then we can minimize the growth of spreading corona virus. this inherently implies that as the days go on the greater number of recoveries of the patient is required to overcome this problem. simplest way it can be said that if we can increase the recovery rate gradually then we can easily reach the minima and will be able to control the covid- epidemic. in case of india the recovery rate is gradually increasing compared to other countries. hence it is possible control covid pandemic in india earlier than other countries. to interpret our model, the daily affected case, recovery number and the mortality number with time are presented below. all the data are considered from month of lock down to days of lockdown. we only consider the data for india to illustrate our model. fig depicts is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint the fitting that the coefficient of t in new case is less than the coefficient of t in recovery case. hence the corona virus spreading can be controlled in india in due course of time. there is no such medication to covid - affected people. firstly hydroxychloroquine (hcq) is seemed to be a good medication for such decease. india is a very popular source of such medicine. sars-cov- utilizes surface receptor like angiotensin converting enzyme (ace ) like covid- and hence it is believed that like . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint chloroquine it can also interfere with ace receptor glycosylation and thus prevents sars-cov attachment to the target cells. moreover, hcq is more potent agent than chloroquine due to less toxic nature. chinese researchers found that chloroquine to be highly effective in reducing viral replication that can be easily achievable with standard dosing due to its favourable penetration in tissues including the lung [ ] . recently an excellent recovery was observed in % of the patients treated with one dose of remdisivir daily, according to an analysis published in the new england journal of medicine [ ] . the recovery takes days of time with single medication and the mortality rate is also very less in such case. remdisivir is medication of ebola virus where as hcq is a for treatment of rheumatoid arthurites (ra). in a recent study in gilead reveals that the average time to clinical improvement was days in the five-day treatment group and days in the -day treatment group [ ] . more than half of the patients in both groups were discharged from the hospital by day . hence remdisivir is supposed to be considered as fast recovering medicine for the age group of to years. hcq application to covid- patient takes a few days more to recover than remdisivir ever after days treatment [ ] . hence, remdisivir and hcq are both good medicine for covid- affected people. who has started a solidarity trail on th march this year on covid- affected people using four medicine [ ], . remdisivir, . lopanavir/ ritonavir . lopanavir and ritonavir with interfirm beta and lastly . hcq. the national institute of allergy and infection decease (naid) has announced remdisivir to be superior than hcq. so, we suggest that remdisivir can also be applicable for india for quicker recovery. moreover, due to other vaccination (bcg, hepatitis etc.) among younger age, the immunity power is very good and hence the recovery is faster (till now almost %). wide coverage of bcg vaccination in india may lead to lesser fatal outcome of the decease but researchers are still working on it and relevant research papers are yet to be published. since india is a tropical country, lots of people use sunscreen gel which are full of zinc oxide. the zinc has excellent power to destroy the replication chain of covid . hence it is also an important factor to stop spreading the corona virus. in this paper we have tried to establish a connection between the spreading of corona virus and recovery of corona virus. we use indian statistical data to establish our theory. the effect of medication on different age of people is also discussed. the scope of further improvement of recovery rate in india is also suggested in terms of application of medicine to covid affected people. hence if the recovery is faster, then the coefficient of . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint t of recovery will be greater and hence we will have control over covid . we invite the researchers from all communities to come forward and work on covid according to their expertise. it may be helpful for fighting against such epidemic disease. our analysis could give well explanation of daily affected people in last days lockdown and in near future. we strongly believe that india will recover soon from the present situation. . cc-by-nc-nd . international license it is made available under a is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. (which was not certified by peer review) the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint bat coronaviruses in china epidemic processes in complex networks statistical physics of vaccination fear of exponential growth in covid data of india and future sketching possibilities of exponential or sigmoid growth of covid data in different states of india subhasis samanta , sabyasachi ghosh, covid- prediction for india from the existing data and sir(d) model