key: cord- - fqxr yz authors: yezli, saber; alotaibi, badriah; al-abdely, hail; balkhy, hanan h; yassin, yara; mushi, abdulaziz; maashi, fuad; pezzi, laura; benkouiten, samir; charrel, rémi; raoult, didier; gautret, philippe title: acquisition of respiratory and gastrointestinal pathogens among health care workers during the hajj season date: - - journal: american journal of infection control doi: . /j.ajic. . . sha: doc_id: cord_uid: fqxr yz background data on the risk of transmission of infection to health care workers (hcws) serving ill pilgrims during the hajj is scarce. methods two cohorts of hcws, the first serving hajj pilgrims in mecca and the second serving patients in al-ahsa, were investigated for respiratory and gastrointestinal symptoms and pathogen carriage using multiplex polymerase chain reaction before and after the hajj. results a total of hcws were enrolled of whom were exposed to pilgrims (mecca cohort), whereas were not exposed (al-ahsa cohort). symptoms were observed only in hcws from the mecca cohort, with . % experiencing respiratory symptoms during the hajj period or in the subsequent days and . % having gastrointestinal symptoms. acquisition rates of at least respiratory virus were . % in the mecca cohort and . % in the al-ahsa cohort (p = . ). acquisition rates of at least respiratory bacterium were . % and . % in the mecca and al-ahsa cohorts, respectively (p = . ). gastrointestinal pathogens were rarely isolated in both cohorts of hcws and acquisition of pathogens after the hajj was documented in only a few individuals. conclusions hcws providing care for pilgrims both acquire pathogens and present symptoms (especially respiratory symptoms) more frequently than those not working during hajj. every year, approximately - million muslims congregate in mecca, kingdom of saudi arabia (ksa), to perform the hajj. the crowded conditions within a confined area and the close contact with others, particularly during rituals, may lead to an increased risk of pilgrims acquiring and spreading infectious diseases. respiratory tract infections (rtis) are the most common infections transmitted among pilgrims, and the majority of whom will develop rti symptoms during their few weeks in saudi arabia, mostly due to viral infection and notably rhinovirus and influenza viruses. , cough attack rates over % have been recorded among pilgrims from various nationalities. gastrointestinal infections, although less frequent than rtis, may also affect hajj pilgrims. for instance, a diarrhea attack rate of % was observed in a cohort of french pilgrims. each hajj season, thousands of health care workers (hcws) are drafted from across the kingdom to oversee and provide health care during hajj. this workforce may be at increased risk of acquiring infection during the event. although many studies regarding communicable disease during hajj have been conducted in pilgrims, not much has been conducted among hcws. one study investigated respiratory viruses among hcws treating pilgrims during the hajj and detected rhinovirus and coronavirus e in . % and . % of the participants, respectively. rhinovirus was detected in % of those who had respiratory symptoms during hajj. transmission of respiratory infections in controlled medical settings is well known. however, the risk of acquisition and transmission of infections in such settings during the hajj is even more significant first, infected pilgrims returning from the hajj may assist in a wider spread outside the borders of the kingdom, and second, hajj hcws may serve as a vehicle to transmit infections to other hospitals within the kingdom on return to work post-hajj. today, this is an even bigger concern in the context of the ongoing detection of middle east respiratory syndrome (mers) coronavirus infections in the arabian peninsula as a potential pandemic virus. this study was conducted with the aim to estimate the prevalence of respiratory and gastrointestinal symptoms, as well as to determine the acquisition of potential respiratory and gastrointestinal pathogens among hcws attending pilgrims during the hajj season and comparing them with hcws not serving in hajj. two cohorts of hcws were investigated. the mecca cohort attended to the hajj pilgrim patients at various hospitals at the holy site of mina, mecca province, in western ksa. these were: mina new street hospital, mina emergency hospital, mina al-jisr hospital, and mina al-wadi hospital. the al-ahsa cohort attended non-pilgrim patients at various hospitals in al-ahsa in eastern ksa approximately km from mina. these were: king fahad hospital, prince sultan cardiac center, and prince saud ben jalawi hospital. hcws were asked to answer a standardized questionnaire that collected information on demographics, vaccination status, and chronic conditions. information on symptoms during the hajj and during the following weeks were also collected. participants were asked to fill in the questionnaire and to provide pre-hajj (september , to september , ) and post-hajj (september , to october , ) samples. during the period september , to october , , hcws were followed for the development of respiratory or gastrointestinal symptoms. hcws were then followed-up by telephone (october , to november , ) to collect information regarding development of symptoms in the weeks after hajj. nasopharyngeal (np) and rectal swabs were collected from each participant before (september , to september , ) and after the hajj (september , to october , ) using commercial rigid cotton-tipped swab applicators (remel, lenexa, ks), placed in universal transport medium (remel) at the time of collection and stored in a − °c freezer within hours of collection. respiratory samples (np swabs and sputum) and/or rectal swabs were also collected from hcws experiencing symptoms during hajj, as appropriate. the specimens were transported in dry ice to aix-marseille university, france for analysis after the end of the sampling period. a -ml volume of sample was transferred to a wells s-bloc (qiagen, venlo, netherlands) for purification using the cador pathogen qiacube ht kit run on a qiacube ht biorobot, according to the manufacturer's recommendations. total nucleic acids were eluted in ml and stored at − °c until processing. all respiratory pathogens were tested using the ftd respiratory pathogens and the ftd hcov-emc kits following manufacturer's recommendations (launch diagnostics ltd, kent, england) except for coxiella burnetii dna, which detection was performed according to previously described protocols. all enteric pathogens were tested using the ftd viral gastroenteritis, the ftd bacterial gastroenteritis, the ftd stool parasites, and the ftd epa kits following manufacturer's recommendations (launch diagnostics ltd), except for tropheryma whipplei dna and human cytomegalovirus dna, in which detection was performed according to previously described protocols. , polymerase chain reaction (pcr) and reverse transcription-pcr reactions were performed using cfx biorad thermal cyclers (bio-rad laboratories, inc., hercules, ca). characteristics of the study population were summarized as frequencies and percentages for qualitative variables and as means, range, and sds for quantitative variables. univariate analyses were performed using the t test, the pearson x test or the fisher exact test, as appropriate, to compare carriage and acquisition rates between the cohorts and to investigate the associations between clinical symptoms and np, and rectal pathogen carriage. all tests for significance were -sided and p values <. were considered statistically significant. all analyses were done using spss version . (ibm corp, armonk, ny) software program. the study was approved by the king fahad medical city ethics committee and the institutional review board. all participants were informed about the study and consented to participate. the study was conducted in accordance with the ethics committee guidelines and good clinical practices recommended by the declaration of helsinki and its amendments. a total of hcws were enrolled of whom ( . %) were exposed to pilgrims (mecca cohort), whereas ( . %) were not exposed (al-ahsa cohort). most hcws were in the - year age range ( . %), were women ( . %), non-saudi ( . %), and nurses ( . %) ( table ). over % of hcws were immunized against meningitis, but only . % were vaccinated against invasive pneumococcal disease. immunization rate against influenza was % in . only . % were current smokers and the prevalence of chronic conditions was low (table ). significant differences were observed between the cohorts with those in mecca being older, with a higher proportion of men, saudi nationals, and physicians compared with hcws in the al-ahsa cohort. mecca hcws were also more likely to be immunized against meningitis and influenza and to be smokers (table ) . no differences in underlying health conditions were observed between the two cohorts (table ) . clinical symptoms were reported only in hcws from the mecca cohort, whereas hcws from al-ahsa were all asymptomatic during the study period. clinical symptoms were reported in . % ( (table ) . fever, cough, and sore throat were the most common symptoms reported in respectively . %, . %, and . % of the mecca cohort hcws during the study period. the median time between pre-and post-hajj sampling was days (range - days). at least respiratory virus was isolated in . % of pre-hajj samples in the mecca cohort, compared to . % in the al-ahsa cohort ( table ). the overall prevalence of respiratory virus carriage increased to . % in post-hajj samples in the mecca cohort, whereas it did not change in the al-ahsa cohort ( . %). post-hajj respiratory carriage was significantly higher in the mecca cohort compared to the al-ahsa cohort (p < ¡ ). acquisition rates of at least respiratory virus were respectively . % in the mecca cohort and . % in the al-ahsa cohort (p = . ). rhinovirus accounted for the majority of positive samples, and its prevalence was significantly higher in post-hajj samples ( . %) compared with pre-hajj samples ( . %) in the mecca group (p = . ), whereas no significant differences were observed in the al-ahsa group ( . % vs . %; p = . ). rhinovirus acquisition rate in the mecca cohort ( . %) was significantly higher than in the al-ahsa cohort ( . %) with p = . . at least respiratory bacterium was isolated in . % of pre-hajj samples in the mecca cohort, compared to . % in the al-ahsa cohort (table ) . compared with pre-hajj samples, no significant differences were observed in the overall prevalence of respiratory bacterial carriage in post-hajj samples in both cohorts ( . % and . %, respectively). acquisition rates of at least respiratory bacterium were respectively . % in the mecca cohort and . % in the al-ahsa cohort (p = . ). staphylococcus aureus and klebsiella pneumoniae accounted for the majority of positive cases either in pre-or post-hajj samples. in the al-ahsa cohort, the prevalence of staphylococcus aureus significantly increased from . % before the hajj to . % after the hajj (p < ¡ ), whereas the prevalence of k pneumoniae significantly decreased from . % pre-hajj to . % post-hajj (p < ¡ ). staphylococcus aureus acquisition rate was . % in the mecca cohort compared to . % in the al-ahsa cohort (p = . ). k pneumoniae acquisition rate was . % in the mecca cohort compared to . % in the al-ahsa cohort (p = . ). no significant effect of tobacco smoking, chronic medical conditions, and vaccination status was observed on the acquisition rates of respiratory viruses in the mecca cohort. no statistically significant association was observed between respiratory pathogen carriage and clinical symptoms in the mecca cohort. enteric pathogens were rarely isolated in both cohorts of hcws, and acquisition of pathogens after the hajj was documented in only a few individuals (table ). of note, clostridium difficile was acquired by hcw in the mecca cohort, and tropheryma whipplei by hcws in the al-ahsa cohort. no statistically significant association was observed between rectal pathogen carriage and clinical symptoms in both cohorts. five hcws in the mecca cohort were sampled at the onset of symptoms during the hajj. one was positive for haemophilus influenzae, had a dual infection with rhinovirus/h influenzae, with rhinovirus/k pneumoniae, and were negative. previous studies addressing the prevalence of respiratory infection in hajj hcws are scant. in a study conducted among personnel ( . % of whom were physicians or nurses) serving at hajj mission hospitals during the season, a . % attack rate of acute respiratory infections during and after the hajj was observed with acute respiratory infections defined by the association of at least constitutional symptom (fever, headaches, and myalgia) and at least respiratory symptom. in a study conducted among hcws from the saudi ministry of health (moh) and other hajj medical missions during the season, . % reported respiratory symptoms during the hajj, and . % were found infected by at least virus post-hajj comparing to . % pre-hajj using a pcr assay. all positive cases were due to rhinovirus, but post-hajj case was due to coronavirus e. we confirm in the current work that hcws attending ill hajj pilgrims present frequently with respiratory symptoms ( %) during and soon after the hajj period. additionally, we show that diarrhea is rare ( %). such symptoms were not observed in another cohort of hcws attending non-pilgrim patients in another region of saudi arabia during the same period of time. hcws attending pilgrims reported symptoms that lasted up to weeks. no symptomatic hcws reported loss of workdays during the hajj in our study, and the number of sick days because of illness post-hajj was not recorded. nevertheless, illness during or post-hajj among hcws does not only affect the wellbeing of the hcws involved, but may also have an impact on work productivity, delivery of health care services, as well as potentially an economic cost. this is especially relevant during hajj when the health care system is under a significant amount of stress and operating at near surge capacity in many hajj areas. numerous studies reported that employee absence is related to decreased job productivity and important economic costs including in the health care sector. [ ] [ ] [ ] further studies are needed for a better understanding of the impact of hajj-related illness among hcws. although no correlation was observed between clinical symptoms and detection of respiratory pathogens, we report that hcws exposed to ill pilgrims carried and acquired a number of respiratory pathogens including acquisition of rhinovirus, enterovirus, respiratory syncytial virus, h influenzae, k pneumoniae, moraxella catarrhalis, staphylococcus aureus, and streptococcus pneumoniae. these organisms have been shown to also be commonly carried by and transmitted among hajj pilgrims. [ ] [ ] [ ] significant acquisition of rhinovirus in superior airways of mecca hcws was recorded at a rate of . %, whereas the acquisition rates of the most frequently detected bacterial pathogens (k pneumoniae and staphylococcus aureus) among this cohort were . % and . %, respectively. in a carriage study among pilgrims from countries in hajj, acquisition rates of rhinovirus, k pneumoniae, and staphylococcus aureus were . %, . %, and . %, respectively. influenza a and b viruses were not isolated, which may be owing to the relatively high rate of influenza vaccination, notably in the mecca cohort ( %). lower rates of influenza vaccination were recorded among hajj hcws in ( %) and ( %). , streptococcus pneumoniae carriage was documented in a few hcws, notably in the al-ahsa cohort, in which the vaccination rate against invasive pneumococcal disease was low ( %). no mers coronavirus was identified in hcws either before or after hajj. this is in accordance with previous reports showing lack of mers coronavirus carriage and infection among hajj pilgrims. [ ] [ ] [ ] [ ] [ ] [ ] acquisition and carriage of potentially pathogenic organisms by hcws do not only constitute a risk for development of disease by the hcws carriers themselves, but also a risk of transmission and infection of the vulnerable patients they care for. the role of hcws as a vector for nosocomial infections is well established, , especially in relation to rtis. therefore, effective infection prevention and control (ipc) strategies in health care settings to reduce the likelihood of infection among hcws and patients are crucial in the hajj context. as such, the saudi moh has a strict ipc training and educational program for hcws deployed for hajj, beyond the standard training programs these hcws undertake throughout the year in their own health care facilities across the kingdom. this is because hcws deployed during hajj come from a wide range of health institutions in ksa with diverse backgrounds on ipc measures. some may be stationed at seasonal hospitals in the mecca holy sites that are only operational during hajj and will be providing care to pilgrims originating from all over the world. therefore, since , the saudi moh requires all hcws deployed during hajj to complete training to acquire a basic infection control skills license (bicsl). the latter involves basic components: proper hand hygiene, proper use of personal protective equipment, application of the n fit test, principles of safe injection practice, as well as compulsory influenza and meningococcal vaccination. for the hajj, , hcws were trained for the bicsl representing % of the targeted number to be trained. the kingdom also ensures that health care centers and hospitals providing services for pilgrims are equipped with the necessary facilities for infection prevention. during the hajj, isolation rooms, negative pressure rooms, and high efficiency particulate air filters were available at the hajj health care facilities. the saudi moh also has developed and published various ipc policies, including those specifically for hajj, to help hcws develop their knowledge and skills in the area and adhere to best practices. in addition, various trainings and drills are conducted pre-hajj for hcws as per their function and in relation to a number of possible infectious risks such as mers. awareness campaigns are also part of the ipc program for hcws during hajj, especially in relation to the importance of immunization, food and safety hygiene standards, and general ipc practices that go hand-in-hand with those awareness campaigns aimed at pilgrims, holy cities residents, and non-hcws. our results indicate that there is a need for better adherence to immunization policies, especially in relation to influenza vaccination for all hcws and meningococcal vaccination for those deployed to hajj. due to various initiatives by the saudi moh, rates of influenza vaccination among hcws in ksa are high in recent years. , nevertheless, we found low influenza vaccination rates among hcws not deployed to hajj in . one possible contributor to this finding is that the influenza vaccination season in ksa for hcws not deployed to hajj runs from september to march. given that our data collection was conducted mid-september, it is possible that a number of hcws from the al-ahsa cohort did not yet receive their influenza vaccination at the time of the study. for hcws deployed in hajj, the rates of immunization in our study were similar to those reported in a study conducted in the - hajj seasons. however, our data indicates that the rate of immunization of influenza vaccination among the hajj cohort was higher than that reported pre- . , in general, since the introduction of the compulsory bicsl license that includes the compulsory influenza and meningococcal immunization section, data from the moh indicate that in , all hcws deployed to hajj were vaccinated with both vaccines. our study has some limitations. although we enrolled an adequate number of hcws in both cohorts and had a good follow-up rate, the number represents a small fraction of the thousands of hcws deployed for hajj. therefore, our results may not be generalizable to all hcws working during hajj and in all specialties. also, data on the number of days off work due to sickness among hcws post-hajj was not collected, and that would have given a better picture of the burden of illness associated with hajj deployment for hcws and the health system at large. finally, although we aimed to match the al-ahsa cohort with our mecca cohort in terms of health care facilities size, type of patients, and other factors, given the specific nature of the hajj, it was impossible to completely match the two cohorts. we conducted the first study to investigate illness and carriage of respiratory and gastrointestinal pathogens among hcws during hajj. we found that hcws providing care for pilgrims both acquire pathogens and present symptoms (especially respiratory symptoms) more frequently than those not working during hajj. the kingdom has a strict ipc awareness, training, and education program for hcws deployed for hajj each year, in conjunction with compulsory influenza and meningococcal vaccination and provision of ipc facilities, and equipment to reduce the risk of transmission and illness among both hcws and patients during the event. the kingdom has also the capacity to deploy extra hcws for hajj in times of need. nevertheless, strict adherence to ipc policies and guidelines among hcws, especially in relation to preventing respiratory infections, and continuous monitoring, feedback, and improvement of ipc strategies for hajj are needed. this to preserve the health and wellbeing of hcws working during hajj, to protect the patients they care for and to prevent potential workdays and economic loss resulting from hcws illness either during or post-hajj. hajj: infectious disease surveillance and control health risks at the hajj respiratory tract infections during the annual hajj: 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on patient satisfaction using routine databases in a university hospital respiratory viruses and bacteria among pilgrims during the hajj mass gathering and globalization of respiratory pathogens during the hajj a cohort study of the impact and acquisition of naspharyngeal carriage of streptococcus pneumoniae during the hajj meningococcal, influenza virus, and hepatitis b virus vaccination coverage level among health care workers in hajj acceptance and adverse effects of h n vaccinations among a cohort of national guard health care workers during the hajj season lack of mers coronavirus but prevalence of influenza virus in french pilgrims after prevalence of mers-cov nasal carriage and compliance with the saudi health recommendations among pilgrims attending the hajj high prevalence of common respiratory viruses and no evidence of middle east respiratory syndrome coronavirus in hajj pilgrims returning to ghana no mers-cov but positive influenza viruses in returning hajj pilgrims, china influenza not mers cov among returning hajj and umrah pilgrims with respiratory illness influenza virus but not mers coronavirus circulation in iran, - : comparison between pilgrims and general population healthcare workers as vectors of infectious diseases healthcare providers as sources of vaccine-preventable diseases general directorate of infection prevention and control. committee for infection prevention and control influenza vaccine uptake, determinants, motivators, and barriers of the vaccine receipt among healthcare workers in a tertiary care hospital in saudi arabia prevalence of influenza vaccine hesitancy at a tertiary care hospital in riyadh, saudi arabia mandatory meningococcal vaccine, and other recommended immunisations: uptake, barriers, and facilitators among health care workers and trainees at hajj key: cord- -mewo w authors: hashim, suhana; ayub, zeti n.; mohamed, zeehaida; hasan, habsah; harun, azian; ismail, nabilah; rahman, zaidah a.; suraiya, siti; naing, nyi nyi; aziz, aniza a. title: the prevalence and preventive measures of the respiratory illness among malaysian pilgrims in hajj season date: - - journal: j travel med doi: . /jtm/tav sha: doc_id: cord_uid: mewo w background. respiratory illness continues to exert a burden on hajj pilgrims in makkah. the purpose of this study is to determine the prevalence of respiratory illness and its associated factors among malaysian hajj pilgrims in and to describe its preventive measures. methods. a cross-sectional study was conducted in makkah and malaysia during the hajj season. a self-administered proforma on social demographics, previous experience of hajj or umrah, smoking habits, co-morbid illness and practices of preventive measures against respiratory illness were obtained. results. a total of proforma were analysed. the prevalence of the respiratory illness was . % with a subset of . % fulfilled the criteria for influenza-like illness (ili). most of them ( . %) had a respiratory illness of < weeks duration. approximately . % were administered antibiotics but only . % of them had been hospitalized. most of them acquired the infection after a brief stay at arafat ( . %). vaccination coverages for influenza virus and pneumococcal disease were quite high, . % and . %, respectively. for other preventive measures practices, only . % of them practiced good hand hygiene, ∼ . % of pilgrims used surgical face masks, n face masks, dry towels, wet towels or veils as their face masks. nearly one-half of the respondents ( . %) took vitamins as their food supplement. malaysian hajj pilgrims with previous experience of hajj (or . ; % ci . – . ) or umrah (or . ; % ci . – . ) and those who have practiced good hand hygiene (or . ; % ci . – . ) were found to be significantly associated with lower risk of having respiratory illness. otherwise, pilgrims who had contact with those with respiratory illness (or . ; % ci . – . ) was associated with higher risk. conclusions. the prevalence of respiratory illness remains high among malaysian hajj pilgrims despite having some practices of preventive measures. all preventive measures which include hand hygiene, wearing face masks and influenza vaccination must be practiced together as bundle of care to reduce respiratory illness effectively. the hajj is an islamic pilgrimage to makkah. it draws in million muslims surging from all over the world which accounts for the largest gathering of people globally on an annual basis. the hajj season began from october to october ( ) ( ) ( ) ( ) ( ) dhu al-hijjah). they perform specific rituals and follow a detailed route. the pilgrims perform their first circumambulations by walking seven times anticlockwise around the kaaba. then, they are required to walk for a total distance of . km between the hills of safa and marwah seven times. on the october, they travel to mina and spend one night there for prayers and additional rituals. the next day, the pilgrims around the world gather at arafat. when the sun sets, they leave arafat and move to muzdalifah, located between arafat and mina. they stay at mina in crowded tents for at least two nights. for the completion of the umrah pilgrimage, which is called the lesser pilgrimage; it is different as it can be performed throughout the year, the pilgrims are not required to perform the brief stay at arafat. for years, the mass gathering during hajj has been associated with the risk of communicable diseases, particularly respiratory infection. extended stays at hajj sites, physical exhaustion, extreme heat and crowded accommodation encourage disease transmission, especially those deriving from airborne agents. crowd densities during hajj are about up to seven people per square metre. respiratory tract infection during hajj continues to exert a burden on pilgrims. the respiratory problems account for % of all medical illnesses reported during hajj seasons. pneumonia being the leading reason for hospital admission in % of all patients. a recent study involving malaysian hajj pilgrims found that % of them had at least one respiratory symptom. respiratory illness is a disease affecting the respiratory system and can be due to infection or non-infection. it is complex to define the syndromes of respiratory illness due to variation in the severity, duration and types of symptoms. the purpose of this study is to determine the prevalence of the respiratory illness among malaysian hajj pilgrims in , to describe its preventive measures and to determine the association between sociodemographic, previous experience of hajj/umrah, co-morbidity, smoking habits, vaccination and preventive measures with respiratory illness. apart from those preventive measures, we also explored the association between good hand hygiene practice and respiratory illness/ili. this is a cross-sectional study involving all consented malaysian hajj pilgrims in november, . an expanded definition of respiratory illness was used for this study. respiratory illness was defined as when the person is having at least one of the respiratory symptoms (non-ili) or ili. with references to other studies and some limitations (mainly logistic problems), ili is defined as the triad of cough, subjective fever and sore throat, those who did not fulfil the criteria of ili were classified into a non-ili group. [ ] [ ] [ ] [ ] sample size was calculated based on two proportion formula. the sample size according to potential associated factors, the largest sample size was given . after adding a possible non-respondent rate of %, the sample size for this study is . the sampling frame was consented to the malaysian hujjaj in who attended the hajj course at universiti sains malaysia (usm) kelantan on august and the august , those who transitted at hajj building complex, malaysia from the th of september until the september and those at the kingdom of saudi arabia (ksa). the sample selection was based on convenient sampling due to logistic problems. the researchers did not have access to the name of all pilgrims and they did not know about the approval of hajj visa status until a few weeks before their departure. the inclusion criteria were hajj pilgrims above years old and able to comprehend and fill up proforma. pilgrims who were very ill and unable to independently respond to the proforma were excluded. data based on the social demographic, co-morbid illness, smoking habits, symptoms of respiratory illness, history of contact with respiratory ill patients, previous experience of hajj or umrah, the practice of preventive measures, influenza and pneumococcal vaccination and supplement intake against respiratory illness were obtained by a self-administered proforma. good hand hygiene or optimal handwashing practices is defined as handwashing for s at least five times per day by using water with soap or a hand sanitizer. , in this study, we define good hand hygiene practice as those who frequently wash their hands using hand sanitizers indicated by centres for disease control (cdc). those using water only, handkerchiefs or disposable tissues were considered as poor hand hygiene practices. history of contact with respiratory illness sufferers is defined as pilgrims who have direct contact or close contact (being within feet ( m) or within the room or care area for a prolonged period of time while not wearing recommended personal protective equipment. brief instructions were given to the hajj pilgrims before receiving proforma. the proforma were given to participants in malaysia before their departure and also at makkah before departing for a brief stay at arafat. all the completed proforma were collected after completion of hajj at makkah and at the local airport upon arrival in malaysia or via postage. the pilgrims were required to complete the proforma at least weeks after their stay at arafat. all respiratory symptoms that occurred weeks after arrival in ksa were considered significant. the statistical package for the social sciences (spss version . ) was exercised for data entry and statistical analysis. descriptive statistics were applied to describe the prevalence, practice of deterrent measures and associated factors. the analysis of association between sociodemographic, previous experience of hajj or umrah, co-morbidity, smoking habits, vaccination and the practice of preventive measures with the respiratory illness were done using simple logistic regression and the variables with p value of < . or variables with clinically significant values will be included further with multiple logistic regression analysis. the risk estimation was carried out using the odds ratio (or) and % confidence intervals (ci) and the p value of < . were significant. variable interaction and multi-collinearity followed by testing on a model assumption was performed before decisions made on the final model. for the final model, the p value of < . were considered as significant. ethical approval was obtained from the usm research and ethics committee before this study (reference number: a total of proforma were distributed to the pilgrims, however, only responded, only %. out of pilgrims who returned the proforma, were excluded from the analysis as grossly incomplete. altogether proforma were analysed. the age for malaysian hajj pilgrims in this study ranged from to years old with a mean age of . (sd . ). the males ( . %) dominated the female pilgrims with an obvious male to female ratio of . . more than one-half of the pilgrims had at least one medical illness ( . %). many of them had hypertension ( . %), followed by diabetes mellitus (dm) ( . %), allergic rhinitis ( . %), bronchial asthma ( . %) and others ( . %). some of the pilgrims still had smoked ( . %) and . % of them were obese ( table ) . the prevalence of respiratory illness symptoms was . % with a subset of . % fulfil the criteria for ili. most of them had a respiratory illness of < weeks ( . %). approximately . % were administered antibiotics, only . % of them were hospitalized. one-half of them had a history of contact with respiratory illness sufferers ( . %). they acquired the infection intensely at arafat ( . %) ( table ) . for the practice of preventive measures, the total number of pilgrims that received influenza vaccinations was ( . %). from those, ( . %) pilgrims had been immunized with influenza and pneumococcal vaccinations. a total of . % of pilgrims wore face mask, i.e. surgical face masks, n face masks, dry towels, wet towels or veils as their face mask. only . % of them practiced good hand hygiene. nearly one-half of the respondents ( . %) took vitamins as their food supplement (table ) . factors associated with respiratory illness among malaysian pilgrims using simple logistic regression analysis was shown in table . all the supplements were seemed able to protect them from the illness, however they were not statistically significant (table ). malaysian hajj pilgrims with previous experience of hajj (or . ; % ci . - . ) or umrah (or . ; % ci . - . ) and those with good hand hygiene (or . ; % ci . - . ) were significantly associated with lower risk of respiratory illness. otherwise, pilgrims having contact with those with respiratory illness (or . ; % ci . - . ) were associated with higher risk ( table ). the percentage of ili was lower ( . %) in those vaccinated with the influenza vaccine than those unvaccinated ( . %). however, it was statistically not significant with a p value of . (table ). the prevalence of the respiratory illness varied by country of origin and by year based on the studies conducted over the past few years. in our study, the prevalence of respiratory illness symptoms among malaysian hajj pilgrims for the season was . %, with a subset of . % fulfilling the criteria for ili. the respiratory illness prevalence was consistent with french pilgrims during the same year ( . %). the prevalence for the african hajj pilgrims was slightly lower ( . %). the results of our study are in parallel with previous studies, . % and . % for the saudi arabia hajj pilgrims and the malaysian hajj pilgrims, respectively. , in contradiction, the percentage was lower for the us pilgrims in who suffered from respiratory illness symptoms ( . %). crowdedness is a major risk factor for the transmission of respiratory illness. all compulsory rituals of hajj involve crowded places, jam-packed with pilgrims. these conditions contributed to almost one-half of the pilgrims ( . %) having contact with people suffering from respiratory illness during hajj. they were at a significantly high risk of developing the respiratory illness by three times higher than those who do not have the contact (p value . ). practising contact avoidance during hajj is imperative as it can shorten the duration of respiratory illness. practicing social distancing and contact avoidance is effective in reducing the transmission of the respiratory symptoms during the us pilgrims and ili symptoms in with the indian pilgrims. , the majority of the respondents was inflicted with respiratory illness after a brief stay at arafat ( . %). it may be correlated with the incubation period of the illness and the peak exposure of pilgrims whilst performing the hajj rituals. other studies estimated approximately one in three pilgrims will experience respiratory symptoms which usually occurred at the end or shortly after performing hajj rituals. influenza vaccination is one of the recommended vaccines for high risk pilgrims to reduce mortality and morbidity. the vaccine uptake for influenza in our study is lower ( . %) in contrast to malaysian pilgrims in ( . %) and saudi arabian pilgrims in ( . %). , the percentage of vaccine uptake among the hajj pilgrims from other countries were as low as . % for french pilgrims and . % for pilgrims from saudi arabia, qatar and australia. , effective influenza vaccine remains debatable and cannot be proven if the study was conducted without virology confirmation. multiple factors such as mismatch between vaccine strains and circulating strains, inappropriate storage and the handling of the vaccine can reduce its effectiveness or waning of immunity in the population. one study systematically reviewed the available studies assessing the uptake and effectiveness of the influenza vaccine among pilgrims. the effectiveness of the influenza vaccine varied across studies, but was effective against laboratory-confirmed influenza with a p value of < . . in our study, the prevalence of ili was not significantly associated with the status of the vaccination which was similar with pilgrims in malaysia ( ), france ( ) and iran ( ). , , the vaccine was not associated with the reduction and number of acute respiratory symptoms nor any relation to the length of stay for malaysian hajj pilgrims in . the findings were not in accordance with the french pilgrims in in which the ili symptoms were less frequently reported in the vaccinated group ( . %) than unvaccinated group ( . %) and was statistically significant (p value . ). in another study, they found that the influenza vaccine appeared to provide some protection in 'at risk' hajj pilgrims but not in the 'not at risk' group. the influenza vaccines prevented clinic visits for ili among malaysian pilgrims in and pakistani pilgrims in . , the influenza vaccination is a protective factor for ili more than for non-ili, giving - % protection for ili and just % protection against the non-ili group. one hundred and forty-nine of our respondents adopted good hand hygiene during hajj ( . %). the results were similar to the french pilgrims in ( . %) and the us hujjaj in ( . %). , however, the adherence of french pilgrims towards hand sanitizer practices in was higher ( . %) than in the hajj season. effective hand hygiene practice in this study could significantly decrease the risk of respiratory illness by % than pilgrims who practiced poor hand hygiene. it was parallel with the us pilgrims in and the french pilgrims in , as regularly washing hands and the use of hand sanitizers significantly causes less of the ili symptoms. , a systematic review on hand-hygiene interventions, including education and the use of alcohol-based hand sanitizers towards respiratory illness indicated that some of the interventions were not efficacious against respiratory illnesses. the consistent application of hand hygiene during critical points in the chain of transmission is likely to play a major role in shaping the relative effectiveness of hand-hygiene interventions in terms of disease outcome. face masks are able to limit the spread of microorganisms, mainly from the respiratory droplets. however, the cdc in usa found that the intermittent use of surgical-type masks was associated with more than a . -fold greater risk of infection. disposable face masks should be used once and replaced when they become moist and are to be disposed of properly. most of the malaysian pilgrims admitted to wearing face masks during hajj ( . %). this finding was in accordance with other studies, . % for malaysian pilgrims in and . % for french pilgrims in . , the percentage was higher if compared with other countries in the hajj season; saudi arabia ( %) and usa ( %). , it has been revealed that face masks either offered no significant protection or were associated with a longer duration of sore throat and fever symptoms among hajj pilgrims. , , a recent study illustrated that many pilgrims at the hajj may not have worn masks correctly (e.g. mistakenly positioning the top of the mask below the nose). a recent review by benkouiten et al. in also mentioned that the effectiveness of the face mask in the prevention of the respiratory symptoms among hajj pilgrims revealed variable results. regular use of a face mask was the most essential practical protective factor in respiratory illness, using it for more than h led to a substantial decrease in the incidence of ili among australian pilgrims in . , these masks were potentially effective at preventing respiratory virus acquisition by household contacts of infected people when worn by healthy people. however, the effectiveness depended largely on adherence to mask use. honey is one of the most promising natural substances that can combat or prevent respiratory illness. approximately . % of pilgrims consumed honey during hajj. however, there was no other study to compare the prevalence of honey intake among hajj pilgrims except for one study to determine the effectiveness of honey in reducing respiratory symptoms. during the hajj, pilgrims undergo great physical and emotional strain. the experienced hajj veterans or even umrah is an advantage as it can help them to be more physically prepared as well as mentally and spiritually ready. however, every year is different and every person's experience is individually specific but they are able to prepare themselves as much as possible for the hajj challenges. the association of previous experiences during hajj or umrah with respiratory illness has not been studied before. malaysian hajj pilgrims with previous experience of hajj or umrah were found to be significantly associated with lower risk of developing respiratory illness (p value of . for both). further study needs to be conducted to explore the factors that contribute to the association of respiratory illness in those who have experienced performing hajj or umrah. the limitations of this study include inadequate sample size and a poor response rate as it could affect the power of the study. the small response rate could be due to a lack of commitment from the respondents following a very packed hajj ritual schedule. shortage of staff to handle and follow-up the respondents in makkah, further added to the problem. in conclusion, the prevalence of respiratory illness remains high among malaysian hajj pilgrims despite having some practicing preventive measures. practicing only certain preventive measures are inadequate. all preventive measures including hand hygiene, wearing face masks and influenza vaccination must be practiced together to reduce the respiratory illness effectively. in our study, good hand hygiene practice was lower compared with other preventive measures; therefore, health authorities should find a way to overcome this problem. further studies are required to develop a health education module to promote a comprehensive preventive measure for hajj 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febrile cough episodes among french pilgrims: a prospective cohort study on the influence of statin use and risk factors effect of influenza vaccination on acute respiratory symptoms in malaysian hajj pilgrims the incidence of vaccine preventable influenza-like illness and medication use among pakistani pilgrims to the haj in saudi arabia circulation of respiratory viruses among pilgrims during the hajj pilgrimage protective measures against acute respiratory symptoms in french pilgrims participating in the hajj of effect of hand hygiene on infectious disease risk in the community setting: a meta-analysis acute respiratory tract infections among hajj medical mission personnel, saudi arabia findings from a household randomized controlled trial of hand washing and face masks to reduce influenza transmission in non-pharmaceutical interventions for the prevention of respiratory tract infections during hajj pilgrimage pilot randomised controlled trial to test effectiveness of facemasks in preventing influenzalike illness transmission among australian hajj pilgrims in hajj-associated acute respiratory infection among hajjis from riyadh a quantitative assessment of the efficacy of surgical and n masks to filter influenza virus in patients with acute influenza infection conventional and alternative medical advice for cold and flu prevention: what should be recommended and what should be avoided? the benefit of tualang honey in reducing acute respiratory symptoms among malaysian hajj pilgrims: a preliminary study the authors acknowledge tabung haji malaysia, especially kelantan branch and sultan ismail petra airport for their continuous support and recommendations. conflict of interest: none declared. key: cord- -q vqlerz authors: zumla, a.; mccloskey, b.; bin saeed, a.a.; dar, o.; al otabi, b.; perlmann, s.; gautret, p.; roy, n.; blumberg, l.; azhar, e.i.; barbeschi, m.; memish, z.; petersen, e. title: what is the experience from previous mass gathering events? lessons for zika virus and the olympics date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: q vqlerz all previous experiences from different mass gathering show that vaccine preventable diseases is the most important infections like influenza, hepatitis a, polio and meningitis. three mass gathering held in africa during the ebola outbreak accepted participants from west africa and was able to handle the theoretical risk without any incident. therefore we believe that the olympic games in rio de janeiro should not be cancelled. the number of visitors to the games is a tiny fraction ( %) of other visitors to zika endemic countries and it will have no measurable effect on the risk of spreading zika virus, if the games was cancelled. prediction is very difficult-especially about the future. thus we have to look at previous experience to allow an informed estimate to be made of the risk of holding the olympic games at the same time as an ongoing epidemic of a vector-borne viral infection. at the other end of the scale are unintentional 'mass gatherings' such as refugees taking shelter in huge camps, often in cramped conditions with poor hygiene. these are not usually regarded as mass gathering events, but nevertheless they pose the same problem in terms of the transmission of pathogens in the situation of a large number of people in a limited space. currently the civil war in syria has displaced many people, and diseases like tuberculosis, cutaneous leishmaniasis, measles, and polio are a risk. such conditions also increase the risk of transmission of zoonoses, with expected closer contact to rodents compared to normal conditions. thus a one health approach is also needed in this situation. mass gathering events are theoretically ideal situations for the spread of infections between people from very different and widespread geographical localities, with potentially different immune responses. one of the first events that focused the international health community on mass gathering events was the outbreak of meningitis in - after the hajj. , however, the spread of infections is rarely caused by mass gathering sports events. all previous experiences from different mass gathering show that vaccine preventable diseases is the most important infections like influenza, hepatitis a, polio and meningitis. three mass gathering held in africa during the ebola outbreak accepted participants from west africa and was able to handle the theoretical risk without any incident. therefore we believe that the olympic games in rio de janeiro should not be cancelled. the number of visitors to the games is a tiny fraction ( %) of other visitors to zika endemic countries and it will have no measurable effect on the risk of spreading zika virus, if the games was cancelled. the spread of severe acute respiratory syndrome coronavirus (sars-cov) from china to hong kong and further to canada was not due to a mass gathering, but to infected individuals travelling late in the incubation period or just after the onset of symptoms. , the introduction of west nile virus to north america was probably through wild birds crossing the atlantic, and it could not have been predicted. lastly, the outbreak of middle east respiratory syndrome coronavirus (mers-cov) in korea was caused by a single traveller waiting in an overcrowded hospital emergency room in south korea. the korean mers-cov outbreak illustrates how difficult it is to predict the future. mers was estimated to have a low epidemic potential, and it was pointed out in this journal that the outbreak was identified as being caused by mers-cov because it happened in a country with the resources (knowledge and laboratory facilities) to rapidly identify the virus. the sendai framework for disaster risk reduction (drr, - ) is the first of three united nations landmark agreements approved in . the sendai framework has an emphasis on health and gives a clear mandate, emphasizing the need for more integrated drr that incorporates bottom-up as well as top-down approaches, local scientific and technical knowledge, and draws attention to synergies with other critical policy arenas including health, climate change, and sustainable development. over the next years, the sendai framework has set out to achieve ''the substantial reduction of disaster risk and losses in lives, livelihoods and health and in the economic, physical, social, cultural and environmental assets of persons, businesses, communities and countries'' -including risk reduction at mass gatherings. the use of science to inform decisions, an integral part of the sendai framework, must also be applied to mass gatherings. some infections like tuberculosis have a long incubation period of several years, and exposure at a mass gathering will not be apparent and may easily be overlooked. the transmission of multidrug-resistant bacteria, for instance gram-negative bacteria hosted in the intestine, is another concern that has not been well studied. asymptomatic individuals are colonized with local bacteria and may be carriers for months. september - , ) shows that it was possible to handle the threat without cancelling the events. the events all accepted participants from west africa. the hindu kumbh mela is a -month long religious conglomeration held every years in four different cities of north india by rotation, the most famous being held in allahabad. this is considered to be the largest human gathering on earth. the last one held in allahabad in had million visitors. kumbh mela does not involve a fixed human settlement, but the creation of temporary settlements of canvas, corrugated metal sheets, bamboo, nails, and rope in the flood plains of the rivers to house and feed millions of people for months every years. for kumbh mela people come by air, road, rail, and foot from within india, making it almost impossible to maintain detailed records of people movements. the hajj, kingdom of saudi arabia the hajj brings approximately three million muslim pilgrims from all over the world to mecca every year. studies and reviews of surveillance data from returning pilgrims have shown that influenza, rhinovirus, and non-mers coronavirus are the most common pathogens, and suggest that influenza immunization before departure may be justified. [ ] [ ] [ ] general screening for infections in pilgrims visiting the hajj has been reported in two other studies, , which found influenza to be the most common respiratory pathogen. meningococcal disease is now rarely recorded. they also noted that gastroenteritis was common, but this is most probably due to lack of hygiene at the event. a study from australia looking at pre-travel prevention among pilgrims found that % were immunized against influenza, % against pneumococcus, and % against pertussis. concern about contracting disease at hajj was the most cited reason for vaccination ( . %). those who obtained pre-travel advice were twice as likely to be vaccinated as those who did not seek advice. since the and outbreak, bacterial meningitis has been a high priority for the kingdom of saudi arabia. several studies have looked at carrier rates of neisseria meningitidis in hajj pilgrims, and overall carriage rates of - % were found, comparable to the rate found in populations in non-epidemic settings. in and , and cases of laboratoryverified neisseria meningitidis were reported; this fell dramatically to - cases per year ( - ) following the introduction of mandatory immunization with the quadrivalent vaccine. the quadrivalent acwy polysaccharide meningococcal vaccine has been a visa requirement for hajj and umrah since . at the same time the saudi authorities introduced a vaccination programme for children and adults living in mecca and medina, healthcare workers, and government personnel serving the pilgrims. a recent study of bacterial infections and resistance to antibiotics in hospitalized hajj pilgrims in mecca found that escherichia coli was the most common bacterium ( %), followed by klebsiella pneumoniae and pseudomonas. methicillin-resistant staphylococcus aureus (mrsa) was found in . %. the potential spread of bacterial infections between hajj pilgrims -whether symptomatic or not -is also a concern because of the unrestricted prescription of antibiotics by local pharmacies to the pilgrims. the most common outbreaks at mass gatherings, including religious mass gatherings other than hajj, sports events, and outdoor festivals, have involved vaccine-preventable infections, mainly measles and influenza, but also mumps and hepatitis a. the psychology of individuals participating in mass gatherings the individual participant behaves in the context of their understanding of the norms associated with the group, and the relationships between group members become more trusting and supportive. understanding these two behavioural changes is key to understanding how and why mass gathering participants may behave in ways that make them more or less vulnerable to the transmission of infection. vaccines are an important preventive tool for mass gatherings and should include the basic coverage provided by childhood immunization programmes, supplemented where appropriate with protection against meningitis and influenza, and yellow fever for mass gathering participants coming from yellow fever endemic countries. a review in this issue discusses the need for vaccines for mass gatherings and draws attention to immunization against pneumococcal infections in elderly pilgrims and highlights that polio may be a risk. an important vaccine for hajj pilgrims, and the arabian peninsula in general, is one against mers-cov. the engineering of live attenuated vaccines has been facilitated by the development of reverse genetics. using one of these methodologies, viruses deleted in the small envelope (e) protein have been developed. these viruses have been attenuated and have induced protective humoral and cell-based immune responses in hamsters and mice after sars-cov challenge. a meta-analysis on the use of face masks and the reduction in risk of upper respiratory infections found a modest effect. compliance is always higher during a study than in the real-life situation, and making face masks mandatory at mass gatherings is not presently recommended. clearly there is a risk of zika virus (zkv) infection, but zkv is already present in more than countries and the risk of spread already exists with or without the olympics. zikv spread from africa to southeast asia without any mass gathering event being involved, as far as we know, and its further spread to south america and between countries in south america has not been linked definitively to any mass gathering event. from the review of mass gathering experience in this special issue of the journal, vector-borne infections have not previously appeared as a particular risk, but experience also shows that potential health risks at a mass gathering can be mitigated effectively if they are recognized and planned for. the health authorities in brazil are aware of the vector-borne risks and have already managed several mass gatherings without evidence of significant international spread (e.g. annual rio carnival, world cup ). the estimated visitors to the olympic games constitute less than % of visitors to the zkv endemic countries (and many of these travellers will come from countries already affected by zkv), so limiting travel to the olympics will not substantially affect the risk of zkv spread. pregnant women should avoid visiting the olympics and those at risk of pregnancy should use contraception. for the individual non-pregnant traveller, zkv is a short febrile illness that leaves no sequelae. there is a small risk of complications like guillain-barré syndrome, but there is also a risk of ordinary influenza turning into severe double pneumonia requiring ventilator treatment, but we do not routinely immunize travellers to the tropics with year-round influenza transmission. travellers should be advised to follow standard precautions against insect bites, including applying repellent, wearing impregnated clothes, and using bed nets if they do not sleep in an airconditioned room. the available evidence does not support cancelling, postponing, or moving the olympic games and we hope that the games in rio de janeiro will be successful for the athletes and enjoyable for the public. conflict of interest: the authors declare no conflict of interest. communicable disease surveillance and control in the context of conflict and mass displacement in syria taking forward a 'one health' approach for turning the tide against the middle east respiratory syndrome coronavirus and other zoonotic pathogens with epidemic potential meningococcal disease and travel hajj-associated outbreak strain of neisseria meningitidis serogroup w : estimates of the attack rate in a defined population and the risk of invasive disease developing in carriers public health. do sports events give microbes a chance to score? clinical features and short-term outcomes of patients with sars in the greater toronto area a major outbreak of severe acute respiratory syndrome in hong kong probable transmission chains of middle east respiratory syndrome coronavirus and the multiple generations of secondary infection in south korea assessing the pandemic potential of mers-cov middle east respiratory syndromeadvancing the public health and research agenda on mers-lessons from the south korea outbreak reducing risks to health and wellbeing at mass gatherings: the role of the sendai framework for disaster risk reduction tuberculosis and mass gatherings-opportunities for defining burden, transmission risk, and the optimal surveillance, prevention, and control measures at the annual hajj pilgrimage prospective study of pathogens in asymptomatic travellers and those with diarrhoea: aetiological agents revisited hosting of mass gathering sporting events during the - ebola virus outbreak in west africa: experience from three african countries public health perspectives from the biggest human mass gathering on earth: kumbh mela, india communicable diseases as health risks at mass gatherings other than hajj: what is the evidence? infections in symptomatic travelers returning from the arabian peninsula to france: a retrospective cross-sectional study the spectrum of respiratory pathogens among returning hajj pilgrims: myth and reality active screening and surveillance in the united kingdom for middle east respiratory syndrome coronavirus in returning travellers and pilgrims from the middle east: a prospective descriptive study for the period - exploring barriers and facilitators of preventive measures against infectious diseases among australian hajj pilgrims: cross-sectional studies before and after hajj bin saeed aa. carriage of neisseria meningitidis in the hajj and umrah mass gatherings meningococcal disease during the hajj and umrah mass gatherings prevention of meningococcal disease during the hajj and umrah mass gatherings: past and current measures and future prospects antimicrobial resistance among pilgrims: a retrospective study from two emergency care hospitals mecca, saudi arabia community pharmacists' knowledge, attitude and practices towards dispensing antibiotics without prescription (dawp): a cross-sectional survey in makkah province, saudi arabia adding a psychological dimension to mass gatherings medicine hajj vaccinations-facts, challenges, and hope middle east respiratory syndrome vaccines uptake and effectiveness of facemask against respiratory infections at mass gatherings: a systematic review summer olympics key: cord- -ltxt dfv authors: elachola, habida; assiri, abdullah; turkestani, abdual hafiz; sow, samba s.; petersen, eskild; al-tawfiq, jaffar a.; memish, ziad a. title: advancing the global health security agenda in light of the annual hajj pilgrimage and other mass gatherings date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: ltxt dfv nan in the second week of september , health ministers from across the world converged in seoul, korea for the nd high level deliberations on global health security agenda (ghsa). this was yet another attempt to galvanize a unified response to infectious diseases that threaten global health security. , this event coincided with the arrival in saudi arabia of nearly . million pilgrims from over countries who will participate in the annual hajj pilgrimage. [ ] [ ] [ ] [ ] amidst the ongoing global transmission of three viral infections associated with high morbidity and mortality rates with epidemic potential, the ebola virus (ebov), middle east respiratory syndrome coronavirus (mers-cov) and avian influenza virus a (h n ). [ ] [ ] [ ] the detection in july of ebola virus from dead body swab of a year old boy in liberia after the declaration of liberia being ebola free in may , and the detection of ebola virus in the dead body of an elderly woman in sierra leone as the country awaits countdown to being declared ebola free, indicate current knowledge gaps of the natural history and pathogenesis. the recent large outbreak of mers-cov in hospitals in seoul, korea and subsequent spillover to china was unprecedented as the largest outbreak outside the middle east. this event illustrated that unless a high degree of awareness and vigilance with effective surveillance and infection control measures are in place, transmission of mers-cov can occur in the home countries can occur upon return of an infected pilgrim. these are all complex challenges that detection of even one case can overwhelm any health systems and adversely affect the economic security of affected countries. although the comprehensive hajj health care and emergency management system of saudi arabia is well positioned to cope with known types of threats and related case management , they are unlikely to detect any incubating transmissions that occurred among pilgrims that remain asymptomatic during the pilgrims stay in ksa. although current ghsa is yet to specifically highlight mass gathering preparedness as a strategic priority even in countries with high participant contribution to mass gatherings, the global health security agenda action packages and the strategies to minimize the implications of mass gathering on public health are similar. the risk of infectious disease transmission during a mass gathering is the same or even more as the risk of transmission that prevails in any one of the home or host countries of mass gathering participants. during the world health assembly , a side event took place to launch the lancet series on mass gathering medicine in may , ( figure ). mass-gatherings are held for various purposes including religious rituals, sports activities, or festivals and therefore the demographics, risks, and the intensity of activities vary. further, the risks are exacerbated during mass gatherings such as the hajj for airborne, droplet, and body fluid-related transmission due to the absence of social distancing among participants; increased susceptibility due to stress, lack of sleep, and changing nutritional factors during peak events; disruption of medications among persons with chronic debilitating diseases; and participation in some of the rituals such as animal sacrifices or the practice of scalp hair shaving practices by self-help groups using unsterile blades rather than in regulated barber shops. given that two-thirds of the emerging diseases are zoonotic, human-animal interaction during some mass gatherings such as the hajj further increases the risk, and saudi arabia imports sacrifice animals from countries. thus, except for vaccine preventable diseases, perfection of disease control strategies in one or few countries alone including in the host country may not offer blanket protection from all types of disease transmission dynamics for epidemic prone disease agents present in any one of the countries. the impact of these challenges on public health during mass gatherings can be minimized by two strategies. first, each of the countries that participate in a mass gathering should have alert systems in place to identify diseases of transmission-potential during a mass gathering, control measures in place to avoid the exportation of such risks, and reduce the participation of individuals at risk increased risk for disease acquisition. for ghsa , this relates to adequate syndromic-and agent-based surveillance, laboratory enhancements, and reporting systems and risk communication managed by adequately trained workforce including one epidemiologist for a population of , . furthermore, countries participating in mass gatherings should have public emergency preparedness in response mode and adequate surge capacity to be able to respond to potential emergencies from participants returning from mass gatherings. existence of a public health emergency operations center with sufficient pool of response manpower and medical countermeasures available will be critical. this can only be functional if relevant a national public health preparedness policies and authorities are in place to coordinate a response with diverse organizational entities such as the ministries of aviation, defense, interior, and health. of note, moving from challenges to disease detection opportunities, it is worth noting that mass gatherings provide an unexploited opportunity as an one-stop surveillance venue to monitor emerging disease threats or existing threats of significance in multiple countries. health examinations and specimen collection is routine for hajj pilgrims prior to departure in their home countries and arrival airports in saudi arabia conduct health screenings. additional surveillance programs using rapid detection tests can be implemented in home and host countries of mass gatherings. furthermore, the hajj emergency health management system operates a network of health facilities with electronic data management systems that can conduct syndromic-and agentbased surveillance on symptomatic individuals who seek care (about , pilgrims on average during each hajj) ( )deliverables that correspond well with the objectives outlined in the ghsa . in summary, it is imperative that opportunities presented by the ghsa in the first round of countries chosen for immediate implementation by the u.s. government , and future beneficiary countries of the ghsa prioritize and program funding and activities that specifically address mass gathering preparedness in addition to sustained routine activities. we now have the knowledge that the world did not have during the hajj and influenza transmission. as the search for vaccines and treatment continue for these novel challenges, first and foremost priority for the global community is to minimize the effects of emerging threats during mass gatherings would be to activate public health emergency management capacities before, during and after these mass gatherings of significance. mass gatherings offer opportunities to implement, test, and assess ghsa objectives in its entirety and can contribute significantly to health security of individuals, nations, and the world. global health-global health security agenda mass gatherings medicine and global health security public health. pandemic h n and the hajj mass gatherings medicine: international cooperation and progress mass gathering and globalization of respiratory pathogens during the hajj the ebola virus disease outbreak. world health organization mers-the latest threat to global health security centers for disease control and prevention, us department of health and human services hajj: infectious disease surveillance and control key: cord- -kg j authors: dao, thi loi; hoang, van thuan; anh ly, tran duc; goumballa, ndiaw; courjon, johan; memish, ziad; sokhna, cheikh; raoult, didier; parola, philippe; gautret, philippe title: epidemiology of human common coronavirus acquisition in pilgrims date: - - journal: travel medicine and infectious disease doi: . /j.tmaid. . sha: doc_id: cord_uid: kg j nan human coronaviruses (hcovs) belong to a group of viruses that primarily cause respiratory illnesses ranging from the common cold to more severe diseases such as bronchitis, pneumonia, and respiratory distress [ ] . currently, seven different hcov species are known to infect humans. these include hcov- e, hcov-oc , severe acute respiratory syndrome cov (sars-cov), hcov-nl , hcov-hku , middle east respiratory syndrome (mers-cov) [ ] and sars-cov- , which was recently identified in humans and is responsible for an ongoing widespread epidemic affecting many countries [ ] . hcov- e, hcov-oc , hcov-nl and hcov-hku are the most common four hcovs, with a global geographical distribution and a seasonal endemic transmission pattern [ ] . we revisited our data by investigating the prevalence of common hcovs in the hajj and grand magal pilgrims and studying the potential risk factors for hcov acquisition in a large number of individuals. at total of pilgrims were include. the m/f gender ratio was . and the median age was . years (ranging from to years). a female predominance was observed in french hajj pilgrims, while international hajj pilgrims were more likely to be males (supplementary table ). senegalese grand magal pilgrims were characterised by their younger age, while hajj pilgrims were mostly middle aged or elderly individuals (supplementary table ). in total, . % of the pilgrims presented at least one respiratory symptom during travel. a cough ( . %) and a rhinitis ( . %) were the most frequent symptoms, followed by fever ( . %) and dyspnoea ( . %) ( table ) . symptoms were more frequent in hajj pilgrims as compared to grand magal pilgrims (supplementary table ) . overall, a total of specimens, including nasopharyngeal pre-travel specimens and post-travel specimens were investigated. in total, / ( . %) samples tested positive for coronaviruses including ( . %) for hcov- e, ( . %) for hcov-nl , ( . %) for hcov-oc and ( . %) for hcov-hku . the prevalence of hcovs in international hajj pilgrims sampled upon arrival in ksa, and thus reflecting the prevalence in origin countries, was . % ( / ). that of french pilgrims sampled before travelling to ksa was . % ( / ) and that of senegalese pilgrims sampled before travelling to touba was . % (hajj pilgrims) [ ] . we also found a . % prevalence of hcovs acquired in asymptomatic individuals, in line with a . % prevalence reported in a us study conducted in asymptomatic adults [ ] . hajj pilgrims were more likely to acquire hcov e, while grand magal pilgrims were more likely to acquire hcovs nl and oc (supplementary figure ) . in univariate analysis, acquisition of hcovs was higher in hajj pilgrims than in grand magal pilgrims. our study also revealed annual differences in the prevalence of hcovs that peaked in and . these associations remained significant in multivariate analysis. factors associated with annual variation in hcov prevalence are currently unclear. such annual variations were also observed in a study conducted in the us [ ] . in addition, hcovs acquisition was more frequent in pilgrims reporting respiratory symptoms, although this was not significant in univariate analysis. clinical data were available for / ( . %) of participants included in this work which unfortunately precluded multivariate analysis. future studies are needed to understand the clinical significance of common hcovs acquisition in these populations. this report reveals the role of participation in a large gathering in common hcovs acquisition and related infections. significant acquisition of hcovs following participation in the hajj pilgrimage has been reported by several authors due to overcrowded conditions encouraging the person-to-person spread of respiratory viruses including hcovs [ ] . this is of particular concern in the current context of the sars-cov- pandemic where international travel including mass gatherings played a key role in the global spread of the disease [ ] . j o u r n a l p r e -p r o o f genetic recombination, and pathogenesis of coronaviruses hajj-associated viral respiratory infections: a systematic review asymptomatic shedding of respiratory virus among an ambulatory population across seasons. msphere human coronavirus circulation in the united states covid- -the role of mass gatherings key: cord- - qqyb sd authors: pane, masdalina; imari, sholah; alwi, qomariah; nyoman kandun, i; cook, alex r.; samaan, gina title: causes of mortality for indonesian hajj pilgrims: comparison between routine death certificate and verbal autopsy findings date: - - journal: plos one doi: . /journal.pone. sha: doc_id: cord_uid: qqyb sd background: indonesia provides the largest single source of pilgrims for the hajj ( %). in the last two decades, mortality rates for indonesian pilgrims ranged between – deaths per , pilgrims over the -week hajj period. reasons for high mortality are not well understood. in , verbal autopsy was introduced to complement routine death certificates to explore cause of death diagnoses. this study presents the patterns and causes of death for indonesian pilgrims, and compares routine death certificates to verbal autopsy findings. methods: public health surveillance was conducted by indonesian public health authorities accompanying pilgrims to saudi arabia, with daily reporting of hospitalizations and deaths. surveillance data from were analyzed for timing, geographic location and site of death. percentages for each cause of death category from death certificates were compared to that from verbal autopsy. results: in , , indonesian undertook the hajj. there were deaths, equivalent to , deaths per , pilgrim years. most pilgrims died in mecca ( %) and medinah ( %). there was no statistically discernible difference in the total mortality risk for the two pilgrimage routes (mecca or medinah first), but the number of deaths peaked earlier for those traveling to mecca first (p= . ). most deaths were due to cardiovascular ( %) and respiratory ( %) diseases. a greater proportion of deaths were attributed to cardiovascular disease by death certificate compared to the verbal autopsy method (p< . ). significantly more deaths had ill-defined cause based on verbal autopsy method (p< . ). conclusions: despite pre-departure health screening and other medical services, indonesian pilgrim mortality rates were very high. correct classification of cause of death is critical for the development of risk mitigation strategies. since verbal autopsy classified causes of death differently to death certificates, further studies are needed to assess the method’s utility in this setting. each year, muslims from all over the world undertake the hajj pilgrimage to and in saudi arabia [ ] . in recent years, over million people from countries undertook the hajj annually, including over , people from indonesia, the world's most populous muslim majority country. performance of the hajj and its rites is physically demanding [ ] . extreme physical stressors such as sun exposure, heat ( °c during the day and °c at night), thirst, crowding, steep inclines and traffic congestions over a prolonged period of time ( days per pilgrim over the -day hajj season) increase health risks. since pilgrims tend to be older and many have medical comorbidities [ ] , these factors exacerbate existing risk for ischemic and congestive cardiovascular disease, fluid and electrolyte abnormalities, and respiratory and other infectious diseases including emerging diseases such as middle east respiratory syndrome coronavirus [ ] . in the last two decades, the mortality rate of indonesian pilgrims, excluding years in which disasters such as stampedes occurred, fluctuated between - deaths per , persons during the ten-week hajj period [ ] . few countries have published pilgrim mortality rates, but compared to where they are available, the indonesian rate is much higher [ ] . for example, in , the hajj mortality rate amongst isfahani pilgrims from iran was per , pilgrimages [ ] . in , the mortality rate for all iranian pilgrims was per , pilgrimages, and in , per , [ ] . even compared to the yearly mortality rate in indonesia, the mortality rate for hajj pilgrims ranged between , and , per , per year; by comparison, the indonesian estimated national crude death rate was per , in [ ] . since , indonesian authorities have provided medical services to hajj pilgrims. pre-departure health screening and vaccination as well as temporary medical clinics staffed by indonesian doctors in saudi arabia were introduced progressively. mortality surveillance was also established to reduce mortality and aid in administrative processes for life insurance claims. prior to , the patterns, causes of death and factors associated with mortality were not well understood for indonesian pilgrims. data collected were limited to basic demographic characteristics and general cause of death. cause of death could only be obtained from the hospital death certificate or the flight doctor's records if a death occurred in the community. these were based on clinical examination and any available laboratory tests as documented in the patient medical record, but they lacked detailed information about the cause of death or the patient's pre-existing conditions. given the hugely elevated mortality risk relative to the general indonesian population, information on cause of death and underlying health conditions is critical to enhance pilgrim health management and to prevent excess mortality. in , the ministry of health introduced an additional surveillance tool -verbal autopsy -to better understand the causes of pilgrim mortality. verbal autopsy allows for the systematic investigation of probable causes of death through structured questionnaires [ ] . the world health organization (who) advocates the use of verbal autopsy in situations where only a fraction of deaths occur in hospitals or in absence of vital registration systems [ ] . previous studies have shown that verbal autopsy improves diagnosis of cause of mortality and the method continues to be used in various countries [ ] [ ] [ ] . this study describes the findings from the mortality surveillance conducted during the hajj in ; the year in which verbal autopsy was introduced. we explore both personspecific and site-specific factors associated with mortality, and compare the cause of death from the routine death certificate to the newly introduced verbal autopsy method. ethics approval for the study was obtained from the ministry of health national institute of health research and development ethics review committee with approval number lb. . /ke/ / . written consent was not obtained from the patients involved, but this was waived by the ethics review committee as mortality data were analysed anonymously. in , , indonesians undertook pilgrimage during hajj. the majority were from java ( %) and sumatra ( %) islands, with small proportions from kalimantan ( %), sulawesi ( %) and other ( %) islands. the majority of pilgrims, anecdotally reported to be %, joined one of the governmentsponsored hajj pilgrimage travel services that include days of travel. the remainder joined private more expensive pilgrimage travel services that are of shorter duration ( days) and provide better accommodation and services. a number of preventive and curative healthcare services were available to all hajj pilgrims prior to and during their travels in saudi arabia. pre-departure, each indonesian pilgrim was required to visit a government healthcare facility for a medical check-up and to receive a pocketbook outlining their health conditions, medications and vaccination status. pilgrims were mandated to receive meningococcal vaccine and were advised to receive influenza vaccine before their departure. flights were chartered by the indonesian government to accommodate - pilgrims. each flight had one doctor and two nurses to accompany the pilgrims. these healthcare workers treated, triaged and conducted health surveillance for pilgrims. hospitalizations and incidental reporting of any deaths occurring outside a healthcare facility were notified daily to the indonesian public health team based in saudi arabia during the hajj. saudi authorities made first aid posts, health centres and hospitals available. in mecca, six hospitals were set up during pilgrimage, while in medinah, pilgrims could access established hospitals. in addition to the saudi facilities, indonesian health authorities set up field hospitals in mecca and medinah specifically for indonesian pilgrims. indonesia also sent specialist doctors including internists, pulmonologists, cardiologists and psychiatrists, public health workers, nurses, pharmacists and sanitarians to support the pilgrimage. all deaths were reported from the flight doctor or the saudi hospital to the indonesian public health team located in saudi arabia during the hajj. mortality data collected by the indonesian public health team were entered into a database for data analysis. standard variables in the database included name, age, sex, home address, employment, flight group, time and place of death, date of arrival into saudi arabia, cause of death as per the hospital or flight doctor death certificate. in , the indonesian ministry of health mandated a verbal autopsy form to be filled out by the flight doctors accompanying pilgrims. the verbal autopsy form was developed based on the standards established by who and adapted to hajj pilgrimage needs [ ] . the verbal autopsy form obtained detailed information about medical history, signs and symptoms, and other circumstances regarding the death from family or friends who travelled with the deceased. in most cases, interviews were conducted with a combination of the treating physician, the deceased person's spouse or pilgrims in the same flight group. the form aimed to increase the specificity of the cause of death by elucidating medical history and recent events. the flight doctors were trained in administering the verbal autopsy form prior to departure from indonesia and were required to complete it within the week of a pilgrim's death. once the form was completed, the indonesian public health team stationed in saudi arabia sent it to the ministry of health in indonesia for analysis and determination of cause of death. the form was analysed separately by two trained staff at the ministry of health to determine the cause of death. if discordant, the staff compared their analyses to achieve consensus. the cause of death based on this verbal autopsy method was then recorded in the database and compared to that reported by the hospital or flight doctor death certificate. we used counts and proportions to describe demographic characteristics of indonesian pilgrims and fatalities. the chi-square test and chi-square test for trend were