study doi jm thank to dr. dipak bhowmik, iit kanpur for valuable reading of manuscript and ms. rinku mondal, university of burdwan for valuable suggestion. all the authors contribute equally throughout the data analysis, mathematical interpretation and paper writing. is the author/funder, who has granted medrxiv a license to display the preprint in perpetuity. the copyright holder for this preprint this version posted may , . . https://doi.org/ . / . . . doi: medrxiv preprint key: cord- -nxjfbo h authors: kumar, amit; mishra, saurabh; taxak, a.k.; pandey, rajiv; yu, zhi-guo title: nature rejuvenation: long-term ( – ) vs short-term memory approach based appraisal of water quality of the upper part of ganga river, india date: - - journal: environ technol innov doi: . /j.eti. . sha: doc_id: cord_uid: nxjfbo h the deteriorating water quality (wq) of the sacred north-flowing perennial indian river, ganga was a serious concern in recent decades for population adjoining to the river and policy planners. the present evaluation attempts to assess the long-term ( – ) physiochemical characteristics of wq of river ganga at five upstream locations (uttarkashi, tehri, rudraprayag, devprayag, and rishikesh) of uttarakhand, india using comprehensive pollution index (cpi) and environmetrics (pca and ca). these methods were used to categorize, summarize expensive datasets, and grouping the similar polluted areas along the river stretches. the wq of river at all the locations were within the good category and most of the physiochemical parameters were well within their acceptable limit for drinking wq. considerably, cpi demonstrated the river wq was in slight pollution range (cpi: . – . ) in the year and at all the five locations. the positive correlation coefficient (r( ) > . ) among no( ) [formula: see text] no( ), ca, na, b, and k indicates the significant contribution of organic and inorganic salts through runoffs from catchments due to weathering of rocks. pca confirmed the input source of nutrients in the river from both natural and anthropogenic sources. moreover, the upstream wq assessed was found to be good as compared to the severely polluted downstream region. due to covid- and shutdown in the country, reduction of pollution load in the river was observed due to the rejuvenation capability of river ganga. this information can assist the environmentalist, policymaker, and water resources planners & managers to prepare strategic planning in advance to maintain the aesthetic and cultural value of ganga river in future. water resources and quality of freshwater are the foremost basic need of flourishing ecological diversity and sustainable development. the rapid growth of human population, urbanization, and industrialization have stimulated the over-extraction of water from the freshwater sources (e.g., river, lakes) for various purposes of the daily demands of a comprehensive study of wq assessment using long term data of physiochemical and biological parameters has not been reported in the upstream of the river ganga. the lack of long term evaluation restricts the visualization of changing wq at one side and reduces opportunities to facilitate enabling conditions for management of water crisis (tripathi and singal, ) . considering the lack of information about temporal changes in the wq and thereby refraining for developing the suitable policies, the present study is focused to analyse the long-term variation in wq of river ganga at the site of culturally important upstream regions (i.e., uttarkashi, tehri, rudraprayag, devprayag and rishikesh) of uttarakhand, india. attainment of this purpose is formulated on the premise to classify the overall wq of the river with respect to the suitability of water for human consumption purposes and to identify the major contaminants that imbalance the wq of river ganga. the data sets for physiochemical and biological parameters were collected on monthly basis during the years - for achieving the objective. primarily, the comparative analysis of individual parameters to the standards prescribed at the regional and international scale is performed to identify the wq for anthropogenic purposes. moreover, the available datasets are used to evaluate water quality indices (wqi) as comprehensive pollution index (cpi) to classify the overall water pollution in the form of single numeric value. several wqi is available to classify the overall water quality of a freshwater body for anthropogenic uses (kumar et al., a,b; khan et al., ; panwar et al., ) , however, cpi a comprehensive numeric evaluation method for evaluation of surface water pollution was preferred for being a concise aggregation of various wq parameters. furthermore, the application of environmetrics like principal component analysis (pca), and hierarchical cluster analysis (hca) was applied to identify the loading source of pollutants and similarity of pollution among the sampling locations. the government of india has formed an administrative body called as national mission for clean ganga (nmcg) under the ministry of jal shakti to look after the planning and implementation of projects related to rejuvenation of river ganga that involves national and international organizations. the result of the present study would provide