used for the analysis of categorical data. to compare the two methods for establishing cause of death (verbal autopsy and death certificate), we compared the percentages for each cause of death category using mcnemar's test. all , indonesian pilgrims were aged years or more, where the majority ( %) were aged between and years ( table ) . most pilgrims were female ( %, table ). according to the pre-embarkation medical assessment, % of pilgrims were classified as high risk due to underlying health conditions such as diabetes, hypertension, other chronic diseases or if they were years or older. pilgrims in , indonesian pilgrims died during the hajj in saudi arabia. the overall mortality rate was deaths per , pilgrimages. mortality rates were highest in those ≥ years of age ( per , pilgrims), and rates significantly increased with increasing age (p< . , table ). mortality rates were higher in males ( deaths per , pilgrims) compared to females ( deaths per , pilgrims, p< . , table ). for the deaths in - year old age-group, were male and were female. according to the death certificates, three died due to cardiac arrest and one due to asphyxia in a patient with active tuberculosis. most deaths occurred in mecca (n= , %), followed by medinah (n= , %) and jeddah (n= , %). the majority ( %) of deaths occurred in hospital, but a large proportion of deaths also occurred in pilgrims' apartments/sleeping areas ( %). most ( %) deaths occurred during pilgrims' active hours between am and pm: mortality rates were higher in the afternoon (possibly due to the heat) and early morning ( figure a ). weekly mortality rates increased in week , exceeding the expected crude mortality rate (cmr) of per , per day [ ] , and remained high until the end of the -week hajj period (figure b ). in week , the number of deaths started to decrease. however, since the overall number of pilgrims also decreased, the mortality rates remained very high since some of the indonesian pilgrims who were hospitalized died in the later weeks of the hajj. for pilgrims on route , the number of deaths increased sharply four weeks after arrival into saudi arabia by which time the pilgrims had already reached mecca (figure b ). for pilgrims on route , the number of deaths peaked in the third week after their arrival into saudi arabia, at which stage the pilgrims were in mecca (figure c ). the number of deaths remained large thereafter until the end of the hajj for those undertaking route . there was no statistical difference in the number of deaths occurring for pilgrims undertaking route ( out of , pilgrims) compared to those on route ( out of , , p= . ). however, the trends from week to week during the hajj period were significantly different between pilgrims on route compared to those on route (χ for trend= . , p= . ). most deaths were due to cardiovascular diseases and respiratory diseases (table ) . a greater proportion of deaths were attributed to cardiovascular disease by the flight doctor or hospital death certificate ( %) compared to the cause of death ascertained using the verbal autopsy method ( %, p< . ). significantly more deaths had unspecified cause based on the verbal autopsy method ( %, versus , p< . ). as part of the demographic data collected for each pilgrim, height and body mass were recorded. based on the hospital/flight doctor death certificate, of the ( %) pilgrims who died had body mass index ≥ . indicating obesity for asian body types [ ] . of these, died due to cardiovascular disturbances, due to respiratory illness, due to metabolic disturbances, had undefined sudden death and due to trauma (neck fracture). this study describes the demographics, patterns and causes of mortality in indonesian pilgrims in . nearly one third of pilgrims undertaking the hajj in were considered high risk due to underlying health conditions or their age. mortality rates were found to be greatest in males and in those aged ≥ years, in whom most deaths were attributed to cardiovascular and respiratory diseases. studies from other countries with pilgrims found similar trends, including a preponderance in male mortality [ , ] . these findings highlight the special characteristics of the hajj compared to other mass gathering events. many muslims wait decades for the opportunity to perform the hajj, and by the time they receive the chance, they may have a multitude of age-related health concerns [ ] . correct classification of deaths is critical to target preventive interventions and provide health services [ ] . this study compared cause of death according to the flight doctor and death certificate records to the newly introduced verbal autopsy method. fewer deaths were attributed to cardiovascular diseases using verbal autopsy but this method resulted in a greater number of deaths having ill-defined cause of death. verbal autopsy method may have reduced misclassification by removing pressure from clinicians having to extrapolate cause of death in situations where it may have been ill-defined or unclear. however, this hypothesis warrants further investigation. since the verbal autopsy method is dependent on the skills of the field personnel collecting the data, the timing to limit recall bias and the method is most suited to diseases with specific symptoms and presentation [ , ] , the use of verbal autopsy for hajj mortality surveillance should be further evaluated. based on both the death certificates and verbal autopsy categories, cardiovascular disease was the leading cause of indonesian pilgrim mortality in . performance of obligatory rites during the hajj constitutes stressful exercise which is not generally recommended by doctors for those with ischemic heart disease, hypertension or heart failure as such exercise may increase the risk of heart attacks [ ] . this risk may be further elevated in the heat, where dehydration may lead to increase in body temperature and heart rate, and a decrease in cardiac output [ ] . an iranian study showed that when patients with severe cardiovascular disease were prohibited from attending the hajj and other patients with cardiovascular disease were provided with appropriate medications and monitoring during pilgrimage, mortality rates were significantly lower than those for other pilgrims [ ] . this supports the need for careful pre-departure health screening, exclusion of the severely ill, provision of appropriate drug therapies or increased physical exercise prior to departure, and monitoring during pilgrimage to reduce mortality. one-third of indonesian pilgrim mortality was attributed to respiratory diseases. pneumonia is a common illness that is life-threatening to the elderly, especially those with comorbidities such as diabetes or hypertension [ ] . a number of studies have shown that pneumonia is the primary cause of critical illness during the hajj and that etiologies include gramnegative organisms, streptococcus pneumoniae, and mycobacterium tuberculosis [ , , ] . for tuberculosis patients, the physical stressors of the hajj may increase the risk of severe illness and mortality, and the intense crowding during the pilgrimage may increase the risk of disease transmission. a recent study found that % of malaysian pilgrims had a significant increase in immune response to quantiferon tuberculosis assay antigen post-hajj compared to pre-hajj [ ] . since indonesia is a high-burden country for tuberculosis [ ] , pre-departure screening should continue to exclude those with active disease. other potential public health measures to reduce mortality due to respiratory diseases include increasing coverage of influenza vaccine and pneumococcal vaccine. such measures were applied by iranian public health authorities in , which halved the incidence of respiratory diseases and decreased the mortality rates from per , in to per , in [ ] . deaths amongst indonesian pilgrims traveling on route who went to mecca first peaked earlier than those traveling on route . most deaths among indonesian pilgrims occurred in the middle-latter weeks of the hajj period during the stay in mecca and afterwards in arafah-mina. obligatory rites conducted at holy sites in mecca and arafah-mina are known to involve intense physical activity [ ] . these may have been too strenuous for some pilgrims, especially older or relatively sedentary pilgrims. surprisingly, % of deaths occurred in the accommodation provided to pilgrims during the hajj. this highlights that despite the presence of an accompanying health team, not all patients were referred to hospital prior to critical stages of illness. one limitation of this study is that further details about deaths occurring in accommodation were not available for analysis. lack of data limited other important analyses including deaths by health risk status and type of travel service (government or private) used. the rates of mortality as well as causes of death may differ based on these categories and may impact recommendations for intervention. pattern of diseases among visitors to mina health centers during the hajj season, h ( g) hajj: health lessons for mass gatherings common health hazards in french pilgrims during the hajj of : a prospective cohort study the epidemiology of hajj-related critical illness: lessons for deployment of temporary critical care services* comparison of mortality and morbidity rates among iranian pilgrims in hajj how to reduce cardiovascular mortality and morbidity among hajj pilgrims: a multiphasic screening, intervention and assessment verbal autopsy: current practices and challenges potential and limits of verbal autopsies factors associated with place of death in addis ababa applying verbal autopsy to determine cause of death in rural vietnam accuracy of who verbal autopsy tool in determining major causes of neonatal deaths in india verbal autopsy standards: ascertaining and attributing causes of death famine-affected, refugee, and displaced populations: recommendations for public health issues appropriate body-mass index for asian populations and its implications for policy and intervention strategies causes of admission to intensive care units in the hajj period of the islamic year clinical and temporal patterns of severe pneumonia causing critical illness during hajj a review of data-derived methods for assigning causes of death from verbal autopsy data physical activity and stroke in british middle aged men influence of graded dehydration on hyperthermia and cardiovascular drift during exercise tuberculosis is the commonest cause of pneumonia requiring hospitalization during hajj (pilgrimage to makkah) high risk of mycobacterium tuberculosis infection during the hajj pilgrimage country profile -indonesia indonesian pilgrims suffer high mortality rates despite predeparture screenings, accompanying medical teams and the availability of specialized health services during the hajj. this study highlights the importance of surveillance during the hajj to understand the health risks and strengthen the evidencebase on which policy can be developed [ ] . further studies are needed to assess verbal autopsy's utility in this setting. the role of the accompanying health teams as first responders needs to be reviewed to determine how they can best reduce indonesian pilgrim mortality. an evaluation of the current mortality surveillance system is also warranted to ensure that the data collected appropriately serves the public health purpose of reducing pilgrim mortality. lastly, lessons need to be learnt from other countries including their hajj mortality patterns and risk mitigation strategies. key: cord- -bjccnp u authors: yavarian, jila; shafiei jandaghi, nazanin zahra; naseri, maryam; hemmati, peyman; dadras, mohhamadnasr; gouya, mohammad mehdi; mokhtari azad, talat title: influenza virus but not mers coronavirus circulation in iran, – : comparison between pilgrims and general population date: - - journal: travel med infect dis doi: . /j.tmaid. . . sha: doc_id: cord_uid: bjccnp u background: the pilgrimage to mecca and karbala bring many muslims to a confined area. respiratory tract infections are the most common diseases transmitted during mass gatherings in hajj, umrah and karbala. the aim of this study was to determine and compare the prevalence of middle east respiratory syndrome coronavirus (mers-cov) and influenza virus infections among iranian general population and pilgrims with severe acute respiratory infections (sari) returning from mecca and karbala during – . methods: during – , a total of throat swabs were examined for presence of influenza viruses and mers-cov in iranian general population and pilgrims returning from mecca and karbala with sari by using one step rt-pcr kit. results: none of the patients had mers-cov but influenza viruses were detected in . % with high circulation of influenza a/h n ( . %). conclusion: this study showed the prevalence of influenza infections among iranian pilgrims and general population and suggests continuing surveillance, infection control and appropriate vaccination especially nowadays that the risk of influenza pandemic threatens the world, meanwhile accurate screening for mers-cov is also recommended. the middle east respiratory syndrome coronavirus (mers-cov) was first identified in a patient from kingdom of saudi arabia (ksa) in june [ ] . according to world health organization (who) report, until september , the number of laboratory-confirmed cases of mers-cov was , with deaths. most of the cases originated from or had a history of travel to middle-east. mecca and karbala are places in the middle-east which are visited by muslims especially during hajj, umrah and arbaeen. ksa hosts about . million muslim pilgrims from more than countries during the hajj pilgrimage annually. hajj is one of the largest mass gatherings of its kind in the world. umrah is a visit to the holy sites in ksa the same as hajj but it can be occurred at any time during the year. during the hajj, respiratory tract infections are the leading cause of hospitalization in ksa [ , ] . karbala is a holly place in iraq which muslims visit there during the year especially arbaeen. arbaeen is a shia muslim ritual that occurs forty days after the day of ashura ( th day of the month of muharram). it celebrates the death of hussein ibn ali, the grandson of prophet mohammad, who was killed on the day of ashura. arbaeen is the world largest annual pilgrimage as more than millions of shia muslims gather in the city of karbala in iraq. mass gathering of people in a confined area specially hajj and arbaeen increases the risk of respiratory tract infections which are very common and responsible for most of the hospital admissions. after june global concern was about the potential for mers-cov spreading by travelers returning from the pilgrimage. for early detection of emerging respiratory viruses, the international health regulations emerging committee established a program for all countries (especially those with returning pilgrims) to strengthen their surveillance to detect and report any new cases. however ksa has been reported the majority of mers-cov cases (> %) since , but in the . million pilgrims in hajj and no mers-cov cases were reported [ ] . influenza viruses are important human respiratory pathogens with high morbidity and mortality that cause both seasonal and endemic infections. nowadays emergence of h n and h n is the concern for https://doi.org/ . /j.tmaid. . [ , ] but there is no published data about the prevalence of respiratory virus infections during arbaeen. among hajj pilgrims, influenza is the most common vaccine preventable virus infection, but its epidemiology is poorly understood in mass gatherings [ ] . beside detection of mers-cov, we designed this study to investigate about the importance of influenza vaccination in general population and pilgrims. in iran, the influenza season starts in late november and lasts until late april, peaking in january and february. the national influenza center (nic) in iran, located at virology department, school of public health, tehran university of medical sciences, examines clinical samples from patients with severe acute respiratory infections (sari) for influenza virus surveillance throughout the year in general population and/or pilgrims. after mers detection in , all suspected cases were tested in nic and the first mers case, a year old woman with a history of hypertension, was confirmed in may , iran [ ] . with continues surveillance totally six mers cases were identified in iran which the last one was in march . the study's primary aim was screening the iranian pilgrims and general population with sari for detection of mers-cov during - . the second aim was to assess the prevalence of influenza virus infections in these patients and the final aim was to comparison of influenza and mers-cov circulation between general population and pilgrims. throat swab specimens according to ministry of health protocol were collected from a total of patients with saris. of them, specimens were collected from general population and specimens were taken from arriving pilgrims at emam khomeini airport in tehran, - . throat swabs were collected in viral transport media and immediately transported to nic, school of public health, tehran university of medical sciences. total nucleic acids were purified from a μl sample using high pure viral nucleic acid kit (roche, germany) according to the manufacturer's instructions. each sample was tested independently in a μl reaction for influenza a/b and mers-cov using quantifast probe rt-pcr kit (qiagen, germany). mers-cov was tested with targeting the upstream region of the e gene (upe) for screening and the open reading frame b for confirmation [ ] . in total patients with saris were included in this study which were returning iranian pilgrims from mecca and karbala and were patients with sari who admitted to local hospitals. iranian pilgrims had symptoms upon arrival or a week later, thereby indicating that the respiratory infections were acquired during the pilgrimage. of pilgrims, ( %) were positive for influenza viruses. during the years of study in all patients, circulating influenza strains differed but the pattern was similar in both pilgrims and general population. in in just in non-pilgrim patients three dual infections of influenza a/h n and a/h n viruses were detected in november. during the years of this study from iranian pilgrims, . % ( / ) returned from karbala, . % ( / ) came from umrah and . % arrived from hajj. we did not have any pilgrims returning from mecca in but just . % ( / ) came from karbala. more information about the prevalence of different influenza strains in hajj, umrah, karbala and general population are shown in table . this paper showed the results of study of mers-cov and influenza virus infections among pilgrims and non-pilgrim patients with sari during - . each year more than million muslims travel from all over the world to participate in hajj and umrah. approximately more than one million pilgrims travel from iran to ksa annually. in recent years more than million iranian pilgrims have been gathering during arbaeen in karbala. in this study . % ( / ) of pilgrims returned from karbala which . % were influenza positive with a/h n predominance. in a study on iranian pilgrims to karbala who admitted to iraqi hospitals, . % suffered from respiratory infections [ ] . in another study from a total of pilgrims admitted to iranian clinics in iraq, the main cause was acute respiratory infections ( %) [ ] . generally performing the pilgrimage in a confined area is associated with an increased occurrence of respiratory infections in the pilgrims. transmission of different infectious diseases during mass gatherings in holly places has a global effect when pilgrims return to their country. in a meningococcal disease outbreak and its global spread during the hajj lead to this fact that meningococcal vaccine became a mandatory vaccine for all pilgrims [ ] . according to the vaccination protocol in iran, all pilgrims had received meningococcal vaccination, but influenza vaccination is not mandatory and we do not have data about its vaccination in this group. however in a review by gautret et al. no remarkable effect of influenza vaccination on the influenza infection of pilgrims was found. apparently this lake of efficiency of influenza vaccine might be the result of mismatch between circulating influenza viruses with vaccine strains [ ] . influenza viruses are common respiratory viruses with high mortality and morbidity especially in young children and elderly. in iran influenza viruses are circulating throughout the year with a big peak during cold months. since besides influenza virus screening nic examines clinical samples for mers-cov detection from suspected patients throughout the year in general population and/or pilgrims. we previously reported that a cluster of mers-cov was detected in kerman/iran in among nonpilgrims [ ] . current study showed that among the population screened, no cases were positive for mers-cov. these results were in accordance with previous studies which have performed among pilgrims of different countries. a cohort of pilgrims attending the hajj showed the lack of mers-cov in nasal carriage [ ] . in a study on french hajj pilgrims in , in spite of high rate of respiratory infections, mers-cov was not detected [ ] . these findings suggest that mers-cov in its current form has poor interhuman transmission and may not have the pandemic potential as seen in influenza a/h n in . however investigation about a highly fatal human coronavirus is necessary as it is a challenge and little is known about its importance, epidemiology and zoonotic total patients influenza positive a/h n - - a/h n b transmission. in pilgrims of this study influenza b accounted for % ( / ) and influenza a for . % ( / ) of positive influenza results in contrast to findings by balkhy et al., in , that % of pilgrims had influenza b and % had influenza a [ ] . the results of a uk study with paired serum samples collected before and after the hajj using hemagglutination inhibition test, showed that % of uk pilgrims had influenza infection during the hajj [ ] . in another study during hajj , % of uk pilgrims with respiratory infections had influenza virus [ ] . rashid et al., in performed a comparative study in symptomatic uk and saudi pilgrims which found infections in % and % of their pilgrims respectively. rhinoviruses were detected in half of uk pilgrims, followed by influenza virus but in saudi pilgrims . % had influenza virus infection [ ] . in , alborzi et al. reported that . % of iranian hajj pilgrims with respiratory infections had influenza [ ] . in , iranian pilgrims with respiratory infections returning from hajj were assessed for detection of a/h n pdm which just five patients ( . %) were positive [ ] . in a survey on serum samples of iranian pilgrims before and after hajj with elisa, . % were influenza positive [ ] . in another iranian study on serum samples of hajj pilgrims in - , before departure and two weeks after respiratory infections, there was a . % seroconversion for influenza viruses. while virus culture on their sputum was . % influenza positive [ ] . in a study on symptomatic iranian hajj pilgrims, ( . %) were influenza positive by virus culture whereas ( %) had influenza with rt-pcr test [ ] . the findings of this research showed that influenza virus infection was the cause of respiratory infections in of ( %) of iranian pilgrims. in a similar study in kashmir, north india during - among returning hajj and umrah pilgrims with respiratory illness, none of the participants tested positive for mers-cov; however, ( %) tested positive for influenza viruses [ ] . in general population, of sari patients, ( . %) were influenza positive during the years of this study with different circulation of the subtypes as seen in other studies: timmermans et al. performed a study on outpatients with influenza-like-illness in western cambodia between may and december . influenza was found in cases ( %). dominant influenza subtypes were a/h n in , influenza b in and influenza a/h n in [ ] . in a study by mancinelli et al. a total of respiratory specimens positive for the influenza a and b viruses were subtyped during the - influenza season in italy. influenza b was slightly more prevalent ( . %) than influenza a ( . %) and the most common subtype was a/h n ( . %) while only . % were a/h n [ ] . in a ten year ( - ) study of influenza surveillance in northern italy, the same as our study influenza a/h n was prominent during - [ ] . the results of this study showed similar pattern of virus circulation in pilgrims and non-pilgrims sari patients. as influenza has high morbidity and mortality, its vaccination is recommended for general population especially for high risk groups and pilgrims before going to pilgrimage. finally accurate screening and testing for mers-cov and other respiratory viruses including influenza, is necessary for early diagnosis to prevent virus transmission and to do effective treatment. as a final point lack of demographic and clinical data was the most important limitation of this study. jila yavarian performed the analyses of the data and wrote the paper. nazanin zahra shafiei jandaghi reviewed the paper critically, and comments were included. maryam naseri performed the tests. peyman hemmati, mohammadnasr dadras were responsible for epidemiological investigation and data collection. mohammad mehdi gouya and talat mokhtari azad were responsible for study design. none. isolation of a novel coronavirus from a man with pneumonia in saudi arabia hajj-associated viral respiratory infections: a systematic review pattern of admission to hospitals during muslim pilgrimage (hajj) public health management of mass gatherings: the saudi arabian experience with mers-cov influenza a common viral infection among hajj pilgrims: time for routine surveillance and vaccination enhanced surveillance of influenza and other respiratory viruses among uk pilgrims to hajj pandemic influenza: mass gatherings and mass infection cluster of middle east respiratory syndrome coronavirus infections in iran detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction the most frequent causes of hospitalization of iranian pilgrims in iraq during a -month period in , and their outcome prevalence of diseases in pilgrims referring to iranian clinics in iraq travel epidemiology: the saudi perspective prevalence of mers-cov nasal carriage and compliance with the saudi health recommendations among pilgrims attending the hajj lack of nasal carriage of novel corona virus (hcov-emc) in french hajj pilgrims returning from the hajj , despite a high rate of respiratory symptoms influenza a common viral infection among hajj pilgrims: time for routine surveillance and vaccination influenza among uk pilgrims to hajj influenza and respiratory syncytial virus infections in british hajj pilgrims viral respiratory infections at the hajj:comparison between uk and saudi pilgrims viral etiology of acute respiratory infections among iranian hajj pilgrims pandemic influenza a (h n ) infection among hajj pilgrims from southern iran: a real-time rt-pcr-based study acute respiratory viral infections among tamattu' hajj pilgrims in iran surveying respiratory infections among iranian hajj pilgrims influenza viral infections among the iranian hajj pilgrims returning to shiraz, fars province. iran influenza other respir viruses influenza not mers cov among returning hajj and umrah pilgrims with respiratory illness human sentinel surveillance of influenza and other respiratory viral pathogens in border areas of western cambodia clinical features of children hospitalized with influenza a and b infections during the - influenza season in italy ten influenza seasons in france: distribution and timing of influenza a and b circulation we thank all staff in national influenza center, virology department, school of public health, tehran university of medical sciences. key: cord- -szkiilb authors: gautret, philippe; angelo, kristina m.; asgeirsson, hilmir; duvignaud, alexandre; van genderen, perry j.j.; bottieau, emmanuel; chen, lin h.; parker, salim; connor, bradley a.; barnett, elizabeth d.; libman, michael; hamer, davidson h. title: international mass gatherings and travel-associated illness: a geosentinel cross-sectional, observational study date: - - journal: travel med infect dis doi: . /j.tmaid. . sha: doc_id: cord_uid: szkiilb background: travelers to international mass gatherings may be exposed to conditions which increase their risk of acquiring infectious diseases. most existing data come from single clinical sites seeing returning travelers, or relate to single events. methods: investigators evaluated ill travelers returning from a mass gathering, and presenting to a geosentinel site between august and april , and collected data on the nature of the event and the relation between final diagnoses and the mass gathering. results: of ill travelers, % were female and the median age was years (range: – ). over % returned from a religious mass gathering, most frequently umrah or hajj. only % returned from the olympics in brazil or south korea. other mass gatherings included other sporting events, cultural or entertainment events, and conferences. respiratory diseases accounted for almost % of all diagnoses, with vaccine preventable illnesses such as influenza and pneumonia accounting for % and % of all diagnoses respectively. this was followed by gastrointestinal illnesses, accounting for . %. sixty-three percent of travelers reported having a pre-travel encounter with a healthcare provider. conclusions: despite this surveillance being limited to patients presenting to geosentinel sites, our findings highlight the importance of respiratory diseases at mass gatherings, the need for pre-travel consultations before mass gatherings, and consideration of vaccination against influenza and pneumococcal disease. attendance at an international mass gathering (mg) may expose travelers to health risks related to crowded conditions, population movement, and inadequate sanitation [ , ] . according to the world health organization, an event can be classified as a mg if the number of people attending is sufficient to strain the planning and response resources of the community, state, or nation hosting the event [ ] . however, much of the available literature describes mass gatherings as those exceeding , persons. we describe demographic characteristics and diagnoses among travelers who attended a mg and presented with a travel-associated illness to a geosentinel site. august , , and april , , were collected by geosentinel, a global clinicianbased surveillance network that monitors travel-related illnesses among international travelers and migrants [ ] . geosentinel was established in as a collaboration between the centers for disease control and prevention and the international society of travel medicine. it consists of clinical sites in countries. geosentinel records ill persons' visits to network sites; well travelers are not captured. attendance at a mg is routinely recorded. during the study period, investigators were directed to enter supplemental details on the nature and location of the mg and to evaluate whether the diagnosis was likely associated with mg attendance. records were excluded if the mass gathering was likely to have < , attendees or if data were missing regarding the type of mg. geosentinel's data collection protocol has been reviewed by a human subjects advisor at cdc's national center for emerging and zoonotic infectious diseases and is classified as public health surveillance and not human subjects research. additional ethics clearance was obtained by participating sites as required by their respective institutions or national regulations. a total of records of ill travelers attending a mg during international travel had surveys completed by the investigator providing their care. thirty-one records were excluded. of ill travelers included, ( . %) were female and the median age was years (range: - ; iqr: - ). purposes of mgs were religious ( cases; . %), cultural (e.g., music, dance, carnival) ( cases; . %), the world scout jamboree ( cases; . %), major sport events ( cases; . %), or a large conference ( cases; . %). the top three specific mgs were umrah or hajj in saudi arabia with cases ( . %), including at umrah and at hajj, followed by the world scout jamboree in japan with cases ( . %), and the olympics in brazil and south korea with cases ( . %) ( [ ] [ ] [ ] [ ] ). sixty-four percent of ill travelers who attended umrah or hajj were hospitalized because of their illness; one traveler who attended the world scout jamboree and no travelers who attended the olympics were hospitalized. overall, of ( %) ill travelers with information available reported having a pre-travel encounter with a healthcare provider. the majority ( of , . %) of acquired illnesses were directly associated with mg attendance, while the relation between the illness and the mg was not ascertainable for travelers ( . %), and the illness was travel-related but not linked to mg attendance for travelers ( . %). only three of nine ( . %) diagnoses among travelers who attended the olympics were associated with attending the mg. a total of diagnoses were reported among the ill travelers whose illness was associated with mg attendance (table ) . respiratory diseases were the most frequently reported disease category with diagnoses ( . %), followed by gastrointestinal diseases ( diagnoses; . %). diagnoses related to attendance at the three most common mgs -umrah or hajj, world scout jamboree, and olympics -are presented in table . geosentinel sites evaluated pilgrims with umrah-or hajj-related illnesses among an estimated million foreign mg attendees over the study period [ ] , scouts among , attendees [ ] and olympic spectators among million attendees [ , ] . it should be noted, however, that geosentinel collects data only on ill travelers presenting to a network site and some geosentinel sites may care for more mg attendees than others, which may not be representative of all travelers attending a mg. in particular, the scouts reported to geosentinel were from a single site in sweden and were identified because of an international alert following a meningococcal outbreak (w st serotype) among six scottish and swedish nationals who attended this event [ ] . ill mg attendees seen at a geosentinel site most frequently attended umrah or hajj, likely due to the large number of travelers to these pilgrimages. these findings are consistent with previously published literature demonstrating that outbreaks are not frequently reported during or after mgs other than umrah and hajj pilgrimages, although they sometimes occur at muslim, christian, and hindu religious events, sports events, and large-scale open-air festivals [ , ] . its size, international recognition, unique multinational component, and yearly recurrence, likely account for the preponderance of umrah and hajj among international mgs responsible for outbreaks. our data are also consistent with previous reports regarding the older age of umrah and hajj travelers [ ] , and the younger age of scout jamboree travelers. the finding that almost three-quarters of ill travelers who attended umrah or hajj were hospitalized is likely due to a recruitment bias, given that ill travelers seen at geosentinel sites may be sicker because of the specialized infectious disease or tertiary care nature of these sites; or to initial clinical suspicion for middle east respiratory syndrome, resulting in hospitalization and isolation pending testing. the paucity of reported trauma is also likely a reflection of the infectious disease specialization of most geosentinel network sites, and of the fact that trauma usually requires immediate attention and is most likely to occur during travel [ ] . the predominance of respiratory tract infections reported in this analysis, including cases of pneumococcal disease with one death, corroborates results obtained in saudi hospitals of pneumonia diagnoses among umrah and hajj attendees [ ] as well as the high number of influenza virus infections observed among both patients in saudi hospitals and patients hospitalized on returning to their home countries from umrah and hajj [ ] . crowded conditions with close proximity of large numbers of attendees at umrah and hajj are a likely explanation for the frequency of respiratory infections among pilgrims, given the transmissibility of these infections. our results confirm the importance of influenza vaccination for umrah and hajj travelers [ ] . although the availability of influenza vaccine may be limited depending on the time of year hajj occurs [ ] , immunization with expired influenza vaccine from the recently ended influenza season may have few associated adverse events [ ] . by contrast, most illnesses among travelers attending the olympics were linked to travel, but not to attending the olympics, and these illnesses' were mild, which may be due to the physical separation of various sporting events at the olympics, the propensity to hold the olympics in high income countries, the relatively short travel duration of attendees and participants, and the relatively young age of participants. this is supported by the rarity of documented outbreaks during olympic games between and [ , ] . our identification of respiratory tract infections, especially pneumonia, among umrah and hajj attendees suggests the need for additional research to document responsible pathogens. such data may have important consequences regarding vaccine recommendations before travel. in particular, it may be possible to validate that the influenza serotypes found are representative of strains circulating during the prior northern winter. these data also may provide justification for recommending pneumococcal vaccination for some high-risk travelers [ ] [ ] [ ] . however, one-third of all travelers in this report did not attend a pre-travel consultation, and this will likely be a barrier to implementation of such recommendations. many countries have a staging area where umrah and hajj attendees gather before departure, or have pre-hajj classes at local mosques. leaders there could raise awareness of recommended (but not required) vaccines and personal protective measures such as carrying and routinely using hand sanitizer may lead to higher level of protective behaviors of traveling pilgrims [ ] . also, primary care physicians should inquire about planned travel to mass gatherings and vaccinate travelers against meningococcus, influenza, and pneumococcus, as appropriate. given its broad international catchment, geosentinel plays a role in identifying emerging infectious diseases with epidemic potential, thus contributing to efforts to create enhanced international multidisciplinary surveillance of mg-associated illnesses, as recently recommended by experts [ ] . since our surveillance was limited to patients presenting to geosentinel sites, to better understand travelassociated illnesses acquired at mgs improved global surveillance mechanisms are needed. geosentinel, the global surveillance network of the international society of travel medicine (istm), is supported by a cooperative agreement (u ck ) from the centers for disease control and prevention (cdc), as well as funding from the istm and the public health agency of canada. the findings and conclusions in this report are those of the authors and do not necessarily represent the official position of cdc. global perspectives for prevention of infectious diseases associated with mass gatherings public health for mass gatherings surveillance for travel-related disease -geosentinel surveillance system japan . rd world scout jamboree available at available at: https:// stillmed.olympic.org/media/document% library/olympicorg/games/summer-games/games-rio- -olympic-games/media-guide-for-rio- /ioc-marketing-report-rio- .pdf, accessed date olympic organizers say tickets are sold, but where are the people? meningococcal disease outbreak related to the world scout jamboree in japan communicable diseases as health risks at mass gatherings other than hajj: what is the evidence? infectious diseases and mass gatherings hajj: infectious disease surveillance and control morbidity and mortality amongst indian hajj pilgrims: a -year experience of indian hajj medical mission in mass-gathering medicine clinical respiratory infections and pneumonia during the hajj pilgrimage: a systematic review hajj-associated viral respiratory infections: a systematic review expected immunizations and health protection for hajj and umrah -an overview mandating influenza vaccine for hajj pilgrims notes from the field: administration of expired injectable influenza vaccines reported to the vaccine adverse event reporting system -united states enhanced surveillance at mass gatherings mismatching between circulating strains and vaccine strains of influenza: effect on hajj pilgrims from both hemispheres. hum vaccines immunother pneumococcal disease during hajj and umrah: research agenda for evidence-based vaccination policy for these events travellers and influenza: risks and prevention preparing australian pilgrims for the hajj mass gathering medicine: public health issues arisinf from mass gathering religious and sporting events key: cord- -nl k uwd authors: barasheed, osamah; alfelali, mohammad; mushta, sami; bokhary, hamid; alshehri, jassir; attar, ammar a.; booy, robert; rashid, harunor title: uptake and effectiveness of facemask against respiratory infections at mass gatherings: a systematic review date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: nl k uwd objectives: the risk of acquisition and transmission of respiratory infections is high among attendees of mass gatherings (mgs). currently used interventions have limitations yet the role of facemask in preventing those infections at mg has not been systematically reviewed. we have conducted a systematic review to synthesise evidence about the uptake and effectiveness of facemask against respiratory infections in mgs. methods: a comprehensive literature search was conducted according to the preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines using major electronic databases such as, medline, embase, scopus and cinahl. results: of studies included, the pooled sample size was participants from countries aged to years, % were female. the overall uptake of facemask ranged from . % to . % with an average of about %. only studies examined the effectiveness of facemask, and their pooled estimate revealed significant protectiveness against respiratory infections (relative risk [rr] = . , % ci: . - . , p < . ), but the study end points varied widely. conclusion: a modest proportion of attendees of mgs use facemask, the practice is more widespread among health care workers. facemask use seems to be beneficial against certain respiratory infections at mgs but its effectiveness against specific infection remains unproven. the risk of acquisition and transmission of respiratory infections amplifies at mass gatherings (mgs) straining healthcare of the host country. for instance, in hajj, one of the largest annual mg events in the world, more than million people attend each year in makkah, and over % suffer from at least one respiratory symptom, the risk of viral respiratory infections increases several folds and more severe respiratory infections such as pneumonia are the leading causes of hospital admission. [ ] [ ] [ ] likewise, a number of influenza outbreaks were reported during the world youth day , a large catholic gathering in sydney. mgs are also linked to globalisation of various infections. for instance, the iztapalapa play passion, a religious festival in mexico, was believed to spark the outbreak of swine flu leading to its accelerated dissemination across the world. therefore, international public health agencies, including world health organization (who), have issued guidelines on mass gathering preparedness to minimise the possible risks. from a public health perspective, one of the key concerns is to prevent global spread of respiratory infections during mgs. interventions like vaccinations against viral and bacterial respiratory infections, anti-influenza prophylaxis and hand hygiene are considered as preventive measures but the measures have limitations. for instance, vaccinations against respiratory infections, such as influenza, are recommended for travellers to mgs such as hajj, and even though a recent systematic review generally supports its effectiveness against laboratory-confirmed influenza at hajj, frequent mismatch between vaccine strains and circulating strains is an important concern. soaring antiviral resistance against both adamantanes and neuraminidase inhibitors is an issue that limits their widespread use in mgs. , similarly, while hand hygiene has been recommended as a protective measure for attendees of mgs, its effectiveness is not fully evaluated in a mass gathering setting and the efficacy is debatable. therefore, the role of another protective measure, facemask, should be explored in the prevention of respiratory infections. facemask is believed to have a protective role in preventing nosocomial infections since the time of spanish influenza. several studies have assessed the usefulness of facemask in household, community and healthcare settings, the findings of which have been summarised in a few reviews. [ ] [ ] [ ] noticeable disparities of facemask effectiveness between these studies were observed. studies conducted in community or health care settings found facemasks to be generally effective against influenza-like illness (ili) or even against severe acute respiratory syndrome (sars) but its effectiveness against respiratory infections at mgs remains unknown. , a review of non-pharmaceutical interventions against respiratory tract infections among hajj pilgrims presented data on the uptake of facemask and acknowledged that compliance was generally poor, but did not evaluate its effectiveness during hajj. subsequently, further data on the uptake and effectiveness have become available, especially from a pilot randomised controlled trial (rct). the aim of this systematic review is to explore the uptake and effectiveness of facemask against respiratory infections in mgs. studies were identified through searching electronic databases including; medline (pubmed and ovid), embase, scopus and cinahl from database inception to february , . we used a combination of mesh terms and text words including: 'crowding' or 'mass gathering' or 'large event' or 'group assembly' or 'holiday' or 'travel' or 'sport' or 'olympic' or 'fifa' or 'festival' or 'hajj' (also alternative spelling 'hadj' or 'haj') or 'pilgrimage' and 'mask' or 'facemask' or 'surgical mask' or 'medical mask' or 'simple mask' and 'infection' or 'respiratory tract diseases' or 'disease outbreaks' or 'infectious disease' or 'respiratory tract infections' or 'influenza' or 'pneumonia'. additionally, an online search of pertinent epidemiology journals, including those not indexed in the mentioned databases (e.g. saudi epidemiology bulletin) was carried out through free hand google engine search. finally, manual search was performed reviewing reference lists of included studies to identify additional potentially relevant studies. the search result was presented according to the preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines ( figure ). in the first phase, three authors (ob, sm and hb) identified the potential titles, and sifted the titles and abstracts against the inclusion criteria. titles of all studies published in english language and reported the use or effectiveness of facemask against respiratory infections in mgs were preliminarily included. studies that dealt with attendees of mgs of any age, gender and country were considered for inclusion. at the end of the screening phase, full texts of potentially relevant studies were retrieved for detailed study. finally studies that met the inclusion criteria were included for data synthesis. duplicates were excluded. five authors (ob, ma, hb, sm and ja) independently extracted the data from each study into a data extraction sheet which was divided in two sections, 'facemask uptake' and 'facemask effectiveness' and five authors subsequently cross-checked the entries (ob, aa, hb, sm and ja),while a sixth author (hr) arbitrated when a discrepancy occurred. the following data were abstracted in each extraction sheet: study design, year of conducting the study, sample size, country of origin, age, gender, diagnostic method used, definitions of study end point, and history of participants' chronic diseases, if available. the quality of the included studies were categorised according to a modified ranking criteria based on oxford evidence based medicine (http://www.cebm.net/) into groups (e.g., a, b, c, d) where a was for rcts of adequate sample size, b for observational studies of adequate sample size with good quality or pilot rcts or non-randomised trial, c for observational studies of inadequate sample size or of poor quality, and d for cases series, such as focus groups or qualitative surveys. the search results are summarised in figure the study sample sizes varied widely ranging from to participants. the included studies contained the pooled data of participants aged between and years (mean age ranged from . to . years in individual studies). about % of the pooled samples were females, in individual studies the proportion of females ranged from % to %. excluding three studies, which involved hcws deployed at hajj, [ ] [ ] [ ] all other included studies involved hajj pilgrims. the origin of the participants varied depending on the study, seven studies included multinational participants, while the other were exclusive to participants from a single country of origin; seven out of ( . %) were from saudi arabia, , - according to study types out of were cohort studies, , , - , - another cross-sectional studies, , - , - two trials (not necessarily rcts) , and one case-series conducted as a qualitative study (table ) . the median uptake of facemask in pooled sample was . %. the lowest reported uptake was . % by elachola et al. among pilgrims in a unique study that involved quantification of facemasks through photo frames from surveillance camera during the hajj in , therefor it is considered as an outlier. the highest uptake was . % observed by al-asmary et al. among health care workers during hajj in . excluding these two studies (elachola et al and al-asmary et al ) , uptake rate among pilgrims has remained generally steady with gradual increase from % in to % in with minor fluctuations (figure ). studies involving hcws reported an uptake from % in to . % in . according to the pilgrims' country of origin, malaysian pilgrims were noticed to be most compliant to using facemasks ( . %), , followed by french ( . %) , , , and iranians ( %) (table ) . only three studies, all involving australian pilgrims, evaluated the reasons of compliance (or non-compliance) of using facemask during hajj. , , the most reported reasons for wearing facemask were to avoid transmission of infectious organisms and protection from air pollution. however, discomfort and difficulty in breathing were the most reported reasons for not wearing facemask. , thirteen studies investigated the effectiveness/efficacy of facemask against respiratory infections, but the endpoints varied very widely. most of these studies ( out of ) used a combination of respiratory symptoms (syndromic) as endpoints with varying definitions. for instance, acute respiratory infections (ari) was used as an endpoint in three studies, , , ili in two, , upper respiratory tract infection (urti) in two, , respiratory illness in two , and respiratory tract infections in one. however a couple of studies used only one respiratory symptom as an endpoint: fever and cough. only one study established laboratory-proven viral infections as an endpoint. definitions for the endpoints are detailed in table . in regards to the effectiveness of facemask, four out of thirteen studies demonstrated significant effect against respiratory infections, , , , two others showed some effect but did not reach statistical significance. , one study assessed its effectiveness against fever but ruled out its protectiveness, and the other six studies did not show effectiveness but results were not statistically significant. , [ ] [ ] [ ] , the pooled data from all studies revealed significant protectiveness of facemasks against respiratory infections in general at hajj (relative risk [rr] = . , % ci: . - . , p < . ) ( table ) . according to the ranking system we used, most of the studies were of average quality (c) whereas two studies were ranked above average (b): a pilot rct and a large cross-sectional study, the other seven studies were of below average quality (d) either because of small sample size or poor study quality (table ) . this systematic review shows that the use of facemask among the attendees of mgs remains essentially unchanged for decades although exceptionally in one study a very high uptake (about %) or a very low uptake rate ( . %) has been reported but such variability can be explained by their unique study designs or population characteristics. the pooled data of this systematic review suggest that facemask is generally effective against respiratory infections at hajj, however the endpoints varied widely. the uptake of facemask among hcws deployed at hajj was generally higher than that among ordinary hajj pilgrims with average compliance among hcws being % compared to % among pilgrims. this finding is similar to what have been found in other studies that examined the uptake of facemask in other settings such as health care and community settings. for instance, the uptake of facemask among hcws in several studies ranged from . % to . % (average . %). [ ] [ ] [ ] [ ] on the other hand, the uptake of facemask among ordinary population in diverse household and community settings ranged from % to . % (average %). [ ] [ ] [ ] [ ] [ ] [ ] [ ] this could be explained by several individual or organisational factors. for example, hcws have firsthand knowledge about the risk of respiratory infections and the role of preventive measurements in hajj. similarly, studies in non-mgs settings showed a positive relationship between hcws' knowledge about the risk of infectious diseases and their compliance to preventive measures including the use of facemask. [ ] [ ] [ ] organisational factors such as ready availability of facemask in health care settings, proper training programs and supportive policy of health care system could have played an important role in improving the compliance of hcws to facemask use. [ ] [ ] [ ] [ ] on the other hand, limited studies explored these individual and organisational factors among hajj pilgrims. a few studies showed that providing educational session on protective measures against respiratory infections (including facemask) before hajj was associated with significantly higher uptake of facemasks among pilgrims. , , , , moreover, adequate accessibility and availability of facemask during hajj may enhance the compliance of pilgrims. abdin et al and barasheed et al revealed a higher uptake of facemask among groups who were provided with sufficient quantity of free facemask ( . % versus . %, p < . , and % versus %, p < . , respectively). , however, reasons for not using facemask during hajj have not been explored adequately. while use of facemask at hajj has been officially recommended by saudi ministry of health since , it is too early to have a significant impact on pilgrims' practice of facemask use. although hajj took place in different seasons (spring, winter and autumn), the uptake of facemask among hajj pilgrims during the last decade remained generally stable (figure ) . findings also showed that there was no significant change in facemask uptake among hajj pilgrims during the course of influenza a (h n ) pandemic outburst in , and the middle east respiratory syndrome corona virus (mers-cov) outbreak since . this does not concur with what has been reported in published studies involving the members of general public over the several outbreaks of respiratory infections in non-mg settings. [ ] [ ] [ ] [ ] [ ] [ ] those studies showed an increase in facemask use during the outbreaks due to participants' perceived threat of infection. poor awareness among many pilgrims of contemporary outbreaks might explain why their uptake of facemask did not increase even during an ongoing outbreak. [ ] [ ] [ ] interestingly, pilgrims of asian origin (e.g. malaysians) had higher facemask uptake compared to pilgrims from other regions. , a polling study that evaluated the uptake of non-pharmaceutical measures during the pandemic influenza a (h n ) of found that participants of asian origin (e.g. japan) had the higher facemask uptake ( %) compared to the uptake of participants of western or latin american origin. presence of several peaks of influenza seasons in some asian countries, overcrowding, dense smog and air pollution in many cities may explain the higher uptake of facemask among people from asian countries; , additionally, cultural acceptance practice of the population around facemask while in public may make a difference. focused studies are required to investigate factors influencing facemask compliance among attendees of hajj and other mgs. in this systematic review, pooled data of facemask effectiveness showed that participants who used facemask during hajj are about % less likely to suffer from respiratory infections compared to those who do not use it. this effectiveness of facemask is inconclusive due to great heterogeneity in study questions, assessment methods, study designs and qualities, and endpoints. in regards to the research questions, three out of studies investigated facemask effectiveness as the primary research objective: all three studies yielded significant results; whereas only one out of the other studies that assessed facemask as a secondary or indirect outcome, yielded significant results. further, there was great heterogeneity in how the frequency and duration of facemask use were assessed. although, most of the studies used a self-reported questionnaire to quantify facemask uptake among participants, the qualitative descriptive terms that the studies used (e.g. ''always'', ''mostly'', ''sometimes'' or ''never'') may have introduced subjective bias, since qualitative description varies depending on participants' perception about the frequency and duration of use. however, only one study used measurable criteria in their questionnaires to quantify the number of facemasks used including the duration (in hours) and frequency of use, finding that using facemask more than eight hours per day was associated with significant decrease in ili symptoms among hajj pilgrims. using surveys with more objective options may decrease bias, and provide more accurate estimate of compliance to facemask use in mgs. study designs also may have contributed to variability in results. for instance, two trials, a pilot rct and a non-randomised trial, reported facemask to be significantly effective against respiratory infections at hajj, whereas only two out of six cohort studies reported significant results. in contrast, none of the crosssectional studies yielded significant results. this may indicate that a higher quality study is more likely to produce convincing results. finally, facemask effectiveness also differed depending on the study endpoints. for example, studies that examined effectiveness of facemask against a single respiratory symptom (such as cough, sore throat or fever) either ruled out or did not fully support its effectiveness. , , this is most likely because singular endpoints are often prone to subjective biases due to their non-specificity. in addition, solitary respiratory symptoms may result from causes other than infections; for instance, cough may result from exposure to dust or smoke during hajj or may be a manifestation of a chronic respiratory condition of non-infectious aetiology, e.g., bronchial asthma. on the other hand, most of the studies that used syndromic criteria (constellation of symptoms) as an endpoint reported facemasks to be effective against respiratory infections during hajj. , , , , this is most likely due to the fact that syndromic endpoints are more specific for an illness than a singular symptom. only one study used laboratory-confirmed infection as an endpoint, but its sample size was relatively small (n = ) and it failed to demonstrate statistically significant protectiveness of facemasks against respiratory viral infections among hajj hcws. similarly, in non-mg settings, effectiveness of facemask varied depending on the study endpoint. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] metaanalysis of rcts involving facemask in non-mgs showed efficacy against ili but not against laboratory-confirmed influenza. , , this study is the first focussed systematic review that describes both the uptake and effectiveness of facemasks against respiratory infections in mgs, and it compiles a data pool of participants originating from more than countries. however, the main limitation is that most of the studies were of 'average' or 'below average' quality. there was only one rct but that was a pilot trial of small sample size, and there was another 'trial' published in a nonindexed journal that did not report methodological details including whether and how randomisation was done. as all included studies were conducted only in the context of hajj, it is not possible to generalise the results to other mgs. a large scale clustered rct is currently in its final phase that will measure the efficacy of facemasks against both 'syndromic' and laboratoryconfirmed viral infections. the full results of the trial, once available, are likely to provide firmer evidence on the usefulness of facemask against respiratory infections among attendees of mgs. in summary, the use of facemask among attendees of a particular mg (hajj) remains almost steady with negligible increase throughout the last decade with an average uptake of %. facemasks seem to be beneficial against certain respiratory infections during hajj but not definitively proven. professor robert booy has received funding from baxter, csl, gsk, merck, novartis, pfizer, roche, romark and sanofi pasteur for the conduct of sponsored research, travel to present at conferences or consultancy work; all funding received is directed to research accounts at the children's hospital at westmead. dr harunor rashid received fees from pfizer and novartis for consulting or serving on an advisory board. the other authors have declared no conflict of interest in relation to 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n influenza epidemic widespread public misconception in the early phase of the h n influenza epidemic anticipated and current preventive behaviors in response to an anticipated human-to-human h n epidemic in the hong kong chinese general population factors influencing the wearing of facemasks to prevent the severe acute respiratory syndrome among adult chinese in hong kong hajj pilgrims knowledge about middle east respiratory syndrome coronavirus attitudes and practices concerning middle east respiratory syndrome among umrah and hajj pilgrims in samsun australian hajj pilgrims' knowledge about mers-cov and other respiratory infections public response to the influenza a h n pandemic: a polling study in five countries influenza seasonality and vaccination timing in tropical and subtropical areas of southern and south-eastern asia air pollution and health -counselling options for physicians validity and reliability of measurement instruments used in research mask use, hand hygiene, and seasonal influenza-like illness among young adults: a randomized intervention trial surgical mask vs n respirator for preventing influenza among health care workers: a randomized trial efficacy of face masks and respirators in preventing upper respiratory tract bacterial colonization and co-infection in hospital healthcare workers a clusterrandomised controlled trial to test the efficacy of facemasks in preventing respiratory viral infection among hajj pilgrims the authors would acknowledge the support of ms. trish bennett, manager, medical library, the children's hospital at westmead, nsw, australia, for help with literature search. key: cord- -sox pp authors: gautret, philippe; benkouiten, samir; griffiths, karolina; sridhar, shruti title: the inevitable hajj cough: surveillance data in french pilgrims, – date: - - journal: travel med infect dis doi: . /j.tmaid. . . sha: doc_id: cord_uid: sox pp background: respiratory tract infections are the most common infection affecting hajj pilgrims, and the ‘‘hajj cough’’ is considered by pilgrims almost de rigueur. methods: french pilgrims were recruited between january –december and information on demographics, medical history, compliance with preventive measures and health problems during travel were collected. results: a total of pilgrims were included with . % aged ≥ years and . % suffering from a chronic disease, most frequently hypertension and diabetes. the prevalence of cough was . % and a high proportion presented with associated sore throat ( . %), rhinitis ( . %) and hoarseness ( . %). myalgia was reported in . % of cases and subjective fever in . %. the incubation time of respiratory symptoms was . days (range – days) and . % of pilgrims presenting with a cough during their stay were still symptomatic on return. among pilgrims with a cough, . % took antibiotics. the prevalence of cough was significantly higher among females than men, but age, chronic conditions and preventive measures had no significant effect. conclusions: the hajj cough is highly common, likely a result of crowded conditions at religious places. pilgrims should be advised to carry symptomatic relief for the hajj cough such as cough suppressant, soothing throat lozenges and paracetamol. use of antibiotics should be discouraged. every year around - million muslims from over countries arrive in the kingdom of saudi arabia (ksa) for a pilgrimage to the holy places of islam [ ] . the crowded conditions within a confined area in close contact with others leads to a high risk of pilgrims acquiring and spreading infectious diseases during their time in saudi arabia [ ] . respiratory tract infections are the most common infections affecting pilgrims [ ] , and the``hajj cough'' is considered by pilgrims almost de rigueur [ ] . attack rates of respiratory symptoms of about - % have been recorded among pilgrims from various nationalities [ ] [ ] [ ] . early reports from the hajj season indicated that upper tract respiratory infections already formed the bulk of the work-load of medical teams attending pilgrims [ ] . recent data indicate that % of ill pilgrims consulting at mina primary health structures suffer respiratory tract infections [ ] . respiratory tract infection is the leading cause of hospitalization in saudi hospitals during the hajj, up to % in one study [ ] . pneumonia accounts for - % of hospitalizations in tertiary care structures [ , ] and for % of admission in intensive care units where they are responsible for % of sepsis [ , ] during the hajj. to better characterize the "hajj cough" symptoms and its outcome, this study provides a clinical description of respiratory symptoms experienced by a cohort of french hajj pilgrims during three consecutive hajj seasons. pilgrims who planned to take part in the hajj were recruited from through from a private specialized travel agency in the city of marseille, which organizes travel to mecca. participants were asked to participate in the study on a voluntary basis if they were years of age or older and were able to provide consent. upon inclusion, the participants were interviewed by arabicspeaking investigators using a standardized pre-travel questionnaire that collected information on demographics and medical history. a post-travel questionnaire, that collected clinical data, vaccination status, and compliance with preventive measures, was completed during a face-to-face interview just prior to the departure for france. health problems that occurred during the pilgrims' stay were recorded by a medical doctor who traveled with them. subjective fever was defined as the pilgrim's report of feeling feverish. influenza-like illness (ili) was defined according to the presence of the triad of a cough, sore throat, and subjective fever [ ] . the protocol was approved by our institutional review board. it was performed in accordance with the good clinical practices recommended by the declaration of helsinki and its amendments. all participants gave written informed consent. the pearson's chi-square test and fisher's exact test, as appropriate, were applied to analyze the categorical variables. statistical analyses were performed using spss software package version (spss inc., chicago, il). p values of . or less were considered significant. a total of pilgrims were included over three years ( . % participation rate) with a sex ratio m/f of . and a mean age of . years (range - years). thirty-nine point three percent of pilgrims were aged years and over. the majority was born in various countries in north africa ( . %) and most of them were first-time pilgrims to the hajj ( . %). a chronic disease was noted in . %, including hypertension ( . %), diabetes ( . %), chronic cardiac disease ( . %), chronic respiratory disease ( . %), immune deficiency ( . %) and chronic renal disease ( . %). thirty-one point six percent of pilgrims declared having received the influenza vaccination in before participating in the hajj; however none received the vaccine in and as it had not been made available in france before the departure dates. . % of participants reported receiving the -valent pneumococcal polysaccharide vaccination (ppsv ; pneumo s ) in the past years before participating in the hajj. fifty-three point seven percent used face masks during the hajj, . % washed their hands more frequently than usual, . % used hand sanitizer and . % used disposable tissues. the prevalence of cough was . % (ranging from . % in to . % in ). symptoms are depicted in fig. . dry cough was reported by . % pilgrims and productive cough by . %. among pilgrims with cough (n ¼ ) a high proportion presented with associated sore throat ( . %), rhinitis ( . %) and voice failure ( . %). a proportion of . % reported myalgia and . % subjective fever. forty-six point percent of pilgrims had ili. pilgrims with cough had associated dyspnea in . % of cases; gastrointestinal symptoms were less frequently associated including diarrhea ( . %), nausea ( . %) and vomiting ( . %). . % of pilgrims with cough had associated conjunctivitis. the incubation time of respiratory symptoms among pilgrims with hajj cough was . days (range - days) with the majority of pilgrims having onset of symptoms during the first week of stay ( . %) (fig. ) . . % of pilgrims presenting with cough during their stay were still symptomatic at the end of their sojourn. among pilgrims with cough, . % took antibiotics and two ( . %) were hospitalized. the prevalence of cough was significantly higher (p ¼ . ) among females than men ( . % vs . %, respectively). age and chronic conditions had no significant association with the prevalence of cough, pilgrims with chronic respiratory disease showed a slightly increased prevalence of cough. none of the preventive measures were effective in reducing cough prevalence with the exception of influenza vaccine, but the effect was not statistically significant (table ) . our study has some limitations. first it was only conducted among french pilgrims and included a relatively small number of individuals so that our results cannot be extrapolated to all hajj pilgrims. second, our clinical description was only based on functional symptoms reported by pilgrims through a questionnaire. it is thus lacking information on clinical signs that could have resulted from physical examination and bias recall may have influenced our results. nevertheless, we believe that this study provides a useful basic description of the "hajj cough" which may guide health providers when preparing hajj pilgrims. our survey shows that the "hajj cough" affected a very high proportion of french pilgrims with an attack rate culminating to . % in . the onset of symptoms was rapid following arrival in saudi arabia and persistent symptoms were observed in one out of two pilgrims despite extensive use of antibiotics. the "hajj cough" affected all individuals independently on their age, comorbidities, vaccination status and use of individual non-pharmaceutical preventive measures against respiratory tract infections. female were more likely than men to suffer hajj cough and we have no explanation for this observation. fortunately, the disease was mild with a low rate of hospitalization and complications. microbiological studies based on pcr detection in respiratory samples were conducted among same cohorts of french pilgrims in the years and before departing from france and just prior to leaving saudi arabia [ ] [ ] [ ] [ ] [ ] [ ] . we observed a high rate of acquisition of viruses, notably rhinovirus, coronavirus e and, influenza virus a (h n ) to a less extent and of streptococcus pneumoniae. a large study based on the same protocol was conducted in among pilgrims from different nationalities and confirmed these results. it also showed a significant acquisition of haemophilus influenzae and klebsiella pneumoniae [ ] . sampling at the time of symptoms was conducted in a small subset of french pilgrims in only and included a restrictive panel of pathogens so that no strong conclusions can be drawn on the role of the respective microbes in the pathogeneses of the "hajj cough". nevertheless, both clinical and microbiological data indicate that transmission of respiratory pathogens in the context of the hajj is highly frequent, which is likely the result of overcrowding with a density of - people per square meter close in certain areas in the grand mosque [ ] . it is also likely that housing conditions in large collective tents at mina encampment play a role in the transmission of respiratory viruses [ ] . finally, air pollutants may play a role through their irritant effect since an increase of carbon monoxide, nitrogen dioxide and tropospheric ozone levels is observed during hajj compared to non-hajj periods [ ] . physicians must be alert to the circulation of common pathogens at the hajj, which silently cause much more casualties than the newcomer like middle-east respiratory syndrome (mers) coronavirus which occupy the forefront of the stage and get all the headlines, despite only umrah-associated mers cases over an estimated million pilgrims who visited mecca from through [ , ] . at the moment, none of the usual preventive measures against respiratory tract infection have been proven effective, including vaccination against influenza which is recommended for all hajj pilgrims by french authorities and vaccination against pneumococcal infections which is recommended for at risk pilgrims suffering chronic conditions and or for those aged years and over [ ] . the "hajj cough" seems therefore inevitable and self-treatment should be provided to pilgrims at pre-travel advice. we suggest symptomatic treatment, using cough suppressants such as dextromethorphan, decongestants to relieve nasal congestion such as phenylephrine and pseudoephedrine, with careful use among patients with hypertension, and paracetamol for symptomatic treatment of fever, myalgia and sore throat. the use of antibiotics is questionable since the respective causality of bacteria and viruses in the pathogenesis of the "hajj cough" is not fully established. nevertheless, prescription of antibiotics to hajj pilgrims suffering mild respiratory symptoms is frequent in local health care structures: - % patients consulting at the ear, nose and throat clinic of a hospital in mecca were prescribed antibiotics while - % presented with upper tract respiratory infection including pharyngitis and tonsillitis [ , ] . similarly, patients consulting at various primary health care centers in mina found that % patients were prescribed antibiotics while % suffered respiratory tract infection with pharyngitis and the common cold the most frequent [ ] . a cohort survey conducted among iranian pilgrims in showed that % experienced respiratory symptoms and that % took antibiotics [ ] . in a cohort survey conducted among indonesian pilgrims, % suffered ili during their stay in the ksa, of which % took antibiotics that were mostly obtained over the counter [ ] . a recent cohort survey showed that % pilgrims from australia used antibiotics during their stay, the main reason being upper respiratory tract infection. thirty percent obtained antibiotics from a local pharmacy without prescription and % pre-emptively carried an antibiotic with them from australia [ ] . the apparent overall overuse of antibiotics by pilgrims is of concern with regards to the development of drug resistance. in this context, the development of pointof-care diagnostic tests would further enhance the ability to differentiate bacterial from viral infections and so decrease antibiotic use [ ] . the hajj cough is highly common, likely a result of crowded conditions at religious places. it affects all individuals independently of their age, comorbidities, vaccination status and use of classical, individual, non-pharmaceutical preventive measures against respiratory tract infections including hand hygiene, use of face mask use and social distancing which effectiveness at the hajj has been poorly investigated [ ] . clinical symptoms are non severe, with few hospitalizations necessary and symptomatic treatment should be prescribed with attempts to reduce antibiotic use in non-severe low-risk cases, unless there is evidence of bacterial infection. hajj: infectious disease surveillance and control health risks at the hajj respiratory tract infections during the annual hajj: potential risks and mitigation strategies hajj: health lessons for mass gatherings the prevalence of acute respiratory symptoms and role of protective measures among malaysian hajj pilgrims patterns of diseases and preventive measures among domestic hajjis from central, saudi arabia trend of diseases among iranian pilgrims during five consecutive years based on a syndromic surveillance system in hajj letter from abu dhabi: welfare of the hajj pattern of diseases among visitors to mina health centers during the hajj season, h ( g) pattern of admission to hospitals during muslim pilgrimage (hajj) causes of hospitalization of pilgrims in the hajj season of the islamic year severe sepsis and septic shock at the hajj: etiologies and outcomes clinical and temporal patterns of severe pneumonia causing critical illness during hajj influenza and the hajj: defining influenza-like illness clinically lack of nasal carriage of novel corona virus (hcov-emc) in french hajj pilgrims returning from the hajj , despite a high rate of respiratory symptoms circulation of respiratory viruses among pilgrims during the hajj pilgrimage lack of mers coronavirus but prevalence of influenza virus in french pilgrims after respiratory viruses and bacteria among pilgrims during the hajj acquisition of streptococcus pneumoniae carriage in pilgrims during the hajj comparison of nasal swabs with throat swabs for the detection of respiratory viruses by real-time reverse transcriptase pcr in adult hajj pilgrims mass gathering and globalization of respiratory pathogens during the hajj social identification moderates the effect of crowd density on safety at the hajj pilot randomised controlled trial to test effectiveness of facemasks in preventing influenza-like illness transmission among australian hajj pilgrims in evaluation of ozone, nitrogen dioxide, and carbon monoxide at nine sites in saudi arabia during imported cases of middle east respiratory syndrome: an update umrah, and other mass gatherings: which pathogens do you expect? beware of the tree that hides the forest haut conseil de la sant ! e publique. health recommendations for travellers road map of an ear, nose, and throat clinic during the hajj in makkah, saudi arabia impact of ph n influenza a infections on the otolaryngology, head and neck clinic during hajj acute respiratory viral infections among tamattu' hajj pilgrims in iran a case-control study of influenza vaccine effectiveness among malaysian pilgrims attending the haj in saudi arabia knowledge, attitude and practice (kap) survey concerning antimicrobial use among australian hajj pilgrims potential risk for drug resistance globalization at the hajj non-pharmaceutical interventions for the prevention of respiratory tract infections during hajj pilgrimage none. key: cord- -xw intn authors: gautret, p.; yong, w.; soula, g.; gaudart, j.; delmont, j.; dia, a.; parola, p.; brouqui, p. title: incidence of hajj-associated febrile cough episodes among french pilgrims: a prospective cohort study on the influence of statin use and risk factors date: - - journal: clin microbiol infect doi: . /j. - . . .x sha: doc_id: cord_uid: xw intn a prospective epidemiological study was conducted to evaluate the incidence of febrile cough episodes among adult muslims travelling from marseille to saudi arabia during the hajj pilgrimage and to assess if use of statin had an influence on this incidence. in total, individuals were presented with a questionnaire. a significant proportion of individuals had chronic medical disorders, e.g. diabetes mellitus ( , . %) and hypertension ( , . %). pilgrims had a low level of education and a low employment rate. sixty ( . %) were treated with statins for hypercholesterolemia. four hundred and fourty-seven pilgrims were presented a questionnaire on returning home. a total of travellers ( . %) experienced fever during their stay in saudi arabia ( attended a doctor) and ( . %) had cough ( attended a doctor); travellers with cough were febrile ( . %). seventy per cent of the travellers who suffered cough episodes developed their first symptoms within days, suggesting a human to human transmission of the responsible pathogen, with short incubation time as evidenced by a bimodal distribution of cough in two peaks at a h interval. none of demographical and socioeconomic characteristics, underlying diseases or vaccination against influenza significantly affected the occurrence of cough. diabetes correlated with an increased risk of febrile cough (or = . ( . – . )) as well as unemployment (or = . ( . – . )). use of statins had no significant influence on the occurrence of cough and/or fever during the pilgrimage. this result suggests that while treatment with a statin has been demonstrated to reduce the mortality from severe sepsis associated with respiratory tract infections, it probably does not play a role in the outcome of regular febrile cough episodes as observed in the cohort studied here. each year, approximately muslims travel from marseille to participate in the hajj, gathering with over two million pilgrims from all over the world. health risks during the hajj are a critical issue due to the extreme congestion of people [ ] . infectious diseases represent a major problem during the pilgrimage with acute respiratory infections (ari) as the most common cause of admission to hospital [ ] [ ] [ ] . hajj pilgrims during their -month stay in saudi arabia experience relatively homogeneous accommodation conditions, and undertake identical rituals, while retracing the footsteps of the prophet mohammed, thus being very likely exposed to the same risk of ari. in recent years, several non-randomized studies have linked statin use with decreased risk of severe sepsis or death from severe infections, including pneumonia [ ] [ ] [ ] . recent prospective cohort studies confirmed previous observations [ ] [ ] [ ] [ ] [ ] while another suggested that the apparent beneficial effect of statins probably reflected a 'healthy user' effect, as statin users appeared to be younger, healthier, better educated, and socially and economically more privileged compared to non-statin users [ ] . these controversial findings also raised questions about the potential role of statins in the prophylaxis of infectious diseases such as pandemic influenza [ ] . muslims departing from marseille to participate in the hajj have been found to have a median age of years, with more than one third being over years old [ ] , and are therefore likely to use statins in a significant proportion. we conducted a prospective epidemiological study to evaluate the incidence of febrile cough episodes among hajj pilgrims from marseille and to assess if statin use could have an influence on this incidence. the socio-economic situation and health characteristics of the travellers were not consistent with the hypothesis of a 'healthy user' effect. a prospective cohort study was carried out in the marseille travel medicine centre (hô pital nord) from november to december . participants in the survey were pilgrims in preparation for the hajj pilgrimage enrolled in the meningococcal vaccination campaign to satisfy compulsory vaccination requirements. pilgrims older than years were included on a voluntary basis and participants were asked to give written consent. pre-travel questionnaires were presented orally, before vaccination, in french, in arabic or in french and arabic, depending on the language fluency level of the participants. post-travel questionnaires were presented by telephone. the pre-travel questionnaire included demographic factors (age, gender, location of residence), indicators of immigration status (country of birth and duration of stay in france), socio-economic indicators (level of education, employment, type of housing, rooms per person and household, complementary health insurance modalities), health status indicators (diabetes, hypertension, chronic respiratory diseases, statin use, vaccination coverage against influenza) and number of previous travels to saudi arabia. the post-travel questionnaire included travel indicators (duration of stay, food and housing conditions) and data about travel-associated diseases (medical consultation, hospitalization, occurrence of cough with or without fever, time of manifestation and duration of symptoms). cough was defined as occurrence of cough with or without sputum in an individual without chronic cough and subjective aggravation of cough in individuals suffering from chronic respiratory diseases. fever was defined as subjective feeling of fever. pilgrims were considered as lost in follow up after three failed attempts to reach them by phone. data were recorded anonymously in a microsoft access database and transferred to epiinfo . software (cdc, atlanta, ga, usa) for univariate statistic analysis. differences in proportions were evaluated using the chi-square test. as selection procedure, a two-tailed p value £ . was considered as significant [ ] . multivariate analysis was performed using the spss version software program (spss, inc., chicago, il, usa). factors with a p value < . in univariate models were included in a multivariate model, as suggested in the classical work of mickey and greenland [ ] . sex, age and statin use were also included in the model. a stepwise procedure based on likelihood ratio criteria was used in order to obtain the best criteria with the lowest akaike criteria (aic) [ ] [ ] [ ] . for the final model, a two-tailed p value £ . was considered as significant. among vaccinees preparing for the hajj pilgrimage, voluntarily participated in the study, yielding a response rate of . %. respondents had an average age of years (range - years) with a sex ratio (m/f) of . (table ) . a total of travellers were living in marseille ( . %), in other parts of southern france ( . %); information was not available in six cases ( . %). most of the pilgrims were born outside of france, with . % having been born in north africa. the mean duration of stay in france was years (range - years). a proportion of . % of travellers had a primary school education or below. thirty-four per cent of individuals were retired. among those under years which is the age of retirement in france, only . % were employed. a proportion of . % was living in state-subsidized housing and % received state subsidies for payment of rent. only . % were property owners. among . % of individuals, the household allocation was less than one room per person. a proportion of . % of travellers was covered by the state-financed complementary health insurance which is accessible to insolvent individuals and . % had a self-financed private complementary health insurance. a proportion of . % were covered under the statefinanced full health insurance coverage in cases of chronic and debilitating disease. forty-three per cent of the pilgrims declared to suffer from chronic diseases, including a total of pilgrims ( . %) were presented a questionnaire upon returning home, six individuals renounced travel ( . %) and the remaining ( . %) were lost to followup. the mean time between return and presentation of the questionnaire was days (range - days). no significant variation was observed between the travellers who answered the questionnaire and the enrolled pilgrims regarding demographic, immigration and socio-economic characteristics, as well as underlying chronic diseases. the mean duration of the pilgrimage was days (range - days). the vast majority of pilgrims declared to have been housed and to have eaten together ( . % and . %, respectively). as shown in table , a proportion of . % of travellers attended a doctor during travel and . % did so after travel. nine individuals were hospitalized (two in saudi arabia, one in algeria and six upon returning to france). among the six patients hospitalized in france, two had a respiratory tract infection. haemophilus influenzae was identified as the responsible pathogen in one of these two patients who was also suffering from diabetes. among the four other hospitalized patients, two had unstable diabetes mellitus and two had haematological disorders. a total of travellers ( . %) experienced fever during their stay in saudi arabia ( attended a doctor) and ( . %) had cough ( attended a doctor). just over % of the travellers with cough were febrile. dates of beginning of fever and cough are shown in fig. . a first peak was observed on december, followed by a second peak on december. the mean duration of fever was days (range - days) while the mean duration of cough was days (range - days). none of demographical and socio-economic characteristics of pilgrims significantly affected the occurrence of cough. similarly, previous travel to saudi arabia, diabetes, hypertension and chronic respiratory diseases, as well as vaccination against influenza had no significant influence on the occurrence of cough during the pilgrimage (table ). when considering only the cases of cough associated with fever, travellers with diabetes appeared to have an increased risk compared to other patients in univariate analysis (or = . ( . - . ), p . ). similarly, individuals of < years and unemployed had a greater risk of cough associated with fever (or = . ( . - . ), p . ). several factors appeared to be related to febrile cough, without reaching statistical significance. none of the other factors influenced the risk of febrile cough ( in the present study, we observed that hajj pilgrims from marseille represent a specific population of travellers with more than one third being geriatric patients, mainly originating from north africa. this is consistent with previous findings [ ] . of particular concern was the finding that a significant proportion of individuals had chronic medical disorders, e.g. diabetes mellitus and hypertension. similarly, high rates of diabetes and hypertension were found in patients [ ] . we also observed that the level of education of hajj pilgrims was particularly low, with a proportion of . % of individuals with a level of education below that of a certificate of primary school education compared to . % in the total immigrant population and . % in the general population of south eastern france (paca) [ ] . the pilgrim employment rate was seven-times lower and the proportion of pilgrims living in social housing in state-owned property was twice that of the total immigrant population in the same region [ ] . these results, together with an overall low rate of vaccination against tetanus, diphtheria, poliomyelitis and influenza [ ] , suggest that hajj travellers departing from marseille represent a category of travellers particularly at risk for travel-related diseases and that their socio-economic conditions should be considered during the pre-travel visit regarding cost-effective vaccines. in our survey, we observed a very high attack rate of cough episodes ( %), higher than that described in other studies. one study reported an incidence of ari of % within a group of pilgrims from riyadh [ ] . a study based on clinical criteria of influenza-like illness among pilgrims from pakistan reported rates of % in influenza-vaccinated pilgrims and % in pilgrims not vaccinated against influenza [ ] . another study involving english pilgrims, based on seroconversion rates, showed an attack rate of % among the vaccinated and % among the non-vaccinated participants [ ] . finally, an ari attack rate of % was recently observed among medical team members treating pilgrims in saudi hospitals [ ] . vaccination coverage against influenza did not influence the occurrence of ari in our experience, which strongly suggests that influenza virus was not the pathogen responsible for the observed symptoms. when investigating the pathogens causing respiratory tract infections in hospitalized patients during the hajj, h. influenzae, klebsiella pneumoniae and streptococcus pneumoniae appeared to be the most common pathogens ( %) in one study [ ] , while mycobacterium tuberculosis was the most common pathogen ( %) identified in a study on communityacquired pneumonias during the hajj [ ] . viral pathogens are also commonly identified during the hajj, representing - % of pathogens responsible for upper respiratory tract infections in hospitalized pilgrims with influenza a and b virus, rhinovirus and adenovirus being the most common [ ] [ ] [ ] [ ] . seventy per cent of the travellers who developed cough episodes in our study developed their first symptoms within days, suggesting human to human transmission of the responsible pathogen, with short incubation time as evi-denced by the bimodal distribution of cough in two peaks at a h-interval. statin use in this study was not associated with a reduction in the occurrence of travel-associated infections during the hajj pilgrimage. occurrence of cough episodes, duration of cough and association with fever were similar in travellers treated with statins and control travellers. to our knowledge, this is the first prospective study investigating a potential role of statins in the outcome of cough episodes in a cohort of individuals exposed to the risk. this result suggests that, while treatment with statin has been demonstrated to reduce the mortality of severe sepsis associated with respiratory tract infections [ ] [ ] [ ] , it does not play a medically significant role in the outcome of regular cough episodes as observed in the cohort studied here. however, the study involved limited numbers of statin users so that no definitive conclusions should be made. in this study, we observed that statin users were older compared to non-users, but the level of education and socio-economic characteristics were similar in both groups. none of the demographic and socio-economic characteristics of travellers affected the incidence of febrile cough in our experience. however, the study does not have the sufficient size for the examination of several risk factors, e.g. a chronic respiratory condition. diabetes mellitus appeared to be correlated with febrile cough in the cohort studied here. it remains uncertain whether diabetes is an independent risk factor for increased incidence or severity of common upper or lower respiratory tract infections [ ] ; however infections caused by certain micro-organisms (staphylococcus aureus, gram-negative organisms and m. tuberculosis) occur with increased frequency. infections due to other micro-organisms (s. pneumoniae and influenza virus) are associated with increased mortality and morbidity [ ] . our study highlights the fact that respiratory tract infections are very likely to occur during the hajj pilgrimage independently of vaccination coverage against influenza. overcrowding and continuous close contact, notably in the desert plains of mina and arafat where accommodation in collective tents is necessary, greatly increases the spread of respiratory tract infections. under these conditions a single case of severe acute respiratory syndrome during the hajj may cause an epidemic of unprecedented scale. during pre-hajj consultation such an event should be considered in counselling travellers. hand disinfection with alcohol-based scrubs should be recommended as it was proven to protect from ari development; it should be acceptable to most pilgrims given the religious insistence on ritual purity before the five daily prayers [ ] . the saudi arabian ministry of health has recommended that masks be used to minimise droplet spread [ ] . however, regular use of surgical facemasks was recently shown to offer no significant protection against ari, and intermittent use of surgical-type masks is associated with increased risk of infection [ ] . furthermore, many muslims consider covering of the face during the hajj to be prohibited; therefore general compliance with this advice is unlikely. vaccination against h. influenzae and pneumococcus should be recommended to travellers suffering from chronic respiratory disease and diabetes mellitus conditions. vaccination against diphtheria, tetanus, poliomyelitis and pertussis should be updated when required and vaccination against influenza systematically proposed. health risks at the hajj pattern of admission to hospitals during muslim pilgrimage (hajj) causes of hospitalization of pilgrims in the hajj season of the islamic year influenza and the hajj: defining influenza-like illness clinically statins: panacea for sepsis? statins and the risk of pneumonia: a population-based, nested case-control study statin treatment and reduced risk of pneumonia in patients with diabetes the effect of statin therapy on infection-related mortality in patients with atherosclerotic diseases statin use and hospitalization for sepsis in patients with chronic kidney disease influenza and copd mortality protection as pleiotropic, dose-dependent effects of statins sørensen ht. preadmission use of statins and outcomes after hospitalization with pneumonia: population-based cohort study of patients prior statin use is associated with improved outcomes in community-acquired pneumonia statins and outcome in patients admitted to hospital with community acquired pneumonia: population prospective cohort study pandemic influenza: a potential role for statins in treatment and prophylaxis pilgrims from marseille, france to mecca: demographics and vaccination status the impact of confounder selection criteria on effect estimation an introduction to model selection categorical data analysis applied logistic regression pattern of medical diseases and determinants of prognosis of hospitalization during muslim pilgrimage hajj in a terciary care hospital. a prospective cohort study les populations immigrées en provence-alpes-cô te d'azur. insee-falsid hajjassociated acute respiratory infection among hajjis from riyadh the incidence of vaccine preventable influenza-like illness and medication use among pakistani pilgrims to the hajj in saudi arabia influenza among u. k. pilgrims to hajj acute respiratory tract infections among hajj medical mission personnel, saudi arabia bacteria and viruses that causes respiratory tract infections during the pilgrimage (hajj) season in makkah, saudi arabia tuberculosis is the commonest cause of pneumonia requiring hospitalization during hajj (pilgrimage to makkah) influenza a common viral infection among hajj pilgrims: time for routine surveillance and vaccination viral respiratory infections at the hajj: comparison between uk and saudi pilgrims infections in patients with diabetes mellitus pulmonary complications of diabetes mellitus: pneumonia hajj and the risk of influenza health conditions for travelers to saudi arabia pilgrimage to mecca (hajj) we are very much indebted to the conseil géneral of provence-alpes-cô te d'azur for providing vaccines against diphtheria, tetanus and poliomyelitis. we thank t. j. marrie for critical review and editing of the manuscript. the authors state that they have no conflicts of interest. key: cord- -peppszqx authors: ishola, david a.; phin, nick title: could influenza transmission be reduced by restricting mass gatherings? towards an evidence-based policy framework date: - - journal: j epidemiol glob health doi: . /j.jegh. . . sha: doc_id: cord_uid: peppszqx introduction: mass gatherings (mg) may provide ideal conditions for influenza transmission. the evidence for an association between mg and influenza transmission is reviewed to assess whether restricting mg may reduce transmission. methods: major databases were searched (pubmed, embase, scopus, cinahl), producing articles that were sifted by title, abstract, and full-text. a narrative approach was adopted for data synthesis. results: twenty-four papers met the inclusion criteria, covering mg of varying sizes and settings, and including observational studies, outbreak reports, event reports, and a quasi-experimental study. there is some evidence that certain types of mg may be associated with increased risk of influenza transmission. mg may also “seed” new strains into an area, and may instigate community transmission in a pandemic. restricting mgs, in combination with other social distancing interventions, may help reduce transmission, but it was not possible to identify conclusive evidence on the individual effect of mg restriction alone. evidence suggests that event duration and crowdedness may be the key factors that determine the risk of influenza transmission, and possibly the type of venue (indoor/outdoor). conclusion: these factors potentially represent a basis for a policy-making framework for mg restrictions in the event of a severe pandemic. it is well established that influenza is transmitted from person to person through close contact with an infected, symptomatic individual. the exact mechanisms by which transmission occurs are still unclear, but is believed to involve multiple routes, including respiratory droplets and direct/indirect contact [ ] with secretions or fomites. aerosol transmission may also occur, but controversy surrounds this [ ] and some further evidence of aerosol transmission has recently been put forward [ ] . this is an important issue as the mechanism of transmission is always a key factor in infection control planning. while uncertainty persists regarding aerosols, droplet and contact transmission remain largely regarded as the most important and likely routes. transmission through these routes clearly requires physical nearness to infected persons, via either direct touch or the propulsion of large droplets across a relatively short distance. this requirement makes the consideration of mass gatherings a crucial issue. whilst there is not a ''standard'' definition of what constitutes a mass gathering, there is an understanding that these are events that involve large numbers of people (suggested minimum of people) [ ] [ ] [ ] congregating in finite geographical areas to share an event or experience. individuals can be in very close proximity for variable periods of time and, if the event is over a number of days, may even share over-crowded and/or temporary accommodation. therefore for those infectious diseases such as influenza, where close contact is the main determinant of transmission, it appears self-evident that mass gathering events could lead to the rapid transmission of a new causative agent. in the event of an influenza pandemic, minimizing transmission of influenza has been a priority for public health action. a variety of non-pharmaceutical public health interventions to reduce close contact between infected and susceptible individuals, or the opportunities for the virus to be picked up by susceptible people such as self-isolation of patients, respiratory etiquette and hand washing have been advocated. banning or restricting mass gatherings has been seen as a logical extension of this policy, however, it is a particular concern of policy makers that the scientific evidence upon which to base guidance for mass gatherings is lacking. this is particularly important given the need to weigh any potential benefits against the economic and social disruption that banning or restricting mass gatherings could have on society. there have been other systematic reviews undertaken in recent years on the broader subject of non-pharmaceutical interventions aimed at reducing transmission of respiratory viral infections [ , ] . these reviews considered a range of such interventions, and they explicitly recognized that there is a paucity of primary evidence regarding restriction of mass gatherings (and other ''social distancing'' measures); thus they did not primarily focus on this specific area. the aim of this review, therefore, was to attempt to reduce this evidence gap by assessing the available evidence base relating to the utility of restrictions on mass gatherings during an influenza pandemic. this is an important policy area not only because of the impact such restrictions could have on public confidence and morale, but also because of the economic and liability issues that such action might generate. the findings of the review may be able to help inform policy statements on the effectiveness of mass gathering restriction interventions that may be deployed to help reduce influenza virus spread during a pandemic. the study protocol was largely based on the university of yorkÕs centre for reviews and dissemination guidance for undertaking reviews in healthcare [ ] . work commenced in mid-july and the main part of it was completed in mid-october . further work was carried out in june to bring the literature coverage up to date. the following specific questions were developed to capture the objectives of the review: • is there an association between mass gatherings and influenza outbreaks or spread? • are there any particular characteristics (such as size or duration) of mass gatherings that influence transmission of influenza? • does the restriction of mass gatherings reduce the spread of influenza within the community (compared with no restriction or with other interventions)? the following types of studies were included in the review: • randomized controlled trial • quasi-experimental study -non-randomized controlled study -before-and-after study • observational study -cohort study -case-control study • outbreak reports -outbreak/cluster reports -historical archival outbreak analyses • surveillance reports -major event infection surveillance reports the list above is largely in hierarchical order of study design quality [ ] , but with the addition of outbreak and surveillance reports, not traditionally included in such lists, important to the topic of this review. to cover the other ''non-standard'' study design encountered, the term ''quasi-experimental'' is employed to describe controlled but nonrandomized studies [ , ] . only studies published in english were included. relevant systematic and narrative reviews and operational description papers were utilized for useful background information. the reference lists of the systematic reviews were scanned to identify potentially relevant primary studies that could be considered for inclusion. case reports, mathematical modelling and human/non-human experimental laboratory studies were excluded from the review. outcome measures included laboratory-confirmed influenza infection (i.e., documented by virus isolation, molecular testing such as polymerase chain reaction, and serological studies) and clinical influenza-like illness as defined by the investigators, whilst recognizing that this is less specific. the search strategy focused on primary studies taking into account the issues detailed above. the term ÔinfluenzaÕ rather than Ôpandemic influenzaÕ was used to reflect the entire spectrum of influenza for which guidance would be relevant. the transmission of other respiratory viruses was also included because of the similarity of transmission and therefore the potential applicability of any results to influenza. an initial ''scoping'' search was followed by further discussions and consultation on the work plan and search strategy. the term mass gathering on its own proved inadequate as a search term as there is no clearly accepted definition of what constitutes a mass gathering. therefore, a range of additional terms were used, such as public gatherings, social gatherings, large crowds, mass events, festivals, olympics, hajj, championship, and others listed in table . transit settings such as long-distance flights and cruise ships were not included, as it was decided that these settings would fit better in a separate review of evidence for influenza transmission through transport. the final search with revised terms and refined using the ''advanced search'' tool on pubmed was carried out as described in table , with no time period restrictions. the initial searches included the literature up till july . a further search was conducted on may to bring the literature coverage up to date as part of an editorial process. in addition, secondary searches were also initially carried out in the following databases: scopus, excerpta medica database (embase), and the cumulative index to nursing and allied health literature (cinahl). these are described in table . in addition to the search results, the reference lists of papers identified from the search were scanned for other potentially relevant studies. efforts were also made to identify studies other than those published in the peer-reviewed literature; the authorsÕ study selection was conducted in stages. at all stages, scanning and reviews were done independently by the authors, who then harmonized their selections. papers identified by the searches were scanned and some excluded on the basis of the Ôti-tleÕ for relevance to the review. the abstracts of the remaining papers were then reviewed to identify studies that appeared to meet the inclusion criteria. the full text versions of all these articles were then sought and read in full. for papers that had relevant titles but no abstracts, the full text articles were also obtained, scanned for relevance, and if relevant they were read in full. in addition, some papers that did not meet the inclusion criteria (e.g. operational descriptions of interventions, commentaries, or editorial reviews of influenza transmission or pandemic influenza) were selected to provide relevant background or supplemental information. data from the selected full text papers were extracted using a pre-designed form. data elements included publication information, study characteristics, participant characteristics, the intervention (if any) and setting, outcome and results. the data extracted were used to determine the eligibility of each paper for inclusion in the review. this process resulted in a final selection of eligible articles that were then included in the review. the main body of this work was undertaken in by the uk health protection agency as part of a comprehensive influenza scientific evidence review informing the uk national pandemic influenza strategy. within this context, the work was carried out within a very tight three-month timeframe and with significantly limited resources. as a result, some of the most comprehensive steps required of a full systematic review could not be realistically accommodated. therefore, a modified process was adopted in conducting this ''rapid evidence assessment'' rather than a full, formal systematic review. rapid evidence assessments are well recognized as a pragmatic approach to include all the major elements of a full systematic review, ensuring an outcome that is as comprehensive as possible while accepting limited compromises in order to meet stipulated deadlines for feeding into the policy process [ ] . due to the time constraints, it was not practical to pursue time-intensive contacts with authors or to seek translations for non-english articles, which were therefore excluded. articles lacking abstracts were largely excluded, and there was a limited search for unpublished studies. however, to try to mitigate these limitations, full draft versions of the review were submitted to national experts at the uk health protection agency and the scientific pandemic influenza committee of the uk department of health, seeking their comments and advice on any papers or documents that may have been omitted. some further work was carried out in may to june to update the literature. at the outset, a strategy was developed to assess the quality of eligible studies using the critical appraisal skills programme (casp) tools as appropriate for each type of study [ ] . however, after completion of the literature search, it was clear that the types of studies and the study design types identified were not suitable for assessment by the casp tools. similarly for the outbreak reports included in the review, no suitable existing framework could be readily identified for quality assessment. the orion tool was not strictly applicable as it is specific to outbreaks of nosocomial infection [ , ] . therefore, a modified approach was adopted, whereby each paper was categorized as having low risk, some risk, or high risk for bias with respect to the relevant review question addressed by that study. the grading was assessed based on the presence of significant methodological limitations. a high risk of bias was attributed to papers with at least three significant methodological issues as identified by the review authors, while papers with at least two issues were classified as having some risk. this approach was adapted from a system previously used by jefferson et al. [ ] . the quality of the review itself was tested against checklists based on the moose [ ] and prisma [ , ] standards. within the restrictions of the time constraints already described, key gaps and issues identified by the checklists were addressed as appropriate and/or acknowledged in sections . (explaining the review context including time constraints) and . (recognizing the study limitations). the data synthesis was restricted to a narrative approach that included an analysis of the relationships within and between studies and an overall assessment of the robustness of the evidence and limitations of both the studies and the evidence review [ ] . in addition, the synthesis considered the implications for policy and guidance development as well as future research. the search identified a total of papers after accounting for overlaps between the different databases. these were reviewed on the basis of ÔtitleÕ for relevance to the review (fig. ) , and on this basis papers were excluded. abstracts for the remaining papers were reviewed and a further were eliminated. full copies of the remaining papers plus papers identified from scanning the reference lists of review papers, and papers retrieved from the authorsÕ hardcopy files, were reviewed and summarized. table provides a classification of the papers that were read in full text. after full text review, papers were classified as meeting the inclusion criteria. these included a quasi-experimental study (a non-randomized trial) [ ] , nine observational studies [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , seven outbreak reports [ ] [ ] [ ] [ ] [ ] [ ] [ ] , three historical outbreak archive analyses [ ] [ ] [ ] , and four event surveillance reports [ ] [ ] [ ] [ ] . details for each of these studies are summarized in table . the papers that were read but not included in the review are listed in table . one quasi-experimental study by qureshi et al. [ ] attempted to investigate the incidence of vaccine preventable influenza-like illness among pakistani pilgrims to the hajj religious gathering in . the hajj is an annual religious event that takes place over a number of days in a very small geographic area of saudi arabia usually involving to million pilgrims from all over the world. accommodation is at a premium during this event and many pilgrims stay in tents specifically erected for the event and that are often over-crowded. although primarily a vaccine efficacy study, the rates of influenza-like illness reported in vaccinated pilgrims were % compared with % in non-vaccinated pilgrims. however, these results were based on clinical endpoints without microbiologic confirmation; a non-randomized design was used, and the study was not designed to address the primary question of this review. nine observational studies estimated the risk of acute respiratory illness and/or influenza-like illness associated with the hajj pilgrimage by attempting to measure its occurrence in pilgrims. four [ ] [ ] [ ] ] of these studies confirmed the cause of illness by laboratory testing, while the other five relied on specified symptom complexes as surrogate indicators. among the nine observational studies were four cross-sectional studies. balkhy and colleagues [ ] tested hajj pilgrims in who presented with symptoms of upper respiratory tract infection in the second week of the event; ( %) of the pilgrims tested positive for influenza. rashid et al. [ ] assessed the burden of laboratory-confirmed influenza and respiratory syncytial virus (rsv) infections in symptomatic british hajj pilgrims in the event. of symptomatic pilgrims who underwent nasal swab testing, (about %) had confirmed influenza (mostly a type), while only ( %) had rsv infection. in the hajj, the same investigators [ ] found comparable levels of laboratory confirmed influenza ( - %) in both uk and saudi pilgrims. these relatively low levels of infection contrasted with the findings in the cross-sectional study by deris et al. [ ] who based their assessment on syndromic influenza-like illness rather than laboratory-confirmed infection. they found an influenza-like illness prevalence of % in malaysian pilgrims who had just completed the hajj. the other five observational studies were similarly designed, involving groups of intending hajj pilgrims who were recruited in their home regions or countries prior to the event, and then re-assessed this was a well-organized systematic prospective influenza surveillance program, described by the authors as the first of its type at a large games event limitations include: -no indication of total numbers of people at the event or in the city -no indication of the background ili activity in the city or country; or whether this was during the local winter influenza season after the pilgrimage. even though three reports were described by their respective authors as ''prospective cohort'' studies [ , , ] , none of these five studies included an ''unexposed'' (non-hajj attending) control group for comparison, indicating that they should be more accurately regarded as ''before and after'' studies. choudhry et al. [ ] assessed saudi residents (attending the hajj from a different part of the country) and found an incidence of influenza-like illness of about %. three studies of french pilgrims by gautret et al. [ , , ] found rates of cough of between % and %; while in el-bashir and colleaguesÕ serological study of uk pilgrims [ ] , respiratory symptoms occurred in more than %, but the seroconversion rate was % of participants. these variable data underline the difficulties of comparing different studies that employ contrasting measures of influenza. interpretation needs to take account of the fact that studies using clinical outcomes suggest much higher levels of influenza-like conditions than the ones that involve laboratory confirmation. even among the laboratory-based studies, differences in laboratory techniques may also be significant. there were four types of outbreaks in the reports that were reviewed. the first of those was a paper by pang et al. [ ] that described the experience of dealing with the sars (severe acute respiratory the next group consists of four reports of influenza outbreaks occurring at a religious event in australia and at three large, open-air music festivals in europe. all of the events lasted several days and involved crowds ranging from , to , people. it is particularly relevant that the three music festivals occurred during the influenza pandemic-two at the beginning and one later during the pandemic. the report by blyth et al. [ ] described an outbreak of influenza at a large, -day religious event in australia during july attended by over , participants from countries. over , of the pilgrims were accommodated in a variety of make-shift, overcrowded venues such as sports halls, community centers and schools. one hundred laboratory-confirmed cases of influenza were identified among attendees. seven different strains of influenza were identified (four influenza a and three influenza b), highlighting the potential for the introduction of novel influenza strains. loncarevic et al. [ ] described an outbreak of influenza at a -day music festival in serbia during july involving over , participants, with a number of them coming from other european countries. many of the participants stayed at a large campsite where overcrowding was an issue. sixtytwo laboratory-confirmed cases of h n ( ) were identified; some of which were secondary cases. although the virus was already present in serbia at the time of the festival, the sudden increase in cases, in particular the secondary cases associated with the festival, suggests possible local spreading. the authors also reported on a small outbreak of influenza at an international sporting event held in serbia in july over a period of days and attended by over , spectators. seven confirmed cases of h n ( ) were identified in six athletes and a volunteer helping at the games. although a much larger event, the numbers affected are considerably smaller and seem to be restricted to participants rather than those attending. gutierrez et al. [ ] described a -day music festival in belgium during early july attended by an estimated , people from all over europe. twelve laboratory-confirmed cases of h n ( ) were identified. although sporadic cases of h n ( ) had been detected in belgium prior to the festival, an increase in cases was observed after the event and the decision to shift to mitigation was taken almost a week after the first festivalassociated cases were identified. the authors suggest that this festival highlights the potential seeding role for these events in the early stages of a pandemic. presentation and discussion paper on data from the - influenza pandemic. the substantial research report arising from the study was included in the study [ ] memish botelho-nevers et al. [ ] depict an outbreak of influenza at a -day music festival in hungary during august attended by , people from all over europe. many of the participants were located on a campsite set up for the festival. eight laboratory-confirmed cases of h n ( ) were identified. cases of pandemic influenza had already been identified in hungary and at the time the community influenza-like illness rate was . per , against an estimated . per , at the music festival. the third type of outbreak report described by saenz et al. [ ] involved a large, international medical conference held in iran during september at the early stages of the / pandemic. the -day conference was attended by over participants from all over the world. it was estimated that about a third of the participants developed an influenza-like illness with an overall attack rate of %. the virus was isolated from throat and nasal washings; this was found to be the pandemic a/hong kong/ virus. there was evidence that close contacts of returning attendees were also affected, but none of the episodes led to a rapidly expanding focus of infection. the high attack rate raises the question of whether the indoor setting may represent a particularly high risk. lastly, there was an innovative study examining the a(h n ) outbreak in mexico [ ] . the authors described the details of cases and then used a series of epidemiological tools to map the spread of the virus throughout the country. they identified two major contributory factors to the rapid spread of influenza: one was the very high population density in parts of mexico city; the other was the massive religious festival involving more than million people, which took place in the cityÕs iztapalapa neighbourhood at the very early stage of the outbreak, shortly before the new virus was identified. it is suggested by the authors that this temporal association between [ ] low schenkel [ ] low the mass gathering event and the subsequent increase in numbers of cases may reflect participants returning to their own neighbourhoods across the city, and from there to other parts of the country. inevitably for a subject of research such as mass gathering restrictions, where prospective studies present serious practical challenges, researchers have sought to utilize historical data to try to draw out major lessons for current impact. this review included three historical analyses of the non-pharmaceutical responses to the - influenza pandemic. markel et al. [ ] examined the variety of nonpharmaceutical interventions that were deployed in american cities during the - influenza pandemic. the combination of school closures and concurrent public gathering bans was implemented in ( %) of the cities and was the commonest combination of measures deployed. applied early in the pandemic, this combination was significantly associated with reductions in the weekly excess death rates. hatchett et al. [ ] undertook a similar analysis on a smaller number of american cities where the timing of different types of non-pharmaceutical interventions was available. they found that the early application of multiple interventions showed a trend towards lower cumulative excess mortality, but that no single intervention showed an association with improved aggregate outcomes for the pandemic. both studies suggested that for non-pharmaceutical interventions to be beneficial, they should be applied early and in a sustained manner. a further review of the u.s. public health response to the pandemic by aimone [ ] gave conflicting results. this review examined the public health response in new york city. in new york during the pandemic, mass gatherings were not prohibited nor were schools closed; instead, the city opted for a policy of staggered business hours to avoid rush-hour crowding, enhanced surveillance so that cases were quickly identified and isolated, and an intensive program of health education. the reported outcome measures for new york city were comparable with those seen in other american cities, and new york city experienced one of the lowest excess death rates on the eastern seaboard of the united states. surveillance reports from four major sporting events within the last decade were considered suit-able for review [ ] [ ] [ ] [ ] . the study by gundlapalli et al. [ ] reported the experience of influenza surveillance during the winter olympics at salt lake city in . no indication of the numbers attending was given, but it is assumed that the numbers were large. twenty-eight cases of confirmed influenza from three clusters of influenza-like illness (ili) were identified and these were restricted to either participants in the games or support staff for the games. the clusters consisted of members of a national team who trained and lived together, participants of a sport and law enforcement officers who worked and lived in close proximity. lim et al. [ ] reported on the experience of managing the asian youth games at singapore in june . these games involved over athletes and officials from countries. although numbers of spectators are not given, it is assumed that the crowds were large. at the start of the games, singapore had already reported confirmed cases of h n ( ). six laboratory-confirmed cases of h n ( ) were identified during the days of the event-four on one football team. no information on the numbers of confirmed h n ( ) in the population after the games was available. there was no increase in ili activity during the winter olympics in torino in [ ] . the final study by schenkel et al. [ ] reported on the experience of syndromic surveillance during the fifa world cup in germany during june/july . at the time, germany was experiencing a very large outbreak of measles. measles is essentially spread by the respiratory route and is highly infectious. however, despite enhanced daily surveillance, no outbreaks of respiratory disease or measles associated with the world cup were detected. as stated in section . , the approach to quality assessment of the reviewed papers was based on a pragmatic framework for categorizing studies into low-or high-risk for bias, depending on the presence or absence of significant methodological limitations. a high risk of bias was attributed to papers with at least two significant methodological problems as identified by the review authors (table ). the evidence to help address important public health questions around mass gatherings and influenza transmission is sparse, especially in the context of an influenza pandemic. in addition, the topic does not lend itself to ease of scientific investigation and there are probably many who may feel that it is self-evident that mass gatherings facilitate the transmission of infectious diseases. this systematic search of the literature identified a limited number of studies that addressed the review questions regarding whether mass gatherings are associated with influenza transmission and whether restricting mass gatherings reduces the spread of influenza within the community. in attempting to understand and describe a situation or intervention, a common understanding or definition is essential. there is currently no generally accepted definition of what constitutes a mass gathering. however, the literature on mass gathering medical care highlights an emerging consensus amongst those providing emergency medical care at organized events. in this setting, mass gatherings are considered to be organized events with more than people in attendance [ ] [ ] [ ] . a recently published guidance document from the world health organisation (who) expanded the term to cover any organized or unplanned event involving enough people to ''strain the planning and response resources of the (host) community, state or nation'' [ ] . the major limitation in trying to define mass gatherings is that any single definition would inevitably be too simplistic as it would need to incorporate events as diverse as the hajj (lasting about month and involving between and million people), and a football match (involving several thousand spectators over a period of about h). a system for classifying mass gatherings on the basis of size and duration is lacking and may be required. in recognition of the difficulties of conducting hypothesis-based studies that directly implement and assess the effects of restrictions of mass gatherings in real life, an indirect approach was taken to address the review questions as follows: to address whether mass gatherings are associated with influenza transmission, evidence was derived from the following: -a quasi-experimental study that was primarily designed to quantify vaccine efficacy in the form of a non-randomized trial. -observational studies that assessed participants before and after exposure to mass gathering events. -reports of influenza outbreaks and other respiratory illnesses at mass gathering events. -communicable disease surveillance reports from some major events. a number of studies [ ] [ ] [ ] [ ] [ ] have consistently demonstrated, over a number of years, that respiratory virus transmission occurs amongst pilgrims attending the annual hajj in saudi arabia, and it is recognized as an issue of international public health significance [ ] [ ] [ ] [ ] that could be particularly important in a pandemic situation. a significant proportion of pilgrims are affected by symptoms of either an influenza-like illness or an acute respiratory illness with the proportion affected reaching about % in some studies [ , ] . the hajj is, however, a unique event with almost million people converging on a relatively small geographic area for a period of at least days, extending up to weeks. crowd density is very high and overcrowding in the living accommodation is common. given the unusual nature of this event, the applicability of these findings to other mass gatherings is therefore limited. there is also a question regarding the fact that several of these studies are based on clinical criteria that could be due to other viral respiratory illnesses besides influenza. in a small number of outbreak studies involving influenza-like illness and confirmed influenza at large music festivals, there is varying evidence about the extent to which influenza transmission occurs. outbreaks were based on laboratory diagnosis, and transmission was confirmed in all, though they had varying infection rates ranging from roughly to per , . two recent studies undertaken during the pandemic suggest that at the beginning of a pandemic, these gatherings may act as seeding events [ ] ; indeed it has been suggested at the early stages of the pandemic a(h n ), a huge easter season mass gathering involving million people may have helped in propelling the first wave of the outbreak throughout mexico [ ] . there is no compelling evidence from event surveillance reports, such as international athletic events, the world cup and the winter olympics, to indicate that these major events significantly increase community transmission of influenza. outbreaks did occur in some cases, but these always seemed restricted to the actual competitors and staff rather than the crowds attending or the wider community. together, all of these reports point to the potential for influenza outbreak and transmission in connection with large, multiple-day, open-air events. thus there is some evidence to indicate that mass gatherings may be associated with an increased risk of influenza transmission, but it seems to be very variable. the type of mass gathering event seems to be of considerable importance in terms of the risk of influenza transmission ( table ) . most of the evidence supporting the role of mass gatherings in the transmission of influenza comes from events where there are crowds with high crowd densities (which may be theoretically estimated at > people per square metre), and where the participants are likely to live close together for prolonged periods, e.g. the hajj pilgrimage [ ] [ ] [ ] [ ] [ ] and large musical festivals [ ] [ ] [ ] . in these events, accommodations which are already likely crowded are also likely to be relatively basic, such as communal camp-style living, with the probable risk of suboptimal hygiene facilities. it seems apparent that events where close contact among participants extends beyond event venues and into accommodation areas are most associated with influenza. event size, per se, does not seem to be a critical factor. in contrast, there is no convincing evidence that major organized sporting events are associated with significantly increased influenza transmission in those attending the event [ ] [ ] [ ] . an important example of this contrast comes from serbia, where two major events of different type and scale happened to coincide in , providing a ''natural experimental'' opportunity for comparison [ ] . in the larger event, only four event-linked confirmed influenza cases occurred at the world university games held over a -day period and involving almost , athletes and staff with about , spectators. however, in a relatively smaller event held in the same month and within the same country, as many as event-linked confirmed cases occurred at a -day music festival with around , participants. furthermore, in surveillance reports from recent major international sports competitions, cases or small clusters of influenza were reported, but these were mainly among the event participants rather than among the overall population of people exposed to the events [ , ] . this was true even for one major event that took place within a pandemic context [ ] . these events showed no clear evidence of influenza transmission, indicating that influenza may not be a significant cause for concern at modern world sports events. this view is supported by the surveillance report from the world cup in germany [ ] , where instances of transmission were not reported, meaning that they were either not detected or very low. this situation may in part be explained by the brief transitory nature of contact in the crowds in highly organized international sports festivals such as the olympics and the world cup, which are usually seated events with good spacing in-between seats and mostly in open-air settings with dilution of any infectious droplets that may be generated. the apparently low or absent influenza transmission at such events may also reflect the contemporary fact that many people who attend major sports championships tend to have planned their visit a long time ahead, as ticket sales usually start months or even years in advance. spectators as well as participants tend to stay in more conventional accommodations such as hotels rather than tents or other forms of portable or camp-style quarters with highly crowded conditions. it is also important to note that contemporary major events are now deploying increasingly developed systems for infectious disease surveillance and control [ ] , which are crucial for early detection and containment where possible. the other situation of note relates to indoor events such as large conferences, typified by the international medical conference held over days in iran during the early stages of the / pandemic [ ] . during this meeting it was estimated that about a third of the participants developed an influenza-like illness with an overall attack rate of %; the pandemic virus was isolated from those cases where testing had been undertaken. this potentially highlights the role that ventilation may play in the reduction of influenza transmission and is another factor worthy of consideration. in summary, the type of mass gathering event seems to influence the risk of influenza transmission, key factors being the degree of crowdedness, the event duration and, possibly, whether the event is held indoors or outdoors. multiple-day events with crowded communal accommodations may be the links to mass gatherings most associated with influenza. to address whether mass gathering restrictions can reduce influenza transmission, the mainly relevant papers found were archival studies of the - influenza pandemic [ ] [ ] [ ] and an analysis of the sars outbreak [ ] . no relevant randomized controlled trials were found, reflecting the practical difficulties that such studies would involve. mass gatherings of varying dimensions were restricted at a large number of american cities during the - period. the reports again highlighted the difficulty of interpreting what was meant by a mass gathering, e.g. including schools, cinemas, theatres and other public places. in general, evidence suggests that these measures had a beneficial effect, especially where implemented early in the course of the outbreak [ , ] . however, these benefits were not universal across all the cities [ ] . restrictions were typically implemented as part of a set of interventions, e.g. combining quarantine and isolation policies with banning mass gatherings. as a result, it is extremely difficult to tease out the individual effects of mass gathering restrictions alone. using multivariate techniques, investigators attempted to isolate the differential effects of individual restriction measures and found indications that certain interventions (such as closures of entertainment venues) had measurable specific impact [ , ] , but this evidence is limited. an analysis of the sars outbreak in china attempted to probe the impact of mass gathering restrictions that were applied in a contemporary setting [ ] . however, as with the historical studies, it was not possible to distinguish the specific effects of mass gathering restrictions from amongst the broad range of other public health interventions that were applied. in summary, there is some evidence that when applied early and in tandem with other public health measures, such as isolation and quarantine and closures of educational institutions, mass gathering restrictions may help in reducing transmission. in a pandemic like that experienced during , it is unlikely that the measures described above could be justified; however, in a much more severe pandemic, the cost-benefit equation could easily shift the other way. the application of bans on mass gatherings and other related public health measures are therefore highly dependent on an early indication of the severity as measured by its impact on individuals and society. there are two further, critical domains of uncertainty that need to be considered in the development of evidence-based guidance and policies regarding mass gatherings. the first domain relates to issues around the current understanding about how influenza is spread, and factors that can affect transmissibility (e.g. host factors, pathogen factors, environmental factors and particle size) [ ] . key questions remain in these areas, which may be important in making specific recommendations regarding particular types and scope of mass gathering restrictions. the second domain impinging on the potential effectiveness of any public policy on mass gatherings includes the whole range of factors affecting adherence and compliance. for instance, the experience of the pandemic has raised significant questions around how willing people might be to comply with bans imposed on mass gathering restrictions [ ] [ ] [ ] [ ] . other challenging issues include the problematic ethical and legal frameworks for implementing restrictions for public health purposes [ , ] , as well as considerable logistical and economic implications. if longplanned events were to be cancelled, who would be liable for the huge personal, corporate and national costs that such cancellations might incur? in considering policy recommendations within a pandemic context, the most practical approach for all but the more severe pandemics may be a strategy of encouraging voluntary restrictions. this would involve giving the public the best available information and advising rather than legislating that organizations and individuals avoid non-essential events where there is at least some evidence of transmission risk. for such a strategy to have a chance of succeeding, it would be most important to have in place a carefully and sensitively prepared communication strategy, since recommendations to avoid public gatherings are likely to run against powerful social pressures to do otherwise [ ] . the success of any public health strategy-and this must be particularly true in relation to a potential or imminent pandemic situation-requires the building of trust [ ] and an intelligent and purposeful engagement of the public even prior to the event [ ] . there are other important issues to note. although this review has focused on mass gatherings, limiting transmission of influenza clearly requires a multifaceted approach. some studies in this review reflected such an approach; for example, in the historical outbreak investigations where restrictions on mass gatherings were combined with other non-pharmaceutical measures [ , , ] . it would be prudent to apply the best evidence relating to other social distancing interventions in conjunction with any specific policies on mass gatherings. an additional question that should be considered is whether non-pharmaceutical health interven-tions such as mass gathering restrictions, actually reduce the health burden of influenza, or only modify the epidemiology by temporarily delaying the eventual impact of an event such as a pandemic. it is tempting to speculate on the possibility of a reduction in disease burden; historically, some of the american cities that implemented mass gathering restrictions during the - pandemic seemed to achieve significant reductions in peak morbidity and mortality that may well have reduced the overall burden. however, pragmatically, countries like the united kingdom aim to achieve a slower spread, to prolong the troughs and to flatten the peaks of the epidemic curves to buy time for countermeasures to take effect and to enable services to cope with a lower volume of activity. in this context, the most important point to emphasize is that mass gathering restrictions must only be a part of a range of interventions. the synergistic effects of multiple interventions is what would allow the best chance to achieve significant reductions in overall burden. more evidence is needed on this subject. there is a need for well-designed studies to more accurately quantify the nature of the infections causing flu-like symptoms at mass gatherings, confirm the key parameters that influence the transmission of influenza in these settings, and to directly assess the impact of mass gathering restrictions. but as ''gold standard'' randomized comparison designs are extremely difficult to apply to this kind of intervention, attention needs to focus on optimal observational study options. from a uk perspective, british people travelling abroad for mass gatherings such as the hajj or other large events could be approached for inclusion in prospective studies for comparison with appropriately matched, nontravelling controls, with care being taken to avoid drawbacks observed in existing studies. within the uk, mass gatherings ranging from indoor events in theatres and cinemas, to outdoor events such as football matches and major musical events like the glastonbury festival or travellersÕ horse fairs represent potential opportunities for carefully designed prospective cohort studies to be undertaken. the biggest issue is persuading funders that given the current paucity of good studies, such further research is still needed. as previously noted, this review has examined an intervention area in which there are a limited num-ber of relevant studies and there is limited common understanding of what constitutes a mass gathering. despite these challenges, it has been possible to extract limited strands of evidence that may be useful towards policy development. also, within the boundaries of the inclusion criteria, and despite the limited work timescale, this review was able to capture all the relevant studies identified by recent systematic reviews investigating non-pharmaceutical interventions designed to limit transmission of influenza and/or other respiratory viral infections [ , , ] . however, due to time constraints in carrying out this work, as described in section . , while every effort has been made to be as comprehensive as possible, it is acknowledged that the rapid evidence assessment process necessarily involved some limitations. the literature search is not necessarily exhaustive and there is therefore a possibility of incomplete retrieval of all potentially relevant studies. while a range of study designs were reviewed, there was not a single randomized controlled trial that was suitable for inclusion. this is of course not surprising, given the formidable logistical, cost and ethical hurdles that make large-scale experimental epidemiological studies of the restriction of mass gatherings impractical and probably impossible. some of the included studies had significant design and quality issues as duly reflected in the individual paper summaries and the discussion, and highlighted in tables and . a common issue with a number of the studies included in the review is that they depended on clinical symptoms like cough or syndromes such as influenza-like illness, rather than laboratory diagnosis of influenza. in such studies it is not possible to isolate the impact of influenza as opposed to other respiratory viruses, and the risk of influenza could potentially be over-interpreted. in the studies where laboratory testing was undertaken, influenza was only confirmed in minority proportions of people with respiratory symptoms, ranging between % and % [ , , ] , but possibly up to a roughly estimated % in one study [ ] . this review did not include specific ''specialized'' settings that may arguably be regarded as mass gatherings, such as groups of people travelling for periods of time on cruise ships. the authors took the view that any transit-related settings would be best considered under a separate evidence review of influenza transmission through transportation. modelling studies were also excluded, and it is acknowledged that their inclusion may offer an additional dimension in order to build a fuller picture. the application of quantitative techniques could have potentially enhanced the simple narrative approach that was adopted for the analysis. however, there are insufficient studies presenting quantitative data on this subject, and moreover, there is a high level of heterogeneity amongst the identified studies. in conclusion, there are limited data indicating that mass gatherings are associated with influenza transmission. some evidence suggests that restricting mass gatherings together with other social distancing measures may help to reduce transmission. however, the evidence is not strong enough to advocate legislation or proscription. therefore, in a pandemic situation a cautious policy of voluntary avoidance of mass gatherings would be prudent. none declared. transmission of influenza a in human beings questioning aerosol transmission of influenza aerosol transmission of influenza a virus: a review of new studies mass gathering medical care: a twenty-five year review massgathering medical care: a review of the literature evidence for excessive incidence of infectious diseases at mass gatherings with special reference to 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influenza a (h n )v virus at a rock festival in belgium public health preparedness for two mass gathering events in the context of pandemic influenza (h n ) -serbia evaluation of control measures implemented in the severe acute respiratory syndrome outbreak in beijing outbreak of a -hong kong- influenza at an international medical conference inside the outbreak of the influenza a (h n )v virus in mexico the influenza epidemic in new york city: a review of the public health response public health interventions and epidemic intensity during the influenza pandemic nonpharmaceutical interventions implemented by us cities during the - influenza pandemic the influenza a (h n - ) experience at the inaugural asian youth games singapore : mass gathering during a developing pandemic enhanced surveillance of infectious diseases: the fifa world cup experience results from the integrated surveillance system for the winter olympic and paralympic games in italy world health organisation. communicable disease alert and response for mass gatherings: key considerations health risks at the hajj prevention of pandemic influenza after mass gatherings -learning from hajj establishment of public health security in saudi arabia for the hajj in response to pandemic influenza a h n pandemic influenza: mass gatherings and mass infection should cities hosting mass gatherings invest in public health surveillance, planning? reflections from a decade of mass gatherings in human infection with new influenza a (h n ) virus: who consultation on suspension of classes and restriction of mass gatherings to mitigate the impact of epidemics caused by influenza a (h n ) listen to the people: public deliberation about social distancing measures in a pandemic responses to pandemic (h n ) sip : social distancing during a pandemic. not sexy, but sometimes effective: social distancing and non-pharmaceutical interventions influenza a(h n ) and pandemic preparedness under the rule of international law ethical and legal challenges posed by severe acute respiratory syndrome: implications for the control of severe infectious disease threats easier said than done: behavioral conflicts in following social-distancing recommendations for influenza prevention situational awareness, health protective responses to pandemic influenza a (h n ) in hong kong: a cross-sectional study including the public in pandemic planning: a deliberative approach physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review key: cord- -y o e k authors: elachola, habida; gozzer, ernesto; zhuo, jiatong; memish, ziad a title: a crucial time for public health preparedness: zika virus and the olympics, umrah, and hajj date: - - journal: lancet doi: . /s - ( ) - sha: doc_id: cord_uid: y o e k nan groups. furthermore, the long-term adherence to a daily injection therapy for patients with non-alcoholic steatohepatitis remains to be determined. most importantly, short-term histological outcomes are used to assess the effi cacy of treatment. unlike in viral hepatitis, histological outcomes are not known to be valid surrogate outcomes in the assessment of non-alcoholic steatohepatitis. after all, the ultimate aim is not to change histology but to prevent the development of cirrhosis and hepatocellular carcinoma. in this respect, results of recent longitudinal studies , showed that fi brosis, but not other histological features of non-alcoholic steatohepatitis, correlated with overall and disease-specifi c mortality. fibrosis progression can also occur in patients with nafld who do not have steatohepatitis, albeit at a slower rate. , these outcomes highlight the urgent need to defi ne reliable surrogate outcomes for the disorder. until the time comes when there are robust surrogate outcomes for the treatment of non-alcoholic steatohepatitis, the follow-up of treated patients for long-term clinical outcomes will be very important. the lean study has introduced liraglutide as a new potential treatment option for patients with non-alcoholic steatohepatitis. the drug should be tested further in large studies with a long duration of follow-up. this study has also raised issues pertinent to drug development in this area. in the meantime, keeping lean remains the most important aspect of management of non-alcoholic steatohepatitis. department of medicine and therapeutics, the chinese university of hong kong, hong kong; and state key laboratory of digestive disease, the chinese university of hong kong, hong kong wongv@cuhk.edu.hk vw-sw has served as an advisory board member for gilead and janssen, as a consultant for abbvie, merck, and novomedica, and has received paid lecture fees from abbvie, echosens, gilead, and roche. gl-hw has served as an advisory board member for gilead and has received paid lecture fees from abbvie, bristol-myers squibb, echosens, gilead, janssen, and roche. the spread of the arbovirus to more than countries, zika virus could be following the geographical spread of dengue and chikungunya, all of which are transmitted by the aedes aegypti mosquito. , the potential role of scheduled international mass gatherings in could exacerbate the spread of zika virus beyond the americas. in brazil, the rio carnival on feb - attracts more than visitors, and on aug - more than million visitors are expected to go to the summer olympics followed by paralympic games on sep - . meanwhile, saudi arabia expects to host more than million pilgrims from over countries for the umrah, between june and september, and the hajj pilgrimage on sept - . , saudi arabia receives about pilgrims from latin america annually. since the rio carnival participants are largely domestic, and the spread of zika virus is already extensive, it will be challenging to assess if there was excess transmission related to the carnival. although winter temperatures mean that mosquito density is expected to be low in brazil at the time of the olympics, given the summer time mosquito density in the northern hemisphere, including in saudi arabia, the introduction of a few infections to the mosquito population might be suffi cient to cause outbreaks of zika virus in other countries. , in brazil, cases of dengue are more frequent from february to may. in the regions of saudi arabia frequented by pilgrims (jeddah, mecca, medina), aedes aegypti larvae are present throughout the year, nearly two thirds in indoor habitats. larvae density is, however, variable and decreases in the months before october. in these regions, where rainfall is rare and unpredictable, reports have suggested all year risk for dengue fever, with dengue seroprevalence ranging from % to % among general patients seeking medical consultations. , although the olympics and the hajj are very diff erent events, each of them might favour transmission of zika virus. the olympics attracts mostly young healthy adults from middle and upper-middle income groups who live in developed countries. such visitors are less likely to have been exposed to arbovirus infections and less familiar with mosquito bite prevention than hajj pilgrims. sexual transmission of zika virus from commercial sex workers with asymptomatic infection might also be a possibility for those who attend the olympics. by contrast, the hajj and umrah participants are more likely to be older adults, many of whom have pre-existing health problems, and about two thirds of them originate from low-income countries and the tropics where personal habits of mosquito bite prevention can be suboptimum. also, umrah and hajj pilgrims' immersion in religious rituals could reduce personal uptake of mosquito avoidance measures. for saudi arabian authorities, it is now a standard procedure to convene international public health consul tations each year before the pilgrimage season to develop disease-specifi c recommendations. brazilian authorities in collaboration with the organizing committee for the olympic and paralympic games have already outlined vector control measures in the olympics vicinity. although both countries may have robust vector control eff orts, no single approach is adequate to prevent mosquito bites and non-vector modes of zika virus transmission; a combination of measures is needed at personal, community, and policy levels. with the emergence of chikungunya and dengue, hajj authorities have been proactive in vector control measures. given that pilgrim fl ow to saudi arabia is continuous, these eff orts will help minimise current transmission of zika virus as well. one important issue is the targeted promotion of options for personal mosquito bite protection-eg, the use of insect repellents, protective clothing, including long-sleeved shirts and trousers, insecticide-treated mosquito nets, and air conditioning in residences. despite the uncertainty about sexual transmission of zika virus, , the promotion of safe sex and provision of condoms is benefi cial from a broader health perspective. health-care providers can be encouraged to use travel health visits as an opportunity to emphasise the need for personal protection against mosquito bites and sexual transmission. health advice for individuals can be provided during predeparture health visits that are usually routine for pilgrims travelling to saudi arabia. additionally, by training athletic coaches on prevention of zika virus transmission, their frequent contacts with athletes can be used to remind athletes about the need for compliance with public health advisories. public health agencies in the home countries of travellers to brazil and saudi arabia can partner with travel agencies and transport services, including airlines, to engage in communication about risks of disease transmission. advice on personal protection can be reinforced at points of departure and arrival in home and host countries. increasing the availability and distribution points of methods to prevent mosquito bites is also crucial. similar approaches were part of prevention eff orts for pandemic infl uenza a h n in and middle east respiratory syndrome (mers) in during the hajj. , , methods for prevention of mosquito bites can be provided to each traveller at the arrival port before immigration control. given that brazil is facing a shortage of supply of insect repellents, global eff orts will be needed to procure and distribute them in adequate quantity. in the absence of commercially available rapid test kits and the asymptomatic nature of most zika virus infections, it is premature to consider mandatory entry or exit screening and restrictions. although there are confl icting reports on the value of exit and entry temperature screening, it can help the detection of a few individuals with symptoms and might persuade some people with febrile illness to avoid travel and can help reinforce health advisories. these mass gatherings provide an additional opportunity to undertake research on the transmission and prevention of zika virus. preparedness has been the key to success of recent hajj mass gatherings held amid known risks, such as pandemic infl uenza a h n , mers, and ebola outbreaks. , lessons from saudi arabia's success with hosting hajj during declared pandemics can be helpful to brazil and the olympics organisers. the next months will be a crucial period for both brazilian and saudi authorities to review emerging research fi ndings on the natural history of zika virus through expert consultations. international stakeholders can facilitate the needed advocacy and support. with proactive planning and preparedness, the eff ect of zika virus infection on mass gatherings participants and their home and host countries can be minimised and the events can be held with a sense of confi dence among organisers, participants, and the global community. by doing so, available global and country resources can be used to address the unanticipated course of the zika virus threat. habida elachola, ernesto gozzer, jiatong zhuo, *ziad a memish incidence of non-alcoholic fatty liver disease in hong kong: a population study with paired proton-magnetic resonance spectroscopy the natural history of nonalcoholic fatty liver disease with advanced fi brosis or cirrhosis: an international collaborative study nonalcoholic fatty liver disease: a feature of the metabolic syndrome liraglutide safety and effi cacy in patients with non-alcoholic steatohepatitis (lean): a multicentre, double-blind, randomised, placebo-controlled phase study liraglutide versus glimepiride monotherapy for type diabetes (lead- mono): a randomised, -week, phase iii, double-blind, parallel-treatment trial liraglutide once a day versus exenatide twice a day for type diabetes: a -week randomised, parallel-group, multinational, open-label trial (lead- ) weight loss through lifestyle modifi cation signifi cantly reduces features of nonalcoholic steatohepatitis orlistat for overweight subjects with nonalcoholic steatohepatitis: a randomized, prospective trial vitamin e, or placebo for nonalcoholic steatohepatitis farnesoid x nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (flint): a multicentre, randomised, placebo-controlled trial surrogate end points and long-term outcome in patients with chronic hepatitis b liver fi brosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease fibrosis stage is the strongest predictor for disease-specifi c mortality in nafld after up to years of follow-up disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at years fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies guangxi centers for disease control and prevention eg is director of peru's instituto nacional de salud. jz is deputy director for guangxi centers for disease control and prevention. we declare no competing interests executive board on zika situation interim guidelines for pregnant women during a zika virus outbreak-united states ihr ) emergency committee on zika virus and observed increase in neurological disorders and neonatal malformations mass gathering medicine: hajj and umra preparation as a leading example kingdom of saudi arabia. hajj -health regulations zika virus transmission from french polynesia to brazil household survey of container-breeding mosquitoes and climatic factors infl uencing the prevalence of aedes aegypti (diptera: culicidae) in makkah city, saudi arabia monitoramento dos casos de dengue, febre de chikungunya e febre pelo vírus zika até a semana epidemiológica the epidemiology of dengue fever in saudi arabia: a systematic review potential sexual transmission of zika virus olympics will inspect for water to help prevent zika pandemic h n and the hajj pandemic h n infl uenza at the hajj: understanding the unexpectedly low h n burden international travels and fever screening during epidemics: a literature review on the eff ectiveness and potential use of non-contact infrared thermometers key: cord- -xjbz fw authors: ahmed, qanta a.; memish, ziad a. title: from the “madding crowd” to mass gatherings-religion, sport, culture and public health date: - - journal: travel med infect dis doi: . /j.tmaid. . . sha: doc_id: cord_uid: xjbz fw human behavior has long engaged in collective behavior assembling in crowds. the christian pilgrimage to the holy land has been recorded since the th century, while the hajj, islam's great pilgrimage, has existed for fourteen centuries, of which a body of literature devoted to the travelogues of the hajj has been recorded for over ten centuries. football is a sport played worldwide by more than . million teams and in , clubs. most however play outside of the officially organized sphere: more than percent of the global population plays football, including million amateur players. assembling for specific events is a uniquely human behavior, though the formal study of crowds did not begin until the mid-twentieth century. today mass gathering medicine focuses on the public health challenges to hosting events attended by a large enough number of people, at a specific site, for a defined period of time, likely to strain both the planning and response to the mass gathering of a community, state, or nation. all of us can recall attending a mass gathering, whether it be watching one's favorite rock group in performance or assembling for religious pilgrimage. certainly, the event itself is transporting and transforming and the unison of behaviors and activities can be enormously enriching, uplifting and overwhelming, just as much as they may be at times dangerous and high risk. this review seeks to draw contrasts and comparisons between sporting gatherings and religious gatherings with a chief focus on hajj, among the largest of all mass gatherings today. we will find there are some powerful similarities as well as stark differences. each bequeaths a legacy which can inform the other and, as we make our observations, we join with you and the legions of other investigators who continue to remain fascinated and enthralled by mass gatherings which are among the most beloved and beholden events of modern humanity. human behavior has long engaged in collective behavior assembling in crowds. built years bce, stonehenge in the british isles is thought to be the first monument and evidence of mass gatherings in the pre-historic era [ ] . numerous burial sites have been found at the now designated unesco world heritage site adding to the belief that it was a focus of spiritual energy and ritual. christian pilgrimage to the holy land has been recorded since the th century. the hajj, islam's great pilgrimage, has existed for fourteen centuries of which a body of literature devoted to the travelogues of the hajj has existed for over ten centuries [ ] . in , thomas gray's 'elegy written in a country churchyard' referred to the 'madding crowd's ignoble strife' at once holding forth the sobriety on common ordinary country folk in contrast to the madding crowd which drove men to disgraceful uncontrolled and even violent behavior captured in the timeless phrase [ ] . in charles mckay published his treatise on "extraordinary popular delusions and the madness of crowds" writing that 'men, it has well been said, think in herds; it will be seen that they go mad in herds, while they only recover their senses slowly, and one by one,". in , the great writer thomas hardy wrote a novel which still remains recognized as a masterpiece of english literature, "far from the madding crowd,' focusing on the lives of rural dwellers who were left behind by the madding crowd of industrialization. even today the 'madness of crowds' continues to fascinate and enthrall. assembling for specific events is a uniquely human behavior, though the formal study of crowds would not begin until the mid-twentieth century. the civil rights movements sweeping across the united states in the s and the crowds that cycles of violent lynchings had drawn prior, first captured the attention of behavioral scientists interested in public gatherings. psychologists referred to the 'collective mind' (first observed by thinker gustav le bon) that developed when large numbers of people gathered to be together, and the 'de-individuation' that followed as a result whereby not individuals, but the larger group determines actions accounting for violence destruction and even murder that could result [ ] . two schools of investigation developed, those focusing on disaster reliefthe public health needs of large number of people escaping or evacuating from a threat-and those who studied protest events. while many theories of behavior were proposed, researches remained mostly removed from the gatherings themselves and very little research was performed by direct observation of public gatherings themselves. at the time, modern travel had not yet permitted some of the massive scale of gatherings which have become commonplace since the late twentieth century. today mass gathering medicine focuses on the public health challenges to hosting events attended by a large enough number of people at a specific site for a defined period of time to strain the planning and response of a community, state, or nation. the definition is purposefully not linked to the size of the gathering or the number of people because each community has a varying capacity to manage crowds of people. all of us can recall attending a mass gathering, whether it be watching one's favorite rock group in performance or assembling for religious pilgrimage. certainly, the event itself is transporting and transforming and the unison of behaviors and activities can be enormously enriching uplifting and overwhelming, just as they may be at times dangerous and high risk. this review seeks to draw contrasts and comparisons between sporting gatherings and religious gatherings with a chief focus on hajj, among the largest of all mass gatherings today. we will find there are some powerful similarities as there as stark differences. each bequeaths a legacy which can inform the other and as we make our observations we join with you and the legions of other investigators who continue to remain fascinated and enthralled by the mass gatherings which are among the most beloved and beholden events of modern humanity [ ] . as this article goes to press, one of the most awaited mass gatherings in modern historythe fifa world cup is underway [ ] . the size of football is difficult to comprehend, nothing else compares in scale: football dwarfs the united nations, and even coca-cola, in international reach. across the globe, almost most five million referees, assistant referees and officials are directly involved in football, a sport played worldwide by more than . million teams and in , clubs. most people however play outside of the officially organized sphere. more than percent of the global population plays football, including million amateur players. . monotheisms, long congregating in mass gatherings, are on the rise most people are religiously affiliated. according to the pew research center report examining the global religious landscape published in december , over . billion people-adults and children-are religiously affiliated [ ] . at the time of this survey conducted examining more than sovereign nations and territories, this amounted to % of the world population. while religions diversity is panoramic, three theisms predominate: christianity, islam and hinduism. the pew study examined censuses surveys and other registers of population finding . billion christians ( % of the world's population), . billion muslims ( % of global population) and . billion hindus ( % of global population). a half billion identify as buddhist and million as jews-followers of judaism [ ] . some billion follow folk or traditional religions (including african traditional religions or chinese folk religions or native american religions). and, while well known, a tiny proportion-less than % of the earth's population-follow other religions including the yazidism, the bahai faith, sikhism, zoroastrianism and others. worth noting is that the religiously unaffiliated are themselves a group of over billion- % of the global population as populous as some leading theisms. the unaffiliated include atheists, agnostics and those declining to identify with any religion on surveys [ ] . yet the fastest growing population in the world is the muslim population-it is expected to increase by % in the next twenty years [ ] . by the global muslim population is expected to reach . billionrising more than twice the rate of the non-muslim population at a . % growth rate compared to . % annual growth rate for non-muslim populations. while slower than the . % annual growth rate of muslims in the past thirty years, by these calculations, muslims will account for . % of the . billion global population estimated by . while the muslim world is long familiar with hosting one of the world's largest mass gatherings-the hajj, islam's pinnacle of worship which centers on mecca in saudi arabia, and to where millions of muslims travel from within the muslim world to the saudi kingdom -a sporting event of the scale of the world cup, itself one of the world's larger mass gatherings is an unprecedented mass gathering event. among religious gatherings, it is also the best studied informing the public health risks of mass gatherings across the world. in some ways football, the beautiful game reaches the dimensions of a religion given its vast appeal and global reach and devoted followers. but it is useful to consider the world cup as a sporting event on a par with the summer olympics and the more recently developed para-olympics while the hajj as a mass gathering centering on islamic belief is better understood within the context of other mass gatherings centered on other theist belief systems including the hindu kumbh mehla, world youth day and other pilgrimages [ ] [ ] [ ] . christian mass gatherings include the world youth day, held every two or three years by the catholic church when almost a quarter of a million young catholics attend a mass gathering centered in varying cities for a live event anchored by the pope, first initiated by the late pope john paul ii in [ ] . world youth day will be next held in more well-known and rooted in centuries of observance may be the christian pilgrimage to lourdes in france, a year-round event drawing more than million in worship. lourdes, a small town in the southern pyrenees, itself has a population only of , yet because of the pilgrimage which has existed since , it is now the second most visited city in france, second only to paris. in the catholic world, it is the third most important site of pilgrimage after the holy land and rome [ ] . in asia, on one day, almost million catholics gather in christian procession for the feast of the black nazarene. the black nazarene is life-sized wooden statue of jesus christ crowned with thorns believed to have been brought from mexico to manila on a galleon in by spanish missionaries. the galleon that carried it to the philippines caught fire, but the charred statue survived and was named the black nazarene. devotees gather for the -h procession around the holy icon which followers believe delivers miracles. the world's largest mass gathering however occurs in india. the kumbh mela is held periodically over twelve-year cycles, rotating in four different indian cities-allahabad, nasik, ujjain and hardwar. over million hindus gather in each location at the banks of major rivers, including the ganges and the yumna in which pilgrims bathe as an act of worship on up to six important bathing days [ , [ ] [ ] [ ] . worshippers assemble at each location over a three-month period during which time the festival is held, alternating at the different locations four times in every twelve-year cycle. festivals go on for days in total. the bbc has reported that on a single day up to million worshipers have gathered simultaneously [ ] . these mass gatherings dwarf hajj, islam's pinnacle of worship centered on mecca, though both share the risk of human stampede [ ] . islam's hajj however is the best studied of all mass gatherings and has driven much of the scientific enquiry into the modern mass gathering. as many as three and a half million muslims from countries around the world gather for what is considered the final pillar in islam returning them to islam's birthplace in order to perform hajj. hajj is a series of week-long religious rites retracing the prophet mohammed's final visit to mecca during which he drew the lines of islamic pilgrimage which still stand today and delivered his final sermon revealing the final verses of the quran and sealing the foundations of islamic belief. even today, true to the prophet mohammed's final hajj, the modern hajj incorporates the prophet abraham's footsteps centuries before islam's inception and the legends of hagar, ishmael, adam and eve. with the rise in muslim population the hajj can be expected to grow in attendance and saudi arabia is preparing for these increased capacities investing in massive construction and infrastructure developments accordingly saudi arabia has committed $ billion in both land and infrastructure expansion with much of this work ongoing [ ] . the king abdul aziz international airport and the expansion of the haram sharif-the grand mosque surrounding the ka'aba-is to be completed / . 