information to nmcg, environmentalists, policy-makers, water resource planners, and managers to understand the sources of pollution, pollutions sites, and making strategic mitigation plan to maintain the aesthetic values of the river. river ganga is one of the sacred freshwater bodies of india, flows in northern part of the country. two himalayan rivers are known as bhagirathi and alaknanda covers km and confluence at devprayag in uttarakhand and carries the name called ''river ganga'' in its flow pathway after this confluence. bhagirathi originates from himalayan gangotri glacier located at an elevation of m amsl, in uttarkashi district, while alaknanda originates near the holy shrine of badrinath, located at an elevation of m in chamoli district of uttarakhand, india. since devprayag, river ganga flows downstream through the mountainous region for about km before entering in the plain at haridwar district of uttarakhand. further, river ganga covers about km of downstream flow stretch across the states of uttar pradesh, bihar, and west bengal of india and finally merges into the bay of bengal (kumar et al., a,b) . in addition to a strong cultural presence among the residents of india specially the hindus, the river has diverse ecological relevance and contributes huge support to the indian economy. each city and ghats located along the stretch of river ganga have religious significance, as being either as a spot for temples or for cremation place, thereby attracting the pilgrims from all over the country and globe (pandey and yadav, ) . the river receives a huge amount of partially/untreated wastewater from domestic, industrial, and agriculture sectors along the stretch from its origin at gomukh (tripathi and singal, ; mishra and maiti, ; . considering the importance of river, entrance of wastewater, and land-use patterns, surface water monitoring, and assessment were carried out in the upstream region of river ganga and its main tributaries. the variation in temperature of the study areas remains in the range from to • c. in pre-monsoon (summer) and monsoon season, average temperature at upstream, midstream, and downstream was found to be - • c, - • c and to > • c, respectively, while during post-monsoon season (winter), the average temperature at upstream, midstream and downstream was - • c, - • c and to > • c, respectively (cwc, ). the water quality data (jan to jan ) were collected from the five major locations, as uttarkashi, tehri, rudraprayag, devprayag, and rishikesh. these locations were part of the himalayan mountain region. the details of the data collection sites are reported in table with their respective locations in fig. . in this study, the sub-surface water samples were collected from the selected sampling locations during the day time between : - : am, on the first day of every month from january to january for evaluations of the physicochemical parameters like ph, dissolved oxygen (do), electrical conductivity (ec), and surface water temperature (wt) using portable analytical instruments. the details are provided in supplementary table s . the composite water samples were filled in three acidrinsed airtight plastic containers of ml volume at each location, which were further stored at • c temperature without freezing to avoid unpredictable changes in quality before analysis. among three contained samples, one sample was fixed in biochemical oxygen demand (bod) bottle for the analysis of bod, while other two contained samples (kept unfixed) were used for the analysis of other water quality parameters. the contained samples were transported to the laboratory within h for experimental analysis. the experimental analysis of water quality parameters was performed in triplicate as per the procedure reported in apha ( ) and the mean value of observations was estimated. the experimental procedure followed for analysis of physicochemical parameters with their abbreviation, measurement unit, and the numeric value of standard acceptable limit in drinking water, prescribed by bis and who , is provided in supplement table s . the water quality data obtained during laboratory analysis were provided by central water commission (cwc; http://india-wris.nrsc.gov.in), a body of ministry of jal shakti under government of india to carry out river water pollution assessment in this study. real-time data of water quality in the river ganga at downstream regions during april has been taken from cpcb ( ) and used to see the effect of water quality during country lockdown (covid- ) at downstream locations. in order to identify the variable parameters that affect the river wq, the data obtained during laboratory analysis of water samples were compared with respect to their respective standard acceptable limit (sal) value. based on that, the collected wq data were used to evaluate the cpi to classify the overall wq status of river ganga in single numeric terms at a particular sampling location in the respective month. the cpi is evaluated based on those parameters whose sal has been prescribed as per bis ( ) and who ( ) . parameters like do, ph, bod, ec, cod, alkalinity, total dissolved solids (tds), total hardness (th), and chloride were used to evaluate the index value. the mathematical equations (eqs. ( ) and ( )) of cpi are expressed below: where pi represents sub-pollution index of ith parameter of water quality, c i represents concentration value of ith parameter obtained during laboratory analysis of collected water samples, s i represents sal of ith parameter for drinkable water, and n is the total number of wq parameters. the wq status classified by cpi value and ranges from to . and divided into five classes for indicating respective wq status as - . (excellent quality); . - . (good quality); . - . (slightly polluted quality); . - . (moderately polluted quality); ≥ . (severely polluted quality). in order to standardize the large dataset of wq parameters, the mean, median, kurtosis, skewness, population standard deviation, and z-test values were calculated, which were further used to assess the comparative responses of different sampling locations on a common scale. as the focus of the study is on overall response across the sampling locations, the z test value is used to centre all year's (january to january ) monthly data on their mean value to reduce the influence of any individual year data, which might have high average raw values of a particular parameter that unduly affect statistical analysis (spears et al., ) . the datasets were used to perform the statistical analysis to identify the root causes of wq deterioration of river ganga. the statistical analysis of wq parameters was performed through the hca and pca using spss, version . software. for hca, a mean value of all year's monthly data of each parameter was evaluated and used to construct cluster of sampling locations that depicts the similarity in pollution load among the sampling locations. further, pca was performed using raw data of wq parameters for each sampling location to identify the most influential parameter of water quality deterioration and to predict the sources of pollution in the river (tripathi and singal, ) . the physicochemical characteristics of water in river ganga were assessed at five upstream locations on the first day of each month from january to january . the descriptive statistics of parameters (like do, ph, ec, bod, ta, f, b, ca, mg, cl, so , na, k, no +no , and wt) obtained from the analysis of water samples were represented as box-whisker plots (figs. and ). the mean of individual parameter was estimated based on all sampling months along with median, kurtosis, skewness, and z-test values ( table ) . the onsite measurement of ph value falling in the range of . - . , . - . , . - . , . - . , and . - . at locations s , s , s , s , and s , respectively, with overall mean value of ∼ . and median value of ∼ . - . at all sampling locations. the maximum value of ph (> . ) was obtained in january at all locations, while it remained stable within the sal (ph . - . ) in other months. the wq parameters wt and ec were within the sal at all locations in sampling period, with maximum values ranging from to • c, and to µs/cm, respectively. the minimum concentration of do was . , . , . , . , and . mg/l, while the maximum bod concentration was . , . , . , . , and . mg/l at s , s , s , s , and s locations, respectively. the lower concentration of do < sal ( mg/l) and higher concentration of bod > sal ( mg/l) at location s were obtained in summer and monsoon months. the location s is an important tourist destination and attracts huge tourists resulting in the excessive anthropogenic hindrance in terms of bathing, river rafting, and other recreational activities in monsoon months. notably, the overall median concentration of do and bod were obtained as ∼ mg/l and ∼ . mg/l at all sampling locations. in addition, input of agricultural and forest runoff from the catchment in monsoon month were the major causes of decline in do with increase in bod concentration in the river at location s . according to cpcb ( ), if the ph and ec of surface water lie within ≤ ph ≥ . , bod ≤ mg/l, do ≥ mg/l and ec < µs/cm, the water could be considered suitable for bathing, and irrigation purposes, but require conventional treatment for using for drinking ((kumar and gupta, ) . the concentration of ta, cl, mg, and so was observed within their sal at all sampling locations at each month. until february , the concentration of fluoride in the river was estimated above the sal value of mg/l, while it became within sal from march to january at all sampling locations. the improvement in wq was due to decline in f concentration indicating the reduction of fluoride contaminated wastewater directly discharged into the river. the reduction is attributed to the impacts of gap-ii (tripathi and singal, ) . mean and median concentration of b was obtained within the sal value of . mg/l during the sampling period. however, during the monsoon season in year , the maximum b concentration of ± . , . ± . , . ± . , . ± . , and . ± . mg/l were observed at sampling locations s , s , s , s , and s , respectively. the mean and maximum value of ca concentration were within the sal value of mg/l at locations s , s , and s during the sampling period. although, the mean value of ca concentration at location s and s were obtained as . and . mg/l during the sampling period, but the maximum ca concentration was above the sal during monsoon months in the year for both locations. the concentration of no +no