'haramain' a high speed above ground railway linking mina to medina, the second holiest city in islam (often included in hajj rites) will be completed this year but opened to the public after extensive testing in . the mecca-metro project connecting a four kilometer long station and two metro stations to the tune of $ . billion will be completed by the decade's end, greatly relieving congestion at the focal site of hajj. possibly the most beloved sporting events of all time are the olympics inspired by the athletic games held in ancient greece as far back as the th century bce. the modern olympics were conceived in with the formation of the international olympic committee which has governed every olympics since the games were first revived in [ ] . olympic games draw mass gatherings. the london olympics in drew million in attendance paying high prices for tickets. the more controversial and beleaguered rio olympics for sold only % of the million tickets available even though the tickets were significantly cheaper [ ] . regardless, the olympics, whether summer or winter and its counterpart, the special olympics, draw millions in attendance to watch the pinnacle of elite amateur sports. nation states win an intensely competitive bidding process to secure the event, which (like the fifa world cup) can define a nation and celebrate its culture. hosting the olympics is considered a rare privilege and nations, once winning the bid, work intensely during the seven-year lead time to the event to prepare both an appropriate legacy and also the necessary infrastructure for the events: olympic villages for the athletes, and the necessary response systems needed for health, security and disaster response. these are enormously costly events. perhaps it is the modern olympic games which have most inspired the foundations of studying medicine during sporting events physicians as david s jones noted physicians 'only slowly became interested' 'mostly in marathons' when the winner of the st. louis olympic marathon required four physicians in attendance after the race, due both to heat exposure and the pre-competition strychnine he had taken for performance enhancement [ ] . by , medical examinations for athletes had become mandated and in . the united states sent its first physician with its olympic team to paris. slowly medicine began to interface with sports, igniting the field of sports medicine for the elite athlete. almost a hundred years later, today all attendees-spectators and athletes alike-are known to be exposed to risks which could endanger health during these spectacular events and the science of mass gathering medicine has come into view informed by the experience of managing the public health at these huge events. equally prestigious and just as hotly contested is the fifa world cup held every four years. this year's fifa world cup in is being held in russia, and the subsequent has been awarded to qatar, in . interrupted only by world war two, the world cup has continued since its founding in held in uruguay, which, even then, drew more than half a million attendees. the brazil world cup in drew . million attendees. in all more than million people around the world have attended a world cup event yet today in the televised era it commands audiences of billions [ ] . the revenue generated by the fifa world cup is extraordinary -$ . billion during brazil -because of the cumulative television audiences watching all the matches and lucrative sponsorship dealsmore than . billion watched the world cup [ ] . audiences can only be expected to be bigger in the era of live-streaming, enabling anyone with an internet connection to tune in, sometimes to watch games more than once. because of its scale, the fifa world cup is the most viewed sporting event today. given its unique experience and unparalleled popularity, fifa has contributed important understandings to the management of mass gatherings in both public health and public security aspects. legacy building has been very critical to fifa and is a deal-breaking aspect of each competitive bid, and often a focus of criticism after events. the crowds at mass gatherings are a captive audience and vulnerable to environmental, physical, infectious and non-infectious hazards. they are also increasingly prime targets for terrorism including bioterrorism. whether a sporting or religious gathering these risks are shared though their nature may vary [ ] [ ] [ ] . both religious and sporting events can be at risk of stampedes which can evolve whenever crowds gather. while human stampede is lethal and devastating (forces of up to n/m can be generated by several people pushing in panic) with death resulting from acute venous hypertension, traumatic asphyxia, crush injuries to the torso and other catastrophic trauma, investigators in the field of human stampede note even in this modern era that there is a serious lack of high-level epidemiological data examining human stampedes. as a result, both experts and casual observers are mistakenly influenced by unbalanced media focus which trains its scrutiny on hajj each year and may be mislead in believing it is the only mass gathering at risk of stampede, and the single most frequent site of human stampedes. neither of these assumptions are true. hsu et al. searched both research and unconventional sources including media reports for evidence of human stampede incidents [ ] . [ ] . certainly, of the top ten most lethal human stampedes, seven occurred at religious gatherings, not exclusively the hajj but also other religious events. in india, % of all human stampedes occurred at religious festivals according to a recent exhaustive review [ , ] . non-religious mass gatherings were also the site of human stampedes including political gatherings, sports events, entertainment venues and spontaneous gatherings. in phnom penh in a shopping stampede on black friday (usually implying major sales) resulted in deaths [ ] . but most human stampedes occurred not in the arabian peninsula -home of the hajj-but in developing nations in africa and southern asia. together south asia and africa suffer over half of the world's human stampede. yet each year, media coverage focuses intensely on saudi arabian hajj sites (mecca, medina, muzdalifah and arafat) devoid of this context. when stampedes occur in the developing world, mortality is more than eight-fold greater than when the stampede occurs in advanced societies like saudi arabia. this increased fatality is a result of lack of planning, inexperience with crowd management and crowd control, scant emergency services, limited trauma care and infield emergency services and limited onsite and first responder communication capabilities. saudi arabia each year goes to intense effort to prevent stampede, one of many physical hazards associated with hajj and as a result stampedes have been few and rare. despite a spiritual reluctance to bar any eligible muslim from hajj, saudi arabia does limit hajj attendees through global visa quotas. also, once a local muslim in ksa has been to hajj, hajj visas cannot be issued for the next five years limiting frequent performers of hajj. yet the major improvements in hajj crowd management have been through engineering: the multilevel bridge at jamarat, site of the stoning ritual which has been a previous site of stampedes at hajj; the re-engineering of the pillars at mina into elliptical columns in place of cylindrical columns to dissipate crowd densities and reduce crowd turbulence from developing, and the development of massive pedestrian causeways which are color coded, one way, and temporally controlled to ensure steady throughput of pilgrims by controlling pilgrim ingress into these causeways through optimized schedules. movement of the hajj crowds in these areas of high density and high emotion -both risk factors for stampede-is monitored in realtime through video graphic analysis. intervention can be implemented real-time, which can be both life-and limb-saving. detailed video recordings achieved at hajj examining crowd dynamics are primarily the means of assessing the flow of hajj crowds. in the future, more sophisticated assessment is likely to be achieved in a number of additional ways-through fixed-laser scanning devices, closed circuit television and fixed gps monitors [ , ] . while a much smaller scale, human stampede at a british football match has been more exhaustively examined than any other stampede in history. the hillsborough stadium stampede was among the most disastrous events in football and examining its causes has been instructive if extremely painful for the football community and britain in particular [ , ] . the fa cup semi-final was held in the hillsborough stadium in sheffield on april th, drawing two intense rivals-liverpool and nottingham forest -for a contest place in the final for the fa cupthe biggest sporting event in british football [ ]. , liverpool fans traveled to sheffield for the event. authorities knew of the rivalries between both teams and because of the propensity for vandalism and hooliganism among fans on both teams, their entry to the stadium was deliberately segregated, as were the 'pens' designated for fans of each team. because of the bottleneck at the entrance and the large numbers of attendees, fans initially poured into two central 'standing only' pens-sections of the stadium demarcated by wire barriers, unaware that to either side of them thousands of empty seats were available. no one directed the congregating crowds to these more lateral areas on the right and left. as the time for kick-off was only minutes away, the chief superintendent (the police commander in charge of the event) allowed an additional gate to open as lines of liverpool supporters outside the stadium had built up. unaware that in the central standing pens crowd density was already high, the surge of additional people resulted in deaths-men women and children and more than injuries. all except one were liverpool fans. hillsborough remains the worst disaster in british sporting history. in , british jurors, delebrating for days (the longest inquest in british history)-emerged to convict the chief superintendent "responsible for manslaughter by gross negligence" due to a breach of his duty of care. the tragedy was compounded by the fact that the hillsborough match had been the first mass gathering under his command. this spiritual commitment which is of the utmost priority for them to complete hajj to the best of their abilities adding to a religious intensity and focused commitment despite harsh and difficult physical conditions imposed on the pilgrim whether by climate or congestion often in the face of sleep deprivation and other forms of self-denial required in the spiritual state of the hajjee. pilgrims are therefore vulnerable not only to their surroundings but to a fear of not completing hajj. stampedes are known to be triggered by fear, panic and as many investigators have noted, even by rumor. live surveillance of hajj crowds is vital to help pilgrims achieve their rites safely. hajj authorities can assess mounting crowd densities, blockage of foot traffic, bottlenecks and dangerous nascent crowd turbulence which can precipitate human stampede. supervision of the crowds at hajj is unlike any other mass gathering in the world [ , ] . interagency communication between various authorities overseeing the hajj (security forces, civil defense and special forces experienced in crowd control) and is continuous and announcements through public communication can be made if needed. sms capable networks (instant messaging via cellphones) are also available and have been used for urgent health messaging to communicate to the vast numbers of attendees simultaneously. because the hajj is so trying and muslims, enjoined by the maker, remain so committed to completing it peacefully and without infringement or desecration of anyone else's efforts in pilgrimmage, the hajj crowd works informally together, shifting to accommodate the weak, the vulnerable, the disabled who are in the teeming crowds next to them. in this way hajj, like other religious mass gatherings, is infused with a collective spirituality that can be of enormous public health benefit. further, this spirit of protecting the entire muslim community is clearly deleinated in the teachings of islam to be a metaphor for life beyond hajj for all the world's muslim community-a reminder that we must live together in harmony to peacefully collaborate and support one another through hardship and vulnerability. additionally, these values greatly enhance the pilgrim populations' receptivity to public health planners and on site security in ensuring disaster management and crisis aversion can be achieved with as much cooperation as possible. unlike religious gatherings, mass gatherings connected to sport or music events can be complicated by the availability of alcohol, recreational and illicit drugs, all of which impede the ablity of an individual to remain safe within the mass gathering and impede the ability of the crowds to behave protectively towards the vulnerable [ ] . these events are usually open air, often held in undesignated locations (particularly when considering electronic dance raves and may not benefit from experienced professional organizers). sometimes events are held in underground locations which were never designed to accommodate such capacities. participants are generally younger in age than those attending religious gatherings or the diverse ages seen in attendance of sports gatherings. music festivals, particularly the electronic dance movement event, are increasingly associated with intoxication and injuries [ ] . targeting young people aged to they draw large crowds, sometimes in unregulated venues, but increasingly today in purpose-built locations. alchohol overuse and recreational drug use are commonly associated with these events. both mdma ( , methylenedioxy-n-methylamphetamine) and the notoriously named date rape drug (gamma hydroxybutyric acid) are liberally used at these events. lund et al. report that in a fifteen year period deaths were recorded of drug related overdose at electronic music dance events. violence at such events has also been recorded with participants reporting stabbingssome severe enough to result in tube thoracostomy. matters are worsened by the fact that many participants self report ' preloading'drinking alcohol prior to entry to the event, a common practice at american events which can occur during 'tailgating'when americans often picnic around the trunk of their cars in the parking lots of the venues. while for most american families this means an innocent meal of hamburgers and hot dogs, for youngsters attending rave events this could mean 'preloading' particularly if attendees to the raves are under legal drinking age, adding to their vulnerability. excessive alcohol consumption with or without recreational drug use increases the risk of injury, sexually transmitted disease and extreme behaviors like the recently fire jumping and more traditional risks of sexual assasult. while the focus of this paper has been primarily planned mass gatherings, mass gatherings can erupt spontaneously. one such phenomenon is the celebratory riot which can develop for instance when a sporting team wins a match or tournament. hawkins et al. describe the spontaneous mass gathering of , fans which assembled when the university of north carolina men's basketball team played in the national collegiate athletic association, final four semifinal and national championship games in st. louis, missouri in the united states [ ] . as a result of the matches, back in the team's home state of north carolina, two mass gatherings assembled on two consecutive nights drawing a total of , fans. celebrating their team, they lit bonfires in the downtown area of chapel hill where they were congregating and began fire jumpingjumping and dancing through the flames by way of a victory dance. a total of revelers needed medical care including from the on-the-ground ems responders and a total of who needed emergency room admission. the average age of the injured was . years and they were predominantly male. most - %had medical complaints relating to alcohol and didn't need hospital admission. of those who were admitted to hospital, one third had burns from firejumping. these injuries are a function of the sponetnaeity and unplanned nature of these mass gatherings which unlike planned mass gatherings lack well defined boundaries. revelers have no idea of how ems will reach them should the need arise, nor of the disruption to access, and public health demands by their incohrenent mass activities. further, such spontaneous gatherings are componded by the use of excessive alcohol and illicit drugs. the crowds unlike a catholic crowd at world youth day or a muslim crowd at hajj is widely diverse in their compositionwhile some revelers maybe hardcore hooligans or hoodlums others have never attended a mass gathering. the propensity for deliberate violence and even sexual assault can be created especially when vulnerable inexperrinced attendees find themselves caught in the melee. even the mood of the crowd-the collective mind-as earlier researchers referred to it-can vary from benign to malignant, from celebratory to activitely destructive. sexual assault can manifest in such circumstances. perhaps one of the most extraordinary sponetaneous mass gatherings of the last decade is now dubbed "tahrir square" first at the time of the arab spring reaching egypt in feburary and later, in response to newly elected mohammed morsi being deposed by a military coup in july . while no academic papers exist in the literature at the time of writing concerning sexual assault at tahrir square, the mainstream media reported extensively on sexual assaults impacting women protestors at tahrir sqaure, shocking many in the region, particularly in the muslim majority world. sampsel et al. published the first reports of mass gathering associated sexual assault [ ] . important data reported by sampsel et al. reveals that sexual assault occurs at mass gatherings peaking on specific holiday events-new years eve, canada day, halloween and university freshmans' week. women were more often assaulted if they were of younger age, had consumed alcohol or drugs and unlike most sexual violence which befalls women aged to , the assailant at mass gatherings was not previously known to the victim. more often than not, victims declined to release the findings of their 'rape kit' as evidence to the police in the hope of seeking prosecution. the sexual assaults at these mass gatherings occurred both within a friend's home and also outdoors, as in tahrir square. unlike sexual assaults occurring independent of mass gatherings, the majority of women did not know their assailants suggesting perpetrators may seek out mass gatherings as cover for predicating sexual assault on vulnerable victims. sampsel noted the increase in sexual assault events in conjunction with mass gatherings which fell on canadian holidays and surmised that in this occassions the consumption of excess alcohol was more likely. sexual assault transpires much more often when the victim has consumed excess alcohol often spiked with covert drugs in an effort to render the victim unconscious and unable to resist assault. these patterns support the view that the nature of the revelry, and the young female revelers assembling in this gatherings are additionally vulnerable because of social behaviors at such mass gatherings leading to drug faciliated sexual assault. sixteen years post / , it is impossible to consider mass gatherings independent of terrorism irrespective of their location. because of both the magnitude of citizens gathering at mass gathering events whether for celebratory or spiritual purposes, the prize of disrupting a civilian event often garnering extraordinary mass media attention proves very tempting for nefarious actors [ ] . terrorists seek two goals: one to physically disrupt, kill and maim as many innocents simultaneously, and do so with maximum digitally transmitted reverberations to enhance the impact of their attacks. but they also act to instill fear and immobilization in the target population both at the event targeted, but more importantly in the desire to return to normal life. mass gatherings present perfect targets for both these goals. vulnerable events include political, sporting, entertainment events-political party conventions, sporting tournaments like the superbowl, the olympics or the fifa world cup. us experts in homeland security remark that when events tie mass gatherings of the american public with specific national events of celebration -independence day celebrations for example, or events honoring the military or the nation's patriotism threats are not only perceived to be tangible but escalating in risk. hazards that must be considered are diverse. biological agents, ever since the anthrax attacks immediately after / targeting government officials, remain a major concern. many events-consider a presidential inaugrationare open air. access is very difficult to limit and the dissemination of a biological agent over such massive crowds (exceeding a million people at president obama's first inauguration) pose terrifying consequences, particularly if military grade biological weapons were released. one agent could kill hundreds or hundreds of thousands of people depending on its virulence and the dose released. it is not inconceivable that sophisticated terrorists release a biological pathogen in a mass gathering of a population with no immunity to this agent. in , homeland security notes that participants in an outdoor concert contracted hepatitis a, causing morbidity among a population never vaccinated for this virus [ , ] . american cities hosting mass gathering events take this public health security threat very seriously. as far back as , when miami hosted the superbowl xli bio-surveillance activities were expanded by three county health departments and the florida state department of health. they were prepared to identify a bioterrorism attack which might have been invisible during the mass event but become apparent within a two-week window of the superbowl xli. because of the enhanced bio surveillance, public health officials identified more illnesses, injuries, accidents and absenteeism than usual. most importantly, three different public health departments were able to successful data share and coordinate their responses to real-time findings. the federal bureau of investigation (fbi) is charged with identifying and generating intelligence about potential and actual terrorist attacks throughout the united states including attacks that can endanger mass gathering events. critical to the success of advance warning for these events is a clear line of communication and excellent education of the fbi concerning mass gatherings. a key recommendation the us committee on homeland security made was for the development of a national medical intelligence program which would enable combined knowledge of public health concerning bioterrorism to be located within a knowledge base of domestic intelligence concerning potential actors. critical to all these events is the collaborative approach. sharing resources across sectors and agencies whether public or private entities is critical to mass gatherings being safe-guarded. without such collaboration, agencies may compete with one another and hoard information, jeopardizing not only the mass gathering event but also the host city which may well swell in population to become transiently some of the largest cities in the country for the duration of the mass gathering event. global health security is a relatively novel concept: galvanizing public health responses to threats which could imperil the global community. most recently three pathogens have captured the imagination driving the movement to formalize a global health security agenda-literally a world prioritization of threats to public health security [ ] . the ebola virus epidemic, the influenza pandemic and the mers-corona virus outbreaks in the arabian peninsula and south east asia all demonstrated the need for urgent coordinated international responses to avert devastating international impact. periodically health ministers from around the world meet to set the global health security agenda and streamline a multidisciplinary and coherent response to contain these threats. while a global health security agenda for mass gatherings has not been proposed, saudi arabia, in its experience of managing the hajj recognized at the inaugural meeting on mass gathering medicine in jeddah formalized the discipline of mass gathering medicine. six years on, it is time the mass gathering community call for proposals to set a global health security agenda for planned mass gatherings around the world. certainly, yellow fever while not yet a global threat, is a serious consideration for all mass gatherings receiving international visitors. certainly, each country hosting a mass gathering, whether religious or sporting, must enact surveillance and disease reporting mechanisms during the mass gathering events themselves to be able to identify case clusters or even infectious disease outbreaks. control measures and means to prevent these infections being exported back by the attendees to the attendees' countries of origin must be in place. countries receiving participants in events whether a religious pilgrimage or a mass sporting event must be ready with a public health surge capacity to respond to returning travelers especially at a time of heightened awareness of outbreak potential. surge capacity is especially important if host country's health systems are not to be depleted or placed under undue strain during mass gathering events. both authors declare no conflict of interest. one thousand roads to mecca: ten centuries of travelers writing about the muslim pilgrimage paperback the myth of the madding crowd (social institutions and social change) by clark mcphail (author) the psychology of health and wellbeing in mass gatherings: a review and a research agenda qatar steps up to global health security: a reflection on the joint external evaluation religious mass gatherings: connecting people and infectious agents a comprehensive review of the kumbh mela: identifying risks for spread of infectious diseases an influenza outbreak among pilgrims sleeping at a school without purpose built overnight accommodation facilities the practice of pilgrimage in palliative care: a case study of lourdes world's largest mass bathing event influences the bacterial communities of godavari, a holy river of india using mobile technology to optimize disease surveillance and healthcare delivery at mass gatherings: a case study from india's kumbh mela safeguarding the faithful -saudi arabia takes the long view olympic medicine twenty years of the fifa medical assessment and research centre: from 'medicine for football' to 'football for health the quest for public health security at hajj: q.a. ahmed the who guidelines on communicable disease alert and response during mass gatherings advancing the global health security agenda in light of the annual hajj pilgrimage and other mass gatherings cambodian bon om touk stampede highlights preventable tragedy the impact of crowd control measures on the occurrence of stampedes during mass gatherings: the hajj experience human stampedes during religious festivals: a comparative review of mass gathering emergencies in india crowd and environmental management during mass gatherings the hillsborough tragedy mass-gathering medicine: risks and patient presentations at a -day electronic dance music event fire jumpers: description of burns and traumatic injuries from a spontaneous mass gathering and celebratory riot characteristics associated with sexual assaults at mass gatherings committee on homeland security. majority staff report examining; public health, safety, and security for mass gatherings key: cord- -uzzs w j authors: ma, xuezheng; liu, fang; liu, lijuan; zhang, liping; lu, mingzhu; abudukadeer, abuduzhayier; wang, lingbing; tian, feng; zhen, wei; yang, pengfei; hu, kongxin title: no mers-cov but positive influenza viruses in returning hajj pilgrims, china, – date: - - journal: bmc infect dis doi: . /s - - - sha: doc_id: cord_uid: uzzs w j background: there is global health concern that the mass movement of pilgrims to and from mecca annually could contribute to the international spread of middle east respiratory syndrome coronavirus (mers-cov). in china, about , muslim pilgrims participate in the hajj gathering in mecca annually. this is the first report of mers-cov and respiratory virus molecular screening of returning pilgrims at points of entry in china from to . methods and results: a total of returning hajj pilgrims participated in this study. the test results indicated that of the travelers, tested positive for influenza a virus, for influenza b virus, for metapneumo virus, for respiratory syncytial virus, and for human coronavirus. there was a significant difference in the rates of positive and negative influenza virus tests between hajj pilgrims with symptoms and those without. the detection rates of influenza virus were not significantly different among the three years studied, at . , . and . % for , and , respectively. discussion and conclusion: the mers-cov and respiratory viruses detection results at points of entry in china from to indicated that there were no mers-cov infection but a . % positive influenza viruses in returning chinese pilgrims. as of november , there had been laboratoryconfirmed cases of middle east respiratory syndrome coronavirus (mers-cov) infection reported to the world health organization, and at least cases had died [ , ] . most cases of mers-cov infection were reported from the kingdom of saudi arabia. annually, more than million muslim pilgrims from countries attend the hajj pilgrimage in mecca, saudi arabia [ ] . this mass gathering of pilgrims presents a global health risk due to the potential spread of infectious diseases, and respiratory infections are the most common infections transmitted between hajj pilgrims [ , ] . the viruses most commonly isolated from symptomatic patients during the hajj pilgrimage were influenza virus and coronaviruses [ ] [ ] [ ] [ ] . there is global concern that travelers returning from pilgrimage could contribute to the international spread of mers-cov. the international health regulations (ihr) emergency committee suggested that all countries perform surveillance for mers-cov among pilgrims during and after hajj [ ] . in china, about , muslim pilgrims participate in the hajj gathering in mecca annually [ ] . this is the first report of the molecular screening for mers-cov and respiratory viruses among returning pilgrims at points of entry in china, carried out from to . the participants in this study were adult hajj pilgrims who traveled in groups to mecca, saudi arabia, and stayed there for - days from september to october, - . in china, the government arranged charter flights for hajj pilgrims to visit mecca. infectious disease monitoring and surveillance of foreigners travelers coming from other countries is the responsibility of aqsiq (general administration quality supervision inspection and quarantine of the people's republic of china). aqsiq supervises entry-exit ports in china, and operates on behalf of the national government. for all chinese hajj pilgrims, personal and flight information was recorded and a medical examination was conducted, including vaccination by a local aqsiq office, before the trip to mecca. xinjiang and gansu province have the highest number of hajj pilgrims visiting mecca each year. in this study, our institute, the chinese academy of inspection and quarantine, cooperated with the xinjiang and gansu entry-exit inspection and quarantine bureau. we randomly selected returning pilgrims arriving at xinjiang and gansu airports, and asked for their consent to participate in this study. in china, every entry-exit airport has an infrared radiation thermometer, installed by aqsiq, to screen travelers' body temperatures. among returning pilgrims, returning pilgrims triggered the alarm on passing through the infrared radiation thermometer installed at the airport to monitor travelers' body temperature. sixteen of these travelers were confirmed by using a clinical thermometer to have the onset of fever (> . °c), and also reported a sore throat or cough on the returning flight. the remaining returning pilgrims did not have a fever or other symptoms. the numbers of travelers with fever in each year were ( ), ( ), and ( ). the mean age of all participants was . years old (sd = . ). in this study, were females and were males, and they were all moslem. all pilgrims were asked to undergo a health examination and were vaccinated against influenza a and b in a local travel health center a week prior to departure. all participants included in this study were voluntary and signed consent forms. for the detection of viral infection, samples included lower respiratory tract sputum, washes, and upper respiratory tract oropharyngeal swab specimens. lower respiratory tract sputum samples were used to test for respiratory viruses during this -year period. all pilgrims were tested for influenza and mers, but only those with fever were tested for the other viruses. all specimens were collected immediately when returning pilgrims arrived at each point of entry, and nucleic acid was isolated and immediately screened by real time rt-pcr for the upe and orf a genes of mers-cov provided by the world health organization [ , ] . all real time pcr protocols for influenza a and b followed those used by a previous study [ ] . samples from travelers displaying a fever were also tested by real time rt-pcr for human metapneumo virus (hmpv), human respiratory syncytial virus (hrsv), and human coronaviruses hku , e, and oc [ ] . according to the infection control and health quarantine rules at airports, the time taken between specimen collection and the reporting of results was within h. all real time rt-pcr results for mers-cov were negative. a total of influenza a and influenza b virus positive samples were detected from to (table ) . of these, the test results from participants with a fever indicated that samples were positive for influenza a, were hmpv positive, were hrsv positive, and participant was positive for each of hku , e, and oc . in addition, influenza a and influenza b positive samples were detected from nonsymptomatic travelers. no dual infections were detected. two hypotheses were tested: ( ) there is a significant difference in the positive and negative rates of influenza virus detection between hajj pilgrims with symptoms and those without. pearson's chi-square analysis indicated that there was a significant difference in the influenza virus detection rates between travelers with fever and those without symptoms (χ = . , p = . ). it is of interest, although of unclear significance, that none of the influenza b positive subjects were symptomatic. ( ) there is a significant difference in the rates of influenza (a and b) virus detection among the years , , and . the rates of influenza virus detection for the years , , and were . , . , and . %, respectively, and statistical analysis revealed that there was no significant difference in the rates of influenza virus detection among these three years (χ = . , p = . ). all participants with fever were followed up, and none of these individuals were admitted to hospital after days. in this study, we did not detect any cases of mers-cov infection but respiratory virus infections including influenza a and b, hmpv, hrsv, and human coronavirus were detected among hajj pilgrims returning to china. this result was consistent with the outcomes of similar studies of respiratory virus detection in hajj pilgrims in france, north india, egypt, ghana, saudi arabia, and the uk [ ] [ ] [ ] [ ] [ ] [ ] . regarding the detection of influenza viruses, these studies reported detection rates of . % in france (no vaccination) [ ] , % in north india ( % vaccination rate) [ ] , % in egypt ( % vaccination rate) [ ] , . % in ghana (vaccination rate unknown) [ ] , and % in the uk ( % vaccination rate) [ ] . in our study, all participants had been vaccinated against influenza virus, but . % tested positive for influenza virus infection. we are unable to measure the direct impact of influenza vaccination on the resistance of hajj pilgrims to influenza infection and further studies are required to understand the efficacy of the influenza vaccine among this population. however, increasing the rate of vaccination will help protect individuals, particularly those travelers that are most vulnerable to infection such as older adults and those that may be immunocompromised. a combination of vaccination and rapid antiviral treatment of symptomatic individuals currently offer the best strategy for the prevention and treatment of infections among hajj pilgrims. in this study, mers-cov was not detected in any of the upper respiratory swabs or sputum specimens tested. however, limiting the time taken for sample collection, the type of samples collected and the selection of participants can all affect the rates of positive detection. in previous studies, most samples were nasal swabs collected from strongly suspected symptomatic participants after they were under investigation in hospital [ ] [ ] [ ] [ ] [ ] . however, in our study, swabs were collected from both suspected and asymptomatic returning pilgrims immediately after their arrival at airports. our sampling design would therefore include some healthy pilgrims, thereby decreasing the rate of detection of respiratory virus infections. in addition, upper respiratory samples (nasopharyngeal swabs and sputum) have been demonstrated to have a lower mers-cov genome load than lower respiratory specimens such as tracheal aspirates and bronchoalveolar lavage specimens [ ] . this may also have limited the detection of mers-cov in our study. the findings from our study demonstrate the risk of influenza infection among travelers during mass gatherings, and confirming the need for effective surveillance of imported infectious diseases at entry points into china. the hajj pilgrimage provides a unique opportunity to test the effectiveness of different infectious disease preventive and detective measures that require a large sample size. continued annual monitoring of mers-cov, influenza viruses, and other respiratory viruses (such as human rhinovirus), is needed to increase our understanding of the epidemic patterns of respiratory virus infections among hajj pilgrims in china. world health organization. global alert and response (gar) middle east respiratory syndrome middle east respiratory syndrome hajj-associated viral respiratory infections: a systematic review high prevalence of common respiratory viruses and no evidence of middle east respiratory syndrome coronavirus in hajj pilgrims returning to ghana prevention of influenza at hajj: applications for mass gatherings the impact of co-infection of influenza a virus on the severity of middle east respiratory syndrome coronavirus world health organization statement on the tenth meeting of the ihr emergency committee concerning mers-cov characteristics of traveler with middle east respiratory syndrome assays for laboratory confirmation of noval human coronavirus (hcov-emc) infection detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction epidemiology of respiratory rna viruses in a cohort of hospitalized children in riyadh, saudi arabia cross-sectional survey and surveillance for influenza viruses and mers-cov among egyptian pilgrims returning from hajj during - . influenza other respir viruses influenza not mers cov among returning hajj and umrah pilgrims with respiratory illness lack of nasal carriage of novel corona virus (hcov-emc) in french hajj pilgrims returning from the hajj , despite a high rate of respiratory symptoms lack of mers coronavirus but prevalence of influenza virus in french pilgrims after viral respiratory infections at the hajj: comparison between uk and saudi pilgrims respiratory tract samples, viral load, and genome fraction yield in patients with middle east respiratory syndrome we wish to thank dr. dexin li for his extensive support and assistance with the study. all data generated or analyzed during this study are included in this published article.authors' contributions xm and fl carried out sample collection and drafted the manuscript. ll, lz, and lm extracted rna and collected clinical samples. aa, lw, wz, and py recorded the experimental data and collated the results tables. kh designed the study, edited the manuscript, and supervised the experiments. all authors read and approved the final manuscript. the study was conducted according to the protocol approved by the human research ethics committee, chinese academy of inspection and quarantine, in compliance with the provisions for human research in the helsinki declaration (es- / / hq). written informed consent was obtained from all participants. not applicable. the authors declare that they have no competing interests. springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. submit your next manuscript to biomed central and we will help you at every step: key: cord- -jkjdglns authors: alotaibi, badriah; bieh, kingsley; yassin, yara; mushi, abdulaziz; maashi, fuad; awam, amnah; mohamed, gamal; hassan, amir; yezli, saber title: management of hospitalized drug sensitive pulmonary tuberculosis patients during the hajj mass gathering: a cross sectional study date: - - journal: travel med infect dis doi: . /j.tmaid. . . sha: doc_id: cord_uid: jkjdglns background: to document the management of drug-sensitive tb patients during the hajj and assess compliance with the saudi tb management guidelines. method: the study was conducted in hospitals in makkah during the and hajj seasons. structured questionnaire was used to collect data on relevant indices on tb management and a scoring system was developed to assess compliance with guidelines. results: data was collected from tb cases, . % ( / ) were saudi residents. sputum culture was the only diagnostic test applied in . % ( / ) of patients. most ( . %, / ) confirmed tb cases were isolated, but only . % ( / ) were tested for hiv and merely % ( / ) received the recommended four st-line anti-tb drugs. guideline compliance scores were highest for infection prevention and control and surveillance ( . / ) and identifying tb suspects ( . / ). the least scores were obtained for treating tb ( . / ) and diagnosing tb ( . / ). conclusions: healthcare providers training and supervision are paramount to improve their knowledge and skill and ensure their compliance with existing tb management guidelines. however, there may be a need for the introduction of an international policy/guideline for tb control and management during mass gatherings such as the hajj to guide providers’ choices and facilitate monitoring. tuberculosis (tb) remains a global public health problem with significant morbidity and mortality. in , the world health organisation (who) estimated that million people developed active tb causing up to . million deaths [ ] . the who's end-tb strategy aims to reduce the overall number of tb deaths by % and the tb incidence rate by % in compared with the baseline incidence and mortality figures [ ] . key to achieving these targets is the early diagnosis and appropriate management of tb cases worldwide according to national and international guidelines [ ] [ ] [ ] [ ] . this includes in the context of mass gatherings such as the annual hajj in makkah, kingdom of saudi arabia (ksa), where over million pilgrims, many originating from tb endemic areas, congregate in crowded settings and worship under conditions that increase the risk of tb transmission [ , ] . in the context of the hajj, respiratory tract infection including those caused by viruses have been researched in detail [ ] . however, while tb cases have been reported during the event [ , ] , tb management approaches during this unique event remained largely undocumented, and it is unknown whether these are consistent with the ksa and international tb management guidelines. hospitals in makkah serve both hajj pilgrims as well as local residents and the hajj workforce during the mass gathering free of charge. the additional stress on these health facilities during hajj may compromise the services provided for all patients during the event, including those diagnosed with tb. this study documents the management of drug-sensitive tb patients during hajj and explores the compliance of healthcare providers with the ksa tb management guidelines in the ministry of health (moh) hospitals in makkah during the mass gathering. this cross sectional study took place in makkah, saudi arabia, and https://doi.org/ . /j.tmaid. . . received january ; received in revised form june ; accepted july included hospitals comprising those serving pilgrims in hajj holy sites. the study was conducted during the hajj lunar month ( st- th dulhija) during the and hajj seasons, corresponding to nd sep- st oct and nd aug- st sep , respectively. all hospitalized adults (> years old) diagnosed with drug-sensitive pulmonary tb (ptb) during the study period were enrolled in the study if they consented. these patients are referred to in the manuscript as "suspected tb patients" until the time they were confirmed to have tb by the healthcare facility there were admitted to. the management of tb patients was documented using a specifically designed data collection form which included patients' demographics data, underlying health conditions and tb risk factors as well as clinical data including various aspects of tb management such as patients' screening, infection prevention and control (ipc), tb diagnosis and treatment and case notification and outcome. data was collected by the study team from patient's records, attending physician and through interviews with patients. all analyses were done using spss . (spss inc., chicago, usa) and sas . (sas institute inc., nc, usa) software program. variables were characterized using frequencies and mean for the respective categorical and continuous variables. a scoring system was developed, having identified four key themes from the questionnaire and literature review which were relevant to tb management in hajj. the themes were ) identifying tb suspect, ) ipc and surveillance, ) diagnosing tb and ) treating drug-sensitive tb. for each theme, relevant indicators were identified from the questionnaire (tables - ) . a score of was assigned for each indicator/variable that was consistent with the ksa tb management guideline [ ] (latest version during study period) and for inconsistency with the guideline. the indicator subscore (x) for guideline consistency was obtained as follows: x = number of cases consistent with guidelines (c)/ total number eligible of cases (d) * the eligible cases summed the consistent and inconsistent responses with tb guideline and strictly excluded missing data and unknown responses. the guideline consistency score for each theme was obtained by calculating the mean of the indicator sub-scores for each theme. the study was approved by the king fahad medical city ethics committee and the institutional review board (irb log: - e) and conducted in accordance with the ethics committee's guidelines. characteristics of the study population are presented in table . for the two-year period, confirmed drug-sensitive ptb patients were recruited for the study. the mean age of the study population was years (sd = . years, range - years). most ( . %, / ) were males and over half were over years old ( . %, / ), with only primary or no formal education ( . %, / ). the tb patients were nationals of countries but the majority ( . %, / ) had been residing in ksa for at least one year (table ) . over one third of the cases ( . %, / ) did not complete their hajj rituals while the status of % ( / ) of the cases was not known. three confirmed tb cases ( . %, / ) did complete their hajj rituals in individual ambulances. no mortality was recorded among the tb patients at the time when the study ended with half ( / ) having been discharged (table ) . in relation to tb risk factors, only . % ( / ) of respondents reported prior travel to high tb burden countries (pakistan and indonesia) and . % ( / ) stated that they had performed hajj or umrah within the past year. the majority ( %, / ) of the previous hajj or umrah pilgrims were saudi residents. a sizable proportion of tb cases declared that they had smoked or were current smokers of tobacco products ( . %, / ) or had chronic diseases ( . %, / ) especially diabetes and hypertension (table ) . upon registration, most ( . %, / ) suspected tb patients were admitted to an isolation room or ward. otherwise, the patients were either admitted into the emergency room (er [ . %, / ]), icu ( . %, / ), neurosurgery ward ( . %, / ), orthopedic ward ( . %, / ) or general ward ( . %, / ). while a proportion ( . %, / ) of suspected tb patients was separated from other patients during registration, the triaging status of . % ( / ) of suspected tb patients was not reported ( table ). the proportion of suspected tb patients put in isolation while waiting diagnosis was . % ( / ) and rose to . % ( / ) once drug-susceptible tb was confirmed. only ( . %) confirmed tb patient was managed in the er. generally, most ( . %, / ) confirmed tb patients spent less than day in the health facilities before they were isolated. in all cases, appropriate symptoms were sought from tb suspects, in particular, cough ≥ weeks ( . %, / ) and fever with chills/night sweat ( . %, / ). the history of contact with active tb cases was obtained from . % ( / ) of suspected tb cases, although the status of this variable was unknown in a further . % ( / ) of the cases (table ). in general, . % ( / ) of the tb suspects were questioned about other tb risk factors. specifically, their country of residence, hiv status and potential occupational exposure to tb (table ) . furthermore, in the majority of cases ( . %, / ) providers used recommended screening test for active tb (chest x-ray) in case management. in terms of diagnostic period, % ( / ) of tb suspected patients within known health facilities visits status had > visits to health facilities before appropriate screening/diagnostic tests were ordered (table ). however, the period between patient registration/arrival in health facilities and order of tb screening/diagnostic test(s) was ≤ h in . % ( / ) of cases. similarly, in most cases ( . %, / ), the period between ordering screening/diagnostic test(s) and confirmation of tb diagnosis was ≥ days. in general, . % ( / ) of cases were diagnosed within days of arrival/registration to healthcare facilities. sputum culture was the diagnostic test utilized in the majority ( . %, / ) of cases (table ). xpert mtb/rif assay was not utilized for tb diagnosis. in one instance, none of the recommended diagnostic tests were ordered for the tb suspected patient. only . % ( / ) of suspected/confirmed tb cases were screened for hiv. in over half of cases ( . %, / ), the tb suspected patients were questioned about their tb history, although for a further . % ( / ), response to this variable was unknown ( based on the duration of hajj season (around one month), the possibility of monitoring treatment completion is unfeasible in a hajj study. thus, appropriate post-hajj referral and provision of drugs to last during the referral period were proxies for estimating possible continuity of care. in most cases it was not known whether confirmed tb patients were referred for further treatment after completion of hajj ( . %, / ) or were given enough anti-tb drugs to last until they arrive in their country of residence ( . %, / ). in . % ( / ) of cases, the confirmed tb cases were reported to the ksa moh preventive medicine department. the reporting status of the rest of the cases ( . %, / ) was unknown. a proportion ( . %, / ) of the confirmed tb cases was reported to the appropriate country medical missions' office. this excludes the . % ( / ) of cases with unknown medical missions' reporting status. among the latter, . % ( / ) were saudi residents. the confirmed tb case status of two residents of pakistan and myanmar were not reported to their respective country medical mission's office. the tb management guidelines compliance scores across the identified themes are presented in table . out of a maximum possible score of , the overall guideline compliance score was highest for the themes ipc and surveillance ( . ) and identifying tb suspects ( . ). the least scores were obtained for the themes treating tb ( . ) and diagnosing tb ( . ). some notable variations in theme's sub-scores were observed. for instance, while the overall score for the identifying tb suspects theme was high, a low score was documented for obtaining history of tb risk factors from patients. inversely, while the overall score for treating tb was average, high score was seen in relation to not starting tb treatment for patient before tb diagnosis. this study exemplifies the compliance of tertiary healthcare providers with the saudi national guidelines for tb management during the hajj. the result showed high level of compliance with the assessed tb management guidelines indices for systematic screening of tb suspects as well as ipc and surveillance, but low compliance scores were obtained for prompt tb diagnosis and use of standardized treatment regimen for drug-susceptible tb. most tb cases in the current study were males and over half were above years old with primary or no formal education. this is in accordance with global and hajj-related data and established risk factors for tb [ , , , ] . however, the prevalence of coexisting chronic diseases ( %, / ) among tb patients, especially diabetes, was higher than that reported internationally as well as previous studies among hajj pilgrims with tb [ , [ ] [ ] [ ] . the presence of chronic diseases, increases the risk of tb disease, predisposes to severe illness and complicates tb treatment [ , ] . as such, the management of comorbidities is now a key focus of the integrated, patient-centered care and prevention strategy of global tb control [ ] . around % ( / ) of the tb cases reported being current smokers and a similar proportion ( / ) indicated that they did smoke in the past. this is higher than that reported in another study among hajj pilgrims with tb ( . %) [ ] but lower than figures from some international reports [ , ] . other risk factors for tb such as visit to, or residence in high-burden countries and occupational exposure were uncommon among tb patients in the study and so was previous hajj or umrah performance. while the latter events are not an established risk factor for tb transmission, hajj is a risk of tb infection and both clinically-recognized or undiagnosed active tb have been reported at the pilgrimage [ , , ] . the majority ( . %, / ) of tb patients in this study were ksa residents. this may be explained by the fact that the study included both pilgrims and non-pilgrims and that healthcare facilities in makkah provide healthcare to pilgrims and non-pilgrims during the hajj. although saudi arabia is not a high tb burden country, tb incidence in the country show significant regional variation with the makkah region showing much higher tb incidence rates than the rest of the country and rising trend [ , ] . in addition to the hosting of the hajj and umrah mass gatherings, this high tb incidence may also be related to the fact that around % of the makkah region population are non-saudis, many originate from and frequently visit high tb burden countries [ , ] . regardless, it is evident that in addition to strategies to control imported active tb [ ] , interventions to prevent transmission during hajj from locals and internal pilgrims with tb should also be developed and implemented. generally, home-based care for tb is preferred to methods of care that are based on strict hospitalization. in the ksa context, medical or mental instability and residence in congregate settings are among factors that may warrant hospitalization [ ] . in this study, most of the suspected and confirmed tb patients were admitted and isolated for tb management. to the best of our knowledge, there is no standardized global protocol guiding the choice of suitable models of care-whether home based or hospitalized care-during international mass gatherings. however, considering the potential of tb transmission in such crowded settings, the constant mobility of pilgrims and challenges in verifiable or stable residences for pilgrims during hajj, hospitalization, although undesirable, seems a logical and practical choice for tb management during the mass gathering. ipc in healthcare settings is one of the key strategies for tb control [ ] . however, implementation of ipc recommendations seems to be inadequate with several studies reporting poor tb infection control measures in health facilities [ ] [ ] [ ] [ ] . further, many hcws are practicing without adequate infection control training and often lack knowledge on tb infection control strategies and guidelines [ , ] . in the current study, we report high compliance with the aspects of tb ipc [ ] . early detection through systematic screening of tb suspects is key to improving tb case detection. the who recommends that persons with signs and symptoms consistent with tb should be evaluated for tb to ensure prompt diagnosis and treatment [ , ] . similarly, the saudi tb guideline recommends that healthcare workers (hcws) should be knowledgeable about tb symptoms to facilitate the efficient identification of tb suspects for diagnosis and treatment [ ] . in the current study, providers utilized presenting symptoms to correctly identify suspected tb patients in all cases. cough and fever with chills/night sweat were the most frequent symptoms among patients. this finding corroborates existing evidence that identifies cough as the most common symptom of ptb [ , ] . further, in majority of cases ( . %, / ), chest x-ray, a recommended screening tool for active tb, was conducted for the tb suspects. chest x-ray is particularly more sensitive for tb screening after a positive symptom screening [ ] . however, we also found that less than half of the tb suspected cases were questioned about tb risk factors. adequate knowledge of tb symptoms and risk factors among providers are prerequisites for correct and prompt identification of suspected tb patients for screening and diagnosis [ , ] . in view of the significant use of both symptom-based and radiological screening methods in this study, a total guideline compliance score of . out of was obtained for the prompt identification and screening of tb suspects theme for tb management. delayed diagnosis of tb can enhance the transmission of infection, worsen the disease and increase the risk of death [ , ] . in the current study, half of the tb cases had more than visits to healthcare facilities before tb screening/diagnosis tests were ordered for the patients. while studies from other settings reported similar findings [ , ] , our results are concerning, as delays in diagnosing tb during hajj may lead to significant transmission given the crowded setting during the event. similarly, sputum culture (which takes at least - weeks to produce results) was the only recommended diagnostic test applied in about % ( / ) of cases. the application of sputum culture as the singular diagnostic test is not consistent with approved standards for tb diagnosis [ ] . as % ( / ) of suspected cases were confirmed to have tb by the third day of arrival in the health facility, it appears that providers relied on screening tests, such as chest x-ray, for the confirmation of tb diagnosis. this practice is inconsistent with both national and international guidelines; chest radiography is only recommended for screening purposes. the ksa tb guidelines recommended the use of xpert mtb/ rif as an initial tb diagnostic test on a conditional basis [ ] . as such, the latter was not included in the scoring criteria for this study. nonetheless, xpert mtb/rif, which could detect tb and mdr-tb by proxy in the same day [ ] , was not applied for tb diagnosis in this study. although available in a number of saudi hospitals and reference labs, the roll out of xpert mtb/rif has been slow and its use for pointof-care testing is limited [ , ] . access to same day diagnosis of tb could prove valuable in a highly mobile hajj population where followup visits to the same health facility may not be guaranteed and where delays in diagnosis may increase the risk of transmission in such crowded settings. as such, ksa authorities should consider the provision of tb molecular testing capability in health facilities within the hajj areas to facilitate rapid (same-day) diagnosis of tb during the mass gatherings. due to the synergistic relationship between hiv and tb, it is recommended that all tb patients should be screened for hiv [ ] . yet, only a fraction of tb patients were questioned about their hiv status ( . %, / ) or tested for hiv ( . %, / ) in this study. this is much lower than what is reported globally [ ] . as a low prevalence setting, knowledge of hiv among healthcare workers is low in saudi arabia [ ] . yet, hiv could be a more frequent comorbidity among pilgrims who arrive with active tb from areas with high hiv disease prevalence [ ] . more so, a missed or delayed hiv diagnosis in a tb patient stalls the commencement of appropriate treatment and results in poor outcomes for the patient, community and health system [ ] . therefore, healthcare providers in ksa ought to be trained and guided to conduct screening for hiv and other comorbidities in all suspected tb patients irrespective of their nationality. in general, because of delays in diagnosis, infrequency of hiv testing and failure to utilize the appropriate diagnostic tests for suspect tb patients, the combined score for the tb diagnosis theme was out of a maximum of , the lowest score of all tb management themes in the current study. treatment of tb in ksa is free of charge for pilgrims and other patients and both the ksa and who guidelines for tb management recommend the use of four st-line anti-tb drugs in the treatment of drug-susceptible tb [ , ] . the guideline compliance score for tb treatment in this study was average; partly because % ( / ) of tb patients received fewer than four st-line anti-tb drugs. in general, inappropriate treatment of tb is common worldwide. in a systematic review that included studies from countries, inappropriate treatment regimens were prescribed in % of the studies and the percentage of patients on inappropriate regimens varied between . % and % [ ] . poor knowledge of national and international tb management guidelines contributes to inappropriate prescription of anti-tb drugs by healthcare providers, and the use of inappropriate regimen drives the occurrence of relapse and the emergence of drugresistant tb [ , ] . both the who and ksa tb guidelines recommend that all patients with ptb being treated with the st-line regimen should have their sputum samples tested by the end of the nd, th and th month of treatment [ , ] . in the current study, all confirmed tb cases with known notification status were reported to the saudi health authorities. however, it is unknown whether the continuum of care was maintained for tb cases who were international pilgrims and who had to return to their home countries soon after the pilgrimage (before the end of the treatment period). any travel-related treatment interruptions could breed treatment relapse and drug-resistance and propagate community spread of tb. both national and international tb guidelines fall short of providing guidance on tb control at international mass gatherings, including procedures for ensuring access to care and support services during travel. thus, the development and dissemination of a multinational hajj and umrah and/or mass gatherings-specific tb management protocols are needed. these protocols should also include pathways for the safe transfer across borders and follow up of tb patients involved in mass gatherings. the current study is among the foremost surveys of tb management at international mass gatherings. while the small number of cases and high proportion of unknown responses for some variables constituted limitations, the tb management indices obtained was a fair representation of the compliance of providers with national and international tb guidelines in moh hospitals during the hajj. the findings provides a basis for the review of existing practices across settingsprivate and public sector vs national and foreign health facilities-and serves as a reference for the development of appropriate guideline and protocol for tb management at the hajj and umrah, as well as other settings with similar health system resources and population dynamics hosting recurrent international mass gatherings. in the short term, availability of rapid molecular diagnostic techniques for tb as we all improving hcws' knowledge regarding tb management guidelines and monitoring compliance are needed to ensure tb patients are management appropriately during hajj and that tb transmission is prevented. no conflicts of interest to declare. none to declare. the study was approved by the king fahad medical city ethics committee and the institutional review board (irb log: - e) and conducted in accordance with the ethics committee's guidelines. all participants gave verbal consent before enrolment. world health organization. gear up to end tb: introducing the end tb strategy. world health organization world health organization. early detection of tuberculosis: an overview of approaches, 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tuberculosis transmission missed opportunities to diagnose tuberculosis are common among hospitalized patients and patients seen in emergency departments time delays in diagnosis of pulmonary tuberculosis: a systematic review of literature roadmap for rolling out xpert mtb/rif for rapid diagnosis of tb and mdr-tb evaluation of genexpert mtb/rif for detection of mycobacterium tuberculosis complex and rpo b gene in respiratory and non-respiratory clinical specimens at a tertiary care teaching hospital in saudi arabia knowledge and attitudes of doctors toward people living with hiv saudi arabia early versus delayed antiretroviral therapy for hiv and tuberculosis co-infected patients: a systematic review and meta-analysis of randomized controlled trials prevalence of inappropriate tuberculosis treatment regimens: a systematic review knowledge of tuberculosis-treatment prescription of health workers: a systematic review multidrug resistance after inappropriate tuberculosis treatment: a meta-analysis world health organization. treatment of tuberculosis: guidelines. geneva: world health organization key: cord- -hffy xtm authors: memish, ziad a.; al-tawfiq, jaffar a. title: the hajj in the time of an ebola outbreak in west africa date: - - journal: travel medicine and infectious disease doi: . /j.tmaid. . . sha: doc_id: cord_uid: hffy xtm nan this issue of travel medicine and infectious disease has a number of papers pertinent to infectious disease risks for pilgrims attending hajj, one of the largest annual recurring mass gathering events that takes place in the kingdom of saudi arabia (ksa). the total number of pilgrims attending the hajj increased from , in to , , in with about , , from countries other than ksa [ ] . the number of pilgrims received from each country is based on the number of muslims living in these countries. national quotas are based on a ratio of visas per one million people. to control the ever rising number of pilgrims attending hajj every year and to give priority to the increasing number of awaiting international muslims to attend, saudi nationals and local residents have to register for the hajj and locals who have already performed the hajj are not issued permits for years. the number of muslims and the average number of pilgrims from the four countries in west africa involved in the current ebola virus disease (evd) outbreak are shown in table . the risk of the transmission of infectious diseases is amplified during the hajj due to the large number of pilgrims, overcrowding and the presence of a large number of elderly pilgrims with comorbid diseases [ , ] . previous outbreaks of infectious diseases such as meningitis and food poisoning have occurred during the hajj. each year there is an early coordination of efforts of multiple ksa agencies in collaboration with international organizations to identify any emerging or potential infectious outbreak [ ] . the occurrence of any public health emergency of international concern (pheic) or the emergence of any infectious disease outbreak any where across the globe requiring notification by the international health regulations (ihr), incite the public health authority in ksa to takes extra-precautions to curtail the introduction and subsequent spread of such infectious diseases during the hajj season. careful review and consultations with international agencies did not result in the restriction of any pilgrims due to the emergence of the middle east respiratory syndrome coronavirus (mers-cov) in e [ ] . there were no travel restrictions due to mers, however the saudi ministry of health recommended that older adults (> years of age), children, and those immunocompromized or with chronic medical conditions should postpone the hajj for e . evd has been recently detected in west africa with the largest outbreak ever in the history of this disease ignited by the first case which was reported from guinea in december . as of august , . ebola had caused a total of , with deaths in guinea, liberia, nigeria, and sierra leone (fig. ). in the last three weeks, > % of the total number of cases occurred. the world health organization (who) director general declared the outbreak a pheic on august , after days of deliberation by the ihr emergency committee [ ] . another outbreak was reported on august , in democratic republic of congo (drc) and was not related to the other west african countries [ ] . and senegal confirmed its st case of evd on friday aug , according to a statement from its health minister. the patient, a guinean national who traveled to senegal, is in quarantine [ ] . currently, the high case fatality rate, the lack of approved preventative vaccines and specific therapy for evd is magnifying the global public health concern. an experimental therapy (zmapp) was tried in a few patients with ebola and subsequently on august , an expert panel for the who considered it is ethical to use an unproven intervention for the treatment or prevention of the ebola virus [ ] . ebola is highly contagious zoonotic disease caused by a virus of the family filoviridae, whose members comprise genera of enveloped, negative, single-stranded rna viruses: marburgvirus and ebolavirus. the incubation period of ebola ranges from to days, and can present initially with nonspecific symptoms such as fever, chills, myalgia, malaise, respiratory and gastrointestinal symptoms followed later by hemorrhagic symptoms in severe cases. the disease is transmitted by close contact and upon exposure to infected blood and body fluid. all global health authorities agree that preventing the ebola spread once diagnosed is possible if human medical capacity and effective protective measures are applied. the hajj season will take place from october to th. and long before the who announcement about pheic, the saudi moh after careful review by its national infectious diseases committee had asked in april that the respective authorities to suspend issuing the hajj and umrah's visas for the people of guinea, sierra leone and liberia [ , ] . based on risk assessment in , the saudi ministry of health excluded pilgrims from uganda and the democratic republic of the congo due to the occurrence of an ebola outbreak at that time [ ] . a mathematical modeling of the risk of ebola introduction from the uganda outbreak in during hajj was estimated to have a mean risk of . Â À (sd z . Â À ) and thought to be negligible [ ] . despite the low risk, the introduction of a single case of ebola during the hajj would have a catastrophic consequences for the global health community. therefor, it is imperative to prevent any such event and take strict preemptive measures for the prevention of ebola importation to the hajj. the saudi ministry of health public health staff who are stationed at all ports of entry into ksa have been trained to observe all arriving pilgrims for any signs or symptoms of infectious diseases requiring medical assessment and/or quarantine by the local public health authorities. they have gained significant experience from the decades of monitoring incoming and departing millions of pilgrims from more than countries. the saudi moh and the us cdc had called to postpone non-essential trips to the most affected west african countries (guinea, sierra leone, and liberia) in order to prevent the spread of evd beyond the boundaries of these countries. ksa provides free health care for all pilgrims at the hajj premises through hospitals, beds including critical care beds and emergency care beds [ ] . the availability of healthcare centers in the hajj area staffed with , specialized healthcare workers further enhance the provision of healthcare for the pilgrims [ ] . since evd spreads mainly between individuals through direct and indirect contact with blood and body fluid, the focus to limit the introduction of the virus and its spread depends on three key elements: high level of vigilance to detect cases early, proper isolation and contact tracing and strict application of appropriate infection control standards with ample supplies of all personal protective equipment (ppe) to be used in the correct way constantly. the provision of enough supply and training of hcws on the correct use of ppe are priorities for the control of the evd outbreak without overuse or underuse [ ] . the challenges facing mass gathering (mg) planners in dealing with ebola will be multiple folds: including finding a simple syndromic surveillance mechanism/criteria that will be sensitive and specific enough to pick up highly suspected cases, development of point of care testing to confirm or rule out suspected cases, the ability to do effective contact tracing and quarantining of suspected cases and their extensive contacts which will disrupt the strict schedule of many of the mg attendees. in addition, lack of effective and approved preventative or therapeutic modalities and communication challenges to overcome the panic that such a disease with a very high mortality rate will generate add further challenges. very elaborate and comprehensive plans need to be drawn up in advance involving all national, regional and international stakeholders to ensure smooth and effective execution at the time of any mg event. as hajj is the largest recurring mg event in the world, planning for the hajj each year starts immediately after completing the previous hajj season. these preparatory plans had evolved over many years with unlimited government financial and logistical support with significant investment in establishing an extensive infrastructure, a cadre of highly trained human resources and deeply established