in river water was found in the range of . - . mg/l, and was lower than the sal (no : mg/l). the comparative analysis of wq datasets with their corresponding sal values reveals that the wq of river ganga was suitable for human use after conventional treatment. our results were within the sal and supported by kumar et al. ( ) based on physiochemical characteristics (i.e., do, bod, cod, and ta) of wq in river ganga at devprayag and rudraprayag. similar to the present estimate, the physiochemical and heavy metal (pb, cu, zn, and ni) concentration was found to be either absent or within the sal with alkalinity (na+ k) type at rishikesh (haritash et al., ) . in order to ensure the variability and statistical significance of data, the raw water quality data was used to evaluate kurtosis, skewness, and z-test values of individual parameters. at location s , the kurtosis of parameters ph, bod, f, b, so , na, k, and no +no were found to be > , meaning heavier tails than a normal distribution. the kurtosis of parameters ta, ca, and wt were evaluated as − . , − . , and . , respectively indicating the flatter peaks and lighter tails than the normal distribution. the negative skewness of − . , − . , . , − . , and − . were obtained for parameters ph, ta, ca, mg, and wt, respectively, indicating the tail of the left side of the distribution is fatter or longer than the tail on the right side. the z-value was zero for parameters ec, ca, and mg and positive for parameters bod, b, na, no +no , and wt, while negative z-value for others that signifies the raw score below the mean average. similarly, the kurtosis, skewness, and z-value of parameter datasets were also evaluated at locations s , s , s , and s . comparatively, a wide variation in kurtosis value of parameters bod, b, cl, na, k, and no +no was obtained at all locations indicating variable input of nutrients through wastewater or surface runoff discharge at different locations. moreover, it is required to draw meaningful information, and classify the overall water pollution status at respective sampling locations in the river. cpi was estimated to classify the water pollution status at upstream region of river ganga from to . in order to present the seasonal water quality status, mean cpi value was evaluated using monthly cpi data for pre-monsoon, monsoon, and post-monsoon seasons and reported in table . the range of the cpi were from . - . , meaning the slightly polluted wq during the pre-monsoon at location s ( , - , , - , , and ) , at location s ( , , - , and ) , at location s and s ( , , - , and ) , at location s ( - , , - , and - ) ; monsoon season at location s ( , , - , , and ) , at location s ( - , - , - , and ) , at location s ( - , , , ) , at location s ( - , - , ) , and at location s ( - , - , ) ; and post-monsoon at location s ( , - , - , - ) , location s ( , , - , ) , location s ( , , - , - ) , location s ( , - , ) , location s ( , - , , ) . considerably, the good quality of water was observed in other sampling periods at all locations. the comparative analysis of the cpi reveals that all sampling locations were slightly polluted during the pre-monsoon season in year , , , and and in the year , , and during the monsoon season, and in the year - , and during the post-monsoon season. in general, cpi results reveal that the wq in river has been slightly polluted during all the sampling months in year , and at all the locations. thus, the assumptions revealed from the comparative analysis of wq parameters with their sal value are found to be viable based on cpi results. in this study, cpi results revealed that the conventionally treated river water could be used for drinking purposes. the early evaluation of the wq based on the nine locations of river ganga between haridwar city to garhmukteshwar during the year - using cpi method reported . and . for pre-and post-monsoon seasons, respectively, signify severely polluted water unsuitable for human use (chaudhary et al., ) . contrary to this, wq of the river ganga at allahabad (prayagraj) based on cpi was poor quality (sharma et al., ) . moreover, in order to identify the similarity and dissimilarity of wq among the sampling locations, statistical cluster analysis was performed using the hierarchical cluster analysis (hca). the overall mean datasets of wq parameters were used for cluster analysis using the hca through ward method. the agglomeration resulted into two clusters in hca and represented by the dendrogram plot (fig. ) . in cluster one, the sampling locations s and s were grouped, and cluster two contains s , s , s , and s . considerably, location s was found in both the clusters, which might be due to the impact of their geomorphologic position and wastewater discharge from both the point and non-point sources. the first cluster signifies input of wastewater into the river and can be mainly from the natural sources; however, the second cluster contained the impact of both anthropogenic and natural hindrances in the river. most of the sampling locations of downstream regions were grouped in the second cluster confirming the input of wastewater through runoffs from the catchment (forest cover and agricultural area). the changing trends in aquatic environment of river ganga at locations uttarkashi and tehri zero point were investigated through evaluating the correlation between wq datasets and the discharge and found good category of water (kumar et al., a,b) . therefore, the results indicate the dilution effect of surface runoffs in the catchment area due to the base flow. further, a pearson correlation coefficient and pca were performed to identify the source of nutrients in the river ganga so that mitigation strategies could be suggested in advance to maintain the safeguard of wq for human consumptive use. the inter-relationship of parameters indicates the input sources or pathways of nutrient-loaded wastewater, thereby alters the water characteristics in a water body (ray et al., ) . the pearson correlation coefficient of wq parameters was estimated to understand the pathway and input source of nutrients in the river using raw wq datasets for each sampling location (see supplement table s -s ) . at location s , the positive correlation coefficient was estimated between k-so ( . ), k-na ( during the comparative analysis, negative correlation between do-wt, and ph-bod at all the sampling locations were found which signifies that the river water tends to be slightly polluted, loaded with organic nutrients. negative correlation between do-ta signifies that increased concentration of inorganic salts (in form carbonate and bicarbonate ions with the so , cl, and no +no anions), resulting into interference with the solubility of oxygen (sharma et al., ) . the positive correlation among no +no , ca, na, b, and k signify the significant contribution of organic and inorganic salts through runoffs from the surrounding natural weathering in mountainous resulting the river water alkaline (mahmoodabadi and arshad, ) . the positive correlation coefficients among the wq datasets indicate their significant mutual dependency, actual nutrients characteristics, and common input sources (singh et al., c) . pca was performed through varimax normalized rotation method using wq datasets to validate the relationship between parameters and to further identify the input source of nutrients for wq. the rotation of the pcs was performed to elucidate an easy and relevant portrayal of the loading factors by adjusting the significant contributor . primarily, scree plot of wq datasets was constructed to estimate the number of components obtained during the pca (fig. ) . for location s , the scree plot indicates the major break after second component, which reveals that the first two components could produce more meaningful information about the loading of nutrients in the river water (supplementary figure s (a) ). the component eigen-values curve in scree plot has dropped after the fourth component which indicates that four components might be useful for better interpretation of nutrient loading. similarly, scree plots curves indicating component eigen-values obtained from the datasets at locations s , s , s , and s have resulted into , , , and pcs, respectively for these locations (supplementary figure s (b-e) ). all the pcs have eigen-value > with a cumulative variance of . %, . %, . , . %, and . % for datasets of location s -s , respectively. moreover, the kaiser-meyer-olkin (kmo) and bartlett's test of sphericity of datasets were estimated before performing the component analysis. the kmo values of . , . , . , . , and . with bartlett's test of sphericity (degree of freedom: ; and zero significance), the chi-square values of approximately . , . , . , . , and . were estimated for wq datasets of all five locations s -s , respectively, which signify the suitability of datasets for pca. the pca component's value and commonalities of datasets are reported in table . all the pcs have high loading of different parameters (fig. ) leading to better insight into the hydrochemical and biological interpretation. pca for location s was resulted into four pcs with pc having . % variance explained with higher positive loading for k, so , na, cl, do, and bod. pc has positive loading of all parameters except f and wt. the positive pc value of . for f was obtained in pc , while wt was positively loaded in pc (pc value of . ), and pc (with highest pc value of . ). in pc , ca, ta, mg, cl, no +no , and ph exhibit their highest positive loading. the highest positive loading of cl ( . ) was obtained in pc , while loading of bod ( . ) and ec ( . ) were obtained in pc . pcs for location s resulted into four pcs, where pc with variance of . % exhibits the highest positive loading of na, ta, k, ca, so , cl, wt, and b, which indicates that the river receives a huge amount of runoffs water from agriculture and forest cover areas. the highest positive loading of parameters bod and ec was obtained in pc , while the highest positive loading of parameters mg, no +no , and ph was found in pc . considerably, the parameters do and f exhibits the highest positive loading in pc . pcs for location s was defined by six pcs, with the highest positive loading of parameters na, k, so , cl, ca, and b were found in pc with the variance . %, while the highest positive loading of parameters mg, no +no , do, ta and ec, parameter wt, parameter ph, and parameter bod were obtained in pc , pc , pc , pc , and pc , respectively. pcs for location s resulted into five pcs, where the parameters