networks, coordination and national, regional and international collaboration. the above investment in developing a state-of-the art global center for mass gathering medicine with all its global partners will be best fitted to face the current challenge and any future emerging infectious diseases challenges. none declared. hajj: infectious disease surveillance and control mass gathering medicine: hajj and umra preparation as a leading example who. who statement on the meeting of the international health regulations emergency committee regarding the ethical considerations for use of unregistered interventions for ebola virus disease (evd) the hajj: updated health hazards and current recommendations for quantitative risk analysis for introduction ebola virus to saudi arabia through hajj pilgrims from uganda. abstract no. ise. . th icid meeting is respiratory protection appropriate in the ebola response? key: cord- -oudj q authors: al-tayib, omar a. title: an overview of the most significant zoonotic viral pathogens transmitted from animal to human in saudi arabia date: - - journal: pathogens doi: . /pathogens sha: doc_id: cord_uid: oudj q currently, there has been an increasing socioeconomic impact of zoonotic pathogens transmitted from animals to humans worldwide. recently, in the arabian peninsula, including in saudi arabia, epidemiological data indicated an actual increase in the number of emerging and/or reemerging cases of several viral zoonotic diseases. data presented in this review are very relevant because saudi arabia is considered the largest country in the peninsula. we believe that zoonotic pathogens in saudi arabia remain an important public health problem; however, more than million muslim pilgrims from around islamic countries arrive yearly at makkah for the hajj season and/or for the umrah. therefore, for health reasons, several countries recommend vaccinations for various zoonotic diseases among preventive protocols that should be complied with before traveling to saudi arabia. however, there is a shortage of epidemiological data focusing on the emerging and reemerging of zoonotic pathogens transmitted from animal to humans in different densely populated cities and/or localities in saudi arabia. therefore, further efforts might be needed to control the increasing impacts of zoonotic viral disease. also, there is a need for a high collaboration to enhance the detection and determination of the prevalence, diagnosis, control, and prevention as well as intervention and reduction in outbreaks of these diseases in saudi arabia, particularly those from other countries. persons in the health field including physicians and veterinarians, pet owners, pet store owners, exporters, border guards, and people involved in businesses related to animal products have adopted various preventive strategies. some of these measures might pave the way to highly successful prevention and control results on the different transmission routes of these viral zoonotic diseases from or to saudi arabia. moreover, the prevention of these viral pathogens depends on socioeconomic impacts, available data, improved diagnosis, and highly effective therapeutics or prophylaxis. rudolf virchow , one of the foremost th century german leaders in medicine and pathology [ ] , noted a relationship between human diseases and animals and then introduced the term "zoonosis" (plural: zoonoses) in [ ] . later, the world health organization (who) in specified that "zoonoses are those diseases and infections which are naturally transmitted between vertebrate animals and man" [ ] . venkatesan and co-authors reported that the term zoonosis is derived from the greek word "zoon" = animal and "noso" = disease [ ] . zoonotic pathogens causing different kinds of diseases are of major public health issues worldwide [ ] . these zoonotic diseases include frequent mixing of different animal species in the markets in densely populated areas, and the human intrusions into the natural habitats of animals, have facilitated the emergence of novel viruses. the most important zoonotic viral diseases of which eight were diagnosed (in dead or diseased animals or through antibody detection) on the arabian peninsula over the last years include rabies, middle east respiratory syndrome (mers-cov), influenza virus (ifv), alkhurma hemorrhagic fever, crimean-congo hemorrhagic fever (cchf), rift valley fever (rvf), west nile fever (wnv), and dengue fever virus. among these eight zoonotic viral diseases, two (alkhurma and mers-cov) were first reported in a patient in and , respectively in saudi arabia [ , ] . these two were transmitted later to several other countries, not only in the middle east but also to africa, asia, and europe. rabies is an almost invariably fatal zoonotic disease, which belongs to the genus lyssavirus of the rna family rhabdoviridae. rabies virus is considered an endemic viral infectious disease in animals in saudi arabia. recent scientific data on rabies cases reported in camels at al-qassim region (one of the thirteen administrative regions of saudi arabia) showed that there is an increasing number of this fatal virus disease [ ] . however, the most significant animal bites which have been recorded in saudi arabia were caused by different species of animals including dogs, cats, rodents, and foxes [ ] . later, al-dubaib reported rabies in dromedaries in saudi arabia in and suggested an incidence of about . % for rabies that was reported among camel herdsmen looking after more than animals [ ] . interestingly, another survey was conducted between and in the al-qassim region of central saudi arabia among camels and showed that about . % of clinical rabies incidence is caused by dogs (may be cause it highly used as a perfect guard for camels), followed by foxes; furthermore, the diagnosis of viral rabies in that region was confirmed among dogs, foxes, camels, and cats [ ] . lately, the relevant government authorities (the moh and ministry of agriculture in saudi arabia) in an updated report between and showed that there were a total of , animal bites to humans in saudi arabia [ ] . furthermore, most cases of animal bites were caused by dogs ( . %) and cats ( . %), followed by mice and rats, camels, foxes, monkeys, and wolves [ ] . moreover, dogs, particularly feral dogs and foxes, are considered the most important host for rabies virus; however, bats are also considered as reservoirs of this disease. humans can become rabid by direct contact with animal mucosal surfaces via bites. according to the moh and ministry of agriculture data in saudi arabia, pets are responsible for most animal bites in humans [ ] , and it is well-known that insufficient vaccination coverage of pets are among the most common hallmarks of the endemic status of rabies worldwide [ ] . more recently, many saudi and expatriate families are keeping pets; however, there are limited number of specialized veterinary clinics (~ ) within the kingdom of saudi arabia that have fully licensed veterinary laboratories with state of the art technologies and veterinary staff. globally, almost % of all human deaths caused by rabies occur in africa and asia [ ] . however, saudi arabia, as one of the asian countries, has scarce publications and epidemic data on rabies status [ , ] . moreover, memish et al., between and in saudi arabia, reported the histologic detection of the virus by identifying negri bodies in the brain samples of animal rabies cases. the study showed that among the suspected rabies cases, (~ . % of all cases) were found to be positive; thus confirming rabies cases among dogs, foxes, sheep, camels, goats, wolves, and cows [ ] . furthermore, more recent data confirmed the transmission of rabies virus in saudi arabia by feral dogs [ ] . in spite of these facts, there are very few studies available, and no case of human rabies has been reported in recent decades from saudi arabia [ ] . however, in march , a scientific work was reported as the first confirmed case of human rabies in saudi arabia from makkah city, which has now been published [ ] . indeed, several previous global epidemiological data confirmed that rabies accounted for , to , human deaths per year [ ] , and more than % of these cases occur in children < years of age [ ] . in september , a -year-old saudi man, presented with different clinical features-such as nausea, vomiting, and epigastric pain, with significant features suggestive of gastritis-at makkah hospital. his past medical history was significant for hypertension and diabetes type . during the clinical diagnostic procedure of this case, he developed respiratory distress and tachycardia, for which he was transferred to the intensive care unit [ ] . because, his case worsened with chest pain and ventricular tachycardia he was referred to the king abdullah medical city in makkah for further management. the written diagnostic report indicated that he had acute anteroseptal myocardial infarction, had coronary angiogram which suggested that two-vessels were diseased with left main involvement, and surgical intervention was planned. after the decision for surgery, he was found to have leukocytosis and severe retching while attempting to drink water (hydrophobic behavior), which necessitated further review by the infectious disease consultants based on the patient's clinical symptoms. the consultant team discovered the history of an unprovoked scratch on the patient's face by a dog in morocco a month prior to the admission at the hospital. also, the patient stated that he only received tetanus vaccine. all diagnostic tests including neurologic examination were unremarkable and his saliva polymerase chain reaction (pcr) test confirmed rabies virus. he was administered verorab rabies vaccine and human hyperimmune rabies immunoglobulin ( iu/kg) intramuscularly (im) [ ] . in addition, he had troponin i ( . ng/ml), creatine kinase isoenzyme mb (ckmb) was found ( . ng/ml), and serum glucose ( mg/dl). on the fifth day of hospital, he had recurrent episodes of ventricular tachycardia, progressively worsening of hemodynamic parameters, and he succumbed to his infection on that day. there is no vaccine against rabies recommended for travelers from/to saudi arabia, and no rabies treatment is offered to pet dogs. however, vaccination is given to dogs before they are infected; otherwise they are euthanized if infected. according to a previous study, most patient injuries from animal bites in saudi arabia showed some variations due to the monthly incidence and/or, according to the animal species [ ] . bites by dogs and cats were reported frequently throughout the year, with a decrease in april and between august and october. however, bites by foxes increase between august and september while camel bites were more frequent between december and march of the subsequent year. the same previous study suggest that these seasonal variations of injuries might be due to the saudi population habits, with people going to the desert for leisure activities during good weather periods. laboratory diagnosis of rabies viral disease occur with the use of the rabies virus direct fluorescent antibody test (dfat) on brain samples and hippocampal tissue [ ] . while rabies is considered nearly % fatal, it is also % preventable, and thus vaccination to pets is the key element to prevent the risk of rabies zoonotic infection [ ] . reports of the epidemiology of rabies virus worldwide, and particularly in saudi arabia, suggest that it is on the increase, thus the implication of this virus' potential to spread across borders from high to low prevalence countries was highlighted [ ] . the mers-cov infection is considered to be a new respiratory disease with a dire global concern [ ] . mers-cov infections are caused by a newly emerging coronavirus (cov), belonging to the designated lineage c of betacoronavirus of the rna family coronaviridae. with respect to viral origin and transmission, bats are thought to be the reservoir host of betacoronaviruses, and the african neoromicia bats in particular are the natural reservoir of mers-cov [ , ] . since its emergence in in saudi arabia, when an elderly patient ( years old) with respiratory illness died after admission to a hospital in jeddah [ ] , the disease was subsequently reported to have been transmitted to several countries worldwide, and has affected more than patients with over % fatality [ , [ ] [ ] [ ] . moreover, a -year-old saudi man was admitted to a private hospital in jeddah, saudi arabia in june with a history of fever, severe acute respiratory syndrome with cough, expectoration, and shortness of breath. he did not smoke; and for the disease, which was suggested to be due to an animal transmission of coronaviruses, he was treated with oseltamivir, levofloxacin, and piperacillin-tazobactam. on day , he died [ ] . after this, a -year-old saudi male with hypertension and diabetes with no history of smoking, reported for surgery. at the time of admission, he was asymptomatic. he was initially screened using nasopharyngeal swab, endotracheal aspirate, and serum sample for mers-cov per protocol with the mers rrt-pcr assay. the results confirmed mers-cov infection. he died three days after admission. it was discovered that the patient owned a dromedary camel barn in saudi arabia, and had a history of close contact with camels, as well as a habit of raw milk consumption of an unknown duration [ ] . two studies have suggested a relationship between the infection and contact with dromedary camels [ , ] . in addition to this, serological diagnostic methods have been used to confirm mers-cov infections in dromedary camels for at least - decades and has thus confirmed camels as an intermediate host for this virus [ , ] . thus, in , a novel coronavirus (mers-cov) was isolated from two fatal human cases in saudi arabia and qatar; and since then, more than clinical cases of mers-cov have been identified, and the great majority of the cases were from saudi arabia [ ] . this previous report author raised a thoughtful comment related to the emerging viral diseases "why we need to worry about bats, camels, and airplanes" [ ] . moreover, another study suggested that mers-cov infection is usually transmitted from human's direct contact with dromedary camels, especially when people drink the milk or use camel's urine for medicinal purposes [ ] . more recently, a metagenomics sequencing analysis of nasopharyngeal swab samples from mers-cov-positive live dromedary camels marketed in abu dhabi, united arab emirates, showed at least two recently identified camel coronaviruses, which were detected in . % of the camels in that study [ ] . however, limited human-to-human infections have been reported. the prevalence of mers-cov infections worldwide still remains unclear. in addition to this, the who reported about cases of these infections since june , with about deaths in different countries, worldwide. recently, a study was conducted from june to july , during which samples were collected from mers-cov infected individuals, from the national guard hospital in riyadh (the saudi arabian capital city), the moh in saudi arabia, and other gulf corporation council countries, to determine the prevalence of mers-cov [ ] . the epidemiologic data that were collected, showed that the highest number of cases (about of patients) were reported from saudi arabia (~ %). among the mers-cov cases from saudi arabia, riyadh was the worst-hit area with infected cases ( . %), followed by the western region of makkah where cases ( . %) were reported [ ] . furthermore, this study also showed that the incidence of mers-cov infections was highest among elderly people aged ≥ years [ , ] ; with speculation that there might be certain conditions or factors involved. it is considered that mers-cov infection might have a peculiar gender predisposition [ ] . recent data examined the mortality in patients with mers-cov and the gender relationships, looking at the survival of cases among females and males. it was suggested that males have a higher risk of death [ , ] ; however, this was contradicted by the findings from two other studies which suggested that males have a low risk of death [ ] ; while another survey which examined the influence of gender on -day and -day survival, found a low risk of death especially in the older age group [ ] . on the other hand, badawi et al., suggested that mers-cov infections could be mild and may only result in death among patients suffering from any kind of immune system disorder and/or any chronic disease [ ] . more recently, data regarding the mortality in patients with mers-cov have been published. according to saudi arabia's moh daily statements, dated from february through march , laboratory-confirmed new cases of mers-cov and deaths occurred [ ] . recently, on february , patients infected while hospitalized at riyadh included two men ( and years old) in stable condition, who were not healthcare workers. according to a february update, a new case involved a -year-old man from the city of buraydah who later died. meanwhile, on march , another mers-cov infection in a riyadh hospital patient, a -year-old man who was listed in critical condition and who likewise had contact with camels, as the other two patients, was reported. thus, the moh stated that the spillover from camels is thought to be the main source of mers-cov in saudi arabia, since all these patients were exposed to the animals before reporting ill [ ] . furthermore, an -year-old patient from riyadh, and other two patients who had camel contacts from hail city in the north central part of saudi arabia were listed in critical condition. the illness in these patients was reported on march . according to a march statement, another patient, a -year-old man from najran located in southern saudi arabia, was reported. the man was listed in a stable condition. of these new cases, only one death, involving the -year-old man from riyadh, according to the march moh statement, was reported [ ] . still, much work is needed to detect the mers-cov infection risk in saudi arabia, because data showed increasing number of cases exist among the eight countries including saudi arabia. thus, the emergence of mers-cov in the region and its continuing transmission from - , currently poses one of the biggest threats to global health security [ ] . most cases (over %) reported to date have been from countries in the region (e.g., egypt) notably from saudi arabia, with cases including deaths [ ] . influenza viruses are considered to be important infectious viral diseases, which is caused by three virus types (a, b, and c) [ ] . due to their zoonotic spread, influenza type a infects both humans and animals, and causes moderate to severe illness, with more likelihood of fatalities in young children and the elderly [ , ] . other types of influenza, including type b and c, infect only humans [ ] . furthermore, influenza a viruses, members of the rna family orthomyxoviridae, are further classified into human, swine, and avian influenza viruses. however, during the influenza pandemic, swine influenza virus infected one-third of the world's population (an estimated million people) and caused approximately million deaths [ ] . since , several infections with this virus have been recorded from various areas worldwide, including saudi arabia [ ] . at the end of april , an outbreak of a new type of influenza, a/h n , started in mexico and the usa [ ] . the who declared the pandemic influenza a (h n ) as a "public health emergency of international concern" following the first few initial cases in mexico, and subsequently in the usa [ , ] . in saudi arabia, the epidemiological data for influenza virus were collected using a predesigned questionnaire with the first confirmed pandemics influenza a (h n ) cases identified by the infectious diseases department from the moh, and the database during the period covered from june to july [ ] . however, according to the saudi moh data, the number of laboratory-confirmed cases of the virus in saudi arabia as at december was , , with deaths [ ] . the virus later spread worldwide, causing a pandemic, and the most recorded cases then, as reported by the who in the middle east, were in saudi arabia with , cases, followed by kuwait [ ] , egypt, and oman; with less number of infected patients [ , ] . nevertheless, between and , a serosurveillance outcome of swine influenza virus from egypt provided evidence of laboratory diagnosis and very early confirmation of the virus in human patients [ ] . in saudi arabia, the influenza surveillance system has been established since . moreover, among people with certain chronic medical diseases or conditions, a trivalent influenza vaccine (tiv), which contains inactivated antigens for two different subtypes of influenza viruses (types a and b), became available in saudi arabia [ ] . indeed, h n is now in the post-pandemic period and has become a seasonal influenza virus that continues to circulate with localized outbreaks of varying magnitude in saudi arabia [ ] . a previous data was collected using a predesigned questionnaire for the first cases of pandemic influenza a (h n ) from different hospitals in saudi arabia. the age of patients enlisted in the data ranged from to years. the age groups with the highest percentage of cases were between: and years ( %), and and years ( %). there were males and females, and % patients had some contacts with infected persons within saudi arabia while about % had history of travels into saudi arabia and/or the philippines [ ] . these facts are similar to the previous relationship noted between the occurrence of zoonotic viral diseases and the gender of patients and/or their ages, as reported for another viral (e.g., mers-cov) infection; provided certain conditions are met [ ] [ ] [ ] [ ] . interestingly, among elderly patients, influenza cases were higher in females than males. this relationship with viral infection occurring particularly with respiratory viral diseases, might pave the way and play a big role of more significant importance in the detection of these diseases, taking into account the influence of climate change and the different environmental factors [ , , ] . nevertheless, between september and october , about samples were taken from several patients presenting with respiratory symptoms to king abdulaziz university hospital, jeddah, saudi arabia. however, during this study conducted to detect the susceptibility to the influenza viruses circulating in the western part of saudi arabia, out of all the tested samples, ( . %) respiratory samples were positive for influenza h n virus, ( . %) was positive for influenza h n virus, and ( . %) were positive for influenza b virus [ ] . furthermore, h n , now in the post-pandemic period, has become a seasonal influenza virus that continues to circulate with localized outbreaks of varying magnitude [ ] . interestingly, the presentation of influenza virus infections in humans usually vary from mild, self-limiting respiratory-like illness, to severe cases that may result in death [ , ] . nevertheless, a recent study has shown that subclinical infection in human exists, as revealed by the serological surveillance [ , ] . therefore, the epidemiological surveillance of influenza in saudi arabia is highly important especially with the fact that influenza cases have also been highly reported can spread globally [ ] . thus, geographic influences on influenza virus infection in saudi arabia must be of concern [ ] . this is relevant because a remarkably high number of egyptian muslims visit saudi arabia yearly to participate in the umrah and/or the hajj pilgrimage; in addition, the impact of the poultry industry in egypt is also worth considering, with an estimated billion birds and several millions of engaged laborers with/without surveillance [ ] . it is well-known that the influenza drugs, antiviral agents, and the current seasonal influenza vaccines are effective in reducing the incidence and severity of the disease, sickness, and/or complications. however, the important strategy for influenza management includes the provision of prophylaxis and treatment [ ] . however, it is possible for widespread drug resistance against antiviral agents or vaccines to emerge in patients who extensively abused the drugs, in addition to those who have never received such treatment, globally [ ] [ ] [ ] . furthermore, influenza viruses pose a challenge to vaccine developers and manufacturers due to the fact that these viruses are continually changing in nature, including hemagglutinin and neuraminidase [ , ] . moreover, while resistance to neuraminidase inhibitors (e.g., oseltamivir and zanamivir) have been reported to sporadically occur, the resistance to oseltamivir has been widely reported since , with a worldwide spread [ ] . this highlights why there is an urgent need for the public health system to monitor continuously via globally active influenza surveillance programs. furthermore, there is need to monitor the circulating influenza viruses strains, as well as the occurrence of any resistance, using appropriate diagnostic methods. this is considered highly essential in saudi arabia. interestingly, survey data has shown an increasing report of the viral infection from egypt, since hajj egyptians has ranked in the top list of countries with the highest number of mecca pilgrims in the last years [ ] . influenza is highly susceptible to antiviral drugs such as oseltamivir, according to a more recent epidemiological study [ ] . although millions of muslims, globally, travel annually to saudi arabia to perform hajj and/or umrah in the holy places including both makkah and al-madinah for very limited period (~ days), this gathering could play a major role in the introduction of new influenza viruses, not only to saudi arabia but also to the rest of the world [ , ] . unfortunately, there is no such influenza surveillance program in saudi arabia, thus this pose a serious public health concern. recently, in a study of pilgrims screened on arrival at the hajj season in saudi arabia, ( . %) had influenza a virus ( out of the had h n virus) [ ] . additionally, the epidemiological data showed that the pilgrims had the potential not only to introduce these viruses to saudi arabia, but also to export the influenza virus back to their home countries [ , ] . this can occur in saudi arabia, despite the availability of a tiv containing inactivated antigens for influenza virus types a and b, which can protect against the influenza virus infection [ ] . importation of resistant and highly pathogenic viruses including influenza viruses can occur worldwide. despite this, there is lack of studies and data on drug susceptibility, and a very limited number of studies and reports on viral isolates, except for one study conducted in jeddah, according to the best of our knowledge [ ] . most importantly, this highlights the importance of circulating influenza viruses in saudi arabia, hence there is need to ensure effective use of antivirals for prophylaxis and treatment of influenza. furthermore, the rate of vaccination against influenza is very low among pilgrims and healthcare workers [ , ] . moreover, studies are needed to provide a clear picture on the impact of drug resistance on saudi arabia's endemic pathogens, including the influenza viruses. in a recent communique, the ministry of environment, water, and agriculture for saudi arabia reported two cases of h n avian influenza in the kharj governorate [ ] . the latest update by the ministry revealed that the number of samples collected from saudi regions since the start of the influenza outbreak had reached , . positive results from samples and laboratory tests indicate positive cases, and the saudi authorities have taken action by culling as many as , birds within a -h period [ ] . in contrast, several epidemic zoonotic cases of influenza h n have been reported in domestic cats in several countries in asia, europe, the usa, and italy [ ] . moreover, the epidemic of influenza in dogs might be related to a serious public health issue and could be shown to have resulted from zoonotic diseases from pets, similar to the avian influenza h n outbreak reported in pet dogs in south korea in [ ] . nevertheless, a recent study has shown that the role of pets, particularly cats and dogs in the epidemic of influenza as a source of human infection seems limited. however, cats were shown to be fully susceptible to experimental infection, and infected cats were able to infect naive cats [ ] . in , pandemic h n infection in a domestic cat in the usa from iowa was diagnosed by a novel pcr assay; thus, human-to-cat transmission was presumed [ ] . despite this prior evidence, the role of pets including cats and dogs seem even more limited in the dispersal of avian influenza to humans. rather, humans may be the source of pet infection, as suggested for influenza h n and/or h n virus infections [ , [ ] [ ] [ ] . most importantly, epidemic zoonotic cases of influenza among pets has highlighted the importance of circulating influenza viruses globally; especially, to ensure the effective use of antivirals for the prophylaxis and treatment of influenza, in particular, with the increase in the number of pets stores in saudi arabia, especially in riyadh [ , ] . surprisingly, previous data focused on the occurrence of zoonotic infection of different influenza virus types, and particularly, the transmission of avian influenza virus h n to domestic dogs [ ] . several studies have examined and confirmed the occurrence of zoonotic infection of the influenza a virus h n pandemic, especially in domestic cats [ , ] . nevertheless, epidemiological studies on different zoonotic infections among the pets in saudi arabia including cats, dogs, and/or baboons are very rare. however, a previous case report confirmed a relationship between some zoonotic diseases causing respiratory symptoms, such as influenza, among pets [ ] . this study suggests that severe lung infection with dry cough and severe anemia should lead to the suspicion of a secondary infection with zoonotic balantidiasis, which infected a hamadryas baboon from saudi arabia in a research center for pets in riyadh [ ] . furthermore, two other epidemiological zoonotic study on balantidium coli protozoan zoonotic infection in camel was reported from riyadh [ ] . in addition, another previous data confirmed the occurrence of toxocara canis zoonotic infection based on respiratory symptoms reported at the pet clinics in saudi arabia (and also in riyadh where the symptoms occurred in dogs) [ ] . still, more such studies are needed to highlight the important issues and/or provide clearer pictures of the zoonotic pathogens among pets in saudi arabia; however, pet ownership has been growing rapidly as well as the number of pet stores among the saudi population. alkhurma hemorrhagic fever virus (ahfv) in humans was discovered in [ ] . the first case reported in a butcher from the city of alkhurma, a district south of jeddah in saudi arabia, died of hemorrhagic fever after slaughtering a sheep. the viral infection has a reported fatality rate of up to % [ ] . interestingly, one of the previous reports regarding this disease showed a misunderstanding of the real name of this infection, called alkhurma, not alkhumra [ , ] . because subsequent cases were diagnosed in patients from the small town known as alkhurma in jeddah from where the virus got its scientific name; the name was accepted by the international committee on taxonomy of viruses [ ] . thus, based on evidence, the first case was confirmed to be the butcher, following the slaughtered sheep [ ] . therefore, a study was conducted among affected patients to address this disease as a public health issue. blood samples were collected from household contacts of patients with laboratory-confirmed virus for follow-up testing by enzyme-linked immunosorbent serologic assay (elisa) for ahfv-specific immunoglobulin (ig) g. samples from persons seeking medical care were tested by elisa for ahfv-specific igm and igg using ahfv antigen. viral-specific sequence was performed by reverse transcription pcr (tibmolbiol, lightmix kit; roche applied science, basel, switzerland). a total of cases were identified through persons seeking medical care, whose illnesses met the case definition for ahfv, and another cases were identified through follow-up testing of household contacts [ ] . subsequently, the virus was isolated from six other butchers of different ages (between and years) from the city of jeddah, with two deaths. the diagnosis was established from their blood sample tests. the serological tests later confirmed four other patients with the disease [ ] . from to , the study on the virus initial identification in the city of alkhurma again identified other suspected cases; with laboratory confirmation of the disease in (~ %) of them. among the , ( %) had hemorrhagic manifestations and ( %) died [ ] . the virus was later identified in three other locations: from the western province of saudi arabia (ornithodoros savignyi and hyalomma dromedarii were found by reverse transcription in ticks) and from samples collected from camels in najran [ , ] . ahfv virus was considered as one of the zoonotic diseases; however, the mode of transmission is not yet clear. recently, it was suggested that the disease reservoir hosts may include both camels and sheep. the virus might also be transmitted as a result of skin wounds contaminated with the blood or body fluids of an infected sheep; through the bite of an infected tick, and through drinking of unpasteurized or contaminated milk from camels [ , ] . in humans, this zoonotic disease may present with clinical features ranging from subclinical or asymptomatic features to severe complications. it is related to kyasanur forest disease virus, which is localized in karnataka, india [ , ] . however, epidemiologic findings suggest another wider geographic location for the disease in western (including jeddah and makkah) and southern (najran) parts of saudi arabia, and the virus infections mostly occur in humans [ , , ] . a study was conducted by alzahrani et al. in the southern part of saudi arabia particularly in the city of najran (with populations of~ , ), an agricultural city in saudi arabia, where domestic animals are reared at the backyard of owners. after the initial virus identification, from january through april , persons with positive serologic test results were identified. infections were suspected if a patient had an acute febrile illness for at least two days; when all other causes of fever have been ruled out [ ] . additionally, data analysis indicated that patients infected with the virus were either in contact with their domestic animals, involved in slaughtering of the animals, handling of meat products, drinking of unpasteurized milk, and/or were bitten by ticks or mosquitoes. symptoms consistent with ahfv infection-including fever, bleeding, rash, urine, color change of the feces, gum bleeding, or neurologic signs-then develop [ ] . fortunately, infected patients responded to supportive care (including intravenous fluid administration and antimicrobial drugs when indicated), with no fatal cases. in summary, ahfv is a zoonotic disease with clinical features ranging from subclinical or asymptomatic features to severe complications. another study highlighted different characteristics of the exposure to the blood or tissue of infected animals in the transmission of ahfv to humans. of the patients confirmed with infections, % were butchers, shepherds, and abattoir workers, or were involved in the livestock industry [ ] . more recently, a study on infection using c bl/ j mice cells showed that the clinical symptoms of the disease were similar to the presentations in humans [ ] . however, alkhurma disease resulted in meningoencephalitis and death in wistar rats, when high titers to the infection occurred [ ] . in addition, exposures to mosquito bites are regarded as potential sources of transmissions of the infection; however, very few available data support this [ ] . although, available data shows that alkhurma virus has been isolated following mosquito bites [ ] . however, another study suggested that mosquitoes may play a role only as a vector in the transmission of the disease [ ]. cchf is a zoonotic viral disease from the bunyaviridae family, and the principal vector for the disease is ticks of the genus hyalomma. it is most commonly endemic in africa, middle east, asia, and eastern europe [ , ] . it is an acute, highly-contagious, and life-threatening vector-borne disease responsible for severe hemorrhagic fever during outbreaks, and a fatality rate of up to % [ , ] . the infectious disease was recognized first in the crimean peninsula in , and it was named crimean hemorrhagic fever virus because the virus was isolated for the first time from a febrile child in from stanleyville (now kisangani), democratic republic of congo [ ] . currently, the virus infects both humans and animals following tick bites [ ] . however, a human can be infected by the animal through contact with the blood or tissues of the infected animal, in particular, exposures at the abattoirs are common. therefore, workers in contact with animals (e.g., veterinarians, farmers' and workers in slaughterhouses) form a high percentage of those affected [ ] . also, different species of infected animals-such as camels, cattle, sheep, goats, and ostriches-might be infected with no clinical signs [ ] . in addition, human-to-human transmission is also documented, mostly through a form of nosocomial or in-house infection [ , [ ] [ ] [ ] . lately, antibodies to the virus have been detected in different animal species, as reported in , in egyptians animals' sera [ ] . the preliminary seroepidemiological survey detected antibodies to the virus in . % of camels' sera and . % of sheep sera, but no antibody was detected against the virus in the sera of other animals such as donkeys, horses and mules, pigs, cows, and buffaloes [ ] . the epidemiology and distribution of cchf in saudi arabia are unclear, but there are reports of cchf as a result of the trading and importing of infected livestock from neighboring countries to saudi arabia [ ] . in , the cchf virus (cchfv) caused an outbreak involving seven individuals in makkah, although the virus had not been reported previously in saudi arabia. therefore, a study on the epidemiology of this virus was carried out in makkah, jeddah, and taif from - . about out of different species of ticks that were capable of transmitting the disease were collected from camels, cattle, sheep, and goats, but camels had the highest rate of tick infestation ( %), and h. dromedarii was the commonest tick ( %). an investigation in makkah between and , which included a serological survey of abattoir workers in contact with sheep blood or tissue, identified human cases of confirmed or suspected cchf with fatalities [ ] . the report from the investigation stated that the virus might have been introduced to saudi arabia through the jeddah seaport via infected ticks on imported sheep; since then, it has been endemic in the western province of saudi [ , ] . in addition, another previous study confirmed that the highest seropositivity rate of the virus in saudi arabia localities was associated with animals imported from sudan [ ] . furthermore, the who reported countries with cchf including saudi arabia; however, all the remaining countries are either close to saudi arabia or are islamic countries with high numbers of muslims who travel annually to saudi arabia for hajj pilgrimage. the same who epidemiological data suggest that in these countries including saudi arabia, in recent years, there has been report of steadily increasing number of sporadic human cases, incidence, and outbreaks of the virus [ ] . furthermore, another study by who investigating cchfv in the eastern mediterranean region (emr) stated that cchf is a clear and growing health threat in the who emr. cases are being reported in new areas, showing a geographical extension of the disease that is probably linked to the livestock trade and the spread of infected ticks by migratory birds. according to ecological models, the increase in temperature and decreased rainfall in the who emr could have resulted in the sharp increase in distribution of suitable habitats for hyalomma ticks and the subsequent drive of cchfv infection northwards [ ] . jazan province, the red sea port city on saudi arabia's southern border with yemen, serves as the east-west portal from sub-saharan africa at djibouti and the south-north route across the yemeni frontier. it is a heavily traveled corridor for humans and animals entering saudi arabia, particularly during the annual hajj pilgrimage. in november , a total of ( %) enrolled soldiers reported symptomatic illness during deployment, ( %) of whom were hospitalized. reported signs and symptoms included fever (n = ), rash (n = ), and musculoskeletal complaints (n = ). a surveillance study was conducted to detect the causes of the several outbreaks through that area, which was reported as endemic over a wide geographic range. from the surveillance, serologic testing for cchfv, ahfv, denv, and rvf was completed for saudi military units from several saudi arabian provinces. these units were previously stationed in other parts of the country, and were deployed to jazan province; the initial screening for igg of each of these viruses was conducted by igm testing for all igg-reactive samples. among the samples from all military forces, the study identified reactive serum samples with a combined seroprevalence of . cases/ soldiers tested. a confirmed serologic status of soldiers who were evaluated for igg and igm elisa reactivity against cchfv, rvf, ahfv, and denv infections were positive for , , , and sample, respectively [ ] . rvf is a common arbovirus zoonotic disease caused by the rvf virus. the virus belongs to the genus phlebovirus and family bunyaviridae. it is most common in domestic animals, and causes mild to life-threatening infections in humans. the name of the disease was derived from the great rift valley of kenya, when the disease was described for the first time in [ ] . epidemiological tests have since been described after a highly fatal epizootic occurred there in [ ] . rvf is a viral zoonosis with evidence of widespread occurrence in humans and animals in africa and the arabian peninsula. the epidemiology of this virus in saudi arabia might be closely related to the ecological factors that are prevalent, as shown from another area, along the great rift valley, which traverses ethiopia and kenya to northern tanzania with the drainage ecosystems [ ] . saudi arabia has many of the world's mosquito vectors of parasitic and arboviral diseases. however, few studies have addressed their geographic distribution and larval habitat characteristics [ ] . there are complex interactions between these factors that significantly impact mosquitoes ecological fitness and vectorial capacity for disease transmission, with important implications for vector management and control at the local and regional levels [ , ] . therefore, studying these factors for different mosquito fauna will help in monitoring potential modifications of larval habitats due to rains, global climate change, or man-made activities. previous studies on the ecology, distribution, and abundance of mosquito species in kingdom of saudi arabia are generally few and sporadic; and most of these studies were conducted in the western and southern regions. these studies were conducted in the asir province in - and - [ , ] [ , ] . these studies reported the presence of many species from many genera, the most important of which are anopheles, aedes, and culex. among these studies, only a few provided the description of habitats of the larvae of these vectors. even fewer studies provided evidence on the active role of some species on disease transmission; the existing ones were mainly for anopheles vectors of malaria [ , , ] , as well as aedes and culex vectors of arboviruses such as sindbis and dengue fever [ , , ] . rvf is not considered a major type in the arboviruses family, which mostly are adapted to a narrow range of vectors; however, among this family, the rvf infection has a very wide range of vector including mosquitoes such as aedes and culex, flies, and often, ticks [ ] . interestingly, for different rvf species, rvf vectors have special roles about how they sustain the transmission of the disease ecologically to humans [ ] . in some cases, the impact of rainfall, soil type, water, the persistence of breeding, and often wind, have significant effect on vector distribution [ ] . epizootics studies indicate that rvf disease follows unusually severe rainy seasons, a situation that may likely favor the breeding of a very large insect population, needed as a vector prerequisite. globally, rvf epidemiology was first reported in africa with the rvf epizootics in kenya when laboratory test reports confirmed virus isolation [ ] [ ] [ ] . in , the disease, for the first time, affected humans and livestock outside africa, with the larger rvf disease incidence following outbreaks, reported in saudi arabia [ ] and yemen. lately, rvf infections have been associated with minimal genetic diversity, epidemiologically; which has lately been considered to be a newly introduced single lineage of rvf viral disease [ ] . epidemiological reports from both saudi arabia and yemen showed that the outbreak, which occurred in , resulted in about human infections, and deaths [ ] . furthermore, the fatality rate reported in southern saudi arabia then, reached %, and was considered the most severe epidemic in that area ever since [ ] . moreover, the disease outbreak was thought to have been transmitted in countries such as saudi arabia by infected imported ruminants from east africa via the port of djibouti and probably from kenya and/or sudan [ ] . however, the fact remains that the rvf epidemic has been around for more than years, with infections occurring at prolonged intervals in eastern and southern africa [ , ] . consistent with this, another report showed that the same virus strain was implicated in the - rvf outbreaks in kenya and the outbreaks in saudi arabia and yemen [ ] . the outbreaks in kenya later resulted in about , human infected with about patients deaths [ , ] . surprisingly, in , jup et al. found the mosquito species that was identified as a potential vector, which led to the assumption that the zoonotic viral disease in saudi arabia was transmitted by culex tritaeniorhynchus [ ] . other species of mosquitoes were implicated in the transmission of this viral disease in other countries closer to saudi arabia [ ] [ ] [ ] . furthermore, another study reported the unexplained rvf virus infection among people from saudi arabia, with isolation and genetic virus characterization associated with illness in livestock, along the southwestern border of saudi arabia in september [ ] . the study reported that vertical transmission of the virus in the epidemic mosquito vector occurred in saudi arabia. in addition, the study stated that the most abundant culicine mosquitoes collected were aedes vexans arabiensis, culex pipiens complex, and culex tritaeniorhynchus, which were considered to be the most important epidemic and epizootic vectors of rvf virus in saudi arabia [ , ] . however, the same study, focusing on a very important issue which occurred during the rainy seasons; suggested that aedes vexans arabiensis has the potential to be an important epidemic and epizootic vector because of the tremendous numbers of individual mosquitoes produced after a flood [ ] . characteristically, once the virus is introduced into permissive ecologies, it becomes zoonotic; thus, they are able to enhance vulnerability of the area to periodic outbreaks, with the potential to spread further into non-endemic environments with favorable conditions [ , ] . saudi arabia is considered a region where rvf virus has circulated actively. noticeable data regarding zoonotic infection from animal to human from the arabian peninsula including saudi arabia has recently showed that it may be due to the consumption of unpasteurized camel milk [ , , ] . wernery reported camelus dromedarius as the animal host and/or reservoir of rvf zoonotic infection, which was diagnosed in the arabian peninsula [ ] . due to the scientific data regarding rvf disease, it is quite clear that globalization of trade and altered weather patterns are a concern for the future spread of more infections, since the causative agent of this viral disease is capable of utilizing a wide range of vectors for its transmission. thus, this poses a significant challenge to outbreak prediction, with inherently complex methods of infection control; therefore, mitigation and management of the virus will require concerted efforts [ , , ] . dengue hemorrhagic fever (dhf) viral disease is a serious global mosquito-borne infection. the clinical manifestation ranges from mild febrile illness to severe sickness which may include dengue shock syndrome [ ] . the dhf virus belongs to the genus flavivirus in the flaviviridae family, which can usually be spread by mosquitoes of the genus aedes aegypti, but less often through the genus aedes albopictus [ , ] . also, this virus is a single-stranded positive-sense rna virus that exists as four different serotypes (den- , den- , den- , and den- ) [ ] . in saudi arabia, the disease is limited to the western and southwestern regions, such as jeddah and makkah where aedes aegypti exists. however, all dhf cases in saudi arabia presented as a mild disease [ , ] . in fact, the first experience of dhf virus isolation from saudi arabia was recorded during an outbreak of the virus in [ ] , where the confirmed cases reported in jeddah were caused by denv- [ ] [ ] [ ] . however, during this first outbreak, in both summer and rainy season, at the end of the year, both denv- and denv- were isolated. in , during the rainy season in jeddah, there was an emergence of the denv- virus [ ] . in subsequent years, from - ; the emergence of dhf occurred with the three identified serotypes (denv- , denv- , and denv- ) isolated in jeddah [ ] . khan [ , ] . however, egger suggested that the reemergence of the disease in saudi arabia might be explained by the growing levels of urbanization, international trade, and travels [ ] . in keeping with the findings of most previous studies, the epidemiological occurrence of dhf infection using the saudi's national data indicated that the majority ( %) of patients with dengue virus infection were saudi nationals [ ] . on the contrary, from the epidemiological report based on saudi's national data in previous publications, an estimated % of patients with dhf presented in jeddah [ ] . kholedi [ ] . in yet another recent study, the virus was reported as % in saudi patients [ ] . all of these saudi studies were conducted in jeddah. from makkah city, the reported epidemiological study identified . % of dhf infection cases among saudi nationals [ ] . similarly, a later study puts the estimate at more than % of saudi nationals [ ] . these previously published studies suggest that differences in proportions may exist between saudi nationals infected with dhf virus in jeddah and makkah city. contrary to previous data from jeddah, in makkah, it was clear that the majority of patients presenting with clinically significant dhf were saudi nationals. therefore, these results emphasized the fact that saudi nationals are at greater risk of dhf infection. the awareness of these results is considered a cornerstone to enhancing the ability of healthcare professionals' identification of the disease; and this might play an important role in the development of effective eradication strategies for the disease in saudi arabia localities. furthermore, the first cases of the virus, confirmed in al-madinah in , showed that the isolated virus serotypes were denv- and denv- [ ] . in , the moh in saudi arabia reported a total of cases of the dhf infection, with an estimated case fatality rate of about . per thousand in saudi arabia [ ] . in august , several countries in asia, including malaysia, singapore, and pakistan reported about , , , and dengue cases including deaths, respectively. in the same period ( ), saudi arabia reported confirmed dengue cases in makkah, of which occurred in august , suspected cases, and cases pending laboratory confirmations. from these epidemic data indicating the reemergence of dhf infection in saudi arabia; jeddah, makkah, and al-madinah were shown to be the more susceptible areas, for this infectious disease, and this could be due to the fact that these cities are the sites of both the annual hajj pilgrimage and/or the minor umrah pilgrimage, which draw millions of muslims to saudi arabia [ , ] . currently, there are few epidemiological studies on dhf virus infection in saudi arabia. a study by al-azraqi et al. was conducted in hospitals and primary healthcare centers in two cities in the southern province of saudi arabia, particularly in jizan, and aseer. the study, which was limited to the seroprevalence among clinically suspected hospital-based patients, detected about . % positive cases of dengue virus igg among randomly selected patients attending the outpatient clinics for any reason. the associated risk factors were male gender, younger age ( - years) , lack of electricity, and having water basins in the house [ ] . the authors suggested that the virus may occur in sporadic cases in jizan, due to the nature of the city. jizan is relatively flat and located at sea level [ ] ; thus the likelihood of the formation of small stagnant water following the rainfall in the city is high [ ] . interestingly, a retrospective cross-sectional study, which compared the clinical findings and/or the diagnostic laboratory results in uncomplicated patients, and patients who developed dhf, was conducted at dr. soliman fakeeh hospital in jeddah, between january and june . about patients with a discharge diagnosis of dhf or dengue shock syndrome were identified [ ] . of these, ( %) were adult patients within the age range - years, and % were children with age ranging from months to years. however, among all these patients, % of the adults and % of the pediatric cases were males. the clinical data from the hospital showed that in the adult patients, about % made a full recovery without complications while two patients died [ ] . more recently in january , the moh began an intensive campaign to eradicate the dhf virus from saudi arabian cities, to enhance public health awareness, and facilitate a change in hygiene behavior of citizens and residents. this resulted in a . % reduction in the number of dhf infection among inpatient cases in jeddah when compared to the same period in the previous year. however, the overall drop in dhf cases reached % in , compared to the previous year [ ] . furthermore, recently, it is well-known that in saudi arabia, the dhf infection has been limited to the western and southwestern regions such as jeddah and makkah where aedes aegypti exists. however, all dhf cases in jeddah, saudi arabia, were mostly mild cases [ , , ] and the prospect of dengue virus control lies with vector control, health education, and possibly vaccine use. west nile fever is one of the emerging zoonotic infections, which is caused by an arthropod-borne virus belonging to the genus flavivirus, of the rna family flaviviridae. the virus' main reservoir, which is responsible for the transmission of the disease, is the genus culex mosquitoes [ , ] . the west nile virus (wnv) derived the name from the site where the first case was isolated in , from the blood of a woman with mild febrile illness living in the west nile district of uganda [ ] . the first outbreak, in - , was reported in israel [ ] . this constituted a turning point in the epidemiology of the virus, because it was thought to have originated from israel following the introduction from africa, and later introduced to the usa in [ , ] . subsequently, the infection was documented across the globe [ ] , with the exception of antarctica [ ] , in various species of vertebrates, including humans, mammals, non-human primates, birds, rodents, reptiles, and amphibians [ ] . however, birds are considered as one of the main reservoirs of the virus [ ] . saudi arabia is geographically close to several of the countries where wnv had circulated actively or had been reported; thus, there is a high risk of the disease being introduced into saudi arabia. wnv is known to cause neurological disease in both humans and horses. however, the clinical manifestations of the disease in horses include ataxia, paralysis of the limbs, recumbency, hyperexcitability, and hyperesthesia. in al-ahsa, saudi arabia, a study was performed on horses to test the incidence of the virus using the clinical examination and serologic elisa test. however, from this previous study, while clinical examination for neurologic signs detected no significant findings, wnv antibodies were positively identified at serology among . % of the tested population [ ] . in , lanciotti et al. found this virus to be responsible for an outbreak of encephalitis in two fatal human cases from northeastern usa in late summer; and suggest a closely relation between this outbreak in the usa to a wnv infection which was isolated from a dead goose in israel in [ ] . the first cases of wnv in horses was identified in egypt and france in the s [ ] ; ever since, wnv has had significant public health impact worldwide due to its resurgence and dynamic epidemiologic features in humans and animals. between and , a study in iran identified wnv antibodies in horses, and the results confirmed the highest activity of the virus reported in the western and southern provinces with seroprevalences of up to % in some areas of iran [ ] . although human cases and/or animal infections with wnv including horses have also been reported in jordan and lebanon (direct and close neighbors of saudi arabia) between and [ ] [ ] [ ] ; however, the reported wnv in patients or horses in these areas might have circulated in natural transmission cycles with close relationship to the wnv isolated from human and horses in jordan, lebanon, and iran in , , and , respectively. humans and horses (incidental hosts), are unable to develop sufficient viremia to infect mosquitoes, hence, they are not included in the wnv lifecycle [ ] . more recently, in , using standard procedures, the central veterinary research laboratory in dubai, the united arab emirates, described the first wnv isolation in a dromedary calf; and this supports the conclusion that wnv is present in the country [ ] . the wnv zoonotic infection was probably transmitted through the human-animal interface; that is through the well-known contact with infected arabian camels in saudi arabia. interestingly, dromedary are exported from the united arab emirates to saudi arabia and vice versa; due to the closely related wnvs genes and their circulation through the natural transmission cycles worldwide, a complete genome sequencing for more wnvs strains, as well as comparative genomic and phylogenetic studies in saudi arabia, are needed to ascertain whether the dromedary infection with wnv exists in the country or not. however, the same facts have been suggested recently ( ), when it was suggested that wnv infection was introduced into turkey at the time of the outbreaks in saudi arabia and yemen. it was further suggested that the virus may have been introduced via unlawful entrance of viremic domestic or wild animals through the borders or through vectors that carry the virus into turkey [ ] . camels play an important role in public health issues regarding zoonosis and they have been involved in most of the zoonotic infections which occurred in saudi arabia in the last three decades. they are reported as sources of infections-including rabies, mers-cov, alkhurma virus, cchfv, and rvf virus [ , , , , , , ] -via direct physical contacts with camels and/or indirectly by having camels within or near the household in saudi arabia. however, some zoonotic infections among camels are sometimes asymptomatic; thus, they play a vital role in the mechanism of transmission of various diseases [ ] . furthermore, wernery et al. reported that wnv can be transmitted by mosquito bites in different species including to humans, horses, camelids, and many other mammalian species as well as reptiles and birds [ , , ] . to the best of our knowledge, there is still no extensive surveillance data regarding this disease among wildlife animals in saudi arabia. strikingly, several of the human zoonotic cases that involve camels-which included different viral, bacterial, and parasitic infections on the arabian peninsula-have recently been highlighted as being caused by the consumption of unpasteurized camel milk [ ] . currently, in this review, some aspects of the most common viral diseases of zoonotic importance in saudi arabia were summarized; these are presented in table . however, data regarding emerging and reemerging zoonotic viral diseases are reported as they occur from time to time from the same, new, and/or different localities from saudi arabia. while other viral zoonotic infections occur in other countries, which are considered to be close to saudi arabia, some infections spread to some localities within saudi arabia because of the geographical proximity as shown in figure . interestingly, some of these zoonotic viral pathogens were first exotic to saudi arabia (e.g., mers-cov and ahfv) and should be of more concern when reported in prevalence studies, and whenever they are detected by saudi authorities. epidemiological data should be focused more on both the trade routes and wildlife migration across the region, since these are potential risks for saudi arabia (e.g., from yemen, egypt, gulf areas, and sudan). fortunately, there are many ways and/or approaches to improve the control of such different zoonotic pathogens in animals and humans in saudi arabia. however, the control measures of these viral zoonotic pathogens will not only benefit saudi arabia or arabian peninsula but will also be of high benefit to other countries, especially those with low prevalence, by stopping or controlling the spread of the epidemic worldwide. prevention, control, and management of several zoonotic diseases usually require several important measures including the following. having vaccination protocols for all suspected animal species by the use of up to date vaccines and compliance with the standards needed for all animals. taking into account the highly needed and important investigation for these zoonotic viral diseases vectors, including vector breeding control (including vectors, hosts, and arthropods), and control of the animals (livestock) movements, with respect to trade and export [ , ] . because an intensive livestock trade exists between saudi arabia and its neighboring countries, there may be increased risk of reemerging viral diseases of all kinds [ , ] . this is supported by several previous studies concerned with the route of livestock trade between saudi arabia and the neighboring countries (e.g., rabies through yemen and/or oman [ , ] interestingly, some of these zoonotic viral pathogens were first exotic to saudi arabia (e.g., mers-cov and ahfv) and should be of more concern when reported in prevalence studies, and whenever they are detected by saudi authorities. epidemiological data should be focused more on both the trade routes and wildlife migration across the region, since these are potential risks for saudi arabia (e.g., from yemen, egypt, gulf areas, and sudan). fortunately, there are many ways and/or approaches to improve the control of such different zoonotic pathogens in animals and humans in saudi arabia. however, the control measures of these viral zoonotic pathogens will not only benefit saudi arabia or arabian peninsula but will also be of high benefit to other countries, especially those with low prevalence, by stopping or controlling the spread of the epidemic worldwide. prevention, control, and management of several zoonotic diseases usually require several important measures including the following. having vaccination protocols for all suspected animal species by the use of up to date vaccines and compliance with the standards needed for all animals. taking into account the highly needed and important investigation for these zoonotic viral diseases vectors, including vector breeding control (including vectors, hosts, and arthropods), and control of the animals (livestock) movements, with respect to trade and export [ , ] . because an intensive livestock trade exists between saudi arabia and its neighboring countries, there may be increased risk of reemerging viral diseases of all kinds [ , ] . this is supported by several previous studies concerned with the route of livestock trade between saudi arabia and the neighboring countries (e.g., rabies through yemen and/or oman [ , ] ; rvf through kenya, djibouti, and/or egypt [ , , ] ; cchf through sudan [ ] ; influenza through oman and egypt [ , , , [ ] [ ] [ ] ; wnv through emirates, egypt, jordan, and israel [ , , , , ] ; and dhfv through egypt [ ] ; as well as mers-cov and ahfv viral infections, which originated and are transmitted globally from saudi arabia) [ , , , , ] . therefore, it is clear that a huge gap still exists in the sharing of published data about the acknowledged epidemiology of zoonotic diseases in saudi arabia, which rigorously prohibits speculations about the health burden of people. currently, there are surveillance activities for some viral diseases-such as rabies, mers-cov, and influenza-but these are still being weakly addressed or neglected, especially at the human-animal interface. the important role of vaccination both in the prevention and control of animal diseases and the need to check the human sources in food or water must not be neglected. also, management of animals, both outdoors and indoors must be taken seriously. however, owners of pets clinics and pets stores should be held responsible in ensuring that they keep their pets' vaccination protocols up to date, and prevent any kind of animal behavior that might result in zoonotic risks to humans through bites or scratches by pets. therefore, pet clinics and/or pets stores should be always considered a serious public health issue and vaccination should be obligatory. therefore, the importance of the annual vaccination routine programs for all stray dogs against rabies, and regular investigation of other animals, should be considered. in addition to this, pet clinics and stores should monitor pets' health records, and their owners should be held fully responsible in ensuring that their animals remain healthy and fully vaccinated. this will guarantee for them and their neighbors a zoonotic disease-free environment (e.g., against rabies virus particularly in dogs). this is particularly important in view of the case of human rabies reported in march from a makkah hospital. this involved a -year-old saudi man who was admitted to the hospital with a history of an unprovoked scratch on his face by a dog. a month after his admission, his saliva pcr test confirmed rabies virus [ ] . nevertheless, rabies is endemic in animals in the arabian peninsula, with increasing numbers of reported cases form certain countries in the area including saudi arabia, yemen, and oman [ , ] . kuwait, qatar, and the united arab emirates are considered to be rabies-free, whereas there is no available information about bahrain [ , ] . furthermore, animal rabies cycle and cases reported in these endemic countries including saudi arabia are characterized by different animal species such as camels, cattle, goats, and sheep; however, the majority of cases are reported in feral dogs [ , ] . fortunately, studies about pets with different zoonotic infections from pet clinics and/or pet stores in saudi arabia have been rarely detected among cats, dogs, and baboons. however, there was a previous study, which reported the occurrence of toxocara canis infection in pets (dogs) in riyadh, saudi arabia [ ] . there were also two previous reports regarding a protozoan zoonotic infection of some pets with clinical manifestation, particularly in papio hamadryas baboon in riyadh [ , ] . in addition to this, another report highlighted the protozoan zoonotic infection in camels, in riyadh [ ] ; however, more of these kind of studies are needed, because, they provide important opportunities to present a clear picture about indoor and outdoor animals and zoonotic pathogens such as viral, bacterial, fungal, etc. which involved, in saudi arabia. by enhancing biosecurity and management in animal farms, the risk of reemerging pathogens particularly responsible for zoonotic diseases caused by viruses, can be reduced. this is a matter of economic importance; in view of the large livestock trade existing or that existed between countries in the indian ocean and eastern africa countries where several zoonotic diseases are endemic. however, a phylogenetic study strongly suggests that some zoonotic infections have been introduced into saudi arabia through ruminant trade [ , ] . furthermore, following the adoption of the recommended guidelines of the world organization for animal health through its office international des epizooties (oie) code, if such policies regarding the exportation and/or importation of animals are exactly followed, these would greatly limit the extent of this risk [ ] . furthermore, an emphasis should be made on surveillance to detect any sign of zoonotic disease that might occur in any animal kept directly in a quarantine station in any country of origin for days prior to shipment to another country to ensure no clinical sign develops during that period. in addition, the longer quarantine periods or restriction of imported animals-particularly pets (e.g., dogs, cats, rodents, and monkeys) or goats, sheep, and camels-from endemic countries may be effective in reducing the introduction of zoonotic viruses. of such measures, the control of vectors (e.g., ticks and mosquitoes), particularly the intermediate hosts and animal reservoirs, should be key components in the intervention strategy for zoonoses in saudi arabia. while the improving, enhancing, providing, and upgrading of laboratory techniques and/or testing in both veterinary and human medicines are fundamental to early detection and containing of any zoonotic disease or transmitted infection. indeed, epidemiologic evidence should be linked with the seasonal time during the year for different zoonoses, and/or with any symptoms related to zoonotic infections that occur on the mainland a few years earlier. up to date ecological factors on evolutionary issues, social movements, economic, and epidemiological mechanisms affecting zoonotic pathogens' or their persistence and emergence, are not yet well understood. however, studies on the ecological, socioeconomic, and health issues are needed to assess the sustainability and acceptability of measures by breeders, as well as information that ensures appropriate slaughtering or consumption practices, which will decrease the risk of infection to humans [ ] . due to these facts about the ecological cascade and evolutionary perspectives, authorities can provide valuable insights into pathogen ecology and can inform zoonotic disease control programs; and thus evaluate their global effect in terms of actual disease and its socioeconomic correlations. enhancing biosecurity and management in the treatments of various zoonotic infections may result in appropriate use of vaccinations, drugs, and antibiotics, however, the overuse of these agents result in various types of resistance. furthermore, regardless of the influenza virus resistance level to treatment, according to a serosurveillance, the enzootic influenza virus h n in egypt is endemic [ ] . the same result to oseltamivir-resistant influenza viruses are reported globally, with a high susceptibility to these antiviral drugs among all reported cases of the virus from egypt. resistance was also found in most infected viral cases that are usually acquired in humans through intensive contacts, particularly with backyard birds, among women and children [ , , , ] . therefore, drug regimens in saudi must include vaccines against this virus during hajj and umrah seasons, for egyptians. most importantly, epidemic zoonotic cases of influenza among pets has highlighted the importance of circulating influenza viruses globally, and the importance of ensuring the effective use of antivirals for the prophylaxis and treatment of influenza, especially because of the increased number of new pets stores in saudi arabia, particularly in riyadh [ , ] . thus, studies on drug resistance are considered to be of a high public health importance, although, this might demonstrate the best scenario of how drug resistance in saudi arabia can pave its own way and/or role into the reemerging of different zoonotic pathogens. on the other hand, few studies have been done in this area to identify the relationship between different gatherings and the occurrence of signs and clinical symptoms of viral infections, especially among humans of different ages and gender. however, there are several suggestions and information regarding zoonoses (e.g., influenza and mers-cov infections) in saudi arabia among the elderly, based on age and gender [ , ] . more recently, increased availability of limited public health data on the prevalence of some zoonotic diseases and associated risk factors or data that identifies the relationship between different zoonotic pathogen antibodies in pregnant women, are of importance [ , ] . central to the profound worldwide changes in religious beliefs and activities is the birth of a new era of both emerging and reemerging diseases that could be arranged under the umbrella of social movements, along with its own role in the spread of zoonotic diseases. thus, any prevention and/or control strategies against any zoonotic pathogen have to take this point of view into account. furthermore, annually, saudi arabia hosts the largest international gathering of hajj where many millions gather in a small geographical area. this puts saudi arabia in the front line of threats of pandemic diseases [ ] . thus, saudi arabia must keep a high level of alertness in monitoring the situation of these pathogens, particularly in view of the potential for global spread of pandemic viruses especially during winter and around the hajj season (e.g., mers-cov infections, ahfv, and influenza viruses). therefore, there is need to prevent further spread of the virus locally, regionally, and internationally. interestingly, with wnv outbreaks, the israeli-like wnv that was isolated in white storks in egypt in - suggests that migrating birds do play a crucial role in the geographical spread of the virus [ ] . recently, the same fact was again suggested in , when the same infection by this virus was introduced into turkey at the time of the outbreaks in saudi arabia and yemen; it was stated that the wnv virus might have been introduced via unlawful entry of the viremic domestic or wild animals through the borders, or by vectors carrying the virus to turkey [ ] . more recently, epidemiological data of zoonotic viral pathogens from saudi arabia and/or from other neighboring countries after it was confirmed through laboratory test isolation from dromedaries (e.g., rabies, mers-cov, rvfv, and wnv) may enhance a high interest in the search for other novel zoonotic viruses in dromedaries [ , , , , , ] . furthermore, the habits of ingestion off unpasteurized milk from camels as a rare delicacy by saudi people need to be checked. moreover, viral pathogens such as rvfv are acquired through the importation of camels, while the remaining pathogens (e.g., rabies and influenza viruses) are endemic worldwide. of these (e.g., influenza virus), there is need for a highly preventive zoonotic control in saudi, due to fact that the isolation and genetic characterization of h n was reported in among vaccinated meat-turkeys flock in egypt, a neighboring country, that was previously reported to have more than , travelers to saudi arabia during hajj pilgrimage seasons, annually [ ] . this might be considered as one of such important risk factor of possible introduction or spread of influenza pathogen in saudi arabia [ , ] . lastly, increased zoonotic pathogens surveillance, particularly influenza, during the hajj season, increased infection control interventions, screening, and quarantine of suspected cases, provision of adequate medical treatment, sustainable awareness, increased education and training of target groups at high risk (e.g., doctors, nurses, veterinarians, and animal workers such as farmers and abattoir workers, etc.) are of great importance to reduce the burden of zoonoses among saudi arabian localities. fortunately, in collaboration with three organizations-including the moh in saudi arabia, the usa centers for disease control and prevention, and the who-a successful preparedness plan during the hajj season was put in place to vaccinate all pilgrims before leaving their home countries [ ] . altogether, there is an urgent need for collaborative surveillance and intervention plans for the control of zoonotic pathogens in saudi arabia. with saudi arabia, the focal point of the ongoing zoonotic pathogens outbreak could be due to the large number of religious pilgrims congregating annually particularly in makkah, jeddah, and al-madinah, the main three cities for hajj and umrah, which drastically increased the potential for uncontrolled global spread of zoonotic infections [ ] . a zoonotic pathogen outbreak could be dramatically decreased among the annual saudi pilgrims if we take into account the fact that: jeddah governorate, the main seaport in saudi arabia is considered to be the main entry point for over million pilgrims coming for hajj or umrah annually. all these numbers of pilgrims arrive through the jeddah islamic port before going on to makkah, for the start of their umrah and/or hajj. surprisingly, the current review showed that during an outbreak, each of these eight most zoonotic viruses (rabies, mers-cov, influenza, ahfv, cchfv, rvfv, dhfv, and wnv) which occurred and/or cases confirmed in saudi arabia particularly from (jeddah and/or makkah) areas with at least one or all of these eight zoonotic viral pathogenic diseases [ , , , , [ ] [ ] [ ] [ ] , , , ] . the spread could also have been due to the fact that jeddah is the main port for animal importation to saudi arabia. at the same time, it is the closest area to several countries where some zoonotic outbreaks were reported. to enhance this spread, the role of the active circulation of zoonotic viruses, during their natural transmission cycle, has been reported, however, an importation might increase risk of disease introduction to saudi arabia. • almost annually, from the more than million pilgrims who come to makkah and madinah from different countries worldwide during hajj and umrah, the kingdom's revenue in was put at more than billion saudi riyals (~about . billion us dollars), % up from the figures. this hajj revenue accounted for % of the gross domestic product for the kingdom of saudi arabia. to avert all that number of health hazards from zoonotic diseases in view of economic facts, the global community and particularly the pilgrims need more gift items made in saudi arabia to control and prevent the spread of zoonotic diseases which could be transmitted among hajj and umrah pilgrims. therefore, the following recommendations are suggested in order to improve public awareness and/or health education of zoonotic viral diseases in saudi arabia: based on findings of previous studies, health education strategies could enhance the awareness of the saudi population regarding viral zoonotic diseases through health education program experiences of other countries, particularly during hajj and umrah seasons. this response can draw on the availability of several studies on how to improve, control, and prevent the spread of several zoonoses in both animals and humans, worldwide [ , [ ] [ ] [ ] [ ] . public health authorities must highlight the importance of promoting health education and facilitate the outcomes of studies for reducing patient cases in saudi arabia. the saudi authorities and government bodies such as the moh should also launch different programs and workshops to increase public awareness about these zoonotic infections. this should involve the cooperation of the saudi regime, and the private and public sectors. different activities may be needed in saudi arabia-such as the practice of self-protection against these diseases, adult control strategies, control activities, and regular workshops-to achieve control and prevention. enhancing of self-awareness among people through health education programs or other strategies for the prevention of viral zoonotic diseases, which require vectors (such as mosquitoes, ticks, and fleas) for their transmission; are important issues on which the saudi population should be educated. they should also be educated about the adverse effects of arbitrary application of insecticides without prior knowledge on dose, resistance, and side effects. increasing the knowledge about the biology and ecology of the animal vectors in society is also crucial. furthermore, the saudi ministry of culture and information should establish intensive health education programs on television channels, radio, and newspapers to increase public awareness and to maintain hygiene conditions within the kingdom and in saudi houses. the saudi ministry of agriculture could play a big role by regularly controlling the application of vaccinations and/or antibiotics on animals which used in the veterinary sector, and also accounting the misuse of such agents following other developed and developing countries on controlling and/or accounting drug strategies [ , , ] . thus, veterinary regulations of animal antibiotics-including overuse of drugs and their application-must be enforced to alleviate the serious public health problems. funding: this research received no external funding. the authors thank the dental oral rehabilitation (dor) research center at king saud university, college of dentistry, kingdom of saudi arabia, riyadh for their support. also the authors wish to appreciate all the researchers whose articles were used in the present research. the authors declare no conflict of interest. the life and work of rudolf virchow - : cell theory, thrombosis and the sausage duel joint who/fao expert 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tracking australian hajj pilgrims’ health behavior before, during and after hajj, and the effective use of preventive measures in reducing hajj-related illness: a cohort study date: - - journal: pharmacy (basel) doi: . /pharmacy sha: doc_id: cord_uid: wln og this study assessed australian hajj pilgrims’ knowledge, attitude and practices throughout their hajj journey to understand their health behaviors, use of preventative measures and development of illness symptoms. a prospective cohort study with data collection at three phases (before, during and after hajj) was conducted among australian pilgrims between august and december . baseline data were collected from pilgrims before hajj, with providing follow-up data during hajj and after their home return. most participants ( % [ / ]) received one or more recommended vaccines; travel agents’ advice was the main factor affecting vaccination uptake. most participants ( % [ / ]) practiced hand hygiene with soap and sanitizers frequently, followed by disposable handkerchief use ( % [ / ]) and washing hands with water only ( % [ / ]). during hajj % ( / ) of participants reported one or more illness symptoms, % ( / ) of these symptoms were respiratory. cough was less often reported among pilgrims who received vaccinations, cleaned their hands with soap or alcoholic hand rubs, while a runny nose was less common among those who frequently washed their hands with plain water but was more common among those who used facemasks. this study reveals that most australian hajj pilgrims complied with key preventative measures, and that tour group operators’ advice played an important role in compliance. pilgrims who were vaccinated and practiced hand hygiene were less likely to report infection symptoms. the hajj pilgrimage attracts over two million pilgrims every year to saudi arabia, making it one of the biggest annual human mass gatherings on the planet [ ] . consequently, with such large numbers of pilgrims from around the world in close proximity to one another, there is amplified risk of transmission of infectious diseases among those present [ ] . to minimize the risks, saudi ministry of health (moh) require a valid vaccination certificate against meningococcal disease for all pilgrims, plus yellow fever and polio vaccines for pilgrims coming from or transiting through endemic countries. additionally, vaccinations against influenza, diphtheria, pertussis, tetanus, mumps and measles are recommended, particularly for pilgrims susceptible to more severe disease [ ] . other relatively inexpensive preventative measures such as hand hygiene and facemask use are also recommended [ ] . studies have consistently shown that there is an extensive variation in vaccine uptake among pilgrims based on their country of origin, demographics and vaccines received. similarly, hand hygiene and other preventative practices also vary among pilgrims, making it more difficult for researchers to ascertain whether vaccine uptake and health behaviors overall have improved in comparison to previous years or studies [ ] [ ] [ ] . although there is some research linking knowledge, attitudes, and beliefs of hajj pilgrims to their use of preventive measures, no studies have explored their knowledge, preparedness and preventive practices over the course of their travel (i.e., following the same cohort before, during and after hajj) [ , [ ] [ ] [ ] [ ] . to address these research gaps, we conducted a cohort study to explore australian hajj pilgrims' knowledge about the risk of diseases during hajj, assess their preparedness and use of preventive measures at three times points (before, during and after hajj) , investigate the factors affecting their preventive health behavior, and determine the number of reported infections during and after hajj. this was a prospective cohort study undertaken between august and december among australian hajj travelers aged years or older. the participants were residents of greater sydney, new south wales, australia. this region was chosen because it contains the largest muslim population in new south wales, australia. the participants were assessed before, during and after returning from their pilgrimage to makkah, saudi arabia. this study was approved by the university of sydney human research ethics committee (hrec) (project no: / ). all overseas pilgrims travelling to saudi arabia require a visa which can only be acquired through approved hajj travel agents [ ] . these tour operators play a pivotal role in pilgrims' preparation leading up to hajj, relaying important travel instructions prior to departure through 'pre-hajj seminars' which almost all prospective pilgrims attend [ ] . this made these seminars an ideal recruitment points for a representative sample. the list of accredited australian hajj tour operators and their addresses were collected from the saudi embassy in canberra, australia. a selection of participating travel agencies was decided on the basis of the number of hajj visas allocated for a given tour operator and the operators with the highest visa quotas were approached first. three questionnaires were used for data collection: ( ) a pre-hajj questionnaire completed prior to departure; ( ) a 'hajj diary' completed daily over six days during the peak hajj period; and ( ) a post-hajj questionnaire, completed upon return to australia. the surveys were mainly in english, with the availability of arabic, turkish and urdu translations for those who preferred it. we attended eleven seminars held by the hajj travel agents in sydney from august to september to explain our research. once pilgrims consented to participate in the study, their characteristics were obtained using a self-administered questionnaire documenting socio-demographic details, their travel itineraries, vaccination records, and presence of chronic medical conditions such as hypertension, diabetes, bronchial asthma and hyperlipidemia. barriers to, and facilitators of vaccine uptake and data on risk perception of diseases at hajj, such as influenza, pneumonia, blood borne infections and their preparedness for using preventive measures during hajj were also collected. we did not ask about the receipt of meningococcal vaccine because our previous survey showed that all australian pilgrims receive this as a mandatory visa requirement [ ] . we travelled to makkah, saudi arabia, during hajj period ( - september ) and identified and met the study participants upon their arrival in mina, greater makkah. the participants were given a diary for self-completion daily over the six consecutive days of hajj (the peak hajj days). they were followed from - september . each participant was asked to record the following in the diary for each day: actual use of preventative measures including, facemask use, hand sanitizer use, hand washing after touching an ill person and use of disposable handkerchiefs. as the data were collected electronically, no respondent could submit their responses with vitally important information missing. any respondent who used a preventive measure ≥ days during the peak hajj days considered to be 'frequently compliant', those who used the preventive measure < days were considered to be 'infrequently compliant' and those who did not use the preventive measure at all were considered 'non-compliant'. any development of symptoms suggestive of respiratory infection including cough, subjective fever sore throat, rhinitis and other symptoms including vomiting, diarrhea and nausea was also recorded. we considered those who complained of cough, subjective fever and sore throat to meet the criteria of influenza-like illness (ili). the respondents participated in a computer-aided telephone interview (cati) seven to days after their coming back to australia (until december ). they were asked about any development of symptoms suggestive of respiratory infection such as cough, sore throat, runny nose, fever, and also about some constitutional or gastrointestinal symptoms like vomiting, diarrhea and nausea after their home return from hajj. facilitators of and barriers to using preventive measures during hajj were also explored. for each participant we made three call attempts before being classified as lost to follow-up. a consecutive sampling strategy was used to ensure a representative sample of hajj pilgrims living in nsw. based on results from previous research, and considering an error margin of % to be acceptable for this survey, a sample size of pilgrims was deemed to be sufficient. considering a loss to follow-up rate of %, participants were targeted, representing % of australian pilgrims attending hajj in . statistical analysis was performed using the spss v. . (spss, inc., chicago, il, usa). chi-squared tests and pearson correlation were used to assess variables and establish associations and correlations. factors with p values < . in univariate analysis were entered into multivariable regression models. binary logistic regression, using the backward wald method, controlling for factors was used to investigate variables related to health behavior. p values less than . were considered statistically significant in multivariable models. a three-point likert scale was used to measure the pilgrims' perception about the risk of diseases during hajj and the effectiveness of the preventive measures. a total of pilgrims were recruited in the first stage of the study (before hajj); out of those, ( %) were followed during hajj; and finally, ( %) were reached after their return to australia ( figure ). of , % were female and their mean age was . (standard deviation [sd] ± . ) years. regression models. binary logistic regression, using the backward wald method, controlling for factors was used to investigate variables related to health behavior. p values less than . were considered statistically significant in multivariable models. a three-point likert scale was used to measure the pilgrims' perception about the risk of diseases during hajj and the effectiveness of the preventive measures. a total of pilgrims were recruited in the first stage of the study (before hajj); out of those, ( %) were followed during hajj; and finally, ( %) were reached after their return to australia (figure ). of , % were female and their mean age was . (standard deviation [sd] ± . ) years. over a quarter ( %) reported having one or more pre-existing medical conditions. over one third of participants ( %) had a university degree or higher qualification and two thirds ( %) were employed. the pilgrims intended to stay in saudi arabia for a median of (range: - ) days, and the majority ( %) were attending hajj for the first time. the participants' further demographic details are presented in table . the majority of participants ( %, [ / ]) received one or more recommended vaccines (i.e., vaccines that are recommended but not compulsory); of those, % ( / ) received only the influenza vaccine, % ( / ) received influenza plus other recommended vaccines while the remaining % ( / ) received only "other than influenza" vaccines. overall, the coverage of influenza, pharmacy , , of pneumococcal and pertussis vaccine was, respectively, % ( / ), % ( / ) and % ( / ) ( table ) . on the other hand, % ( ) did not receive any recommended vaccine. * some pilgrims cited more than one reason. thirty-one percent ( / ) were in an at-risk category; of those, % ( / ) were aged ≥ years and % ( / ) aged < but had one or more chronic medical condition (e.g., diabetes). the influenza vaccination rate among at-risk group was % ( / ), while the uptake of pneumococcal vaccine was % ( / ) . no significant differences of influenza and pneumococcal vaccine uptake were noted between 'at risk' and not 'at risk' groups. participants reported different sources of vaccination advice including, hajj (table ). multivariate analysis showed that being aged between and years was significantly associated with the receipt of recommended vaccines compared to being aged ≤ years or ≥ years (adjusted odds ratio [aor] = . , % confidence interval [ci] = . - . , p < . ). moreover, those who had a university qualification or higher education were more likely to receive vaccine than those who had lower level of education (aor = . , % ci = . - . , p < . ). . those who were very concerned about blood borne diseases (aor = . , % ci = . - . , p = . ) and pneumonia (aor = . , % ci = . - . , p < . ) were twice as likely to receive hepatitis b and pneumococcal vaccines respectively. yet, no association was found between the level of concern about influenza and the receipt of influenza vaccine. (table ). in addition, % ( / ) of pilgrims used antibiotics during hajj. there was no significant association between pilgrims' intended use of non-pharmacological measures and their actual use during hajj (table ) . in multivariate analysis, no demographic factors were associated with using hand hygiene with soap and sanitizers, but those who were concerned about developing pneumonia during hajj (aor = . , % ci = . - . , p = . ) were more likely to practice hand hygiene with soap and sanitizers during hajj compared to those who were not concerned. those aged ≥ years (aor = . , % ci = . - . , p = . ) were more likely to practice hand hygiene with alcoholic hand rubs than those aged < years. moreover, males were more likely to wash their hands with water only (aor = . , % ci = . - . , p < . ) and wash hands after touching an ill person (aor = . , % ci = . - . , p < . ) but were less likely to use disposable handkerchiefs (or = . , % ci = . - . , p < . ) compared to females. on the first day of hajj, some pilgrims were symptomatic; % had a cough, % had a sore throat, and % had a runny nose. however, on the th day up to % became symptomatic. the reported onset of daily symptoms among pilgrims during the peak days of hajj is presented in figure . on the first day of hajj, some pilgrims were symptomatic; % had a cough, % had a sore throat, and % had a runny nose. however, on the th day up to % became symptomatic. the reported onset of daily symptoms among pilgrims during the peak days of hajj is presented in figure . overall, % ( / ) of participants reported one or more illness symptoms throughout the hajj journey. eighty-six percent ( / ) of these symptoms were respiratory, including cough, % ( / ); sore throat, % ( / ); runny nose, % ( / ); and fever, % ( / ). ili was only reported among % ( / ) of participants. additionally, % ( / ) reported diarrhea, % ( / ) nausea and another % ( / ) reported vomiting. twenty six per cent ( / ) of respondents did not report any symptom during hajj. over half ( % [ / ]) reported symptoms after returning from hajj; of those, % ( / ) reported cough ( %, [ / ] of these also had cough during hajj), % ( / ) sore throat ( %, [ / ] of them reported sore throat during hajj), %, ( / ) runny nose ( %, [ / ] reported runny nose during hajj) and % ( / ) had fever ( %, [ / ] had fever during hajj). ili was reported in % ( / ) of participants; of those, % ( / ) also reported ili during hajj. moreover, % ( / ) reported diarrhea, % ( / ) nausea and another % ( / ) reported vomiting. as shown in table , cough was less likely to occur among those who were vaccinated against influenza and those who used alcoholic hand rubs. runny nose was less likely to occur who frequently washed their hands with plain water but was more common among those who used facemasks. vomiting was less likely to be reported among those who washed their hands frequently with soap and sanitizers during hajj, but more common in those who used disposable handkerchiefs. no association was found between use of any of the preventive measures and reduction in fever and sore throat. overall, % ( / ) of participants reported one or more illness symptoms throughout the hajj journey. eighty-six percent ( / ) of these symptoms were respiratory, including cough, % ( / ); sore throat, % ( / ); runny nose, % ( / ); and fever, % ( / ). ili was only reported among % ( / ) of participants. additionally, % ( / ) reported diarrhea, % ( / ) nausea and another % ( / ) reported vomiting. twenty six per cent ( / ) of respondents did not report any symptom during hajj. over half ( % [ / ]) reported symptoms after returning from hajj; of those, % ( / ) reported cough ( %, [ / ] of these also had cough during hajj), % ( / ) sore throat ( %, [ / ] of them reported sore throat during hajj), %, ( / ) runny nose ( %, [ / ] reported runny nose during hajj) and % ( / ) had fever ( %, [ / ] had fever during hajj). ili was reported in % ( / ) of participants; of those, % ( / ) also reported ili during hajj. moreover, % ( / ) reported diarrhea, % ( / ) nausea and another % ( / ) reported vomiting. as shown in table , cough was less likely to occur among those who were vaccinated against influenza and those who used alcoholic hand rubs. runny nose was less likely to occur who frequently washed their hands with plain water but was more common among those who used facemasks. vomiting was less likely to be reported among those who washed their hands frequently with soap and sanitizers during hajj, but more common in those who used disposable handkerchiefs. no association was found between use of any of the preventive measures and reduction in fever and sore throat. this cohort study captured and compared the health behavior, knowledge, attitudes and practices of australian hajj pilgrims regarding preventative measures against communicable diseases throughout the course of hajj travel (before, during and after the journey). vaccinated pilgrims and those who washed their hands and used alcohol rubs were less likely to develop respiratory symptoms during hajj. influenza vaccination coverage was relatively higher ( %) among australian pilgrims, compared to that reported in studies from other countries, but was lower compared to that in australian pilgrims in ( %) and in ( %) [ , ] . in contrast, coverage of other recommended vaccines, such as the pneumococcal vaccine, was suboptimal ( %), as has been reported in previous studies involving australian hajj pilgrims and other international pilgrims [ , ] . the coverage of influenza vaccine among pilgrims with high-risk conditions was %, while that of pneumococcal vaccine was only %; compared to the influenza vaccination coverage among pilgrims with high-risk conditions from other countries, australian hajj pilgrims had a higher vaccination rate [ ] . the low pneumococcal vaccine uptake is a concern because pneumococcal diseases, including invasive pneumococcal disease, are major causes of morbidity and mortality in the extremes of age and in individuals with chronic medical conditions worldwide, including hajj pilgrims [ , ] . of note, while the influenza vaccine is highly recommended by the saudi moh for hajj attendance, particularly for pilgrims aged ≥ years [ ] , there is no formal recommendation regarding the pneumococcal vaccine. this study found that a large number of participants were willing to use non-pharmacological preventative measures to reduce the prevalence of illnesses during hajj. however, there was no significant correlation between their intention to use measures and their actual use during hajj. although the level of concern for pneumonia and diarrhea was higher among first time hajj goers and pilgrims < years of age, these factors were not shown to be significant in their actual use of preventive measures during hajj. pilgrims who were concerned about catching diseases and those who joined hajj for the first time were more likely to accept the use of non-pharmacological measures before hajj. however, these intentions were not associated with actual use of preventive measures. previous studies have not explored if demographic factors were associated with an intention to use non-pharmacological protective measures before travel and their actual use during hajj. nonetheless, earlier studies did conclude that health education prior to departure was significantly associated with greater compliance with preventative practices, particularly the use of facemasks and hand sanitizers [ ] [ ] [ ] [ ] . demographic factors had minimal association with pilgrims' health behavior such as vaccine uptake, and the factors associated with pilgrims' willingness to use preventive measures were not associated with their actual use during hajj. consequently, these findings pose questions of other possible causes that might affect pilgrims' behaviors during hajj. in this study, several factors were identified as influencing pilgrims' health behavior, including disease risk perception, awareness of recommendations, the influence of people around them, age and medical history, the source of their travel health advice, and the lived experience of using preventive measures during hajj. these factors can be stratified into five categories: individual, interpersonal, organizational, community-associated and policy-related. relying on a single factor does not fully explain the interplay and dynamics between pilgrims' health behaviors and their influencers; rather, consideration of multiple factors at different levels may help to understand these cross-cutting relationships. these dimensions fit within the 'social-ecological model' which emphasizes the connectivity and relationship among multiple factors affecting health behavior, as shown in figure . the overlapping circles in the model illustrate how factors at one level influence factors at another level. this framework is based on evidence that no single factor can explain why only some people comply with preventive measures while remain influenced by multiple inter-related factors. the core of the model is at the individual level, surrounded by the outer four bands representing the interpersonal, organizational, community and policy levels ( figure ). it is important to understand and find the most common or influential reasons and the link between these levels to enhance pilgrims' health behavior uptake in regards to each measure. in addition, while some interventions such as vaccines are known to be clinically effective, their acceptability to pilgrims is a vital part of their overall effectiveness as a public health intervention. effective behavioral change is only made when changes interconnect between the individual, community, organizational and policy levels. this includes addressing underlying and related factors such as individual beliefs, culture, and miscommunication between organizations as well as government policies. this can help promote lasting changes in practices; on an individual level, cultural and religious beliefs; in attitudes and perception; in communication between the health care providers such as gps and the community; providing the service suppliers such as the travel agent with up-to-date health recommendations and also improving the communication between the international and local health policies (figure ) [ ] . future studies could be grounded in 'social ecological' theory, in order to further articulate the inter-level relationships between health behavior factors identified in this study, encouraging new insights to promote the health interventions among hajj pilgrims. care providers such as gps and the community; providing the service suppliers such as the travel agent with up-to-date health recommendations and also improving the communication between the international and local health policies (figure ) [ ] . future studies could be grounded in 'social ecological' theory, in order to further articulate the inter-level relationships between health behavior factors identified in this study, encouraging new insights to promote the health interventions among hajj pilgrims. during hajj, about % of participants reported developing one or more respiratory symptoms; a cough and sore throat were the commonest symptoms similar to what was found in earlier studies involving australian pilgrims who attended hajj in [ ] , and among french, iranian and malaysian pilgrims who attended hajj between and [ ] [ ] [ ] . during hajj, ili was reported by % of pilgrims in this study, a similar rate was reported previously among australian hajj pilgrims in [ ] . in other studies involving hajj pilgrims the reported incidence of ili varied (from % to %) [ ] . the risk of disease was equally high among returning pilgrims, with % to % of them reporting cough, sore throat and runny nose, and % suffering from ili as found in other studies [ ] [ ] [ ] . countries should continue to monitor the pilgrims and their contacts after the pilgrims' return from hajj to estimate the risk of post-hajj infections. influenza vaccine effectiveness was studied in several studies. in two studies conducted in and , a reduction in ili was observed, while in a few other earlier studies no significant reduction was noted [ ] . a synthesis of published and raw data from eleven hajj years between and showed that the rate of ili decreased among hajj pilgrims as the vaccination rate increased (relative risk . , p < . ) [ ] . subsequently, a 'test-negative' case-control study using data from individual hajj years involving participants from multiple countries shows trivalent influenza has an effectiveness of . % ( % ci . % to . %, p = . ) against laboratory-confirmed influenza [ ] . the varying results may due to heterogeneity in defining ili or may be because of ili symptoms representing non-influenza infections or even due to confounding factors such as use of facemasks or hygienic interventions [ , , ] . there are some limitations; % respondents failed to complete the study. this is a little higher than the expected loss to follow up ( %), however as this study was conducted over three months during hajj, about % of participants reported developing one or more respiratory symptoms; a cough and sore throat were the commonest symptoms similar to what was found in earlier studies involving australian pilgrims who attended hajj in [ ] , and among french, iranian and malaysian pilgrims who attended hajj between and [ ] [ ] [ ] . during hajj, ili was reported by % of pilgrims in this study, a similar rate was reported previously among australian hajj pilgrims in [ ] . in other studies involving hajj pilgrims the reported incidence of ili varied (from % to %) [ ] . the risk of disease was equally high among returning pilgrims, with % to % of them reporting cough, sore throat and runny nose, and % suffering from ili as found in other studies [ ] [ ] [ ] . countries should continue to monitor the pilgrims and their contacts after the pilgrims' return from hajj to estimate the risk of post-hajj infections. influenza vaccine effectiveness was studied in several studies. in two studies conducted in and , a reduction in ili was observed, while in a few other earlier studies no significant reduction was noted [ ] . a synthesis of published and raw data from eleven hajj years between and showed that the rate of ili decreased among hajj pilgrims as the vaccination rate increased (relative risk . , p < . ) [ ] . subsequently, a 'test-negative' case-control study using data from individual hajj years involving participants from multiple countries shows trivalent influenza has an effectiveness of . % ( % ci . % to . %, p = . ) against laboratory-confirmed influenza [ ] . the varying results may due to heterogeneity in defining ili or may be because of ili symptoms representing non-influenza infections or even due to confounding factors such as use of facemasks or hygienic interventions [ , , ] . there are some limitations; % respondents failed to complete the study. this is a little higher than the expected loss to follow up ( %), however as this study was conducted over three months in three different settings (before, during and after hajj) in two countries (australia and saudi arabia), it was very challenging to follow all participants, some of whom may have taken a side trip to other countries at the end of the hajj. a french study revealed that over a quarter of the pilgrims intended to delay their return to france after hajj, a situation that makes difficult to ensure maximum follow up [ ] . information and recall bias may have occurred due to the anecdotal nature of some survey questions, especially those of the post-hajj survey. although our results cannot be generalized to all pilgrims, this study is the first of its kind to assess pilgrims' kap continuously throughout the hajj journey to understand their health behaviors, experience of using preventative measures and the development of acute respiratory infections, and other symptoms of infections. in the meantime, studies conducted in france and malaysia have shown that compliance to some preventive measures such as hand hygiene and face mask use has increased, while the uptake of recommended vaccines including influenza and pneumococcal vaccines still remains low [ ] [ ] [ ] ; therefore, awareness campaigns should be continued to tackle respiratory infections including the ongoing covid- pandemic that, thus far, has taken a toll of over , people across the world (as of april ) and affected many muslim countries including saudi arabia [ ] . to mitigate the epidemic, the saudi arabian authority has already temporarily cancelled umrah (minor pilgrimage) visit to makkah [ ] ; the decision on whether this year's hajj pilgrimage (late july to early august) should be cancelled or not remains to be decided and may depend on the progress of the pandemic [ ] . our findings mean 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malaysian hajj pilgrims acute febrile respiratory infection symptoms in australian hajjis at risk of exposure to middle east respiratory syndrome coronavirus prevalence of influenza at hajj: is it correlated with vaccine uptake? health related experiences among international pilgrims departing through king abdul aziz international airport the prevalence and preventive measures of the respiratory illness among malaysian pilgrims in hajj season changes in the prevalence of influenza-like illness and influenza vaccine uptake among hajj pilgrims: a -year retrospective analysis of data influenza vaccine effectiveness among hajj pilgrims: a test-negative case-control analysis of data from different hajj years pilot randomised controlled trial to test effectiveness of facemasks in preventing influenza-like illness transmission among australian hajj pilgrims in travel reported by pilgrims from marseille, france before and after the hajj: table hajj in the time of covid- respiratory tract infections among french hajj pilgrims from abubakar baaba, a. assessment of knowledge, attitude and practice towards prevention of respiratory tract infections among hajj and umrah pilgrims from malaysia uptake of recommended vaccines and its associated factors among malaysian pilgrims during hajj and umrah saudi arabias measures to curb the covid- outbreak: temporary suspension of the umrah pilgrimage the cancellation of mass gatherings (mgs)? decision making in the time of covid- this article is an open access article distributed under the terms and conditions of the creative commons attribution (cc by) license key: cord- - qcgpe authors: refaey, samir; amin, marwa mohamed; roguski, katherine; azziz‐baumgartner, eduardo; uyeki, timothy m.; labib, manal; kandeel, amr title: cross‐sectional survey and surveillance for influenza viruses and mers‐cov among egyptian pilgrims returning from hajj during ‐ date: - - journal: influenza other respir viruses doi: . /irv. sha: doc_id: cord_uid: qcgpe background: approximately egyptians participate in hajj pilgrimage annually. the purpose of this study was to estimate influenza virus and mers‐cov prevalence among egyptian pilgrims returning from hajj. study: a cross‐sectional survey among returning egyptian pilgrims from to was conducted. nasopharyngeal (np) and oropharyngeal (op) swabs were collected from all participants. sputum specimens were collected from participants with respiratory symptoms and productive cough at the time of their interview. specimens were tested for influenza viruses, and a convenience sample of np/op specimens was tested for mers‐cov. thirty percent of participants met the case definition for influenza‐like illness (ili), % tested positive for influenza viruses, and none tested positive for mers‐cov. self‐reported influenza vaccination was %. conclusions: high prevalence of reported ili during pilgrimage and confirmed influenza virus on return from pilgrimage suggest a continued need for influenza prevention strategies for egyptian hajj pilgrims. an evaluation of the ministry of health and population's current risk communication campaigns to increase influenza vaccine use among pilgrims may help identify strategies to improve vaccine coverage. pre-departure vaccination against influenza a(h n )pmd for all pilgrims during the season. since then, the mohp has required seasonal influenza vaccination for all pilgrims as part of the saudi visa application process. although the requirement is not always enforced, seasonal influenza vaccine is available at local health offices for all egyptian pilgrims throughout most of year. the mohp has additionally conducted an annual survey among pilgrims returning from hajj to explore the risk of influenza virus transmission to the broader community. following the emergence of mers-cov in saudi arabia, the mohp expanded the survey to test for mers-cov. a cross-sectional survey was conducted at cairo international airport among egyptians returning from hajj during the week following the end of hajj each year from to (table ) . cairo airport was selected for this survey as it is the main point of entry into egypt for returning hajj pilgrims. cairo airport receives - flights during working hours ( am- pm) from saudi arabia, accounting for approximately - pilgrims per day. a team from the mohp sought to enroll a convenience sample of approximately % of pilgrims from each flight returning from hajj and congregating at the airport carousels, regardless of age, sex, and illness status. after providing verbal consent, participants were asked about demographic information, respiratory symptoms, and whether they received vaccines as part of their hajj visa application process. both nasopharyngeal (np) and oropharyngeal (op) swabs were collected from all participants regardless of the presence of respiratory symptoms. sputum specimens were collected from participants who presented with respiratory symptoms and a productive cough at the time of their interview. travelers who reported a history of subjective fever (a proxy for measured fever) and cough with symptom onset in the previous days were categorized as having influenza-like illness (ili). for minors, consent and survey responses were provided by accompanying parents. specimens positive for influenza a were subsequently tested for influenza a virus subtypes. sputum specimens and a convenience sample of np/op specimens were tested for mers-cov according to who guidelines. the proportion of samples testing positive for influenza virus from participants was compared to those collected from ili casepatients through the national surveillance system during the same time period. t a b l e the distribution of egyptian pilgrims surveyed by season according to gender, age group, presence of influenza-like illness (ili), vaccination status and influenza laboratory test result < y ( ) ( . ) ( . ) ( . ) ( . ) -< y ( ) ( ) ( ) ( ) ( ) -< hajj: infectious disease surveillance and control respiratory tract infections during the annual hajj: potential risks and mitigation strategies hajj-associated viral respiratory infections: a systematic review middle east respiratory syndrome coronavirus (mers-cov) -saudi arabia risk factors for primary middle east respiratory syndrome coronavirus illness in humans, saudi arabia hospital outbreak of middle east respiratory syndrome coronavirus mers-cov outbreak in jeddah-a link to health care facilities state of knowledge and data gaps of middle east respiratory syndrome coronavirus (mers-cov) in humans pandemic (h n ) and hajj pilgrims who received predeparture vaccination who surveillance case definitions for ili and sari world health organization. laboratory testing for middle east respiratory syndrome coronavirus, interim recommendations high prevalence of common respiratory viruses and no evidence of middle east respiratory syndrome coronavirus in hajj pilgrims returning to ghana respiratory viruses and bacteria among pilgrims during the respiratory tract samples, viral load, and genome fraction yield in patients with middle east respiratory syndrome prevention and control of seasonal influenza with vaccines: recommendations of the advisory committee on immunization practices -united states cross-sectional survey and surveillance for influenza viruses and mers-cov among egyptian pilgrims returning from hajj during - key: cord- -mbiojk authors: benkouiten, samir; al-tawfiq, jaffar a.; memish, ziad a.; albarrak, ali; gautret, philippe title: clinical respiratory infections and pneumonia during the hajj pilgrimage: a systematic review date: - - journal: travel med infect dis doi: . /j.tmaid. . . sha: doc_id: cord_uid: mbiojk background: the islamic hajj pilgrimage to mecca is one of the world's largest annual mass gatherings. inevitable overcrowding during the pilgrims' stay greatly increases the risk of acquiring and spreading infectious diseases, especially respiratory diseases. method: the medline/pubmed and scopus databases were searched for all relevant papers published prior to february that evaluated the prevalence of clinical symptoms of respiratory infections, including pneumonia, among hajj pilgrims, as well as their influenza and pneumococcal vaccination status. results: a total of papers were included in the review. both cohort- and hospital-based studies provide complementary data, and both are therefore necessary to provide a complete picture of the total burden of respiratory diseases during the hajj. respiratory symptoms have been common among hajj pilgrims over the last years. in cohorts of pilgrims, cough ranged from . % to . %. however, the prevalence rates of the most common symptoms (cough, sore throat, and subjective fever) of influenza-like illness (ili) varied widely across the included studies. these studies have shown variable results, with overall rates of ili ranging from % to . %. these differences might result from differences in study design, study period, and rates of vaccination against seasonal influenza that ranged from . % to % among study participants. moreover, the definition of ili was inconsistent across studies. in hospitalized hajj pilgrims, the prevalence of pneumonia, that remains a major concern in critically ill patients, ranged from . % to . %. conclusions: large multinational follow-up studies are recommended for clinic-based syndromic surveillance, in conjunction with microbiological surveillance. matched cohorts ensure better comparability across studies. however, study design and data collection procedures should be standardized to facilitate reporting and to achieve comparability between studies. furthermore, the definition of ili, and of most common symptoms used to define respiratory infections (e.g., upper respiratory tract infection), need to be precisely defined and consistently used. future studies need to address potential effect of influenza and pneumococcal vaccine in the context of the hajj pilgrimage. ksa for several weeks throughout the month-long hajj season, presenting a major public health and infection control concern, and a challenge both for the saudi authorities, as well as for the national authorities of the countries of origin of the pilgrims. in addition to physical exhaustion, sleep deprivation [ ] , and heat stress [ ] , inevitable overcrowding, both in housing and ritual sites, especially in mina encampment (this is approximately a -kilometer square area where pilgrims are accommodated in air-conditioned semi-permanent tents, some with up to - people) and inside the sacred mosque in mecca (with up to six pilgrims per square meter) [ ] , greatly increases the risk of acquiring and spreading infectious diseases [ ] [ ] [ ] , especially respiratory diseases [ , ] . to minimize the spread of infections during the pilgrimage or in the pilgrims' home countries upon their return, vaccination and non-pharmaceutical interventions are thus recommended by national and international public health agencies [ , ] . we carried out a systematic review of cohort and hospital studies that reported the prevalence of clinical symptoms of respiratory infections and pneumonia among pilgrims during the hajj, and both their influenza and pneumococcal vaccination status, with the aim to provide data allowing the investigation of the impact of this large mass-gathering event on public health policies and services and to identify potential targets for preventive measures. this review was performed according to preferred reporting items for systematic reviews and meta-analyses (prisma) guidelines (http://www.prismastatement.org). the medline/pubmed and scopus databases were searched for all relevant papers published prior to february , using the terms: in addition, the saudi epidemiology bulletin (http://seb. drupalgardens.com/) was hand searched for additional papers for inclusion. finally, the reference lists of reviewed articles were searched for additional relevant papers. for inclusion, the article had to meet the following criteria: ( ) original study involving hajj pilgrims; ( ) detailed description of the study population, including influenza and pneumococcal vaccination status when available; ( ) clinical or self-reported respiratory symptoms and diseases. only articles published in english were included for review. we excluded cohort studies with less than participants and case reports. we also excluded studies conducted among selected groups of individuals suffering from respiratory tract infections, due to lacking denominator data. the two authors independently performed the searches, screened titles/abstracts for eligibility, selected papers that appeared to be relevant according to the review's inclusion criteria, and reviewed each of the selected manuscripts in full. the data were extracted from the included papers by one reviewer (sb) and collected in the summary table that was included in the review. the extracted data were checked by the two authors (sb and pg) for accuracy. minor discrepancies were resolved by the authors' discussion. the search strategy initially yielded records, of which were duplicates. twenty-nine additional papers were identified through manual searches. of the papers identified records were excluded after screening the title and abstract. of the full text articles reviewed, were deemed suitable for inclusion in this review influenza-like illness (ili) was defined according to the presence of the triad of cough, subjective fever and sore throat. c ili was defined as subjective (or proven) fever plus one respiratory symptom (e.g. dry or productive cough, runny nose, sore throat, shortness of breath). d ili was defined as subjective (or proven) fever and at least one respiratory symptom such as cough, sore throat and rhinorrhea. e ili was defined as symptoms and signs such as: sudden headache, dry cough, high grade fever, myalgia, coryza, malaise and loss of appetite with an abnormal general appearance. f upper respiratory tract infections (urti) was defined as any person who reported having developed at least one of the constitutional symptoms (fever, headache, myalgia) and one of the local symptoms (running nose, sneezing, throat pain, cough with/or without sputum) after reaching mecca for the hajj or within weeks from return to riyadh. g acute febrile respiratory infection (afri) was defined as the presence of subjective fever plus at least one respiratory symptom (cough, sore throat, runny nose or breathlessness). h two travelers who reported ''bronchitis'' as a symptom were also included. i ili was defined as fever plus sore throat and/or coughing. j common cold was defined as sore throat with coryzal symptoms, and low grade fever. k ili was defined as fever > . °c, myalgia, low back pain, coryzal symptoms and cough. l acute respiratory infection (ari) was defined as one of the constitutional symptoms (fever, headache, myalgia) along with one of the local symptoms (running nose, sneezing, throat pain, cough with/without sputum, difficulty breathing). m ari was defined as any person suffering from at least one of the constitutional symptoms (fever, headache, myalgia) along with one of the local symptoms (runny nose, sneezing, throat pain, cough with/without sputum, difficulty in breathing) developing after reaching makkah for the hajj. n ili was defined as cough and fever > °c with or without the coryzal symptoms and myalgia. o ari was defined as any person suffering from at least one of the constitutional symptoms (fever, headache, myalgia) along with one of the local symptoms (runny nose, sneezing, throat pain, cough with/without sputum, difficulty in breathing) developing after reaching mecca for the hajj. p ili was defined as sore throat with either temperature ≥ . °c or cough. q cough or sore throat or rhinorrhea or muscle ache or headache. according to the inclusion/exclusion criteria. the results of the search strategy are shown in fig. . a total of publications were identified. these studies were conducted among cohorts of pilgrims from the through the hajj seasons. the results of these studies are presented in table . various study designs were used, including cross-sectional studies, case-control studies, and prospective cohort studies with follow-up of pilgrims, before, during and after the hajj. participants were from different countries and continents (africa, north america, asia, europe, as well as from australia), with the majority from iran, and they were recruited from different settings, including travel medicine clinics, vaccination centers, hajj travel agencies, international airports and transit zones, mecca's city and mina encampments. their numbers varied widely in these studies, ranging from to , . respiratory symptoms were common during the hajj. overall, the prevalence of cough ranged from . % in domestic and international pilgrims in [ ] to . % in malaysian pilgrims in [ , ] ( table ) . more recent studies, conducted in different populations of pilgrims during the - hajj seasons, reported prevalence of cough ranging from . % to . % [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . these studies also reported a comparable prevalence of sore throat ranging from . % to % among pilgrims [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . in addition, many of these studies have investigated the epidemiology of respiratory tract infections among pilgrims by estimating the common prevalence of upper respiratory tract infection (urti), acute respiratory infection (ari) or influenza-like illness (ili), which were inconsistently defined across studies by a combination of general symptoms (e.g. cough, sore throat and fever). overall prevalence of ili varied in these studies from % to . % [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] ( [ , ] . however, the ili syndromic case definition used in the - study (ili was defined as cough and fever of more than °c with or without the coryzal symptoms and myalgia) [ , ] was different with that used in the - study (ili was defined as symptoms and signs such as sudden headache, dry cough, high grade fever, myalgia, coryza, malaise and loss of appetite with an abnormal general appearance) [ , ] . also, it is unclear from the study [ ] if the definition used was consistent with those used in the two previous studies [ , , , ] . in a recent large study, conducted among egyptian pilgrims between and , the prevalence of ili was . % (ili was defined according to the world health organization definition as the presence of measured fever of ≥ c°, and cough; with onset within the last days) [ ] . other studies of different sizes (from to ) and design were conducted from through among different populations of pilgrims using a common ili definition (the association of cough, sore throat, and subjective fever). these studies have shown variable results, with overall rates of ili ranging from % to . % [ ] [ ] [ ] , , [ ] [ ] [ ] , , , , ] . thus, during the hajj season, while the highest prevalence of ili was observed among malaysian pilgrims, with a prevalence estimated at . % [ ] , a lower prevalence was observed among french pilgrims ( . %) [ , ] . coverage of seasonal influenza vaccination among pilgrims was evaluated in many studies, which have yielded varying results, with reported rates of influenza vaccination ranged from . % to % [ , , , [ ] [ ] [ ] , , , , [ ] [ ] [ ] [ ] , , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] . a variation over time in influenza vaccination coverage was observed, as exemplified by a rate of . % observed in a survey of pilgrims from riyadh in [ ] , but . % in a similar survey in [ , , ] . during the hajj season, influenza vaccination rates also varied according to pilgrims' country of origin [ ] , with % observed among saudi pilgrims, % among qatari pilgrims, and % among australian pilgrims, while a study involving french pilgrims interestingly reported that none of them had received the influenza vaccine before departing for the hajj because the vaccine was not available at this time [ , ] . the majority of the studies reported influenza vaccination coverage among pilgrims, but only [ , , [ ] [ ] [ ] , , , , [ ] [ ] [ ] ] reported their pneumococcal vaccination status, with rates ranging from . % among a multinational cohort of pilgrims from countries (from africa, asia, usa and europe) in [ ] to . % among a small study of french pilgrims in [ , ] . of the publications that were included in this review, specifically addressed ill hajj pilgrims at health care facilities from through hajj seasons. medical facilities included primary health care centers (phccs) and different specialized wards in tertiary care hospitals, including ear, nose and throat (ent) departments, intensive care units, emergency units, infectious disease units and unspecified medical units. pilgrim participants were included either as inpatients or outpatients. the results of these studies are summarized in table . overall, the prevalence of upper respiratory tract infections (urti) ranged from . % to . % (table ). this prevalence was . % among pakistani pilgrims who attended the king abdul aziz hospital in medina during the hajj [ ] and . % among saudi and non-saudi patients ( . % of them were pilgrims) who attended the ent clinic at al-noor specialist hospital in mecca during the hajj [ ] . pharyngitis was also frequently reported among ill pilgrims. thus, in this study of pilgrims during the hajj, the overall prevalence of pharyngitis was . % [ ] . more recently, in , the prevalence of pharyngitis in a large cohort of outpatients patients from nationalities who attended randomly selected mina phccs ( . % of whom were pilgrims) was found to be . % [ , ] , and % in a study of saudi and non-saudi patients ( . % of them were inpatients) [ ] . however, in this second study of patients, only . % were pilgrims. on the contrary, lower prevalence rates of bronchitis were reported during the hajj ( . %- . %) [ ] [ ] [ ] [ ] [ ] . a recent retrospective cross-sectional multicenter study of turkish inpatients ( . % were pilgrims) who returned to turkey from the arabian peninsula countries between and reported a slightly higher prevalence of acute tracheobronchitis ( . %) [ ] . in addition, in this study, pneumonia was among the most common clinical diagnosis among the hospitalized hajj patients and represented about half of diagnoses [ ] . as pneumonia remains a major concern in critically ill patients, most of them reported the prevalence of pneumonia among pilgrims [ , , , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] , with reported rates ranging from . % in in randomly selected mina primary health care centers [ , ] to . % in in two icu in mecca [ ] (table ). the prevalence of pneumonia was not reported in papers [ , , ] . pneumonia was the second most common admitting diagnosis ( %) in a study of patients admitted to the icus in four hospitals in mina during the hajj [ ] . this result is further confirmed by a recent study of critically ill hajj patients, of over nationalities, admitted to hospitals in and . in this study, pneumonia was defined as the primary cause of critical illness ( . %) of all icus admissions during the hajj [ ] . also, in another prospective study of pilgrims admitted in two major icus in mecca for the hajj season, community acquired pneumonia (cap) was the commonest source of sepsis, . % [ ] . [ ] acute bronchitis: . % a upper respiratory tract infection (urti) was defined as an acute infection that includes tonsillitis, pharyngitis, laryngitis, sinusitis, otitis media, and the common cold. b acute tracheobronchitis was defined as a patient with dry cough and/or low-grade of fever (< °c), sub-sternal pain, and fatigue in the absence of opacities on chest x-ray. c acute exacerbation of chronic obstructive pulmonary disease (copd) was defined as an association with increased frequency and severity of coughing and/or shortness of breath and wheezing, increased amount of sputum production, and/or a change in appearance of sputum in a patient with copd. d was not defined. the purpose of this review was to provide syndromic surveillance data that may be useful, in conjunction with microbiological data that will be presented in further papers, for the surveillance of respiratory infections and pneumonia during the hajj. despite the fact that some of the included studies in our review were performed among small numbers of pilgrims and cannot be extrapolated, it is clear from this work that respiratory symptoms have been common among hajj pilgrims over the last years, as evidenced by the high prevalence of cough (over %) among malaysian pilgrims during the hajj [ ] . cough is a common symptom among pilgrims [ , ] and likely results from crowded conditions during the hajj. this close contact among such individuals may increase the risk of the transmission of respiratory pathogens, and therefore may contribute to respiratory disease outbreaks. climatic conditions and air pollution in mecca and surrounding holy sites during the hajj [ ] may also play a role. recent follow-up studies thus evidenced a significant acquisition of respiratory viruses, particularly rhinovirus, influenza virus, and coronaviruses other than middle east respiratory syndrome coronavirus (mers-cov), and of bacteria, including streptococcus pneumonia, hemophilus influenza, staphylococcus aureus and klesiella pneumonia by hajj pilgrims upon their return from the hajj [ , ] . respiratory diseases are the most common diseases observed among pilgrims attending mina primary health care centers [ ] and a major cause of hospital admission during the hajj [ ] , with pneumonia a leading cause of admission to intensive care units [ , ] , where they are responsible for about half of the cases of sepsis [ ] . unfortunately, while numerous articles on hajj pilgrims were retrieved from our literature search, relatively few recent articles specifically addressed ill pilgrims in the context of hospital settings. the use of cohort studies allows investigators to evaluate the actual incidence of clinical events in hajj pilgrims since it provides a denominator, but may not identify and capture the prevalence of some underlying conditions and of severe forms of respiratory tract infections, which are more likely to be evidenced in hospital patient populations. conversely, hospital studies use data that may be biased, frequently lacking denominator values, and so probably overestimating the occurrence of severe illness. moreover, a hospital-based study will, by definition, not capture some minor illness cases that do not require hospitalization. the prevalence rates of cough, sore throat and subjective fever varied widely across the included studies. these differences may result from differences in study design that may lead to potential biases (for example bias related to the method of data collection, using either selfreport questionnaires or telephone interview), study period (with regards to the seasonality of respiratory viral infections), and rates of vaccination against seasonal influenza among study participants which may widely vary from one study to another, as described in this review. thus, all data regarding the pilgrims, including demographic data, medical history, clinical data and information on vaccination status and compliance with non-pharmaceutical preventive measures, should be carefully collected by using standardized questionnaires. in addition, in the context of syndromic surveillance for respiratory pathogens, data regarding the pilgrim's symptoms should be collected prospectively during face-to-face interviews by trained medical investigators who travel with the pilgrims. one important result of this review is the finding of a lack of consistency ili syndromic case definitions across included studies. thus, in a study (that did not fulfill the inclusion criteria for this review) [ ] , of malaysian pilgrims who had a clinic visit for upper respiratory tract symptoms at five clinics during the hajj, with the aim of determining influenza vaccine effectiveness against clinically defined ili, % had ili (defined as sore throat in combination with either temperature ≥ °c or cough) and % had influenza by the cdc definition (defined as measured fever [≥ °f ( . °c)] and a cough and/or a sore throat). only one of the studies reported here used the cdc definition of ili or the who definition (an acute respiratory infection with measured fever of ≥ c°a nd cough, with onset within the last days) [ ] . in his paper, rashid et al. demonstrated the low sensitivity of the cdc criteria and proposed therefore the use of the triad of 'cough, sore throat and subjective fever' to clinically define ili at the hajj or other mass gatherings, since this new simple clinical case definition is more specific and sensitive than the cdc definition [ ] . this definition was used over the last years by french [ , , , [ ] [ ] [ ] , ] , malaysian [ , , ] , indian [ ] and afghan [ ] investigators leading cohort studies among hajj pilgrims, thus allowing more reliable comparisons of findings between studies (table ) . respiratory diseases are a major concern during the hajj. nonpharmaceutical interventions (e.g., hand hygiene, wearing face masks, social distancing) are known to reduce the spread of respiratory viruses from person to person and are therefore recommended to pilgrims by public health agencies. although hand hygiene compliance is high among pilgrims, face mask use and social distancing remain difficult challenges. data about the effectiveness of these measures for preventing acute respiratory infections at the hajj are limited, and results are contradictory, highlighting the need for future large-scale studies [ ] . in addition to non-pharmaceutical interventions, vaccination against influenza is recommended for all hajj pilgrims by the ministry of health of saudi arabia [ , ] . differences in study design and heterogeneity in the ili definition across studies make it difficult to compare findings from different studies and inhibits the drawing of conclusions regarding the potential effects of this vaccination on related clinical symptoms of influenza disease. however, recent papers by alqahtani et al. and alfelali et al. found the influenza vaccine to be effective, respectively, against both laboratory-confirmed influenza [ ] and clinical influenza [ ] . as influenza vaccination is generally considered effective in reducing influenza-related infections, the scientific committee for influenza and pneumococcal vaccination guidelines (scipv) thus recommends, in its recent guidelines, an influenza vaccination for all people, especially those at high risk, at least weeks before the hajj [ ] . it also recommends, for the next hajj seasons that will take place from june to september, the administration (prior to the hajj) of the southern hemisphere influenza vaccine for pilgrims from the southern hemisphere (where influenza positivity rates are higher during this period). furthermore, as the influenza vaccine is not expected to be available for pilgrims from the northern hemisphere before these next hajj seasons, the scipv also recommends the administration of the southern hemisphere influenza vaccine for those pilgrims from the opposite hemisphere before the hajj [ ] . because of the mismatching between circulating and vaccine strains that has frequently occurred since [ ] , alfelali et al. recommends, when the composition of influenza vaccines differs and whenever logistically feasible, taking into consideration the dual vaccination of hajj pilgrims with both the southern and northern hemispheres' vaccines. however, such strategy is impaired by the frequent unavailability of the southern hemisphere influenza vaccine in the northern hemisphere. the issue of influenza vaccine availability to match southern and northern hemispheres was discussed by the saudi ministry of health in consultation with the who and it was recommended to use the available hemisphere strain as long as there is a match in circulating strains [ ] . despite the risk of acquisition of s. pneumoniae during the hajj, there is currently no consistent guideline on the use of pneumococcal vaccine for hajj pilgrims across pilgrim countries of origin [ , ] . thus, and because many of the hajj pilgrims are elderly and have chronic illnesses and underlying risk conditions for which pneumococcal vaccination is recommended [ ] , the scipv also recommended, in its pneumococcal vaccination guidelines, pneumococcal vaccination of the atrisk population at the appropriate time before the hajj, using the types of pneumococcal vaccines that are currently available: the valent polysaccharide pneumococcal vaccine (ppsv ) and the -valent conjugate vaccine (pcv ) [ ] . however, it did not recommend providing a pneumococcal vaccine routinely to healthy persons aged less than years, because of lack of evidence. in addition, it has been well demonstrated that the conjugate vaccine against s. pneumoniae targets the most virulent serotypes associated with invasive pneumococcal diseases (ipd) that are also associated with antibiotic resistance [ ] . these arguments reinforce the need for compliance with current recommendations for vaccinating at-risk hajj pilgrims against ipd and influenza [ ] . respiratory tract infections, including influenza, continue to be a major concern during the hajj. both cohort-and hospital-based studies provide complementary data and potentially useful information, and both are therefore necessary to provide a complete picture of the total burden of respiratory diseases during this mass gathering. large multinational follow-up studies are thus recommended for clinic-based syndromic surveillance, in conjunction with microbiological surveillance. matched cohorts ensure better comparability across studies, particularly in terms of origin of pilgrims and possible travelling conditions. however, the study design and data collection procedures should be standardized, to facilitate reporting and to achieve comparability between studies. furthermore, the definition of ili, and of most common symptoms used to define respiratory infections (e.g., urti), needs to be precisely defined and consistently used. future studies need to address the potential effects of influenza and pneumococcal vaccine in the context of the hajj pilgrimage. moreover, because of the mismatching between circulating and vaccine strains that has frequently occurred since [ ] , alfelali et al. recommends, when the composition of influenza vaccines differs and whenever logistically feasible, taking into consideration the dual vaccination of hajj pilgrims with both the southern and northern hemispheres' vaccines. however, such strategy is impaired by the frequent unavailability of the southern hemisphere influenza vaccine in the northern hemisphere. despite the risk of acquisition of s. pneumoniae during the hajj, there is currently no consistent guideline on the use of pneumococcal vaccine for hajj pilgrims across pilgrim countries of origin [ , ] . thus, and because many of the hajj pilgrims are elderly and have chronic illnesses and underlying risk conditions for which pneumococcal vaccination is recommended [ ] , the scipv also recommended, in its pneumococcal vaccination guidelines, pneumococcal vaccination of the at-risk population at the appropriate time before the hajj, using the types of pneumococcal vaccines that are currently available: the -valent polysaccharide pneumococcal vaccine (ppsv ) and the -valent conjugate vaccine (pcv ) [ ] . also, it did not recommend providing a pneumococcal vaccine routinely to healthy persons aged less than years, because of lack of evidence. respiratory tract infections, including influenza, continue to be a major concern during the hajj. both cohort-and hospital-based studies provide complementary data and potentially useful information, and both are therefore necessary to provide a complete picture of the total burden of respiratory diseases during this mass gathering. large multinational follow-up studies are thus recommended for clinic-based syndromic surveillance, in conjunction with microbiological surveillance. matched cohorts ensure better comparability across studies, particularly in terms of origin of pilgrims and possible travelling conditions. however, the study design and data collection procedures should be standardized, to facilitate reporting and to achieve comparability between studies. furthermore, the definition of ili, and of most common symptoms used to define respiratory infections (e.g., urti), needs to be precisely defined and consistently used. future studies need to address the potential effects of influenza and pneumococcal vaccine in the context of the hajj pilgrimage. none. the authors have no conflicts of interest to declare. the general authority for statistics in the kingdom of saudi arabia from hajj services to mass gathering medicine: saudi arabia formalizes a novel discipline hajj: journey of a lifetime social identification moderates the effect of crowd density on safety at the hajj hajj: infectious disease surveillance and control global perspectives for prevention of infectious diseases associated with mass gatherings health risks at the hajj 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research team. changes in the prevalence of influenza-like illness and influenza vaccine uptake among hajj pilgrims: a -year retrospective analysis of data the saudi thoracic society guidelines for influenza vaccinations mismatching between circulating strains and vaccine strains of influenza: effect on hajj pilgrims from both hemispheres expected immunizations and health protection for hajj and umrah -an overview prevention of pneumococcal infections during mass gathering pneumococcal infections at hajj: current knowledge gaps the saudi thoracic society pneumococcal vaccination guidelines- emergence of drug resistant bacteria at the hajj: a systematic review none. supplementary data to this article can be found online at https:// doi.org/ . /j.tmaid. . . . key: cord- -ovfqfurf authors: memish, ziad a; stephens, gwen m; steffen, robert; ahmed, qanta a title: emergence of medicine for mass gatherings: lessons from the hajj date: - - journal: lancet infect dis doi: . /s - ( ) - sha: doc_id: cord_uid: ovfqfurf although definitions of mass gatherings (mg) vary greatly, they consist of large numbers of people attending an event at a specific site for a finite time. examples of mgs include world youth day, the summer and winter olympics, rock concerts, and political rallies. some of the largest mgs are spiritual in nature. among all mgs, the public health issues, associated with the hajj (an annual pilgrimage to mecca, saudi arabia) is clearly the best reported—probably because of its international or even intercontinental implications in terms of the spread of infectious disease. hajj routinely attracts · million muslims for worship. who's global health initiatives have converged with saudi arabia's efforts to ensure the wellbeing of pilgrims, contain infectious diseases, and reinforce global health security through the management of the hajj. both initiatives emphasise the importance of mg health policies guided by sound evidence and based on experience and the timeliness of calls for a new academic science-based specialty of mg medicine. defi nitions of mass gatherings (mgs) vary greatly, with some sources specifying any gathering to be an mg when more than individuals attend, whereas others require the attendance of as many as people to qualify. , irrespective of the defi nition, mgs represent large numbers of people attending an event that is focused at specifi c sites for a fi nite time. these gatherings might be planned or unplanned and recurrent or sporadic. examples of mgs include world youth day, the summer and winter olympics, rock concerts, and political rallies. mgs pose many challenges, such as crowd management, security, and emergency preparedness. stampedes and crush injuries are common, the result of inevitable crowding. outdoor events are associated with complications of exposure, dehydration, sunburn, and heat exhaustion. other health hazards arise from lack of food hygiene, inadequate waste management, and poor sanitation. violence is unpredictable and diffi cult to mitigate whether the mg is a political rally or a sporting competition. with few exceptions, however, the rates of morbidity and mortality resulting from these hazards are rarely increased outside the event. global mgs, however, can lead to global hazards. mitigation of risks requires expertise outside the specialty of acute care medicine, event planning, and venue engineering. for centuries, muslim pilgrims have converged in mecca, saudi arabia, for the hajj (fi gure ) to participate in a series of sacred rituals that defi ne islam. with about · billion muslims and the obligation on believers to attend hajj at least once in their lifetimes, this event has become the largest annually recurring mg in the world, with attendance reaching more than · million in despite warnings about pandemic infl uenza. pilgrims come from more than countries, leading to enormous diversity in terms of ethnic origin and socioeconomic status. men, women, and children of all ages attend hajj together; however, a disproportionate number of people will be middle aged or older before they can aff ord the journey. comorbidities are common. the public health implications of the hajj are huge-nearly pilgrims arrive from low-income countries, many will have had little, if any, pre-hajj health care, added to which are the saudi arabia's safety and security policies for hajj attendees are well developed after decades of planning the annual event. lessons learned have led to comprehensive programmes that are continually revised and coordinated by government sectors. public health has involved global partners for decades. far from being the only mg that aff ects global health, the hajj is a useful model to understand the nature of risk management and the benefi ts of international collaboration and cooperation. pilgrimage is central to many belief systems and also appeals to mankind's recurring desire to be homo viator-a universal fi gure common to many cultures and civilisations, who wanders in search of spiritual enlightenment. in hellenic civilisation, delphi-home to pythia the oracle-was long a focus for pilgrimage. ancient tribal populations such as the huichol of western mexico, the lunda of central africa, and the shona people of southwest africa all included pilgrimage in their cultures. institutionalised pilgrimage came to prominence with the advent of world religions. buddhism invites pilgrimage to nepal, the birthplace of siddharta. hindus journey to benares in india, and followers of judaism to jerusalem. christendom has a complex history of pilgrimages through the ages including the modern era. until the advent of modern air travel, the journey was associated with the greatest risks. a review of the historical data for the hajj shows these dangers: "…the oscillatory movement of the camel produces miscarriages, followed frequently by haemorrhage and death of the infant and mother. the caravan however cannot stop, and it is impossible to nurse effi ciently while the (journey) continues. if any portion of the caravan stopped it would certainly be attacked…" kumbh mela is a huge hindu pilgrimage held at various locations along the river ganges according to the zodiac positions of the sun, moon, and jupiter. purifi cation rites involve bathing in the ganges and are believed to interrupt the cycle of reincarnation. the highest holy days arise every years, but the normal kumbh mela is celebrated every years, and often attract thousands of non-hindu enthusiasts. this is the largest human gathering, so large that in movements of the amassed individuals could be seen from space. , the ardh kumbh mela in attracted million pilgrims over days in allahabad; on the most auspicious day of the festival, more than million participated. celebrations are accompanied by singing, religious readings, and ritual feeding of holy men and the poor. managing rival sects is a recurring challenge. administrators overseeing the event have to negotiate bathing schedules. clashes have resulted in deaths-eg, in , a vehicle carrying members of the juna sect struck several people, setting off a stampede. in , a stampede killed people. the festival probably contributed to the - asiatic cholera pandemic. pilgrims are believed to have carried the bacteria from an endemic area in the lower ganges to populations in the upper ganges, from there to kolkata and mumbai, and across the subcontinent. british soldiers and sailors took it home to europe and then to the far east. the epidemic ended abruptly in after a very cold winter. although cholera returned to the kumbh mela in , authorities of the hardiwar improvement society reacted to contain the outbreak. diarrhoeal diseases, including cholera, continue to be a risk at the gathering despite rapid monitoring and prompt public health interventions. another pilgrimage with a focus on water and religious rites is to lourdes, france. this village in the pyrenees attracts more than million catholics and other enthusiasts every year. their destination is a shrine and nearby spring where a young village girl witnessed apparitions of the virgin mary in the mid s. drinking and bathing in lourdes' water is believed to ensure health and cure disease, and is featured at the water walk where religious stations are situated and water is available for drinking or bottling. spring water is also routed to a series of bathing stalls used by more than pilgrims every year. although health issues have not been associated with lourdes' waters, the french writer emile zola visited the spring in and provided a graphic description of the baths at the time: "and the water was not exactly inviting. the grotto fathers were afraid that the output of the spring would be insuffi cient, so in those days they had the water in the pools changed just twice a day. as some hundred patients passed through the same water, you can imagine what a horrible slop it was at the end. there was everything in it: threads of blood, sloughed-off skin, scabs, bits of cloth and bandage, an abominable soup of ills...the miracle was that anyone emerged alive from this human slime." stampedes and fi res continue to be major causes of death and injury at mgs-eg, the sabarimala in kerala, india, and the feast of the black nazarene in manila, philippines. inaccessible for years after their construction, hindu temples of sabarimala in kerala's western ghat mountains have become increasingly popular despite the location and winter openings. with the increasing crowd sizes, tragedies have occurred. in , pilgrims burned to death when sheds containing fi reworks caught fi re, and more than perished in when a hillside collapsed under the weight of assembled worshipers triggering a stampede. more than million attended the most recent rites in series january, , uneventful until the last day when a motor vehicle accident caused a panic that triggered a stampede, killing people. , although authorities off ered compensation packages, they could not quell unprecedented public criticism of kerala authorities and the national government. manila's feast of the black nazarene has fared a little better after religious leaders and municipal authorities joined forces to change the route of the annual jan procession after two deaths in , and many stampedes and injuries caused by fi reworks and trauma over the years. the authorities responsible for the mg also recruited thousands of volunteers to manage the crowds. these changes and the addition of an information campaign have helped calm crowds and reduce injuries. despite an estimated attendance of - million in , no deaths or serious injuries were reported. protests during the arab spring in drew millions of largely peaceful protesters to central locations of tunis, tunisia, and then cairo, egypt. more than million were present when the departure of egypt's president hosni mubarak was announced in february, . other mgs include political protests of the antiwar movement during the vietnam war. was marked by massive student marches in major european, asian, and latin american capitals. chicago, il, usa, had a particularly violent succession of mgs that became riots after the assassination of the civil rights leader martin luther king and again a few months later during antiwar protests at the democratic national convention. by contrast, european marches in protest of the us-led invasion of iraq were larger and more peaceful. more than million attended the largest march in rome in (fi gure ). in , antiglobalisation protesters assembled in seattle, wa, usa, ahead of a scheduled world trade organization meeting. along with international anticorporate interests and assorted domestic supporters, they successfully occupied seattle's downtown core and the convention centre. violence increased during the days, culminating in a full-scale riot after anarchists joined in and police responded with tear gas and rubber bullets. the battle in seattle as it came to be known, caused damages that were estimated at more than us$ billion. despite the violence and very large crowds, estimated to be hundreds of , violent sports fans are as old as history. in , the nika riots in constantinople pitted rival charioteer factions and athletes against each other and emperor justinian. during the month insurrection that ensued, half the city was destroyed and more than people died. although sports violence continues to be a risk during matches between rival teams, the massive crowds, crowds in motion, and immovable barriers cause the greatest loss of lives. the worst sports riot in history occurred in south america during a football playoff game between peru and argentina when fans responded in protest after a controversial decision to annul a goal by peru. police responded by throwing teargas canisters into the grandstand. more than fans were injured and another died. most were crushed trying to escape the locked stadium, others died from teargas asphyxiation. the disaster in hillsborough, uk, in was the worst stadium tragedy in british history. fans died and another were injured as crowds surged into the stadium crushing others in front who were pinned against fences. many of the deaths resulted from compressive asphyxia while standing. ineff ective crowd control and poorly designed venues have also resulted in deaths at music festivals, most recently in during the love parade in duisburg, germany, in which people were crushed to death and were injured as a result of a stampede in a narrow tunnel. occasionally, mgs cause structural stresses that threaten safety and security. in , the th anniversary of the golden gate bridge, san francisco, ca, usa, was celebrated by closing it to vehicular traffi c. though not catastrophic, the suspension cables had the greatest load factor ever when pedestrians crowded onto the deck, fl attening its centre span. although the hajj was undertaken in the middle east before the arrival of islam, the movements and rituals of pilgrims today have not changed since the prophet mohammad inaugurated the islamic hajj in his lifetime. it has been recorded in arabic literature known as adab al rihla. persian literature records hajj in the safarnameh (travel letter). at the core of islamic belief is trust and this trust has been best exemplifi ed by the risks muslims take when travelling. the muslim individual must trust in his maker and, in ancient times, in the benevolence of strangers who would host him on his perilous journey to mecca. nowadays, as a result of the dissemination of islam across the world, hajj removes national, cultural, and social boundaries between diverse people like no other event. hajj has been the focus of public health initiatives for centuries, as shown in contemporary medical reports. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] during the th century, the hajj attracted the interest of european powers, particularly the maritime travel to the hajj, which dominated until the arrival of air travel. colonial powers at the time were suspicious of political islam, which was referred to as wahabism. direct engagement in hajj-related aff airs was seen as too intrusive by politically savvy imperialists who recognised the sanctity of this little understood religious pilgrimage. instead, supervision, albeit series displaced, and management of hajj were gradual processes, including surveillance, regulation, secure passage through the red sea and protection of british littoral interests, and eventually formal organisational processes, which would quickly become central to these hidden concerns. imperial organisations linked cholera morbus, a non-epidemic diarrhoea, to hajj, allowing a public health industry to develop that used health concerns to control immigration, pilgrim passports, proof of suffi cient funds to allow return travel, maritime regulation, and vessel quarantine procedures. by the mid th century, most of the muslim populations using maritime travel for hajj were from the malay peninsula and indian subcontinent. about pilgrims travelled from the malay peninsula and between and arrived from the indian subcontinent. although there are few reliable data, the total number of pilgrims was estimated to be . "according to the turko-egyptian sanitary commissioners at mecca, the number of mohammedan pilgrims collected in and about the holy city…amounted to two hundred thousand persons; composed of natives of turkey, india, egypt, morocco, arabia, syria, persia, java etc." most travellers came in small vessels of - tons under diff erent international aegis. departures were concentrated around singapore, calcutta and madras in india, aceh in indonesia, and other regional cities. most pilgrims then, like today, disembarked in jeddah, though some would land on southern arabian coastal ports and then make a land journey through yemen to hijaz. well into the th century, the conditions of passage were often appallingly cramped and unsanitary. many people died along the route from infection and dehydration. pilgrims died on board a maritime vessel, which had embarked from jeddah with pilgrims en route home to singapore. "when she drew abreast of the watcher she proved to be a pilgrim ship; the afternoon being hot, the travellers had all crowded to the port side to catch what little wind was stirring. their numbers were so great that they appeared to cover all the deck space, while the ship was unable to right herself from the list…" eff orts to manage hajj were initiated by dutch-indonesian authorities, not for wholly altruistic reasons. the dutch had established an association between returning pilgrims and societal unrest, so they introduced heavily surcharged passports as a way of restricting the number of travellers to mecca. the ruling empires focused on health issues and justifi ed inspections of hajj sites for compliance with contemporary public health directives, often focusing on quarantine as a means of protection at a time when many international arrivals, including maritime travellers, were reaching mecca. their inspections were disappointing-the annual sanitary commission visited the sites of hajj and noted that the focus was not on prevention, but rather on the easy option of quarantine. when cholera was reported at hagar's well within the holy mosque in mecca, the british consul at jeddah requested a scientifi c assessment. samples were analysed at the royal college of chemistry in the south kensington museum, london, uk, and compared with those of london sewage, which was a source of cholera at that time. recommendations after their alarming fi ndings were sent to the secretary of state for india who reported the well to be infected with the bacterium. , similarly, entrepôt cholérique (cholera reservoir) was noted when authorities visited pilgrims from india intending to do the hajj. these pilgrims were routinely detained on the island of camaran as a quarantine station in the red sea to restrict the ingress of cholera into the holy sites. , pilgrims were detained for - days without adequate provisions or clean water. the long exposure to sun, however, was thought to be benefi cial for elimination of infection. after quarantine, pilgrims were often permitted into the site. results of later studies showed a link between the pilgrims quarantined on camaran with a series of eight subsequent outbreaks. the conclusions drawn from a review of these events at an international public health meeting at the international sanitary conference of paris, france, , were that the "turkish possession of camaran remains the greatest hindrance to the abolition of cholera at mecca". infection was a frequent feature of the hajj in the th and th centuries, not unexpected since infectious disease medicine became better elucidated and the fascination with the developing specialty increased. epidemics of smallpox occurred in iraq and sudan between october, , and april, . a small epidemic of plague occurred pamela das www.thelancet.com/infection vol january series in upper egypt and a larger one in morocco ( cases). cases of typhus were reported in egypt and in palestine during the same period. these fi ndings led to some strong recommendations that are still relevant: "the yearly pilgrimage will remain a danger to all the countries from which pilgrims are drawn as long as the conditions of transport and accommodation remain…as at present. effi cient reorganization of the pilgrimage in every direction is needed and should be facilitated by the governments of the large number of the countries involved." by the early th century, non-muslim european powers were heavily engaged in the management of the hajj and would remain so until modern saudi arabia came into existence and acquired fi nancial independence through petrochemical wealth. the comparison of hajj in the imperial era with the modern hajj shows the absence of muslim public health experts or authorities in managing this pilgrimage. , this absence would gradually change and with the arrival of ibn saud's modern kingdom and its investments in hajj. from this point, muslims would solely administer the modern hajj in its entirety. , the islamic calendar is a lunar calendar, so the date of the hajj moves forward by - days every year, presenting planners with additional challenges of health risks that are associated with seasonal variation. temperature fl uctuations in mecca might be extreme depending on the time of year; daytime highs can be °c and higher, and night-time temperatures occasionally fall to °c. hajj can coincide with the northern hemisphere's infl uenza season, as in , increasing public health risks. [ ] [ ] [ ] [ ] [ ] attendance in was not blunted despite offi cial recommendations encouraging pregnant women, and elderly and very young people to stay at home. more than · million people attended, including · million foreign citizens, of whom did not have valid hajj permits. to put the event in its local context, the infl ux of pilgrims is so great that it trebles the resident population of mecca, which is normally · million. access to the hajj for pilgrims has changed greatly with air travel gradually replacing maritime and overland travel. in the past decade, the breakdown includes about % of pilgrims arriving by air, % making the maritime journey, and % travelling over land. although a few pilgrims will arrive at medina's international airport, jeddah remains the major port of entry for all travellers as it has been for centuries. increasing numbers of people attending the modern hajj led to a decision by saudi aviation authorities to partition jeddah's king abdulaziz international airport and create a separate south terminal to serve all pilgrims. now two-thirds completed, the terminal's capacity is travellers at any time. when completed, its fi nal capacity will be greater than million passengers per year. important new features include health-screening systems, customs, and immigrations security. each of its hubs receives pilgrim fl ights; all hubs have two examination rooms. the terminal also features large holding areas that allow effi cient reviews of selected arrivals in segregated parts of the terminal. this permits verifi cation of the immunisation status and administration of any prophylactic drugs and vaccines according to set protocols. the overall design of the terminal permits visitors arriving without required visas and health records to be managed outside the main fl ow of pilgrims who continue through the facility to join assigned groups or agents who are responsible for coordinating details of travel and housing. these regulated services will also escort their charges through the hajj site. in islam, umrah is a shorter pilgrimage to mecca. although not compulsory, umrah draws an additional million pilgrims per year to the country; jeddah's airport plays a major part throughout the year, controlling access and enforcing health protocols. groups exiting the country and returning home are also monitored, allowing comparative studies between the two populations. at various times of the year, but most intensely during the hajj season, public health teams, both stationary and mobile, use mobile devices to monitor inbound and outbound populations. protocols are based on regularly reviewed case defi nitions. gathered data are sent to centralised databases for real-time analysis. many diseases are monitored during a hajj season. those given specifi c attention every year include both mild and severe respiratory diseases, food poisoning and gastroenteritis syndromes, haemorrhagic fevers, and meningococcal diseases. reports of all diseases, but particularly those with immediate eff ect worldwidesevere acute respiratory syndrome (sars), infl uenza, cholera, yellow fever, polio, plague, meningitis, and viral haemorrhagic syndromes-are expedited to who epidemiologists who work closely with saudi authorities reuters/jim young series to analyse information and coordinate a response. the airport is also equipped with clinics for management of medical problems. humility, faith, and unity are emphasised throughout the hajj. the pilgrims wear simple clothing, women and men comingle, women are enjoined not to cover their faces, children and adults of all ages are included, and families journey together. on arrival in mecca, hajj pilgrims do a series of synchronised acts based on events in the lives of ibrahim (abraham), his wife hajra (hagar), and their son ishmael. each pilgrim does an initial circumambulation (tawaf ) around the central ka'aba seven times. when completed, the pilgrim leaves for arafat, about km east of mecca. hajj culminates in arafat on the day of standing, when all · - · million visitors stand and supplicate together on the mountain. mount arafat is believed to be the site of mohammad's last sermon to his followers. many people attempt to pray at the summit believing prayers there are the most blessed. on the way to arafat, the pilgrims make overnight stops for prayers and contemplation in mina. leaving arafat, the pilgrims return to muzdaliff ah, where stones are gathered; on the way to mina, they stop at jamarat bridge to throw stones at the pillars that are effi gies of satan. when the pilgrimage is complete, the new hajjee (pilgrim who has completed the hajj) makes an animal sacrifi ce thanking allah for accepting his hajj. this is often a proxy sacrifi ce because the saudi government has established modern abattoirs that are staff ed by professionals who will do this on behalf of the pilgrims. meat is then distributed to the poor, family, and friends. the fi nal farewell is undertaken with another seven circuits around the ka'aba. muslim men on completion of a successful hajj shave their heads. after completion of the hajj, most pilgrims exit the country at jeddah airport, which has congestion so great that the telecommunications infrastructure has to be constantly updated to allow suffi cient capacity. a smaller number of pilgrims will visit the holy mosque in medina. some will also visit tourist sites in the hijaz and the old city of jeddah. because all hajj pilgrims travel as part of small informal groups, there is order in what could otherwise be chaos. groups take their shepherding of individual pilgrims seriously, with easily identifi ed group leaders who carry placards and fl ags and lead the entire group through the rituals without losing stragglers, infi rm individuals, or temporarily distracted people. further, this fl exibility safeguards hajj at the most pressured points, which could otherwise become treacherous. despite this fl exibility, hajj stampedes have been recurring events, most notably at the jamarat site. according to islam, only adults should undertake the hajj. the age at which hajj is undertaken varies according to culture. some nationalities seem to undertake hajj at a uniformly young age (eg, indonesian and malaysian), whereas other nationalities defer hajj until the late phase of life as a precursor to preparing for death. there might also be diff erences in sex distribution. malaysia for instance has had a female dominated hajj attendance for more than three decades. in keeping with the islamic spirit of compassion, muslims are enjoined to undertake hajj only when adequately healthy. despite this strong scriptural admonition, many muslims insist on hajj even when wheelchair bound. special accommodations for wheelchairs are provided at the holy mosque despite the tremendous crowd densities. these channels are wide enough to admit wheelchairs and one person pushing the wheelchair and are divided into two lanes (one for each direction). pilgrims who are not well are provided transport by the ministry of health ambulance to hajj sites as needed so they can complete their pilgrimage. because of the islamic belief that death during the hajj has a benefi cial outcome in the afterlife, a few sick pilgrims attend, hoping for death during the hajj. public health and religious offi cials do much to dissuade this belief, which is often tenacious. this cultural belief system aff ects care providers at hajj, all of whom are muslims (non-muslims are not permitted to enter the holy sites). anecdotally, this belief aff ects resuscitation eff orts of those in cardiac arrest, which once initiated (if the patient reaches the emergency rescue services in time) are unlikely to be pursued if not immediately successful. a do-not-resuscitate status is often requested by pilgrims who can speak for themselves. hajj itself has several qualities that aid public health security. attendees must practise specifi c behaviours for their hajj to be considered valid, and these requirements are strict and closely adhered to by both clerical and community leaders. crime is strictly forbidden at hajj and the risk of violent altercation is reduced because of the weapon-free, drug-free, and alcohol-free environment. tobacco intake is also banned, curtailing the risk of inadvertent fi re hazards. by contrast with some other mgs, sexual relations are not allowed during hajj and male and female pilgrims are accommodated separately even when travelling as families, eliminating the risk of sexually transmitted disease. this observant, penitent, and sober crowd engrossed in worship is thus likely to remain cooperative and coherent if sudden events demand rapid cooperation with authorities. insurrection, rioting, disinhibited behaviour, or hooliganism of any kind does not arise even in these extraordinarily massive crowds. pilgrims are urged to safeguard themselves or others at all times, aiding the infi rm and assisting the fallen, behaviours that symbolise peaceful islamic societies that enhance the public health security. the spirit of cooperation is central to a successful series acceptance of the hajj by allah in the islamic belief system and reduces the potential risk of disastrous events in such massive crowds. saudi arabia's responsibility for the hajj has aff ected the country's advanced health-care infrastructure and its multinational approach to public health. although other jurisdictions have administered the hajj, saudi arabia has invested in it. within the immediate vicinity of the hajj, there are primary health-care centres and hospitals with a total capacity of beds including beds for critical care. the latest emergency management medical systems were installed in healthcare centres and staff ed with specialised personnel. more than doctors and nurses provide services, all at no charge. this event requires the planning and coordination of all government sectors; as one hajj ends, planning for the next begins. infection and prevention strategies are reviewed, assessed, and revised every year. coordination and planning requires the eff orts of supervising committees, all reporting to the minister of health. the preventive medicine committee oversees all key public health and preventive matters during the hajj and supervises staff working at all ports of entry. public health teams distributed throughout the hajj site are the operational eyes and ears of the policy planners. in hosting the modern hajj, saudi arabia has weathered a th century world war, global outbreaks due to newly emerging disease (including sars and meningococcal meningitis w ), and regional confl icts. in this time, the country has acquired a unique, resilient expertise concerning hajj-related public health. important observations that are relevant to public health planners everywhere are part of this experience. one of the best examples of such cross-cultural translation has been in the preparation for barack obama's presidential inauguration and crowd management informed by the hajj experience. yet the process of exchanging expertise is possibly even more instructive. collaborative work on this scale shows the increasingly important global health diplomacy in which the muslim world has an enormous part to play. first articulated by the us health and human services secretary tommy thompson, global health diplomacy usually includes the provision of a service by one nation to another. the usa's rebuilding of maternity hospitals in afghanistan or the deployment of the ship uss comfort to serve as a site for temporary clinics in vietnamese coastal waters are two recent examples. as they struggled with the best responses to the global threat of pandemic infl uenza a h n , which coincided with the hajj in , colleagues at the us centers for disease control and prevention and the saudi ministry of health worked together to deploy one of the largest real-time mobile databasing systems, which was designed to detect disease in real time at any mg. senator john kerry discussed precisely this joint eff ort in a speech in doha at the us-islamic world forum. , this international collaboration was realised only through both intense personal dedication and the confi dence the agencies had in their people. such collaboration strongly resonates with president obama's renewed hopes for us engagement with the muslim world, as articulated in his speech in cairo, egypt, in june, . people who collaborate, write, and disseminate information internationally have long been aware of the latent value of such informal, positive exchange. in the fl at world of medical academia, individuals have immediate and palpable eff ects. fostering such professional dialogues are everyday (albeit unseen) acts of global health diplomacy. when investigators and physicians work in a shared space, unfettered by the global geopolitics, global health diplomacy becomes alive and vibrant. hajj medicine, as part of the emerging specialty of mg medicine, provides an extraordinary platform. saudi arabia's experience in international service through public health is substantial and is promoting the emergence of the formalised specialty of mg medicine. hajj continues to provide insights into advanced and complex public health challenges, which are unlocked through collaborative exchange. disease and suff ering remain universal, even in the st century. solving these challenges is relevant to humanity everywhere. islamic scholars have long referred to hajj as a metaphor for ideal societal behaviour. at the centre of these ideals is a unifying theme: collaboration. saudi arabia's experience of hajj medicine contains rapidly developing public health solutions to several global challenges. multiagency and multinational approaches to public health challenges are likely to become major factors in the specialty of global health diplomacy, engaging societies globally, and drawing the west a little closer to the east. in view of the global public health threats that might originate from mgs, medicine relevant to mgs has become an essential specialised, interdisciplinary branch of public health, particularly hybridised with global health response, travel medicine, and emergency or disaster planning. agencies outside the realm of public health should be closely involved in mg medicine. in the operation and management of an mg, several sectorshealth care, security, and public communications-need to know how to interface with public health services and resources quickly and eff ectively. involving public health experts with the broader civic planning for any mg helps with parallel transparency in needs and expectations, ensuring that public health considerations are factored into the entire planning process instead of intruding too late in development, relegating public health security series concerns to little more than ineff ective afterthought. delayed entry of these actors into the planning process can debilitate or completely disable adequate responses to potential diseases during mgs. experts must educate civic planners about the values of early collaborative approaches to mgs for these reasons. conventional concepts of disease and crowd control do not adequately address the complexity of mgs. the need for mg health policies that are guided by sound evidence but anchored in experience shows the importance of calls for a new academic medical and science-based discipline. mgs have been associated with death and destructioncatastrophic stampedes, collapse of venues, crowd violence, and damage to political and commercial infrastructure, but little is known about the threats from mgs to the global health security. who has worked closely with international agencies to address such risks. [ ] [ ] [ ] mgs pose complex challenges that require a broad expertise and saudi arabia has the experience and infrastructure to provide unique expertise with respect to mgs. zam and gms co-wrote the text. imperial powers and th century hajj, hajj culture, and most of the global health diplomacy sections were contributed by qaa. rs compiled the table. we declare that we have no confl icts of interests. we identifi ed references for this review by searching medline and the national health service hospital search service for articles published in english from to august, . additional articles were identifi ed through searches of extensive fi les belonging to the authors. search terms used were "mass gathering", "disease", "pilgrimage", "hajj", "outbreak", "public health", "prevention", "travel", or "modeling". we reviewed the articles found during these searches and relevant references cited in the articles. mass gathering medicine: a predictive model for patient presentation and transport rates mass gathering medical care: a twenty-fi ve year review from medieval pilgrimage to religious tourism: the social and cultural economics of piety the lancet. a mohamedan doctor on the mecca pilgrimage kumbh mela pictured from space millions of hindus wash away their sins five die in stampede at hindu bathing festival what is hinduism?: modern adventures into a profound global faith epidemics and pandemics: their impacts on human history use of telemedicine in evading cholera outbreak in mahakumbh mela the baths lourdes: body and spirit in the secular age another black friday for sabarimala pilgrims sabarimala stampede death toll crosses sabarimala stampede, injured list of largest peaceful gatherings in history promed mail. varicella, asian games-qatar ex maldives centennial olympic park bombing summer olympics procopius: justinian suppresses the nika revolt muhammad: a biography of the prophet return pilgrims from mecca. egyptian quarantine at torr. (from a correspondent) the pilgrimage to mecca: medical care of pilgrims from the sudan the lancet. the origin of cholera in mecca cholera at mecca and quarantine in egypt the lancet. the risks of the mecca pilgrimage the lancet. the mecca pilgrimage the cholera and hagar's well at mecca hagar's well at mecca camaran: the cause of cholera to mecca pilgrims sanitation and security: the imperial powers and the nineteenth century hajj mecca pilgrimage quarantine and the mecca pilgrimage-the growth of an idea the lancet. a medico-sanitary pilgrimage to mecca the lancet. the pilgrimage to mecca guests of god pilgrimage and politics in the islamic world pandemic h n infl uenza at the hajj: understanding the unexpectedly low h n burden global public health implications of a mass gathering in mecca, saudi arabia during the midst of an infl uenza pandemic infl uenza a (h n ) in the kingdom of saudi arabia: description of the fi rst one hundred cases and the jeddah hajj consultancy group. establishment of public health security in saudi arabia for the hajj in response to pandemic infl uenza a h n pandemic h n and the hajj health conditions for travellers to saudi arabia for the pilgrimage to mecca (hajj) royal embassy of saudi arabia. , , million pilgrims participated in hajj global public health implications of a mass gathering in mecca, saudi arabia during the midst of an infl uenza pandemic emergency room to the intensive care unit in hajj. the chain of life the quest for public health security at hajj: the who guidelines on communicable disease alert and response during mass gatherings citation?related-urls=yes&-legid=healthaff remarks by the president on a new beginning. www.whitehouse. gov/the_press_offi ce/remarks-by-the-president-at-cairo-university- - - chairman kerry addresses the us-islamic world forum jeddah declaration on mass gatherings health international health regulations who. communicable disease alert and response for mass gatherings: key considerations we thank abdullah a al rabeeah, the saudi minister of health, for his leadership and support for hosting the lancet conference on mg medicine: implications and opportunities for global health security, jeddah, saudi arabia, oct - , , which generated the series of reviews. key: cord- -bcocsjij authors: memish, ziad a.; assiri, abdullah m.; alshehri, mohammed; hussain, raheela; alomar, ibrahim title: the prevalance of respiratory viruses among healthcare workers serving pilgrims in makkah during the influenza a (h n ) pandemic date: - - journal: travel med infect dis doi: . /j.tmaid. . . sha: doc_id: cord_uid: bcocsjij despite the high risk of acquiring respiratory infections, healthcare workers who treat pilgrims at hajj have not been studied in previous research on respiratory diseases during hajj. the objective of this study was to determine the prevalence of different respiratory viruses among healthcare workers who treated pilgrims during hajj , the year of the influenza a h n pandemic. a cross-sectional study was performed just before and after hajj ( – november, ). nasal and throat swabs were tested for respiratory virus types and subtypes. a total of healthcare workers were examined. most were men ( %) with an average age of years. before the hajj, rates of seasonal influenza vaccination were higher ( %) than rates of pandemic influenza a h n vaccination ( %). after the hajj, participants reported high rates of maintaining hand hygiene ( %), cough etiquette ( %), and wearing a face mask ( %). among all the viruses tested, only two were detected: rhinovirus was detected in . % and coronavirus e in . %. rhinovirus was detected in % of those who had respiratory symptoms during hajj. influenza a (including h n ), influenza b. respiratory syncytial virus, other coronaviruses, parainfluenza viruses, human metapneumovirus, adenovirus, and human bocavirus were not detected. the finding of high rates of rhinovirus infection corresponds to their frequent occurrence in adults. none of the participants had influenza a h n , possibly because it was also infrequent among the pilgrims. the prevalance of respiratory viruses among healthcare workers serving pilgrims in makkah during the influenza a (h n ) pandemic keywords hajj; viral; respiratory; healthcare workers; h n summary despite the high risk of acquiring respiratory infections, healthcare workers who treat pilgrims at hajj have not been studied in previous research on respiratory diseases during hajj. the objective of this study was to determine the prevalence of different respiratory viruses among healthcare workers who treated pilgrims during hajj , the year of the influenza a h n pandemic. a cross-sectional study was performed just before and after hajj ( e november, ). nasal and throat swabs were tested for respiratory virus types and subtypes. a total of healthcare workers were examined. most were men ( %) with an average age of years. before the hajj, rates of seasonal influenza vaccination were higher ( %) than rates of pandemic influenza a h n vaccination ( %). after the hajj, participants reported high rates of maintaining hand hygiene ( %), cough etiquette ( %), and wearing a face mask ( %). among all the viruses tested, only two were detected: rhinovirus was detected in . % and coronavirus e in . %. rhinovirus was detected in % of those who had respiratory symptoms during hajj. influenza a (including h n ), influenza b. respiratory syncytial virus, other coronaviruses, parainfluenza viruses, human metapneumovirus, adenovirus, and human bocavirus were not detected. the finding of high rates of rhinovirus infection corresponds to their frequent occurrence in adults. none of the participants had influenza a h n , possibly because it was also infrequent among the pilgrims. ª elsevier ltd. all rights reserved. healthcare workers are exposed to many respiratory infections when they see patients, and they may transmit these infections to their patients or colleagues. for example, during the outbreak of severe acute respiratory syndrome (sars) in , attack rates were more than % in healthcare workers. healthcare workers who see pilgrims during hajj (the annual muslim pilgrimage to makkah) may be at higher risk of acquiring respiratory and other infections. , because of these risks, special immunization requirements have been proposed to protect healthcare workers, although healthcare workers have not been included in previous studies of respiratory diseases during hajj. , hajj is the largest annual mass gathering in the world; it brings more than two million people from different countries together in a small, confined area. the extreme overcrowding of pilgrims during hajj reaches about persons per meter; combined with fatigue and extremely hot weather during much of the year, this crowding may increase the risk of transmitting air-and droplet-borne infectious diseases, particularly respiratory viruses. , e an estimated one in three pilgrims experience respiratory symptoms. several transmissible bacterial and viral respiratory pathogens have been reported among pilgrims, notably meningococci of all serotypes, streptococcus pneumoniae, gram-negative organisms, atypical organisms, mycobacterium tuberculosis, influenza a and b viruses, rhinoviruses, respiratory syncytial virus (rsv), parainfluenza viruses, enteroviruses, and adenoviruses. , , e in april of , a novel influenza a strain (h n strain) in mexico spread globally. , the toll was particularly heavy in saudi arabia, which ranked fourth of countries in the eastern mediterranean region in deaths and probable h n cases. the hajj took place in november, six months later, and presented a public health challenge for infection control authorities in saudi arabia. several practices to minimize disease transmission among pilgrims and healthcare workers were instituted even before the beginning of hajj season, since pre-hajj data showed low acceptance rates of h n vaccine among healthcare workers. , this study evaluated the prevalence of viral respiratory pathogens among healthcare workers during the hajj which coincided with the influenza a h n pandemic. healthcare workers, including physicians, nurses, health inspectors, and others, who served pilgrims during the hajj season were included. three-fourths of the healthcare workers in the study were from the saudi ministry of health (moh), and the rest were from medical missions other than moh. most of the healthcare workers had treated pilgrims previously and had been practicing medicine for more than years. the main religious activities of the hajj season started on th november with a visit to the holy kaaba and continued for or days at different holy sites in mina, arafat, and muzdalifa. the current study was a cross-sectional study performed in two phases. the first phase was conducted during the week before the start of hajj on november th, and the second phase was conducted in the week following the end of hajj on november th. healthcare workers were asked to answer a questionnaire and provide nasal and throat swabs both before and after hajj. the pre-hajj questionnaire was about demographics (age, sex, occupation, and nationality), medical history (chronic disease and smoking), vaccination history (including h n and seasonal influenza), and knowledge of h n influenza (symptoms, transmission, and prevention). the post-hajj questionnaire included questions about exposure to infections during hajj and compliance with infection control practices (hand hygiene, cough etiquette, and wearing a mask). nasal and throat swabs were collected using the same method during both phases of the study. nose and throat swabs were collected in viral transport media using dacron swabs on stainless steel wire and plastic shafts, respectively (remel, microtest m rt, usa). immediately after collection, samples were transported to the jeddah regional laboratory where they were stored at À c until tested. nucleic acid was extracted using the x-tractor gene, corbett from qiagen using vx dna/rna purification protocol. the multiplex pcr using micro fluid arrays and luminex x-map system, with xtag respiratory viral panel fast assay (manufactured by luminex molecular diagnostics, inc, toronto, on, canada, distributed by abbott molecular, wiesbaden-delkenheim, germany) was used for nucleic acid testing for circulating respiratory virus types and subtypes: influenza a, influenza a h , influenza a h , influenza b, rsv, coronavirus e, coronavirus oc , coronavirus nl , coronavirus hku , parainfluenza , parainfluenza , parainfluenza , parainfluenza , human metapneumovirus, rhinovirus, adenovirus, and human bocavirus. the xtag data analysis software for rvp fast(tdas rvp fast) analyzed the data and provided a report summarizing which viruses were present. the rvp fast detects influenza b, influenza a h seasonal, and influenza a h only. if any other subtypes are present, it will indicate the presence of influenza a matrix protein only. therefore the samples in which influenza a matrix protein was detected were run separately by a singleplex pcr to detect h pandemic strain using artus inf/h lc/rg rt-pcr kit (qiagen) and for avian influenza a h n (subtype asia) by lightmix kit (tib, molbiol,gmbh, berlin, germany), according to the manufacturer's instructions. any strain in which rna was not detected for these four influenza a types (i.e., h , h seasonal in rvp fast and independent singleplex pcrs for h pandemic strain, and h n [subtype asia]) was labeled as unsubtypeable influenza a virus. demographics, medical history, vaccination history, knowledge of h n influenza, and compliance with infection control practices are presented as frequencies. the prevalence of respiratory viruses is presented as number of viruses per healthcare workers. differences in the prevalence of respiratory viruses before and after the hajj were examined using non-parametric paired statistics a total of healthcare workers who treated pilgrims during the hajj season were included in the study. of these, answered the (main) pre-hajj questionnaire and answered the (short) post-hajj questionnaire. a total of combined nasal and throat swabs were obtained during the pre-and post-hajj periods. demographic and clinical characteristics of the sample are shown in table . the majority of the healthcare workers were males ( %) with an average age of . ae . years (range e years), non-saudi ( %), physicians ( %), with more than years of medical experience ( %) as well as previous experience of serving in hajj medical services ( %). most of the healthcare workers ( %) described their own health as very good to excellent. chronic disease, namely hypertension, diabetes, and asthma were present in % and % were current smokers. compliance of healthcare workers with pre-hajj vaccination and infection control is shown in table . eighty four percent of them got at least one vaccine before hajj. the coverage of hepatitis b, meningococcal and seasonal influenza vaccines were relatively high ( %, % and %, respectively), while the coverage of h n vaccine was considerably low ( %). the main reasons described for not getting the vaccine were worries about the side effects, ( %), non-availability ( %), and fear of developing h n symptoms ( %). approximately % of the healthcare workers did not get seasonal influenza vaccine in the past year due to the belief of being healthy ( %), lack of knowledge about the place to get the vaccine ( %), and the assumption that influenza is not a serious illness ( %). compliance with hand hygiene was noted in %, cough etiquette in % and wearing face mask in % of the healthcare workers. the exposure risk as defined by being within m from a person with ili was reported in %, handling biological specimens in % and examining patients in %. about % of them got sick or injured during hajj. background knowledge of the healthcare workers about h n is shown in tables and . eighty five percent believed that h n is a serious disease, % were worried about catching h n influenza during hajj and % were aware of the main symptoms of h n influenza. the main source or vehicle of h n transmission as recognized by them were contact with people infected with h n ( %), contaminated fomites ( %) and air ( %). appreciable level of knowledge about measures to avoid h n infection were noted as described by maintenance of hand hygiene ( %), wearing a mask ( %), cough/sneeze etiquette ( %), staying away from sick people ( %), using hand sanitizer ( %), avoiding crowds/public gatherings ( %) and taking h n vaccine ( %). among the circulating respiratory virus types and subtypes, only two were detected in the healthcare workers in the pre-and post-hajj period: rhinovirus (n z , . %) and coronavirus e (n z , . %) . rhinovirus was detected more before the hajj (n z , . %) than after (n z , . %), but the difference was not statistically significant. the only isolate of coronavirus was detected in the post-hajj period. two healthcare workers had rhinovirus detected both before and after the hajj. rhinovirus was detected in . % of those who had respiratory symptoms and . % of those who got sick during hajj. no other respiratory viruses were detected in any of the samples. the prevalence (per persons) of respiratory viruses according to age, sex, profession, smoking, vaccine, sickness, and wearing a mask is shown in fig. . the prevalence was slightly higher in healthcare workers who got sick during hajj, in nurses, and in those who did not wear masks than in smokers; however, the difference was not statistically significant. hajj, the annual pilgrimage of muslims is a time of a unique mass gathering event in makkah. around two million people are confined to small area and the chances of having infections acquired by respiratory tract are increased. al-tamami et al, during the hajj, found cases of meningitis of all types, mainly in indians, whose ages ranged from to years, and in twice as many women as men. balkhy et al, in , studied symptomatic pilgrims, . % of whom had positive viral cultures. of these, influenza b accounted for %, followed by herpes simplex virus ( . %), rsv ( . %), parainfluenza ( . %) and influenza a ( . %). a comparative study of respiratory tract infections in symptomatic uk and saudi pilgrims by rashid et al. in found infections in % of uk pilgrims but in only % of saudi pilgrims. half of the infections in uk pilgrims were due to rhinoviruses, followed by influenza virus, parainfluenza, and rsv. the saudi pilgrims had higher infection rates with influenza virus ( . %) than with rhinovirus ( . %). in , alborzi et al. also reported that . % of patients tested had viral pathogens: influenza in ( . %), parainfluenza in ( . %), rhinovirus in ( . %), adenovirus in ( . %), enterovirus in ( %), and rsv in ( . %) and coinfection with two viruses in patient ( . %). the current study evaluated the prevalence of respiratory viruses in healthcare workers who saw pilgrims after the h n pandemic had been declared. we tested for respiratory virus types and subtypes in the healthcare workers and found primarily rhinoviruses and a single coronavirus e. rhinoviruses were more prevalent after the hajj ( . %) than before ( . %). none of the healthcare workers tested positive for any influenza virus, including the h n pandemic strain. this is explained by the fact that among more than two million pilgrims in , the ministry of health reported only cases of h n and deaths. the high case-fatality ratio may be because pilgrims were committed to completing hajj and delayed seeking medical care until their condition had worsened. , since the overall number of cases among pilgrims was low, therefore, the chances of transmitting it to healthcare workers were very small. rhinoviruses are present in about two-thirds of persons with common colds and probably are responsible for more human infections than any other agents. , they are common in all age groups, occur throughout the year, and are present worldwide. louis et al. found that rhinovirus was responsible for half of the respiratory infections in residents and staff in a long-term care facility for elderly persons, although in community-dwelling elderly, they cause % of respiratory infections. renois et al found rhinoviruses to be most prevalent in cases of influenza-like illness in infections with one agent ( %) as well as in coinfections with influenza a h n viruses ( %). our finding that rhinoviruses are the most prevalent viruses in healthcare workers during the hajj are consistent with the other studies of rhinoviruses in the general population, in patients with influenza-like illness, and also in pilgrims. arruda et al. studied the natural history of rhinovirus infections in adults during autumn and found that among persons with colds, % ( ) had rhinovirus infections and % had coronavirus oc and e. these findings agree with our finding of rhinovirus as the predominantly isolated virus ( . %), followed by coronavirus e ( . %), in a group of subjectively healthy healthcare workers. arruda et al. isolated a high percentage of viruses because the subjects were symptomatic, while in our study rhinovirus was detected in % of participants with respiratory symptoms and in % who got sick during hajj. rhinoviruses spread efficiently in families, in school groups, among university students, and on military bases. , linde et al. found an increase in the proportion and number of rhinovirus diagnoses that roughly parallels a decrease in influenza diagnoses, after the summer holidays and start of schools. they hypothesize that a rhinovirus epidemic could interfere with the spread of pandemic influenza in a warm and humid climate, which decreases the spread of influenza by aerosol. a similar phenomenon may be responsible for the frequent isolation of rhinoviruses in the present study. rhinoviruses may protect the host from being infected by other viruses such as influenza a virus, parainfluenza virus, adenoviruses, coronaviruses, bocavirus, metapneumovirus, and rsv. rhinovirus shedding is commonly limited to e days in immunocompetent subjects. however viral rna may be present from days before symptoms occur to five or more weeks after they go away. , the influenza a h n vaccination rate in healthcare workers has been reported to be lower than the seasonal influenza vaccination rate , , and was % versus % in the current study. these results are also comparable to the data obtained from the united states for the same period: where vaccination coverage for h n in healthcare workers was % and for seasonal influenza it was %. , in conclusion, we found that rhinoviruses were the most frequently isolated viruses in a group of subjectively healthy middle-aged healthcare workers who treated hajj pilgrims during the influenza a h n pandemic. respiratory symptoms were present in % of the healthcare workers in which the virus was detected. none of the participants had influenza a h n , despite that only % of them were vaccinated against h n vaccine, possibly because it was also infrequently found among pilgrims. usa, dr abduraman abudawod and dr. nedal almasri for their assistance in the data collection. risk of respiratory infections in healthcare workers: lessons on infection control emerge from the sars outbreak acute respiratory tract infections among hajj medical mission personnel, saudi arabia health risks at the hajj association of national health occupational physicians (anhops) respiratory tract infection during hajj influenza a common viral infection among hajj pilgrims: time for routine surveillance and vaccination mecca bound: the challenges ahead viral respiratory infections at the hajj: comparison between uk and saudi pilgrims viral etiology of acute respiratory infections among iranian hajj pilgrims risk factors of bacterial meningitis in makkah during hajj h: a pilot study outbreak of swine-origin influenza a (h n ) virus infection e mexico, marcheapril update: swine influenza a (h n ) infections e california and texas world health organization. the regional office of eastern mediterranean global public health implications of a mass gathering in mecca, saudi arabia during the midst of an influenza pandemic establishment of public health security in saudi arabia for the hajj in response to pandemic influenza a h n acceptance and adverse effects of h n vaccinations among a cohort of national guard health care workers during the hajj season prevention of pandemic influenza after mass gatherings e learning from hajj pandemic h n influenza at the hajj: understanding the unexpectedly low h n burden human rhinoviruses: the cold wars resume acute respiratory symptoms in adults in general practice the seasonality of rhinovirus infections and its implications for clinical recognition rhinovirus outbreak in all long term care 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association with symptomatic illness and effect of season influenza vaccination of health-care personnel: recommendations of the healthcare infection control practices advisory committee (hicpac) and the advisory committee on immunization practices (acip) should healthcare workers have the swine flu vaccine key: cord- -m dflwmm authors: alqahtani, amani s.; wiley, kerrie e.; mushta, sami m.; yamazaki, kaoruko; bindhim, nasser f.; heywood, anita e.; booy, robert; rashid, harunor title: association between australian hajj pilgrims’ awareness of mers-cov, and their compliance with preventive measures and exposure to camels date: - - journal: j travel med doi: . /jtm/taw sha: doc_id: cord_uid: m dflwmm through a prospective cohort study the relationship between travellers’ awareness of mers-cov, and compliance with preventive measures and exposure to camels was evaluated among australian hajj pilgrims who attended hajj in . only % of australian hajj pilgrims were aware of mers-cov in saudi arabia. those who were aware of mers-cov were more likely to receive recommended vaccines [odds ratio (or) . , % confidence interval (ci): . – . , p < . ], but there was no significant difference in avoiding camels or their raw products during hajj between those who were aware of mers-cov and those who were not (or . , % ci: . – . , p = . ). hajj pilgrims’ awareness is reflected in some of their practices but not in all. as of june , middle east respiratory syndrome coronavirus (mers-cov) infection has been identified in people in countries with % mortality. recent studies have demonstrated the potential role of camels, the only known zoonotic source of mers-cov, in the transmission of mers-cov to humans. , saudi arabia, the epicentre of mers-cov (with > % of global mers-cov burden), hosts the hajj pilgrimage in mecca, where - million people assemble annually. millions also visit mecca and medina throughout the year on a minor pilgrimage called umrah. although no mers-cov cases have been reported in relation to hajj, several imported cases have been recorded among returning umrah pilgrims in the uk, malaysia, tunisia, algeria and the netherlands. [ ] [ ] [ ] potential sources of infection are exposure to camels or their products, other mers patients and hospital visits. previous studies assessing awareness of mers-cov among french, australian and turkish hajj pilgrims found that between and % pilgrims were unaware of the presence of the disease in saudi arabia. [ ] [ ] [ ] however, no study has attempted to investigate the association between hajj pilgrims' awareness of mers-cov, and their compliance with preventive measures and exposure to camels. therefore, we conducted a prospective cohort study among australian travelers who attended hajj pilgrimage in . brief communication cruited participants were then followed up during hajj, and again after their return from hajj. before hajj, between mid-august and the first week of september , the researchers attended pre-hajj seminars run by eleven specialist hajj travel agents in sydney. most prospective pilgrims attend these seminars as part of their preparations for travel to mecca, making it an ideal place to recruit a relatively representative and generalizable sample. all pilgrims attending these seminars were approached and invited to participate in the study. upon consent, data on socio-demographic characteristics, details of their travel itinerary and receipt of pre-travel health advice from medical (such as a general practitioner [gp]) and nonmedical sources (tour operator) were collected in a selfadministered questionnaire. the respondents' knowledge, attitudes and perceptions regarding mers-cov, their willingness to use preventive measures while at hajj, and their understanding of the risk of mers-cov infection from exposure to camels, were descriptively analyzed using a three-point likert scale. during hajj, we endeavored to meet all the same participants in mina, saudi arabia and followed them daily throughout the peak days of hajj (from to th of september ). a separate questionnaire, in the form of diary card, was administered to determine their actual use of preventive measures such as facemask and hand hygiene, and document development of symptoms suggestive of acute respiratory infection retrospectively for three days before arriving in mina, then daily for seven consecutive days. after hajj, the participants took part in a computer aided telephone interview (cati) to days after their return to australia (until th of december, ). pilgrims were asked about the history of their contact with camels and consumption of camel products (e.g. milk and meat) at hajj and development of respiratory symptoms after their return from hajj. data collected before, during and after hajj were linked by a unique barcode. a non-random sampling plan was used to gather a sample which was representative of pilgrims residing in nsw. the sample size calculation was based on a previous study where a sample of % of the target population ( australian pilgrims in ) was deemed sufficient. we estimated that about % australian pilgrims would be aware of mers-cov, and considering an error margin of . %, a sample of was deemed to be sufficient for this study; with compliance adjustment of % a total of participants were approached. statistical analysis was performed using the statistical package for social sciences (spss) v. . (spss, inc., chicago, il, usa). pearson correlation coefficient and chi-square test were used to assess variables and determine associations and correlations. univariate factors with p values < . were entered into multivariate regression models. two-tailed p values < . were considered statistically significant in multivariate analyses. this study was reviewed and approved by the human research ethics committee (hrec) at the university of sydney (project no: / ). a total of pilgrims were enrolled in the study; their demographics are described in table . their median duration of stay in saudi arabia was (range: - ) days. the majority ( %) of participants received one or more recommended vaccines: % ( / ) received influenza vaccine and % ( / ) additionally received pneumococcal vaccine. fifty eight percent ( / ) of pilgrims received pre-travel medical advice before hajj; many consulted other sources as shown in table . of the participants enrolled, ( %) were followed during hajj, and ( %) could be reached by cati after their return home. twenty eight percent ( / ) of respondents were aware of mers-cov before travelling to saudi arabia. of those who were aware, % ( / ) answered correctly that the virus affects the respiratory tract, and % ( / ) were 'very concerned' of contracting mers-cov at hajj ( table ) . none of the demographic factors were associated with mers-cov awareness. pilgrims who were aware of mers-cov were more likely to receive recommended vaccines than those who were not [odds ratio (or) . , % confidence interval (ci): . - . , p < . ]. overall, % ( / ) believed that there was a moderate to high risk of contracting disease from consumption of raw camel milk, % ( / ) thought the risk was low or nil, while about % ( / ) did not know of the risk. pilgrims who were aware of mers-cov were significantly more likely to consider it a risk to drink unpasteurized camel milk as high than those who were unaware ( % vs %, p < . ). the acceptability of preventive measures, and participant's actual compliance are presented in table . those who were aware of mers-cov were more likely to intend to avoid contact with camels (or . , % ci: . - . , p ¼ . ) and consume their raw products (or . , % ci: . - . , p ¼ . ) than those who were unaware. moreover, participants who were concerned with catching mers-cov during hajj were more likely to accept to use facemask compared with those who were not concerned (or . , % ci: . - . , p < . ). however, except for vaccination, no significant difference was observed in the actual uptake of preventive measures between those who were aware or concerned of mers-cov and those who were not. seven pilgrims ( %) reported actually coming in contact with camels and/or consuming their products during hajj; five ( %) were unaware of mers-cov before travel. the type of exposure to camels included taking photographs [ . % ( / )] with camels, consuming boiled [ % ( / )] or raw milk [ . % ( / )] and meat [ . % ( / )]. out of seven pilgrims who came in contact with camels four ( %) developed respiratory symptoms during and/or immediately after hajj. no significant differences were found in avoiding camels or their raw products during hajj between those who were aware (or . , % ci: . - . , p ¼ . ) or concerned (or . , % ci: . - . , p ¼ . ) of mers-cov and those who were not. this study shows that only % of australian pilgrims were aware of mers-cov before attending the hajj , with some engaging in high risk behaviours such as exposure to camels ( %), and non-compliance with preventive measures. awareness was lower compared with previous surveys of similar australian studies showing that up to % of pilgrims were aware of mers-cov; , other studies have shown % of turkish and % of french pilgrims to be aware. , importantly, this study showed that pilgrims who were aware of mers-cov were twice more likely to intend to avoid contact with camels and consume their raw products during hajj than those who were unaware. similarly, those who were concerned of catching mers during hajj were approximately four times more likely to intend to use facemask during hajj. this may indicate that pilgrims' awareness of infectious diseases is reflected in how acceptable they find using some preventive measures and is consistent with a previous study by our team that showed that pilgrims who were aware of mers-cov were also significantly more aware of its risks from drinking unpasteurized camel milk compared with those who were unaware ( % vs %, p < . ). conversely, this study highlights that while the knowledge and perceived susceptibility to the disease were associated with their intention to use preventive measures, these factors were absent in their actual use. theoretically, the frame work of "precaution adoption model" sets forward stages of health behavior change in an individual and the factors that lead people to move from one stage to another such as awareness, perceived severity and susceptibility, and cues to action. however, in this study we observed that perceived severity and susceptibility did not seem to play much role in motivating the pilgrims to comply with preventive measures (figure ). although majority of pilgrims who were concerned with contacting mers-cov at hajj planned to use preventive measures, in practice few applied the measures and no significant difference was observed between those who were concerned and those who were not. this may indicate that among hajj pilgrims, there may be unique factors and barriers that affect their compliance with preventive measures against the infectious diseases which needs further investigation. other studies have documented the pilgrims' willingness to comply with mers-cov preventive measures, , in practice many participants might not have adhered to those as seen in this study. two percent (n ¼ ) of pilgrims actually came into contact with camels or consumed their products during their pilgrimage, which is an improvement compared with the previous year when between and % pilgrims were reported to be exposed to camels. , this apparent decline may be attributed to the saudi arabian authorities' banning of bringing and sacrificing camels into hajj sites in . to our knowledge, this is the first cohort study which has assessed pilgrims' awareness about mers-cov and their actual practice of risk avoidance, especially their contact with camels at hajj; however, the study findings have limited generalizability outside of australia. additionally, the pilgrims' participation in the pre-travel survey may have increased their awareness of the recommended preventive health measures, leading to higher reported usage (known as 'the hawthorne effect'). although this is certainly a theoretical consideration, research into the hawthorne effect on practice-based research suggests that its impact is minimal. moreover, the exact site and time of camel exposure were not explored, and data collection relied on self-report. in conclusion, this study showed that many australian pilgrims are unaware of the risk of mers-cov in saudi arabia; and some engaged in high-risk practices such as coming in contact with camels. pilgrims' awareness of the risk is reflected in their vaccine uptake but not in their avoidance of camel exposure. middle east respiratory syndrome coronavirus co-circulation of three camel coronavirus species and recombination of mers-covs in saudi arabia mers-cov in upper respiratory tract and lungs of dromedary camels, saudi arabia middle east respiratory syndrome coronavirus: current situation and travel-associated concerns imported cases of middle east respiratory syndrome: an update middle east respiratory syndrome coronavirus (mers-cov) infections in two returning travellers in the netherlands australian hajj pilgrims' knowledge about mers-cov and other respiratory infections hajj pilgrims knowledge about middle east respiratory syndrome coronavirus attitudes and practices concerning middle east respiratory syndrome among umrah and hajj pilgrims in samsun exploring barriers to and facilitators of preventive measures against infectious diseases among australian hajj pilgrims: cross-sectional studies before and after hajj camel exposure and knowledge about mers-cov among australian hajj pilgrims in a model of the precaution adoption process: evidence from home radon testing pilot use of a novel smartphone application to track traveller health behaviour and collect infectious disease data during a mass gathering: hajj pilgrimage saudi arabia, animal reservoir, camels, hajj. archive number: . an assessment of the hawthorne effect in practice-based research professor robert booy has received funding from baxter, csl, gsk, merck, novartis, pfizer, roche, romark and sanofi pasteur for conducting this research, travel to conferences or consultancy work; all funding received is directed to research accounts at the children's hospital at westmead. dr a.e.h. has received grant funding from gsk and sanofi pasteur for investigator-driven research. dr h.r. has received fees from pfizer and novartis for consulting or serving on an advisory board.conflict of interest: none declared. key: cord- -h i t cr authors: hoang, van-thuan; dao, thi-loi; ly, tran duc anh; belhouchat, khadidja; chaht, kamel larbi; gaudart, jean; mrenda, bakridine mmadi; drali, tassadit; yezli, saber; alotaibi, badriah; fournier, pierre-edouard; raoult, didier; parola, philippe; de santi, vincent pommier; gautret, philippe title: the dynamics and interactions of respiratory pathogen carriage among french pilgrims during the hajj date: - - journal: emerg microbes infect doi: . / . . sha: doc_id: cord_uid: h i t cr we conducted this study to describe the dynamics of the acquisition of respiratory pathogens, their potential interactions and risk factors for possible lower respiratory tract infection symptoms (lrti) among french pilgrims during the hajj. each participant underwent four successive systematic nasopharyngeal swabs before and during their stay in saudi arabia. carriage of the main respiratory pathogens was assessed by pcr. pilgrims were included and . % reported respiratory symptoms during the study period. the acquisition of rhinovirus, coronaviruses and staphylococcus aureus occurred soon after arrival in saudi arabia and rates decreased gradually after days and . in contrast, streptococcus pneumoniae and klebsiella pneumoniae carriage increased progressively until the end of the stay in saudi arabia. haemophilus influenzae and moraxella catarrhalis carriage increased starting around days and , following an initial clearance. influenza viruses were rarely isolated. we observed an independent positive mutual association between s. aureus and rhinovirus carriage and between h. influenzae and m. catarrhalis carriage. dual carriage of h. influenzae and m. catarrhalis was strongly associated with s. pneumoniae carriage (or = . ). finally, our model showed that m. catarrhalis carriage was negatively associated with k. pneumoniae carriage. chronic respiratory disease was associated with symptoms of lrti. k. pneumoniae, m. catarrhalis-s. aureus and h. influenzae-rhinovirus dual carriage was associated with lrti symptoms. our data suggest that rtis at the hajj are a result of complex interactions between a number of respiratory viruses and bacteria. each year, an increasing number of people travel to the kingdom of saudi arabia (ksa) for the hajj and umrah pilgrimages, which attract around million pilgrims annually from more than countries. more than two million pilgrims from outside saudi arabia participated in the hajj pilgrimages in [ ] . each year, about , pilgrims from marseille, france, participate in the hajj [ ] . the event presents major challenges for public health, including inter-human transmission of infectious diseases, notably respiratory tract infections (rtis), due the crowded conditions experienced by pilgrims [ ] . in a recent study on morbidity and mortality among indian hajj pilgrims, infectious diseases represented % of outpatient diagnoses, with rtis and gastroenteritis being the most common [ ] . between . % and . % of french pilgrims presented rti symptoms during the hajj [ ] . a recent literature review suggested that etiology of rtis at the hajj is complex; several studies showed a significant acquisition of respiratory pathogens by pilgrims following participation in the hajj in both symptomatic and asymptomatic individuals [ ] . in a systematic review of studies, al-tawfiq et al. showed that human rhinovirus (hrv) and influenza viruses were the most common viral respiratory pathogens isolated from ill hajj pilgrims [ ] . in addition, human non-mers coronaviruses (hcov) were also a common cause of rtis during the event [ ] . on the other hand, streptococcus pneumoniae, haemophilus influenzae and staphylococcus aureus were shown to be the most commonly acquired respiratory bacteria at the hajj [ ] . rtis are caused by the antagonistic and synergistic interactions between upper respiratory tract viruses and predominant bacterial pathogens [ ] . pathogens are usually studied individually, although in their natural environment they often compete or coexist with multiple microbial species. similarly, the diagnosis of infections often proceeds via an approach which assumes a single agent etiology [ ] . nevertheless, complex interactions occur between the different infectious microorganisms living in the same ecological niche and mixed infections are frequent [ ] . a better understanding of polymicrobial interactions in the nasopharynx among hajj pilgrims is important for many reasons. carriage of more than one pathogen is common among hajj pilgrims, whether or not they present with respiratory symptoms [ ] . colonization is the initial step in the disease process [ ] . nasopharyngeal colonization is likely to be a reservoir for respiratory pathogens resulting in interhuman transmission between pilgrims during close contact experienced during the hajj ritual. furthermore, antibiotic use or vaccines, which target specific pathogen species, may alter polymicrobial interactions in the nasopharynx and have unanticipated consequences [ , ] . to our knowledge, the dynamics and interaction between the main respiratory pathogens acquired during the hajj pilgrimage have not been specifically investigated, to date. risk factors for possible lower respiratory tract infection (lrti) symptoms at the hajj have not been studied. we conducted this study among french pilgrims during the hajj, to describe the dynamics of the acquisition of respiratory pathogens and their potential interactions. in addition, we investigated risk factors for possible lrti symptoms. participants and study design ( figure ) pilgrims travelling to mecca, saudi arabia during the hajj from marseille, france, were recruited through a private specialized travel agency. potential adult participants were invited to participate in the study. they were included and followed-up by two bilingual (arabic and french) medical doctors who travelled with the group. all participants departed to ksa on the same date, were housed in the same accommodation during their stay and performed the rituals together. upon inclusion, before departing from france, pilgrims were interviewed using a standardized pre-hajj questionnaire that collected information about demographic characteristics, medical history and immunization status. pilgrims were considered to have been immunized against influenza when they had been vaccinated within the past year and until before days of the date of travel. pilgrims were considered to be immune to invasive pneumococcal disease (ipd) when they had been vaccinated with the -valent conjugate pneumococcal vaccine (pcv- ) in the past five years [ , ] . a post-hajj questionnaire was completed two days before the pilgrims' return to france. clinical data, antibiotic intake and information on compliance with face masks use as well as hand washing, the use of hand gel disinfectant and disposable handkerchiefs was collected. to evaluate the dynamic and interaction of respiratory pathogens during the hajj, all pilgrims underwent four successive systematic nasopharyngeal swabs at different times: pre-travel, five to six days post arrival, - days post arrival and just prior to leaving ksa (post-hajj). the hajj rituals took place from - august. influenza-like illness (ili) was defined as the presence of cough, sore throat and subjective fever [ ] . possible lrti was defined by presence of productive cough without nasal or throat symptoms; febrile productive cough; dyspnea or febrile dyspnea [ ] . based on the who classification, "underweight" was defined as having a body mass index (bmi) below . , "normal" corresponded to a bmi between . and , "overweight" corresponded to a bmi ≥ , and "obese" referred to those with a bmi ≥ [ ]. nasopharyngeal swabs were obtained from each pilgrim, transferred to sigma-virocult® medium and stored at − °c until processing. the sampling was done by the doctors accompanying the group, in a standardized way ( cm in the nostril, turns; post wall of the pharynx, streaks). the rna and dna were extracted from the samples using the ez advanced xl (qiagen, hilden, german) with the virus mini kit v . (qiagen) according to the manufacturer's recommendations. all quantitative real-time pcr were performed using a c touch™ thermal cycle (bio-rad, hercules, ca, usa). one-step simplex real-time quantitative rt-pcr amplifications were performed using multiplex rna virus master kit (roche diagnostics, france) for influenza a, influenza b, hrv and internal controls ms phage [ ] . hcov was detected by one-step duplex quantitative rt-pcr amplifications of hcov/ hpiv-r gene kit (ref: - , biomérieux, marcy l'etoile, france), according to the manufacturer's recommendations. real-time pcr amplifications were carried out using lightcycler® probes master kit (roche diagnostics, france) according to the manufacturer's recommendations. the shd gene of h. influenzae, phoe gene of klebsiella pneumoniae, nuca gene of s. aureus, lyta cdc gene of s. pneumoniae and copb gene of moraxella catarrhalis were amplified with internal dna extraction controls tiss, as previously described [ , ] . human adenovirus, human metapneumovirus, respiratory syncytial virus, bordetella pertussis and mycoplasma pneumoniae were not tested because a low proportion (< %) of returning french pilgrims or international pilgrims were found positive for these pathogens in previous works [ , , , ] . negative controls (pcr mix) and positive controls (dna from bacterial strain or rna from viral strain) were included in each run. positive results of bacteria or virus amplification were defined as those with a cycle threshold (ct) value ≤ . a threshold value of was used in each experimental run and we calculated the rfu cut off value recommend by cfx manager software version . (bio-rad) [ ] in order to verify the positive cases. results were considered positive when the cycle threshold value of real-time pcr was greater than the cut off value. pilgrims were considered to be positive for respiratory pathogens during the hajj if they were positive at the days and and/or days and sample. stata software version . (copyright - statacorp llc, http://www.stata.com) was used for statistical analysis. the main outcomes of interest were the relationships between respiratory pathogens among pilgrims during the hajj. we evaluated the carriage of hrv, hcov, s. aureus, s. pneumoniae, h. influenzae, k. pneumoniae and m. catarrhalis using logistic mixed models. because each pilgrim provided four successive samples, we used a repeated measures design to take into account the variability of series samples from each pilgrim. to evaluate the effect of covariates on each respiratory pathogen carriage, we modelled carriage of hrv, hcov, s. aureus, s. pneumoniae, h. influenzae, k. pneumoniae and m. catarrhalis separately. we did not separately model the outcome of carriage of influenza a and b viruses because of the low prevalence of these viruses. only the variables with a prevalence ≥ . % were considered for statistical analysis. unadjusted associations between respiratory pathogen carriage with multiples factors: sociodemographic characteristics (gender, ≥ years), chronic respiratory disease, bmi classification, smoking status; individual preventive measures (vaccination against influenza, vaccination against ipd, use of a face mask, hand washing, disinfectant gel and disposable handkerchiefs); antibiotic intake days before each sample; respiratory virus or bacteria and dual carriage were analysed by univariable analysis. variables with p values < . in the univariable analysis were included in the multivariable analysis. a mixed model with the subject being random effect was used to estimate the relationships between respiratory pathogens and to take into account the repeated measures for pathogen carriage for each subject. regarding risk factors for lrti, the outcome was possible lrti symptoms reported during the hajj. the independent factors were sociodemographic characteristics (gender, ≥ years), chronic respiratory disease, smoking status, bmi classification; vaccination against influenza, vaccination against ipd, respiratory virus or bacteria and dual carriage during the hajj. unadjusted associations between multiple factors and possible lrti symptoms were examined using univariable analysis. variables with p values < . in the univariable analysis were included in the multivariable analysis. a logistical regression model was used to estimate factors' adjusted odds ratios regarding possible lrti. the results were presented by odds ratio (or) with a % confidence interval ( %ci). results with a p value ≤ . was considered to be statistically significant. the protocol was approved by the aix-marseille university institutional review board ( july ; reference no. -a - ). the study was performed according to the good clinical practices recommended by the declaration of helsinki and its amendments. all participants provided their written informed consent. the study included pilgrims. the sex ratio of the population was : . and the median age was years with . % of pilgrims aged years and over. most pilgrims were born in north africa ( . %) and sub-saharan africa ( . %). there was a high prevalence of overweight ( . %), obesity ( . %), diabetes mellitus ( . %) and hypertension ( . %) and . % participants reported that they suffered from chronic respiratory disease. in line with french recommendation, / pilgrims ( . %) had an indication for vaccination against ipd [ , ] ( table ) . a total of / ( . %) pilgrims reported that they had been vaccinated against influenza in the past year. only / ( . %) pilgrims with an indication for ipd had been vaccinated against pneumococcal disease (pcv- ) in the past five years. regarding non-pharmaceutical preventive measures, / ( . %) pilgrims reported using face masks during the pilgrimage. also, / ( . %) and / ( . %) pilgrims reported washing their hands more often than usual and using hand gel, respectively during the pilgrimage. finally, / ( . %) reported using disposable handkerchiefs during the hajj. a total of / ( . %) pilgrims presented at least one respiratory symptom during their stay in ksa. a cough and rhinitis were the most frequent symptoms affecting . % and . % of participants. over half of the pilgrims ( . %) reported expectoration and . % reported a dry cough. voice failure was reported by . %, fever by . % and ili by . % of participants. antibiotic use for rtis was reported by . % pilgrims. only one ( . %) pilgrim was hospitalized in ksa. regarding possible lrti symptoms, / ( . %) participants reported a productive cough without nasal or throat symptoms. in addition, / ( . %), / ( . %) and / ( . %) pilgrims presented febrile dyspnoea, dyspnea and a febrile productive cough, respectively. at total of / ( . %) pilgrims with respiratory symptoms were still symptomatic at return. the mean time between arrival in ksa and the onset of symptoms was . ± . days (range = - days) (data not shown). most ill pilgrims presented the onset of respiratory symptoms when stationed at mecca with a second minor wave in mina (figure ). table shows the prevalence of the carriage of respiratory pathogens according to sampling time and figure show the dynamics of most prevalent pathogens over the study period. overall, / ( . %) of all samples tested positive for at least one pathogen. s. aureus was the pathogen most frequently isolated with . % of all samples testing positive. high positivity rates were also observed for h. influenzae ( . %), k. pneumoniae ( . %), hrv ( . %) and m. catarrhalis ( . %). only . % of the samples were positive for coronaviruses and . % for s. pneumoniae. very few samples tested positive for influenza viruses. no case was positive for hpiv. of the positive samples, the proportion that was positive for more than one pathogen was . % ( / ). a total of / ( . %) samples were positive for two pathogens, / ( . %) for three pathogens, / ( . %) for four pathogens and / ( . %) for five pathogens (data not shown). in pre-travel samples, virus carriage was very low with only a few participants testing positive for hrv and hcov (< %). bacterial carriage was higher, notably for h. influenzae ( . %) m. catarrhalis ( . %) and s. aureus ( . %). k. pneumoniae and s. pneumoniae carriage were relatively low ( . % and . %, respectively). a dramatic increase in hrv carriage was observed on days and of the pilgrimage with prevalence times higher than that of pre-travel. hrv carriage decreased progressively in subsequent samples but was still eight times higher in post-hajj samples compared to pre-hajj. a seven-fold increase of hcov carriage was observed on days and that persisted on into days and of the pilgrimage and tended to slightly decrease in post-hajj samples. regarding bacteria, carriage of s. aureus increased by a factor of three on days and and decreased progressively in subsequent samples but was still double in post-hajj samples compared to pre-hajj. interestingly, the carriage curves of hrv and s. aureus were strictly parallel. m. catarrhalis carriage was about - % in pre-travel, days and and and samples and increased to % in post-hajj samples. k. pneumoniae carriage increased three-fold between pre-hajj and days and samples and slightly increased in subsequent samples. s. pneumoniae carriage increased constantly overtime with a seven-fold increase in post-hajj samples compared to pre-hajj. finally, h. influenzae carriage first decreased on days and and and by a factor . and then increased in post-hajj samples to a carriage rate which was higher than that of pre-hajj samples. table shows the factors that were independently associated with the carriage of respiratory pathogens on swabs from pilgrims. a positive association was observed between males and carriage of hrv and s. pneumoniae. chronic respiratory disease was also associated with s. pneumoniae carriage. finally, the use of disposable handkerchiefs was associated with a decreased carriage of h. influenzae. antibiotic intake ten days before each sampling was positively associated with hcov and k. pneumoniae carriage. regarding interactions between pathogens, we observed that hrv carriage and s. aureus carriage were mutually positively associated. the same applied to h. influenzae and m. catarrhalis carriage. pilgrims carrying s. pneumoniae were more likely also to carry m. catarrhalis. patients with a dual carriage of h. influenzae and s. pneumoniae were six times more likely also to be carrying s. pneumoniae. by contrast, m. catarrhalis carriage was associated with a reduced carriage of k. pneumoniae. table shows the results of multivariable risk factor analysis for possible lrti symptoms. chronic respiratory disease was associated with all possible lrti symptoms. obesity was associated with dyspnea. carriage of k. pneumoniae or m. catarrhalis-s. aureus or h. influenzae-rhinovirus combination was associated with a four-fold, -fold and eight-fold increase of dyspnoea prevalence, respectively. finally, m. catarrhalis-s. aureus dual carriage was associated with a five-fold increase in the prevalence of febrile dyspnea (table ). despite the recommendation to take individual preventive measures to prevent rtis [ , ] , these infections remain common among hajj pilgrims. overcrowding during the event is thought to increase the risk of the transmission of infectious diseases, but interaction between respiratory pathogens is probably one factor contributing towards the development of rtis. to our knowledge, no study on respiratory microbiota alteration among pilgrims during the hajj has been conducted. our results about the occurrence of rti symptoms are in line with previous results obtained regarding french pilgrims [ ] and others [ , ] . notably, we observed that rti symptoms occur soon after the pilgrims' arrival in mecca, with most symptoms starting between and days after arrival, corresponding to the period when pilgrims are stationed in mecca hotels and are visiting the grand mosque daily, where highly crowded conditions are common [ ] . we also confirmed that an overall increase in the carriage of respiratory viruses and bacteria can be seen when comparing pre-travel samples and post-hajj samples, as previously documented [ , , , [ ] [ ] [ ] . higher acquisition rates were observed for rhinovirus with a nine-fold increase when comparing pre-travel to post-hajj carriage and for s. pneumoniae with a seven-fold increase, but an increase was observed for all pathogens tested in this study. the unique design of our study with sequential systematic sampling at regular intervals allows for a better understanding of the dynamics of pathogen carriage during the pilgrimage. carriage rates of bacteria and viruses in this study are in line with those observed during recent studies conducted on french pilgrims and in pilgrims of other nationalities, using the same methods of detection [ , , [ ] [ ] [ ] . the acquisition of respiratory viruses and s. aureus occurred soon after arrival in saudi arabia and decreased gradually after days and . by contrast, s. pneumoniae and k. pneumoniae carriage increased progressively until the end of the visit, h. influenzae and m. catarrhalis carriage increased later, after an initial clearance. we hypothesize that the brutal acquisition of respiratory viruses upon arrival was the initial step that triggered subsequent changes in the relative abundance of resident bacteria [ ] that were already present in the nasopharynx of pilgrims. the apparent simultaneity of viruses and s. aureus carriage increase and the initial wave of respiratory symptoms, suggests that this pathogen association was responsible for the rtis that affected most pilgrims soon after arriving in mecca. the subsequent increase in resident bacteria that occurred during the second half of pilgrims' stays in saudi arabia appears to be contemporaneous with a second wave of respiratory symptoms, suggesting that these rtis were of bacterial origin. regarding interaction between respiratory pathogens, we observed a very clear pattern of positive association between the carriage of s. aureus and rhinovirus with acquisition curves which were strictly parallel. furthermore, an independent positive mutual association between the carriage of the two pathogens was evidenced in our multivariate model. several studies revealed a positive interaction between natural or experimental rhinovirus infection and s. aureus nasal carriers [ ] [ ] [ ] [ ] [ ] . these studies also underlined that rhinovirus infection may facilitate the propagation of s. aureus from staphylococcal carriers to the environment and the transmission of the bacterium between humans. among healthy persons who were experimentally infected by rhinovirus, the relative abundance of s. aureus first increased and then returned to its baseline level after the rhinovirus infection was cleared [ ] . these results suggest that changes in the composition of the respiratory microbiota following rhinovirus infection may play a role in the development of bacterial superinfection. morgene et al. proposed several potential mechanisms through which rhinovirus may increase bacterial infection [ ] . rhinovirus infection promotes pro-inflammatory cytokines and ifn production mainly through the activation of nfκb. in rhinovirus infected cells, the adherence of s. aureus was significantly higher compared to uninfected cells. the inflammation due to rhinovirus infection also increased cellular patterns that facilitate the adhesion and internalization of s. aureus within host cells [ ] . we also observed a parallel increase of h. influenzae and m. catarrhalis carriage in days and and post-hajj samples. an independent positive mutual association between the carriage of the two pathogens was evidenced in our multivariate model. dual carriage of h. influenzae and m. catarrhalis strongly associated with s. pneumoniae carriage which in turns associated with m catarrhalis carriage. these results are consistent with those of several studies conducted among children with upper rtis [ ] [ ] [ ] . in these studies, the competitive interaction between s. pneumoniae and h. influenzae was dependent on neutrophils and complement. the additional carriage of m. catarrhalis might alter the competitive balance between h. influenzae and s. pneumoniae [ ] . co-colonization of s. pneumoniae or h. influenzae with m. catarrhalis associating with increased risk of otitis media has been documented [ ] . using in vivo models, mixed species biofilms play a role in increasing the persistence of ear disease [ ] . other proposed mechanisms for positive associations between bacterial species include interspecies quorum sensing and passive antimicrobial resistance, which have been observed in experimental models of otitis media [ ] . finally, our model showed that m. catarrhalis carriage was negatively associated with k. pneumoniae carriage which, to our knowledge, has not previously been published. additionally, we found that the male gender was independently associated with an increase in rhinovirus and s. pneumoniae carriage. we have no explanation for this unexpected observation. the carriage of s. pneumoniae was higher among pilgrims with chronic respiratory disease which support the current french recommendations that vaccination against ipd be proposed to at-risk pilgrims [ ] . in one of our recent studies, pilgrims who were vaccinated against ipd were seven time less likely to harbour s. pneumoniae after the hajj compared to unvaccinated pilgrims [ ] . in this study, the use of disposable handkerchiefs was associated with a significant decrease in h. influenzae carriage. non-pharmaceutical individual preventive measures such as cough etiquette, hand hygiene, use of a face mask, disinfectant gel and disposable handkerchiefs are recommended for hajj pilgrims [ ] . nevertheless, the effectiveness of these measures has been poorly investigated and available results are contradictory [ ] . the apparent association between antibiotic use and hcov and k. pneumoniae carriage warrants further investigation to better explore this unexpected observation. we also confirm that chronic respiratory disease is a risk factor for lrti. we also evidenced the role of respiratory bacteria including k. pneumoniae and m. catarrhalis-s. aureus association and h. influenzaerhinovirus association in the occurrence of possible lrti symptoms. this reinforces the need for antibiotic use in case of lrti symptoms [ ] . our study has some limitations. the study was conducted among french pilgrims only with a relatively small sample size and cannot be generalized to all pilgrims. qpcr used to detect respiratory pathogens does not distinguish between dead and living micro-organisms. only a small number of respiratory pathogens were investigated. respiratory bacteria serotypes were not investigated. influenza viruses were not included in the model due to low carriage rates. in addition, we did not recruit a control group of individuals that did not participate to the hajj. a study addressing interactions between respiratory pathogens in the general french adult population could be of interest. nevertheless, our study is the first study on the dynamics of and interaction between the respiratory pathogens that are most frequently isolated among hajj pilgrims. our data suggest that rtis at the hajj are a result of complex interactions between a number of respiratory viruses and bacteria. further studies aimed at studying the respiratory microbiota with tools allowing the identification of larger numbers of pathogens will be necessary to better elucidate these ecological changes and their potential role in the occurrence of respiratory symptoms. mass gatherings medicine: public health issues arising from mass gathering religious and sporting events travel reported by pilgrims from marseille, france before and after the hajj morbidity and mortality amongst indian hajj pilgrims: a -year 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randomised study haut conseil de la santé publique. bull epidemiol hebdo. recommandations sanitaires pour les voyageurs ministère des affaires sociales, de la santé et des droits des femmes influenza and the hajj: defining influenza-like illness clinically antibiotic use for respiratory infections among hajj pilgrims: a cohort survey and review of the literature rna and dna bacteriophages as molecular diagnosis controls in clinical virology: a comprehensive study of more than , routine pcr tests mass gathering and globalization of respiratory pathogens during the hajj quantitative detection of moraxella catarrhalis in nasopharyngeal secretions by real-time pcr circulation of respiratory viruses among pilgrims during the hajj pilgrimage respiratory viruses and bacteria among pilgrims during the miniopticon system instruction