na, k, so , bod, cl, ca, and b exhibits highest positive loading in pc with the variance . %, while the highest positive loading of the parameters mg, ta, no +no , and ec, f and wt, ph, and do were obtained in pc , pc , pc , and pc , respectively. pca for location s was based on five pcs, where the parameters na, k, so , bod, cl, ca, b, and ta exhibits the highest positive loading in pc with variance . %, while the highest positive loading of the parameters mg, no +no , and ec, wt, do and ph were obtained in pc , pc , pc , and pc , respectively. the parameters loading in pc governed the nutrient input source from natural sources, while positive loading of parameters in pc defined the nutrient input through direct discharge of partially or untreated treated domestic or industrial wastewater into the river kumar et al., ) . during the comparative analysis of parameters loading in pcs at all locations, it was noted that the parameter k, so , na, and cl were positively loaded in pc , which signified the input of their salts from both natural source through runoff or landslides and anthropogenic agricultural activities (where use of chemical herbicides, fertilizers, pesticides, and mining operations occurs) (dalakoti et al., ) . in this study, the trend of parameters loading in different pcs was found to be almost similar at all locations. loading of parameters in pc was due to the input of nutrients specifically from the anthropogenic activities including agriculture, while parameters loading in the pc , pc , pc , and pc were defined based on the input from the natural sources (rajkumar et al., ) . the upstream ganga river basin's catchment area (lies in active himalayan mountain) is mainly covered by forest and agriculture land with scarce industrial setup compared to the downstream plain areas with dense industrial setup. therefore, the surface runoff and landslide due to weathering of parent materials often occur in the area, which might be the major input source of nutrients in the river ganga. researchers across the domain have investigated the water characteristics of river ganga all along the stretch ( table ) . the river water quality in the upstream region (from uttarkashi and tehri zero point bridge via devprayag to rishikesh) has been reported to be good and safe for human consumption. the observations and findings in this study also supported the similar water characteristics at these locations. compared to the upstream region, the downstream region (plain area from haridwar to kolkata) of river ganga is found to be highly polluted due to excessive anthropogenic hindrance, large input of domestic and industrial wastewater into the river (kumar et al., , a . in order to control infectious spread of pandemic flue disease caused by the pandemic coronavirus , the government of india implemented the lockdown of country since th march . during the lockdown period, human life comes to a standstill and all the major industrial activities (except medical and food industries) were shutdown (yunus et al., ) . for decades, water pollution along the stretch of river ganga has been a prime concern and a matter of research that is reported by numerous researchers in the literature (table ). based on the literature available, the major cause of water pollution has been identified as direct discharge of partial or untreated wastewater from industries located in the basin of river ganga and its tributaries. during the lockdown, since all the anthropogenic activities were prohibited and closed down for weeks, it was expected that pollution load could decrease in the environment (yunus et al., ) . according to cpcb ( ) real-time wq analysis of river ganga, it is observed that the wq is improvised and found suitable for life-supporting purposes in the studied stretch (cpcb, ). previously, the river ganga water at sampling locations like haridwar city, kanpur city, varanasi city, prayagraj, and others were found to be severely polluted (do < mg/l, unsuitable biotic environment) in every month and seasons as well, reported by mishra et al. ( ), chaudhary et al. ( and others. considerably, the wq at these locations becomes suitable for human use as the parameters like bod, do, ec, ph, wt, cl, cod, f, no , and k are found within their permissible limit during the lockdown period in april (table ) . moreover, river ganga has self-assimilative or purification capability, which seems to be enhanced during the recent lockdown period (dwivedi et al., ) . the results of wq in preceding years were compared and it is observed that the aim of rejuvenation of river ganga could not be achieved with gap-i and gap-ii, however, during lockdown, the wq was improved significantly and become suitable for human consumptive use. therefore, it can be inferred that if the discharge of industrial effluent and wastewater in river ganga would be checked, the river would rejuvenate herself. moreover, this study draws further attention to the wq of the river after the upliftment of the lockdown once the industrial activities will be resumed and the pollutants along with the wastewater will eventually be discharged into the river. therefore, it is suggested that appropriate and stipulated actions should be implemented immediately to reduce the risk of environmental damage to the sacred river ganga ecosystem with maintaining ecological health. present study will act as a reference to the water planners & managers, governors, environmentalists, and policy-makers to take strategic mitigation plan to maintain the aesthetic and cultural value of the river. the long-term study estimates the wq of river ganga based on the physiochemical parameters at the five upstream locations of uttarakhand, india using cpi, pca, and hca to categorize the wq into different classes for understanding the hydrochemistry and cluster of similar water quality status. the values of physiochemical parameters were within the acceptable limits signified good wq of the ganga river and suitable for life-supporting purposes after conventional treatment. pca revealed the enrichment of k, so , na, and cl in the river through the runoffs and discharge from natural sources (i.e., surface runoff from catchment, weathering of rocks, and landslides). comparative analysis of upstream wq with the downstream locations revealed that downstream river water is severely polluted. the prime sources of river wq deterioration were discharge of domestic, industrial, and agricultural wastes at the downstream of river ganga and contamination from local villages into the river water. during the country lockdown due to pandemic coronavirus disease , the wq at downstream region was improved and became suitable for life support purposes. it is found that the self-cleansing property of river was enhanced and rejuvenated during lockdown period, which has been troublesome tasks to achieve in decades. this study yields the valuable information of different indices and multivariate statistical techniques in the investigation and explanation of the compound datasets in recognizing contaminant sources, and in understanding dissimilarities in water quality for better designing of action plans for river rejuvenation. the rejuvenation should be achieved by reducing livestock activities and domestic discharge around the river, discharge of wastewater otherwise; over pollution have the potential effect on the human population leading to socio-economic disaster. these determinations should be considered for future planning and management of the river for realizing the potential ecosystem services to the inhibiting population along the river. amit kumar: conceptualisation, data analysis, preparation of the first draft, proofread the final version of manuscript and agreed for publication. saurabh mishra: conceptualisation, data analysis, preparation of the first draft, proofread the final version of manuscript and agreed for publication. a.k. taxak: data collection, extraction, formal analysis, proofread the final version of manuscript and agreed for publication. rajiv pandey: proofread the manuscript and agreed for publication. zhi-guo yu: proofread the manuscript and agreed for publication. the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. the data that support the findings of this study are available from the corresponding author upon reasonable request. assessment and occurrence of various heavy metals in surface water of ganga river around kolkata: a study for toxicity and ecological impact impact of climate change on indian water resources awwa and wpcf standard methods for the examination of waters and waste waters assessment of ganga river ecosystem at haridwar, uttarakhand, india with reference to water quality indices estimating the value of improved wastewater treatment: the case of river ganga human health risk assessment due to agricultural activities and crop consumption in the surroundings of an industrial area an inter-disciplinary approach to evaluate human health risks due to long-term exposure to contaminated groundwater near a chemical complex evaluating the performance of polystyrene sulfonate coupling with non-ionic triton-x surfactant as draw solution in forward osmosis and membrane distillation systems estimation of water pollution and probability of health risk due to imbalanced nutrients in river ganga managing the socio-ecology of very large rivers: collective choice rules in iwrm narratives the ganga river is dying under the weight of modern india pollution assessment: river ganga. central pollution control board restoration of polluted river stretches. central pollution control board, government of india cpcb, . real time water quality monitoring of river ganga environmental evaluation study of ramganga major irrigation project. central appraisal of water quality in the lakes of nainital district through numerical indices and multivariate statistics the ganga and the gap: an assessment of efforts to clean a sacred river use of water quality index and multivariate statistical techniques for the assessment of spatial variations in water quality of a small river self-cleansing properties of ganga during mass ritualistic bathing on maha-kumbh the role of water use patterns and sewage pollution in incidence of water-borne/enteric diseases along the ganges river in varanasi assessment of water quality and suitability analysis of river ganga in rishikesh river development & ganga rejuvenation report ( ) of (performance audit), ministry of water resources; 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