manual for miniopticon real-time pcr detection system with cfx manager spfware expected immunizations and health protection for hajj and umrah -an overview non-pharmaceutical interventions for the prevention of rtis during hajj pilgrimage bacterial respiratory carriage in french hajj pilgrims and the effect of pneumococcal vaccine and other individual preventive measures: a prospective cohort survey a cohort study of the impact and acquisition of nasopharyngeal carriage of streptococcus pneumoniae during the hajj impact of the hajj on pneumococcal transmission respiratory viral infection-induced microbiome alterations and secondary bacterial pneumonia airborne dispersal as a novel transmission route of coagulase-negative staphylococci: interaction between coagulase-negative staphylococci and rhinovirus infection gesundheit!" sneezing, common colds, allergies, and staphylococcus aureus dispersion preventing the airborne spread of staphylococcus aureus by persons with the common cold: effect of surgical scrubs, gowns, and masks dispersal of staphylococcus aureus into the air associated with a rhinovirus infection coinfection can trigger multiple pandemic waves changes in microbiota during experimental human rhinovirus infection staphylococcus aureus colonization and non-influenza respiratory viruses: interactions and synergism mechanisms carriage of streptococcus pneumoniae, haemophilus influenzae, moraxella catarrhalis, and staphylococcus aureus in indonesian children: a cross-sectional study microbial interactions during upper respiratory tract infections nasopharyngeal bacterial interactions in children bacterial and viral interactions within the nasopharynx contribute to the risk of acute otitis media residence of streptococcus pneumoniae and moraxella catarrhalis within polymicrobial biofilm promotes antibiotic resistance and bacterial persistence in vivo divergent mechanisms for passive pneumococcal resistance to β-lactam antibiotics in the presence of haemophilus influenzae ministère des affaires sociales, de la santé et des droits des femmes no potential conflict of interest was reported by the authors. this study was supported by the institut hospitalo-universitaire (ihu) méditerranée infection, the french national research agency under the "investissements d'avenir" programme, reference anr- -iahu- , the région provence alpes côte d'azur and european feder primi funding. key: cord- -ixn hxb authors: zumla, alimuddin; azhar, esam i.; shafi, shuja; memish, ziad a. title: covid- and the scaled-down hajj pilgrimage - decisive, logical and prudent decision making by saudi authorities overcomes pre-hajj public health concerns date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: ixn hxb nan the abrupt appearance of sars-cov- as a novel lethal zoonotic pathogen causing disease in humans in late december, (who, ) , and its explosive global spread caught health authorities worldwide by surprise and exposed the ill-preparedness of global public health systems worldwide to deal with the appearance of a new pathogen. apart from generic prevention and control issues of public health and lockdown measures to limit epidemic spread, specific issues of mass gathering (mg) sporting and religious events came under specific spotlight (alzahrani et al, ; baloch et al, ; mccloskey et al, ; . mass gathering events present important health challenges related to the public health services and health of the host country population, the attendees and their home countries (memish et al, ; memish et al, ) . the hajj was held during the hin influenza pandemic and focused attention on developing mass gatherings medicine as a formal discipline, resulting in the formation of a coalition of global academic and public health faculty and virtual who mass gathering collaborating centres to guide development of, and update, optimal public health and medical prevention and treatment guidelines at mass gathering events (memish et al, ) . who with global mg partners, developed comprehensive key recommendations for covid- , and since end of february, , there was a stepwise increase in cancellation, temporary suspension or postponement of international and national religious, sporting, musical, and other mgs, as countries worldwide took public health and other measures (who, b; mccloskey et al, ; petersen, mccloskey et al, ) . apart from focus on major sporting j o u r n a l p r e -p r o o f events, global focus has been on saudi arabia and the umrah and hajj pilgrimages. approximately million people from countries travel to saudi arabia annually for the hajj and umrah pilgrimages (memish et al, ; ) . the umrah pilgrimage can be performed anytime during the year saudi arabia with its extensive experience and commitment to pilgrim safety and wellbeing, was quick off the mark and on february th, , restricted inbound flights and local and international pilgrims were prevented from travelling to makkah and madinah for the umrah pilgrimage. for the july hajj approximately . million pilgrims were expected in saudi arabia (saudi ministry of hajj and umrah, ) but they knew that the growing covid- pandemic may put their plans into disarray. the saudi ministry of health made regular announcements that the format of the hajj was being debated and evaluated based on covid- situation globally and domestically. several countries from where large numbers of muslim pilgrims originate (malaysia, indonesia, india and singapore) subsequently announced that they were barring their pilgrims from attending the hajj. these cancellations were anticipated to have major social and economic impacts on national economies, individual livelihoods and on public morale. the umrah and hajj pilgrimages together generate over $ billion annually for businesses and the economy and limiting or cancelling the hajj would come at a huge cost. alzahrani et al ( ) in early june , after careful consideration, the saudi government took decisive, logical, logistical and prudent decisions (saudi ministry of hajj and umrah, ) to overcome these pre-hajj nightmares of public health, political, economic and religious concerns. for the first time since the kingdom of saudi arabia was formed in the decision to bar pilgrims arriving in saudi arabia from foreign countries was made. the hajj was scaled down considerably, and participation for hajj rituals restricted to only , people with a negative covd- test, residing within the kingdom of which 'foreign' residents would comprise two thirds of all selected pilgrims from a pool of local workers, health care workers and security personnel especially those who had recovered from covid- . those aged years and over and those with co-morbid conditions would be barred. whilst all holy sites would remain open, adequate physical distancing and disinfection measures were put in place with j o u r n a l p r e -p r o o f oversight and assistance at regular intervals during the pilgrim's journey. wearing masks was mandatory and pilgrims would be subject to temperature checks and placed in quarantine if required. all pilgrims were given well thought out kits that include disinfectants, masks, a prayer rug, the ihram (a seamless white garment required to be worn by pilgrims), sterilised pebbles for the stoning ritual at jamaraat. throughout the pilgrims would have to keep a social distance of one and a half meters and were guided by well laid out markers and hajj coordinators. no pilgrims would be allowed to touch the kaaba or kiss the black stone at its corner -both of which are regular customs during the hajj. pilgrims would also have to be quarantined for days after the pilgrimage. the hajj was a public health success and ended on monday rd august, . the decisive, logical and prudent decision making by saudi authorities which enabled the pre-hajj nightmare of public health, political, economic and religious concerns to be overcome. the successful completion of the hajj is a major tribute to the leadership and commitment of the saudi authorities, and it reflects their extensive experience of organising the annual hajj pilgrimage, and continued commitment to improvement public health issues related to mass gatherings events. the decisive actions, public health preparedness and strict implementation of public health prevention and intervention measures, pre-hajj, during hajj and post-hajj, serves as an exemplar for other mass gathering religious and sporting events. the hajj was not the first time the hajj has been scaled down. historically, the hajj has been scaled down several times before due to infectious diseases outbreaks. between and , there were at least cholera outbreaks among pilgrims in mecca (peters f, ) . massive cholera outbreaks throughout the th century resulted in the suspension of hajj in and . the cholera outbreak in in saudi arabia led to establishment of quarantine ports to limit the spread of the disease during hajj. since saudi arabia's foundation in the hajj has never been cancelled and has not missed any year. the ongoing sars-cov- pandemic, yet once again, highlights the continuing threat of new emerging infectious diseases with epidemic potential, including the persistent threat of the middle east respiratory syndrome (mers) (perlman et al, ; memish et al, b) to global health security. as of nd august , there have been , , confirmed cases of covid-j o u r n a l p r e -p r o o f decisive leadership is a necessity in the covid- response forecasting the spread of the covid- pandemic in saudi arabia using arima prediction model under current public health interventions hajj in the time of covid- unique challenges to control the spread of covid- in the middle east saudi arabia's drastic measures to curb the covid- outbreak: temporary suspension of the umrah pilgrimage the continuing -ncov epidemic threat of novel coronaviruses to global health -the latest novel coronavirus outbreak in wuhan, china a risk-based approach is best for decision making on holding mass gathering events hajj: infectious disease surveillance and control mass gatherings medicine: public health issues arising from mass gathering religious and sporting events pausing super spreader events for covid- mitigation: international hajj pilgrimage cancellation middle east respiratory syndrome confronting the persisting threat of the middle east respiratory syndrome to global health security the hajj: the muslim pilgrimage to mecca and the holy places covid- travel restrictions and the international health regulations -call for an open debate on easing of travel restrictions transmission of respiratory tract infections at mass gathering events saudi ministry of hajj and umrah the annual hajj pilgrimage-minimizing the risk of ill health in pilgrims from europe and opportunity for driving the best prevention and health promotion guidelines key planning recommendations for mass gatherings in the context of the current covid- outbreak infectious diseases epidemic threats and mass gatherings: refocusing global attention on the continuing spread of the middle east respiratory syndrome coronavirus (mers-cov) key: cord- -d ll ka authors: alotaibi, badriah m.; yezli, saber; bin saeed, abdul-aziz a.; turkestani, abdulhafeez; alawam, amnah h.; bieh, kingsley l. title: strengthening health security at the hajj mass gatherings: characteristics of the infectious diseases surveillance systems operational during the hajj date: - - journal: j travel med doi: . /jtm/taw sha: doc_id: cord_uid: d ll ka background: hajj is one of the largest and the most ethnically and culturally diverse mass gatherings worldwide. the use of appropriate surveillance systems ensures timely information management for effective planning and response to infectious diseases threats during the pilgrimage. the literature describes infectious diseases prevention and control strategies for hajj but with limited information on the operations and characteristics of the existing hajj infectious diseases surveillance systems. method: we reviewed documents, including guidelines and reports from the saudi ministry of health’s database, to describe the characteristics of the infectious diseases surveillance systems that were operational during the hajj, highlighting best practices and gaps and proposing strategies for strengthening and improvement. using pubmed and embase online search engines and a combination of search terms including, ‘mass gatherings’ ‘olympics’ ‘surveillance’ ‘hajj’ ‘health security’, we explored the existing literature and highlighted some lessons learnt from other international mass gatherings. results: a regular indicator-based infectious disease surveillance system generates routine reports from health facilities within the kingdom to the regional and central public health directorates all year round. during hajj, enhanced indicator-based notifiable diseases surveillance systems complement the existing surveillance tool to ensure timely reporting of event information for appropriate action by public health officials. conclusion: there is need to integrate the existing hajj surveillance data management systems and to implement syndromic surveillance as an early warning system for infectious disease control during hajj. international engagement is important to strengthen hajj infectious diseases surveillance and to prevent disease transmission and globalization of infectious agents which could undermine global health security. the number of pilgrims participating in the hajj religious mass gathering has increased significantly over the years, with million pilgrims attending annually in the last years compared with in . , unhygienic practices and close contacts between pilgrims in overcrowded situations during the hajj rituals, as well as international travel, increase the risks of outbreaks and the spread of infectious diseases among pilgrims. the risk of infectious diseases transmission may extend to the local saudi population and to the home population of returning pilgrims after hajj. , this could strain the public health services in saudi arabia and may threaten global health security. historically, several outbreaks of infectious diseases have been reported at the hajj. these include an outbreak of cholera during the hajj that caused an estimated deaths among pilgrims and a number of international hajj-related outbreaks of meningococcal diseases in , and . the introduction of a number of pragmatic public health preparedness strategies for hajj, including vaccination and chemoprophylaxis and improved food safety and waste management, ensured that no outbreaks of cholera and meningococcal meningitis occurred during the event in recent years. however, both diseases remain a priority for public health control as do other infectious disease with global significance such as tuberculosis and zika virus disease. , in addition, new and emerging corona and influenza viruses, such as influenza h n virus, severe acute respiratory syndrome coronavirus and the middle east respiratory syndrome coronavirus (mers-cov) remain an ever present threat to mass gatherings such as hajj. as yet, no confirmed cases of mers-cov were reported during hajj. however, given the current outbreak of the disease in the kingdom, mers-cov continues to be a major risk during the event. effective health information management and dissemination allow the formulation of appropriate strategies to prevent and/ or control outbreaks and the international spread of diseases. the use of appropriate surveillance systems during mass gatherings ensures the timely collection, analysis and interpretation of health data for effective planning and response to infectious diseases threats. additionally, public health surveillance systems play a substantial role in providing reassurance of the absence of a deleterious public health event to mass gathering organizers and political office holders during an international mass gathering. in the context of hajj and saudi arabia, mers-cov is a case in point. thus, an effective infectious diseases surveillance system (idss) during hajj should be highly sensitive to detect infectious diseases events in a timely manner and to minimize the threats to the safety and well-being of pilgrims and their contacts after the mass gathering. in practice, several idsss are operational during hajj. a regular idss is applicable kingdom-wide and generates routine reports from the health facilities to the regional and central public health directorates of the ministry of health (moh) all year round. during hajj, this system is complemented by enhanced idsss to ensure timely reporting of event information for appropriate action by public health officials. however, there is little documentation of the components and operations of each system, their advantages and disadvantages as well as their efficiency in terms of timeliness of alerts and channels of reporting. here, we describe the characteristics of the idsss that were operational during the hajj, highlighting best practices and gaps and propose strategies for strengthening and improvement. the main hajj rituals take place on day - th of dhu-al hijjah (hajj month in the islamic calendar). the saudi moh collaborates with other organizations, such as the municipality and the ministry of hajj to ensure food and water safety, vector control, waste management and to provide other public health services during hajj. to that end, the moh conducted various risks assessments in preparation for the hajj, including an international health regulations (ihrs) public health core capacity assessment at the points of entry and disseminated the updated pre-travel advice and health requirements for pilgrims and workers involved in the hajj. the latter includes details of the vaccination requirement for meningococcal meningitis, yellow fever, seasonal influenza and polio. in line with ihr , pilgrims arriving from certain countries in africa and south and central america were required to present a valid yellow fever vaccination certificate on arrival. all pilgrims were required to present valid certificate of vaccination with quadrivalent (acyw ) meningococcal vaccine, and those arriving from countries in the african meningitis belt, were given mg of oral ciprofloxacin as chemoprophylaxis to lower meningococcal carriage rate among these pilgrims. oral ingestion of ciprofloxacin was directly observed by healthcare workers to ensure adherence. all pilgrims travelling from polio risk countries received dose of oral polio vaccine at borders points on arrival in saudi arabia regardless of age and vaccination status. the moh also recommended the administration of seasonal influenza vaccine to all pilgrims before arrival for hajj, particularly pilgrims at risk of developing severe complications of seasonal influenza, including pregnant women, elderly individuals, children aged months to years, pilgrims with coexisting medical conditions and healthcare workers. the command and control centre (ccc) is a special moh unit created in the aftermath of the mers-cov outbreak in to coordinate an appropriate response to infectious diseases outbreaks in saudi arabia. as the crisis management arm of the moh, the ccc coordinated the outbreak response plans of the moh during the hajj, establishing clearly defined interfaces between various moh departments and international organizations to ensure appropriate and timely response to outbreaks of infectious diseases. the ccc created three situation rooms at key locations in hajj sites; the health directorate of makkah region, almahbat mina and the mina emergency hospital. these sites were selected because pilgrims spend most of their time in makkah and mina, performing hajj rituals which potentially impacts on their safety and well-being. overall, pilgrims, including saudis and non-saudis from countries participated in the hajj. within makkah city and the holy areas, the saudi government provided free healthcare services through primary healthcare centres and hospitals including, seasonal health facilities only operational during hajj. the hospitals had a combined bed capacity of beds. this indicator-based idss is implemented country-wide in saudi arabia for routine facility-based notification of infectious diseases events all year round, including during hajj. each regional public health directorate is made up of - administrative sub-units known as 'health sectors'. these sub-units receive and review infectious disease surveillance data from the health facilities within specified geographical areas in the region for reporting to the regional public health directorates. the surveillance teams at the regional-level collate data pooled from the health sectors on disease-specific excel sheets for monthly reporting to the central directorate of public health at the moh headquarters. despite limited data management capabilities, this surveillance system was proven effective in detecting and triggering timely responses to outbreaks of measles and scabies in the kingdom in / and , respectively. enhanced idsss are activated during the hajj season to ensure early detection and prompt response to infectious diseases outbreaks. for the hajj, the enhanced surveillance became operational from the first dhul-qa'dah (islamic calendar month preceding hajj) with the arrival of the first batch of pilgrims, and continued until the end of moharam (first month of the islamic year following hajj) after the departure of the last group of pilgrims. this system is active at three main points: key points of entry to the kingdom, healthcare facilities in the hajj areas and medical office for pilgrims (formerly known as medical missions). each of these is described later. effective surveillance at the points of entry is required to prevent and control the international spread of diseases during mass gatherings, including the importation of infectious agents to the host country. during the hajj, public health surveillance teams trained to detect and report public health threats and to monitor the compliance of arriving pilgrims with the health requirements for the hajj were deployed at the kingdom's hajj entry points. these teams consisted of personnel at jeddah airport, at jeddah seaport and at medina airport. approximately % of international pilgrims arrive through these three points of entry. at each point of entry, the surveillance teams reviewed the vaccination status of arriving pilgrims by checking their vaccination cards, reported any cases of unvaccinated pilgrims or those with unverifiable vaccination status and recommended appropriate actions for these cases. the surveillance teams were also responsible for identifying and managing ill pilgrims, as well as the notification and transfer of suspected cases of infectious diseases. hospital-based surveillance teams were operating in each hospital within the hajj areas in . these were hospital staff trained to rapidly detect and report manually and electronically cases of infectious diseases presenting to the hospitals. suspected cases of infectious diseases identified at primary health centres were referred to pre-specified hospitals for confirmation of diagnosis, further management and notification to the ccc. the hospital teams were reinforced by fixed and mobile surveillance teams from the regional directorates to ensure -h active surveillance during the hajj. whereas each fixed team consisted of medical doctor and health inspector, each mobile team was made up of medical doctors (a male and a female), health inspector and driver. these personnel were drawn from different regional health directorates, across the country and mobilized for a -day refresher course, accredited by the saudi commission for health specialties. among other relevant topics, the refresher course was focused on discussing the current trends in the management and control of infectious diseases as well as the reporting formats and tools for infectious diseases surveillance during hajj. the fixed surveillance teams were assigned to each hospital operating in the hajj areas and reviewed admission logbooks for cases with clinical features of infectious diseases and followed up on cases admitted into the wards to identify and report suspected cases of notifiable diseases to ensure no cases were missed by the hospital surveillance teams. the mobile surveillance teams were tasked to conduct field investigations for reported cases of infectious diseases. these included active case finding and safe transfer of suspected cases to designated facilities, contact tracing, risk communication and liaison with medical office for pilgrims (see later) to facilitate case reporting and effective follow-up of contacts of cases. additionally, supervisory units composed of epidemiologists and infectious diseases specialists were established by the regional directorates to monitor the activities of the mobile and fixed surveillance teams and to serve as an intermediary between these surveillance teams and the regional directorates ( figure ). the supervisory units were also responsible for the isolation of suspected cases, follow-up of laboratory investigations and clinical status of hospitalized cases, as well as monitoring to ensure the implementation of the appropriate infection prevention and control procedures for patients, healthcare personnel and visitors. although the surveillance teams investigated all suspected infectious diseases cases, the following diseases were listed as high priority during hajj, and clear guidelines were provided for reporting suspected cases of these disease: mers-cov, ebola virus disease (evd), cholera, meningococcal meningitis, yellow fever, polio, rift valley fever, crimean fever, dengue fever, malaria, influenza and food poisoning. of all suspected cases detected by the idsss in the hajj, cases of malaria, cases of influenza h n , cases of food poisoning, cases of dengue and cases of non-meningococcal meningitis were confirmed after investigations. there were no confirmed cases of mers-cov illness, evd or cholera during the hajj season. hajj medical office for pilgrims refers to the healthcare representatives of some countries which send pilgrims for the hajj and accompany pilgrims during the event. they may set up clinics or hospitals within the hajj areas and provide healthcare services for their own pilgrims in compliance with the saudi moh rules and regulations. the composition of the medical office for pilgrims varies from country to country; however, it is recommended that a minimum of % of their staff should have a public health background. a memorandum of understanding is established between the saudi authorities and the medical office for pilgrims for effective coordination and communication of the standard public health requirements for the hajj. the medical offices are required to comply with the standard sanitary requirements for food preparation and handling, to educate pilgrims on personal hygiene and proper waste disposal and to submit a valid contract with an accredited firm for medical waste management to the regional directorates. additionally, they are required to provide daily reports on notifiable diseases, to establish isolation areas for suspected cases and to coordinate with the public health supervisory teams for the safe transfer of these cases when necessary. of the country medical offices operational during the hajj only ( %) were found to be compliant with the standard requirements of the saudi moh. the inconsistency of some medical representatives, with regards to compliance with the requirements of the moh and the frequent change of medical teams by countries sending pilgrims, often soon after the hajj limits sustainable partnership between the moh and the medical offices for pilgrims. locations. , overall, two electronic surveillance systems were operational during the hajj: the health electronic surveillance network (hesn) and the electronic statistical system for hajj referred to as citrex. hesn is a web-based electronic solution, introduced by the saudi moh to improve communication among public health professionals involved in outbreak management as well as to provide quality health data for planning and effective allocation of resources. hesn was initially implemented as a pilot in makkah region of saudi arabia in . by january , a country-wide implementation was initiated to control the outbreak of mers-cov in the kingdom. during the hajj, in addition to the traditional data capture and reporting tools, the hospital surveillance teams also collated and entered infectious diseases data directly into hesn once a notification was received from the laboratory, emergency rooms, isolation wards and other departments in hospitals. the uploaded data were immediately displayed on electronic dash boards in the ccc's situation rooms. data were analysed and reports generated in real-time that could be immediately accessed by public health officials and decision makers or disseminated through phone messages to responsible persons for immediate action. citrex is a web-based electronic solution that predates hesn and was used in the preceding hajj seasons. in hajj, this system was operational alongside hesn. unlike hesn which is implemented country-wide, citrex is used only during hajj to manage infectious diseases data captured inreal time from the health facilities in the holy areas (makkah, medina, arafat and mina). although the hospital surveillance teams handled data entry into hesn, the fixed surveillance teams captured the same health data into citrex for analysis and notification on distinct electronic dashboards at the ccc. over the years, the saudi government has allocated substantial resources to protecting public health during the hajj. this contributed to the development of modern surveillance systems for the hajj, evolving from the paper-based reporting tools to a more efficient web-based electronic surveillance systems. enhanced idsss were introduced to complement the conventional surveillance system in addressing the increased risks of infectious diseases transmission and outbreaks during the hajj. existing electronic surveillance systems (hesn and citrex) automatically generates reports and have the advantage of timeliness, as public health personnel at different locations can access and synchronize information management once data is captured at the reporting sites. however, the implication of having parallel systems capturing and interpreting the same health data has some potential implications, including duplication of work, depletion of already limited resources during hajj and uncertainty of the accuracy of the data. therefore, there is a need to conduct operational studies to assess the feasibility of integrating the diverse surveillance systems utilized during hajj into one efficient tool. prioritizing systems that remain operational for routine surveillance after hajj may promote the most efficient use of resources. furthermore, there is need to sustain the enhanced surveillance system and other public health interventions at key locations in the kingdom, including the points of entry, after the hajj, as a prevention and control strategy for the international spread of diseases during other mass gatherings with international dimensions, principally the umrah pilgrimage. it is estimated that over million pilgrims arrive to the kingdom yearly to participate in the umrah, which occurs nearly all-year round. syndromic surveillance could complement the existing notifiable disease surveillance systems, as an early warning system for public health threats during the hajj and umra mass gatherings. various risk assessments have shown that case-based notification systems do not meet the surveillance requirements for international mass gatherings, in terms of timeliness and coverage of possible risks groups. , quite often, time-consuming laboratory processes required for making diagnosis may stall the disease notification process, and hence prolong the time for initiating an intervention to a potential threat. symptomatic pilgrims who prefer 'quick-to-access' pharmacies may not present to the health facilities, eluding the current notifiable disease surveillance systems operational during hajj. syndromic surveillance uses aggregated data of symptom groups from a wide range of sources that precedes clinical diagnosis to set thresholds for responding to a threat. this kind of surveillance is also useful for dispelling or confirming rumours of outbreaks, based on changes in the reported number of aggregated cases in an area. the potential benefits of syndromic surveillance during mass gatherings were reported during previous olympic games. for example, the syndromic surveillance system implemented during the beijing olympic games improved the detection and response time to potential outbreaks during the games. additionally, the daily syndromic surveillance data captured during the london olympics and paralympic games reassured public health officials and political office holders of the absence of outbreaks, which substantially impacted on planning, and boosted the legacy of the event. thus, the moh through the global centre for mass gatherings medicine (gcmgm) and the saudi field epidemiology training programme is setting up a syndromic surveillance system for the hajj and umra mass gatherings to complement the enhanced idss, as an early warning system for public health threats. this system may become operational during the hajj. ensuring the health and safety, security and well-being of pilgrims are top priorities for the kingdom. achieving this is a collective responsibility that needs to be shared by saudi arabia and each country that sends pilgrims to the hajj. this is because the hajj experience is not limited to the few days pilgrims spend performing the hajj rituals. rather, it starts well before they arrive to the kingdom and lasts long after they have returned to their home countries. prevention of importation and exportation of infectious agents in hajj is key for global health security and effective infectious disease surveillance both in the kingdom during hajj, as well as in the countries of origin of pilgrims, is crucial in achieving this. therefore, it is apparent that there is a great need for the development of a well-structured, harmonized and effective collaboration, data collection and information sharing network involving the saudi health authorities and representatives from all countries sending pilgrims to the hajj. such a network would be crucial in strengthening infectious disease surveillance, preventing illnesses and responding to outbreaks during hajj, minimizing disease transmission as well as strengthening global health security through adherence to the ihrs, including notifiable diseases reporting to the who. for these reasons, the gcmgm in collaboration with the who intends to create this global network by the appointment of a hajj and umra focal point in each country which sends pilgrims to saudi arabia for these mass gatherings. considering the potential diplomatic and practical hurdles that may stall the implementation of such an international system, both organizations aim to prioritize countries sending the largest number of pilgrims to the hajj, and to retrain existing who ihr country focal point or who country office staff to function as focal point and to coordinate the activities of the network in each country. these focal points shall engage in public health preparedness activities such as dissemination of health education messages, monitoring pilgrims' health status and compliance with the hajj and umra health requirements, as well as routine surveillance for public health emergencies of international concern. additionally, they shall develop and maintain a database on pilgrims' demographics and health information as well as on public health threats including disease outbreaks in pilgrims' home countries. this database will allow the focal point to generate periodic and on-request reports on infectious disease to the who, the gcmgm or the local health authorities as required, facilitating the monitoring of disease patterns and trends globally and strengthening the kingdom's public health hajj preparedness and response capabilities. during the recently concluded hajj, the ministry of hajj introduced an electronic wrist bracelet, which pilgrims were urged to wear at all times during the pilgrimage. the bracelet captured salient demographic information for each pilgrim, including age and nationality, and was global positioning system (gps) enabled to track pilgrims' location and inform crowd control and risk communication priorities during the hajj. the moh is already exploring ways of incorporating vital health information, such as comorbidity, blood type and known allergies, in the electronic device to provide relevant data for health planning and improved health services delivery during future hajj. the saudi authorities have invested significant resources in developing model idsss for the hajj to ensure the safety and wellbeing of pilgrims, the saudi population and the population of countries sending pilgrims for the hajj. existing surveillance systems operating during hajj would be complemented by syndromic surveillance systems to ensure timely response to potential public health threats. since the hajj experience is not limited to the short time pilgrims spend performing the hajj in saudi arabia, there is a need for sustainable international collaborations between the saudi authorities, countries which sends pilgrims for the hajj and international organizations to strengthen infectious diseases surveillance and to prevent disease transmission and globalization of infectious agents which could undermine global health security. conflict of interest: none declared. the pilgrimage and its implications in a regional malaria eradication programme. who/emro inter-regional conference on malaria for the eastern mediterranean and european regions world health organization report who/mal/ hajj: infectious disease surveillance and control health risks at the hajj outbreak of serogroup w meningococcal disease after the hajj pilgrimage mass gathering and globalization of respiratory pathogens during the hajj a treatise on asiatic cholera meningococcal disease during the hajj and umrah mass gatherings tuberculosis and mass gatherings-opportunities for defining burden, transmission risk, and the optimal surveillance, prevention, and control measures at the annual hajj pilgrimage rapid spread of zika virus in the americas-implications for public health preparedness for mass gatherings at the brazil olympic games what is epidemic intelligence, and how is it being improved in europe olympic and paralympic games: public health surveillance and epidemiology health conditions for travellers to saudi arabia for the pilgrimage to mecca (hajj) manual of notification of infectious diseases world health organization. public health for mass gatherings: key considerations. geneva; who ministry of health. documentation of the hajj infectious diseases surveillance capacity meeting of heads of medical missions on public health preparedness for hajj enhanced surveillance of infectious diseases: the fifa world cup experience ministry of health. all-hazard health risk assessment for ministry of health world health organization. the health legacy of the beijing olympic games: success and recommendations. manila: who regional office for the western pacific key: cord- -r wqywwe authors: memish, ziad a.; almasri, malak; turkestani, abdulhafeez; al-shangiti, ali m.; yezli, saber title: etiology of severe community-acquired pneumonia during the hajj—part of the mers-cov surveillance program date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: r wqywwe background: pneumonia is the leading cause of hospital admission during the annual islamic pilgrimage (hajj). the etiology of severe pneumonia is complex and includes the newly emerged middle east respiratory syndrome coronavirus (mers-cov). since , the saudi ministry of health (moh) has required screening for mers-cov for all cases of severe pneumonia requiring hospitalization. we aimed to screen hajj pilgrims admitted to healthcare facilities in with severe community-acquired pneumonia (cap) for mers-cov and to determine other etiologies. methods: sputum samples were collected from all pilgrims admitted to healthcare facilities in the cities of makkah and medina, saudi arabia, who were diagnosed with severe cap on admission, presenting with bilateral pneumonia. the medical records were reviewed to collect information on age, gender, nationality, and patient outcome. samples were screened for mers-cov by pcr, and a respiratory multiplex array was used to detect up to other viral and bacterial respiratory pathogens. results: thirty-eight patients met the inclusion criteria; they were predominantly elderly (mean age . years, range – years) and male ( . %), and all were from developing countries. fourteen of the patients died ( . %). mers-cov was not detected in any of the samples. other respiratory pathogens were detected in ( . %) samples. of these, bacterial pathogens were detected in . % ( / ) and viruses in . % ( / ). twenty-one ( . %) samples were positive for more than one respiratory pathogen and ( . %) were positive for both bacteria and viruses. the most common respiratory virus was human rhinovirus, detected in . % of the positive samples, followed by influenza a virus ( . %) and human coronaviruses ( . %). haemophilus influenzae and streptococcus pneumoniae were the predominant bacteria, detected in . % and . %, respectively, of the positive samples, followed by moraxella catarrhalis ( . %). conclusions: mers-cov was not the cause of severe cap in any of the hospitalized pilgrims investigated. however we identified a variety of other respiratory pathogens in the sputum of this small number of patients. this indicates that the etiology of severe cap in hajj is complex with implications regarding its management. severe community-acquired pneumonia (cap) is not uncommon during hajj. mandourah and colleagues investigated all critically ill patients, who were of over nationalities, admitted to hospitals in two cities in the and hajj seasons. pneumonia was the primary cause of critical illness in . % ( cases) of all icu admissions and occurred most commonly in the second week of hajj, corresponding to the period of greatest pilgrim density. severe cap accounted for . % of all icu admissions. worldwide, pneumonia is a common illness that is potentially life-threatening, especially in older adults and those with comorbid diseases. , the etiology of pneumonia differs between and within countries depending on regional differences in prevalence and types of microorganism, and other factors such as the frequency of use of antibiotics, environmental pollution, awareness of the disease, and life-expectancy of the population. the etiology may also differ depending on whether the pneumonia is community-or hospital-acquired. , in this context, the hajj is a special case as it brings a large number of people, many elderly with underlying diseases, from various regions of the world, into close proximity to perform physically exhausting religious rights. these factors, combined with the common use of antibiotics among pilgrims, make the etiology of pneumonia during hajj complex, and hence standard guidelines for the management of the disease may not always work during this mass-gathering event. although many pathogens have been associated with pneumonia, a small range of key pathogens are usually the cause of most cases. , in recent years, the middle east respiratory syndrome coronavirus (mers-cov) has also emerged as a cause of serious illness including severe pneumonia. since the first reported case of mers in saudi arabia in , the saudi ministry of health (moh) has set up an ongoing mers-cov surveillance system. as part of this surveillance, it is required that all cases of severe cap with bilateral pneumonia requiring hospitalization are investigated for mers-cov. hence, we used molecular techniques to screen the sputum of hajj pilgrims diagnosed with severe cap requiring hospitalization in for the presence of mers-cov. other etiologies were also investigated using a respiratory multiplex array to detect bacterial and viral respiratory pathogens. all pilgrims attending the hajj who were admitted to healthcare facilities in the cities of makkah and medina, saudi arabia, and diagnosed on admission with bilateral pneumonia, were included in the study. the medical records of the patients were reviewed to collect information on age, gender, nationality, and patient outcome. during the period september to november , sputum samples were collected from each patient on admission, prior to any antibiotic therapy. samples were kept refrigerated until processing. mers-cov was detected in the samples using reverse transcriptase polymerase chain reactions (rt-pcr) targeting the region upstream of the e gene (upe) and the open reading frame (orf) a (nsp protein), as described previously. , briefly, nucleic acid was purified from a -ml volume of sample using the magna pure lc nucleic acid extraction kit (roche, in, usa). each sample was independently tested with the two rt-pcr assays in a -ml reaction containing ml of rna, . ml of x buffer (superscript iii one-step rt-pcr with platinum taq (invitrogen, ny, usa)), . ml of mgcl ( mm), ml of forward primer ( mm), ml of reverse primer ( mm), ml of probe ( mm), we collected sputum samples from all pilgrims hospitalized in hospitals of two cities in saudi arabia who were diagnosed with severe cap during the hajj season. thirty-eight patients fulfilled the inclusion criteria; they were predominantly elderly (mean age . years, range - years) and male ( . %). all patients were from developing countries, the majority of whom ( . %) were from asia. the nationalities most represented were indonesia ( . %), pakistan ( . %), and india ( . %). of the patients, ( . %) required icu admission. fourteen ( . %) patients died, while the remaining patients recovered and were discharged. the mortality rate among those admitted to the icus was . %. mers-cov was not detected in any of the sputum samples. other respiratory pathogens were detected in ( . %) of the samples, while the remaining samples were negative for the respiratory pathogens in the testing panel (table ). of the positive samples, bacterial pathogens were detected in . % ( / ) and viruses in . % ( / ). twenty-one ( . %) samples were positive for more than one respiratory pathogen and ( . %) were positive for both bacteria and viruses. the most common respiratory virus was human rhinovirus, which was detected in . % of the positive amples, followed by influenza a virus ( . %) and human coronaviruses ( . %). h. influenzae and s. pneumoniae were the predominant bacteria, detected in . % and . %, respectively, of the positive samples, followed by m. catarrhalis ( . %). respiratory tract infections are common illnesses during the hajj, and pneumonia is the leading cause of hospital admission, including admission to the icu, during the pilgrimage. [ ] [ ] [ ] [ ] for instance, a study of hospital admissions in makkah and mina during the hajj reported that % of hospitalizations were for pneumonia. in the current study, as part of the saudi moh mers-cov surveillance, we investigated the etiology of severe cap in pilgrims attending the hajj requiring hospitalization. most of the patients were elderly, with a large proportion of males, and all were from developing countries. these observations are similar to those of previous reports investigating pneumonia during hajj. , for example, alzeer and colleagues investigated patients admitted with pneumonia to hospitals in the hajj season. nearly all patients were from developing countries; their mean age was years (range - years) and % were males. the overall mortality rate among the patients we investigated was . %, and among those admitted to icus was . %. internationally, the reported mortality of patients with severe cap requiring icu admission is over % and the long-term mortality of cap is between . % and . % at years. , , our results are in agreement with these figures. a few investigations have reported the mortality rates from pneumonia during hajj. one study during the hajj season reported a pneumonia case fatality rate of %, while another reported a mortality rate of % among patients admitted to hospitals in the hajj season. mandourah and colleagues investigated severe pneumonia during the and hajj seasons. pneumonia was community (hajj)-acquired in . % of cases and the overall short-term mortality (during the weeks of hajj) was . %. most patients with diagnosed cap are treated empirically and the role of microbiological testing for patients with cap is still a matter of debate. however there is a clear rationale for establishing the causative agent to allow the optimal selection of agents against a specific pathogen and to limit the misuse of antibiotics and its consequences; it is also important to identify pathogens associated with notifiable diseases such as legionnaires' disease and tuberculosis. the possible involvement of mers-cov is an additional, current, reason. knowledge of the etiological agent of pneumonia-related illness is a challenging step in the management of pneumonia in hajj. [ ] [ ] [ ] in general, the identification of the etiology of cap remains difficult in any setting despite advances in microbiological and serological methods. molecular diagnostic tests for common and atypical causative pathogens of cap are now available and have increased the diagnostic yield and decreased the time required to render results dramatically. [ ] [ ] [ ] although many pathogens have been associated with cap, a small range of key pathogens are the cause of most cases. internationally, the predominant pathogen in cap is s. pneumoniae. , other causative agents include, but are not limited to, h. influenzae, m. pneumoniae, c. pneumoniae, legionella spp, chlamydia psittaci, coxiella burnetii, enteric gram-negative bacteria (enterobacteriaceae), pseudomonas aeruginosa, staphylococcus aureus, anaerobes, and respiratory viruses (influenza virus, adenovirus, respiratory syncytial virus, parainfluenza virus, coronavirus). , the frequencies of other causes, such as mycobacterium tuberculosis, c. psittaci, c. burnetii, francisella tularensis, and endemic fungi (histoplasmosis, coccidioidomycosis, blastomycosis) vary between epidemiological settings. recently, mers-cov has also emerged as a cause of serious illnesses including pneumonia and is the subject of worldwide concern. the primary objective of the study was to determine if mers-cov was the cause of the severe pneumonia in the hospitalized patients. our results indicate that mers-cov was not the etiological agent of the illness. these results support previous reports suggesting that mers-cov has not so far been problematic during hajj. a study conducted during the hajj, the same year as our study, found no evidence of mers-cov nasal carriage among hajj pilgrims screened. two reports on french pilgrims during the and hajj seasons also reported a lack of mers-cov nasal carriage among the pilgrims screened despite a high rate of respiratory symptoms. , we found s. pneumoniae to be prevalent in the sputum samples. this is in accordance with many international reports. , studies performed during previous hajj seasons have reported the organism as a cause of respiratory tract infections including penumonia. , , for example, among sputum samples collected from hajjis with respiratory tract infections in and , s. pneumoniae was detected in . % and . %, respectively. among the patients with pneumonia admitted to two tertiary hospitals in makkah during the hajj, s. pneumoniae was detected in . % of the cases. in addition to s. pneumoniae, other common pathogens identified in our sputum samples were h. influenzae, m. catarrhalis, and viral agents, in particular human rhinovirus, influenza a virus, and human coronaviruses. studies from the gulf corporation council (gcc) states have found similar results. the common pathogens causing cap in gcc states were found to be s. pneumoniae, h. influenzae, and m. catarrhalis. , in addition, the importance of atypical pathogens including m. pneumoniae, c. pneumoniae, and l. pneumophila in the etiology of cap in the gcc region has been documented. other etiologies, particularly influenza viruses, varicella zoster virus, and m. tuberculosis, are increasingly recognized as causative pathogens of cap within the region. in the context of hajj, in addition to s. pneumoniae, a number of other organisms have been reported as the cause of pneumonia. these include influenza a (h n ), m. tuberculosis, , , , s. aureus, fungi such as candida albicans, , and gram-negative organisms including p. aeruginosa, l. pneumophila, acinetobacter sp, and members of the enterobacteriaceae family. , , some, however, have dismissed many of these organisms as more likely to be respiratory tract colonizers rather than the causative agents. in our study, respiratory pathogens were detected in . % of sputum samples ( / ) and . % ( / ) of these were positive for more than one pathogen. this is a higher proportion than that reported previously by asghar et al., who isolated more than one pathogen in only . % of the samples from patients with confirmed cap in the hajj. in another study, a higher percentage ( %) was reported. the differences in detection rates may reflect the differences in identification methods used in the various studies. our study has some limitations. in addition to mers-cov, our test panel detects a specific set of bacterial and viral respiratory pathogens. this means that other respiratory pathogens including fungi and other viruses and bacteria not included in the panel could have been missed. this may be of importance, as organisms not included in the panel such as m. tuberculosis, enterobacteriaceae, p. aeruginosa, and fungi, have been reported as causative agents of pneumonia during hajj. , , also, we only used sputum samples for identification, and no microbiological investigations of other samples (e.g. blood) were performed to confirm the cause of pneumonia. finally, some of the organisms identified may have been respiratory tract colonizers and not the causative agents. in this context, a strength of our study is that the sputum samples were obtained on admission and before the start of antibiotic therapy. collecting sputum samples after the start of antibiotic treatment would have been of little value as it would have detected mainly respiratory tract colonizers. in conclusion, we investigated the etiology of severe cap in hospitalized hajj pilgrims. mers-cov was not the cause of pneumonia in any of the patients. however, we detected a variety of pathogens in sputum samples of the patients, with most samples containing more than one agent. this observation, along with previous reports on cap in hajj, indicates that typical pneumonia treatment regimens may not work well during the hajj season due to the wide variety of organisms that may be involved. this may necessitate more active investigations into the causes of pneumonia for identification and sensitivity testing in order to provide optimal treatment and a good outcome. molecular methods can be a quick and sensitive means to determine the possible causative agents. pneumonia is a significant illness during hajj and interventions to reduce its burden during the pilgrimage should be adopted. measures to reduce respiratory tract infections during hajj are already in place. other strategies may include improved respiratory tract infection surveillance and optimization and dissemination of recommendations for adult vaccination. , continuous surveillance for mers-cov during hajj and outside the pilgrimage season is crucial to monitor the mers-cov situation in saudi arabia. conflict of interest: no conflict of interest to declare. causes of admission to intensive care units in the hajj period of the islamic year causes of hospitalization of pilgrims in the hajj season of the islamic year clinical and temporal patterns of severe pneumonia causing critical illness during hajj severe sepsis and septic shock at the hajj: etiologies and outcomes health hazards and risk factors in the h ( g) hajj season comparison of mortality and morbidity rates among iranian pilgrims in hajj community-acquired pneumonia bts guidelines for the management of community acquired pneumonia in adults: update bacteriological and clinical profile of community acquired pneumonia in hospitalized patients the bacterial aetiology of adult community-acquired pneumonia in asia: a systematic review state of knowledge and data gaps of middle east respiratory syndrome coronavirus (mers-cov) in humans isolation of a novel coronavirus from a man with pneumonia in saudi arabia detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction assays for laboratory confirmation of novel human coronavirus (hcov-emc) infections respiratory tract infection during hajj pattern of admission to hospitals during muslim pilgrimage (hajj) tuberculosis is the commonest cause of pneumonia requiring hospitalization during hajj (pilgrimage to makkah) profile of bacterial pneumonia during hajj empiric antibiotic therapy and mortality among medicare pneumonia inpatients in western states patients with community acquired pneumonia admitted to european intensive care units: an epidemiological survey of the genosept cohort practice guidelines for the management of community-acquired pneumonia in adults. infectious diseases society of america diagnostic tests for agents of community-acquired pneumonia molecular diagnostics for detection of bacterial and viral pathogens in community-acquired pneumonia etiology of community-acquired pneumonia: increased microbiological yield with new diagnostic methods lack of nasal carriage of novel corona virus (hcov-emc) in french hajj pilgrims returning from the hajj , despite a high rate of respiratory symptoms lack of mers coronavirus but prevalence of influenza virus in french pilgrims after bacteria and viruses that cause respiratory tract infections during the pilgrimage (haj) season in makkah, saudi arabia microbiology of community-acquired pneumonia in the gulf corporation council states demographics and microbiological profile of pneumonia in united arab emirates aetiological agents of community acquired pneumonia respiratory tract infections during the annual hajj: potential risks and mitigation strategies pneumococcal disease in the arabian gulf: recognizing the challenge and moving toward a solution the potential for pneumococcal vaccination in hajj pilgrims: expert opinion key: cord- -ktrlohm authors: razavi, seyed mansour; mohazzab torabi, saman; salamati, payman title: treatment and prevention of acute respiratory infections among iranian hajj pilgrims: a -year follow up study and review of the literature date: - - journal: med j islam repub iran doi: nan sha: doc_id: cord_uid: ktrlohm background respiratory diseases/syndromes are the most common causes of referring to physicians among pilgrims in hajj. they lead to high morbidity, impose high costs on the health system and are among the major obstacles for pilgrims to perform hajj duties. the main aim of our study was to determine types, frequencies, etiologies, and epidemiologic factors of respiratory diseases among iranian hajj pilgrims and to suggest some preventive and treatment strategies. methods: to determine the types and frequencies of respiratory syndromes, we implemented a syndromic surveillance method in iranian health care system for hajj during consecutive years. to achieve the etiology of these diseases, we performed concurrent before and after studies. we also evaluated efficacy of the flu and pneumovax vaccines among iranian hajj pilgrims in studies. to determine some other epidemiological factors, we conducted additional studies. results: the most common problem was common cold like syndrome. origins of the most upper respiratory problems were infections, and allergies were less involved. among infectious agents, viruses were the most common agents and their frequencies were as follows respectively: adenoviruses ( . %), rhinoviruses ( %), influenza type b virus ( %). bacteria were often the secondary causes and their frequencies were as follows respectively: intestine bacillus ( . %), chlamydia pneumonia ( . %), haemophiluses ( . %) and streptococcus (a,c and g) ( . %). we introduced some epidemiological factors as effective in creating respiratory diseases. conclusion: in this paper, we suggested some applied points for prevention, treatment, and correction of common malpractices in the treatment of respiratory diseases of the pilgrims. every year, more than million muslims travel from countries in the world to saudi arabia for performing the hajj ceremonies. changes in routine activities (sleep, physiological habits and nutrition, etc.) as well as fatigue and anxiety resulting from traveling and performing pilgrimage ceremonies makes the pilgrims susceptible to diseases ( ) . in addition, high density of population causes transmission of resistant respiratory organisms among pilgrims from different countries ( ) ( ) . consequently, respiratory diseases are very prevalent during hajj ceremony. they lead to high morbidity, impose high costs on the health system, and are among the major obstacles for pilgrims to perform hajj duties ( ) ( ) ( ) ( ) . ap-proximately, , iranian pilgrims have participated in hajj rituals each year in recent years ( ) . in this regard, the following questions are raised: what forms of respiratory diseases have been emerged? what is the most common form? what are the etiological causes of these diseases? do these diseases have infectious origin? if they are infectious, what class of infectious agents (viruses, classic bacteria, atypical bacteria, and air dispersed fungal spores) is more effective on creation of the diseases? in case of infections, which organisms play a more important role? what are the roles of respiratory allergies? what are the roles of physical factors such as weather dryness, direct exposure to cold air, drinking cold liquids in sweating? does the gastroesophageal reflux play a role in causing the diseases? what are the common errors which occur in management of the diseases? to what extent chemical agents such as irritating odor of disinfectants and diffused toxins interfere? what are the ways to prevent and reduce the occurrence of these diseases? what are the best therapeutic methods? the aim of our study was to determine types, frequencies, etiologies, and some of other epidemiologic factors of respiratory diseases among iranian hajj pilgrims and to suggest some preventive and treatment strategies based on our years of experience and literature review. to determine the types and frequencies of respiratory syndromes, we implemented a syndromic surveillance method, proposed by the center for control and prevention of diseases (cdc) ( ) in iranian health care system for hajj. consequently, we reviewed the physicians' reports about respiratory diseases of , iranian pilgrims between and ( ). to study the etiological causes of respiratory diseases in hajj, we conducted concurrent before and after studies in ( ) ( ) ( ) ( ) . six educational departments (mi-crobiology, virology, immunology, mycology, social medicine, statistics and epidemiology, all affiliated to tehran university of medical sciences) cooperated with this study. we evaluated , serum samples ( samples before and samples after the journey) for serological assessments, samples for studying pharyngeal classic bacteria, pairs of samples for studying pharyngeal secretions in terms of viruses, pairs of fresh blood samples for studying nitro blue tetrazolium test (nbt) and immunological tests, pairs of serum samples for studying atypical bacteria and samples for studying antibody of respiratory fungi and questionnaires for evaluating the epidemiological issues. serum samples were gathered at the time of departure from the country and weeks after their return to the country, and were kept at - ºc. fourfold increase of antibodies values were considered as acceptable for confirmation of changes. laboratory tests which were used for detection of organisms were as follows: direct smear assessment, culturing the organisms in specific medias, hemagglutinin inhibition test, immune-fluorescence tests, elisa, specific medias and tests for viruses such as dmea media and dako kits, count immune electrophoresis, latex agglutination tests, and nbt for investigating fresh blood. etiological factors that were examined in this study were as follows: immunological tests include: nbt, immunoglobulin (a-g-m-e), interleukin , and gamma interferon. we also evaluated the efficacy of the flu and pneumovax vaccines among iranian hajj pilgrims in studies ( - ). to determine some of other epidemiological factors, we conducted additional studies ( - , , ) . we used the results of above mentioned studies and reviewed the literature, and offered a guideline for the treatment and prevention of acute respiratory infections (aris) in hajj. we used independent-t, paired t-tests and anova for numerical data, mann-whitney u, wilcoxon and kruskal-wallis as non-parametric tests, chi-square and fisher exact tests for nominal data and odds ratio for evaluating the efficacy of vaccines. the frequencies of symptoms and types of reported respiratory disorders through syndromic surveillance system were as follows (each patient may suffer from more than one disorder) ( the above tests were performed on pairs of oropharynx gargling secretions and serums ( ) . . fungi: seroconversion of opportunistic fungi like aspergillus-candida albicans, and cryptococcus were negative showing that fungi were not involved. laboratory tests were performed on pairs of serums before and after the journey ( ). immunological investigations  nbt test: the test was used for the function of neutrophils, the defensive cells in body against infections. the before and after the travel difference was statistically significant (p= . ).  gamma interferon: this agent significantly enhances the phagocytic ability of neutrophils. the before and after the travel difference was statistically significant. (p= . ). in the other word, these two agents were investigated as infection markers which showed statistically significant differences ( ) .  interleukin : no statistically significant difference was observed.  ige: this immunoglobulin increases in allergies. there was not statistically significant difference between before and after titers.  iga: this immunoglobulin plays an important role in mucosal defense. no statistically significant difference was observed (p= . ).  igg: this immunoglobulin could be a marker for chronic or previous infections. there were no statistically significant difference between the before and after tests (p= . ).  igm: this marker has a role in acute infections. the difference between before and after tests was statistically significant (p= . ). the above tests were performed on pairs of before and after the travel serums. other epidemiological investigations  in this part, the behavioral and environmental factors, affecting the occurrence of respiratory diseases among the pilgrims were studied. some of these factors included:  use of the flu and pneumovax vaccines (solely or combined) before the trip. based on our study published in , the effectiveness of influenza vaccine was %. we found that injection of influenza vaccine could decrease the influenza-like illness (ili) incidence ( ). we also conducted a similar study in which showed that the effectiveness of the flu vaccine was not statistically significant ( ) .  we reported some epidemiological factors affecting the occurrence of respiratory diseases among iranian pilgrims in ( ) . these factors were as follows:  increase in the age: the higher the age of the pilgrims, the higher the percentage of respiratory diseases was.  increase in the vulnerability of the pilgrims: respiratory diseases raised with the increase of the number of high risk pilgrims in the caravans.  score of management: we developed a new scoring system for evaluating managerial performances in each caravans. the percentage of respiratory diseases among pilgrims of related caravan decreased as the managerial performance scores in each caravan increased.  score of health management: we also developed a new scoring system for evaluating the physicians of caravans. as the health management scores of the physicians increased in each caravan, the percentage of respiratory diseases among pilgrims of the caravan decreased.  screening of the pilgrims: screening of the pilgrims before the journey was an effective way for reducing respiratory tract disorders. cdc in a paper entitled "syndromic surveillance: an applied approach to outbreak detection" has suggested a method for immediate and easy identification of diseases. in this method, by establishing a documented, telephonic or electronic reporting system, health managers can find manifestations and trend of the diseases via collecting symptoms of patients ( ). the method has been used several times and has many different names such as:  early warning systems  prodromal surveillance  outbreak detection systems  information system-based sentinel surveillance  bio-surveillance systems  health indicator surveillance  symptom-based surveillance ( ). using the above mentioned method, in this study the most common respiratory syndrome was common cold like syndrome. allergy just mimics the symptoms of common cold. thus, it can lead to over diagnosis or malpractice. in this condition, the main question is whether the respiratory involvements of pilgrims in hajj have infectious or allergic origin? the following points suggest that the pilgrims' respiratory problems had mostly infectious origin.  significant difference values of nbt test before and after travel showed that respiratory diseases of pilgrims might have infectious origins.  significant difference values of gamma-interferon before and after the travel, also showed that respiratory diseases of pilgrims could be infectious. ( ) .  the difference between the levels of interleukin in serum before and after the travel was not statistically significant. so, the respiratory diseases in hajj pilgrims could not have allergic origin.  the levels of ige in serum before and after the travel did not show a statistically significant difference. so, the respiratory diseases were not allergic.  the differences in the values of immunoglobulin a, g were no statistically significant before and after the travel, but igm levels increased after the journey, supporting the infectious origin for the diseases ( ) . unfortunately, more than % of the physicians in caravans assumed that respiratory problems of the pilgrims were originated from allergy and they attempted to prescribe corticosteroids for their patients ( , ) . this not only did not help the patients, but it also caused loss of immunity and deteriorated the patients' conditions. viral infections are more prevalent than bacterial infections. fungal infections do not play any role in respiratory infections ( ) . therefore, considering the absence of the effect of antibiotics on viruses, irrational prescription of antibiotics has no scientific basis. prescription of antibiotics without paying attention to the indication, disturbs the normal flora of mouth and throat, which play an effective role in defending the body against other organisms. among the viruses, adenoviruses were more prevalent than the other viruses which have no special treatment ( ) . transmission of this virus is perhaps one of the reasons for the prevalence of severe conjuncti-vitis in outbreaks. in our study, most frequent viruses were: adenoviruses, rhinoviruses and coronaviruses. currently there are no treatments available for these viruses. another common virus is the influenza virus which has a special treatment. however, it is not easy to confirm it in hajj ceremony. in a study by al-tawfiq et al., most common respiratory tract infection viruses were influenza and rhinoviruses ( ) . in a study by alborzi et al. on patients in hajj, the rates of viral causes were reported as follow: influenza . %, parainfluenza . %, rhinovirus . %, adenovirus . %, enterovirus %, and rsv . % ( ). in another study by moattari et al. it was stated that both seasonal and pandemic influenza infections occurred among the iranian hajj pilgrims; seasonal viruses were more common than the pandemic viruses even though all pilgrims were vaccinated against seasonal influenza ( ) . the findings of this study are in line with our findings. among atypical bacteria, chlamydia pneumoniae plays a more prominent role in respiratory diseases of the pilgrims than the other atypical bacteria. by comparing serum values of igg and igm antibodies against chlamydia pneumonia, we found that this organism plays an evident role in respiratory infections of the pilgrims ( ) . comparison of the samples before and after the travel indicated no recent affliction of the pilgrims with infections caused by legionella pneumophila. also, mycoplasma pneumoniae did not play any role in respiratory infections of the pilgrims. the results of this study showed that the most prevalent bacteria were enteric bacilli ( . %) and chlamydia pneumonia ( . %) ( ) . therefore, in case of need for empiric antibiotic therapy, antibiotics of macrolides and fluoroquinolone groups should be used. fungi had no role in the respiratory diseases of the pilgrims ( ), thus, we should consider this fact in our management. our experiences of dealing with patients with respiratory diseases during hajj period for years are summarized in following suggested statements:  in most cases, affliction with severe respiratory infections occurs during or after tashriq days and it seems that the disease spread point is masharolharam (the holly place for muslims in mecca, saudi arabia). anxiety, fatigue, inevitable population density, and low hygienic standards in masharolharam compared with other locations are probably among the effective factors.  based on observations, the most severe side effects emerge at the end of travel.  according to physicians' reports, some people refer to the physicians of the caravans for more than times during their travel (means every day of the journey) only for their bothering coughs which were alleviated over time. the finding suggests that the treatments were not completely effective, doctors did not spend a lot of time to explain the trend of diseases for their patients, or the expectations of pilgrims were not matched with the reality of conditions. in these conditions we need to educate pilgrims because, the duration of diseases may take up to weeks ( ) . a vaccine should be injected to prevent influenza. sometimes the disease is emerged from a strain other than the strain which vaccine has been made. therefore, the pilgrims may claim in this subject, particularly individuals who paid for the expenses of their own vaccines. therefore, we should educate all the pilgrims before the travel.  it seems that high risk people play some roles in increasing of the affliction rate and spread of respiratory diseases among healthy ones ( ) . educating these groups is more important than the healthy pilgrims. a valuable experience in this case was pilgrimage of which iran prevented high risk people to travel due to spread of type i influenza (h n type). according to the al-towfiq et al. report, despite the occurrence of pandemic of h n during hajj period in , the available literature did not show an increased rate of respiratory infection in hospitalized patients in ( ) . it might be owing to the screening of high risk groups and the more attention paid to the personal hygiene. within years (from to ), we have seen some therapeutic physicians' mistakes on the pilgrims:  some syndromes such as exudative pharyngitis and allergy were overdiagnosed.  antibiotics were used excessively and irrationally and were early shifted to another antibiotic due to mental pressure of the pilgrims.  corticosteroids were excessively prescribed.  antibiotics (ceftriaxone, gentamycin, etc.) were prescribed in single dose.  prescribing a combination of drugs including tramadol, dexamethasone, and penicillin l.a, named "cocktail", whereas, tramadol was excluded from iran pharmacopoeia some years ago (the drugs were prepared by physicians themselves).  prescribing antacids for the treatment of coughs by diagnosing the reflux (it is true that some coughs are caused by reflux, but we should use the medicines which block the entrance of acids to esophagus instead of prescribing the antacids).  homeotherapy and energy therapy were used, whereas, the effectiveness of them should be studied more.  one of the important and vital factors in bad therapy is continuous mental pressures of the pilgrims. correction of this problem needs long-term cultural efforts. . treatment of the common cold ( ):  rest.  gargling warm normal saline.  drink adequate fluids.  avoid eating spicy foods.  administration of a first generation anti-histamine such as chlorpheniramine (every hour, mg until days) for rhinorrhea (administration of ipratropium can also reduce rhinorrhea).  administration of acetaminophen or one nsaid (eg. ibuprofen, indomethacin, or naproxen)  lozenges including topical anesthetics.  administration of vitamin-c, zinc, vitamin-e, probiotics, hand-washing recommendations and exercising are useful but further investigation is needed.  administration of expectorants like guaifenesin are not effective for the elimination of cough ( ). some points -new non-sedating antihistamines are not more useful than the first generation antihistamines; this may be due to their differences in their passage from brainblood barrier (bbb). -nsaids reduce headache, malaise, and cough, this may be due to their inhibitory effect on prostaglandins. -combination of prescribing first generation antihistamines and nsaids alleviate nasal congestion. so, there is no need to prescribe anti-congestions. -if it is necessary to prescribe decongestants, administration of oral products is preferred to topical drugs such as phenylephrine or oxymetazoline. -dextromethorphan and codeine are useful in reducing cough. -in a large meta-analysis, researchers demonstrated that administration of vitamin-c in prevention of common cold is beneficial ( ). however some other literatures confirmed that it has a short term effect on the treatment of common cold and its preventive effect was not confirmed. benefit of echinacea and herbal medicines are not approved and they even might have suppressive effect on cd cells. although it was shown that they were effective in of trials. evidences suggest that the use of probiotics for prevention or treatment of the common cold had no more benefits ( ). despite application of the above mentioned medications, we have to wait until the disease course is over. . treatment of influenza or influenza-like illness (ili):  rest  intake abundant of fluids  gargling warm normal saline  administration of analgesics like acetaminophen.  administration of amantadine or rimantadine for influenza type a (if confirmed)  administration of zanamivir or oseltamivir for influenza types a and b. (if confirmed). attention: oseltamivir is not in pilgrim's drug list now.  rest voice  humidification with normal saline  symptomatic treatment in case of viral laryngitis.  administration of antibiotics for viral laryngitis is not helpful. ( )  if the patient did not feel better after days, it might be non-viral laryngitis and administration of an antibiotic such as azithromycin is useful. administration of dexamethasone has temporary effect. so, it is not suggested for routine use. unfortunately, physicians prescribed corticosteroids in more than . % of cases ( ) . they might have temporary effects and could suppress body immune system. administration of oral or intra muscular dexamethasone ( . mg/kg) for the treatment of acute laryngo-tracheobronchitis (croup syndrome) is suggested. ( )  acute bronchitis does not need antibiotics administration.  * a mixture including brompheniramine, naproxen or chlorpheniramine, ibuprufen relievs the cough especially with nasal interferon alfa.  administration of oseltamivir, in case of ili or approved influenza.  administration of azithromycin or other macrolides and quinolones are not useful for bacterial bronchitis caused by mycoplasma or chlamydia.  early treatment of bronchitis caused by bordetella pertussis with tetracyclines or macrolides can prevent transmission of disease.  conservative treatments. . treatment of copd with super imposed infections: *amoxiciline for the treatment of haemophilus influenza and pneumococcus, doxycycline for the treatment of moraxella, macrolides for the treatment of chlamydia and fluoroquinolones for the treatment of pseudomonas ( ). viral causes do not need antibiotics and are not distinguishable from bacterial infections. . treatment of acute pneumonia ( ) : if needed, referring to medical centers for hospitalization. pneumonia is a significant cause of hospital admission accounting for - % of the admissions ( ) . treatment for outpatients -in individuals with healthy condition without taking antibiotics: administration of erythromycin -in individuals with healthy condition with taking antibiotics: azithromycin and co-amoxiclav -in individuals with history of diseases such as: copd-diabetes mellitus -renal failure -cardiac failure or malignancy, without taking antibiotics: administration of azithromycin -in individuals with above mentioned diseases and history of taking antibiotics: azithromycin and cefuroxime -in individuals with pneumonia suspicious to aspiration: co-amoxiclav -in individuals with pneumonia with a history of influenza: cefuroxime. with a history of taking antibiotics: clarithromycin plus ceftriaxone preventive points:  screening of high risk groups before the journey ( ).  education is necessary for pilgrims continually before and during the hajj period ( ) .  reports of previous years indicated that the most prevalent cause of deaths of iranian pilgrims was cardiac diseases. in addition, about . % of the pilgrims were vulnerable (high risk groups) and were mostly afflicted with critical respiratory diseases ( ) . thus, we should emphasis on screening of vulnerable pilgrims for the diseases such as cardiac diseases, cancers, and respiratory disorders before the journey.  stress, fatigue, and anxiety cause immunity suppression in human beings ( ) and these factors are among the reasons for the establishment and continuation of dis-eases. therefore, it is suggested to prevent all the factors which can lead to such conditions.  contaminated hands are one of the most common ways of diseases transmission ( , ). therefore, repetitive hand washing, avoiding from shaking hands with the patients and not touching eyes and respiratory mucus membranes by contaminated hands are among the effective preventive ways.  it is useful to inject influenza and pneumovax vaccines solely or jointly to reduce respiratory diseases occurrence, mortality, and hospitalization ( - ) particularly in people over years of age, and patients who suffer from diabetes, renal failure, liver failure, cardiac diseases, asthma and copd at proper time ( to weeks before the trip). although a few studies doubted the effectiveness of influenza vaccine ( ) , other studies strongly recommended vaccination of pilgrims ( ) ( ) . these results show that causal patterns of respiratory infections were different in various years and effectiveness of vaccines will also be different and the pilgrims should be educated in this regard.  to avoid excessive and unreasonable use of antibiotics and corticosteroids for therapeutics or preventive purposes.  not attending unnecessary crowded locations such as recommended tavafs (going around kabah) in high densities situations ( ) .  correct and timely treatment of pneumonia and its side effects.  some specialists recommended sucking antiseptic lozenge before attending the crowds for reducing affliction with respiratory infections but this matter has not been approved by the preliminary studies and should be studied more.  garlic tablets and its medicinal derivatives have been suggested for prevention of influenza ( ) .  social distancing is one of the behavioral variables which influence respiratory illnesses ( ) . it is necessary for the patients to consider distance of longer than meter from healthy individuals or conversely. however, it is impossible under pilgrimage conditions. therefore, the distance could be considered between beds in pilgrims' rooms.  it is unreasonable to use masks for the prevention of viral diseases ( ) . however, it is useful to prevent entrance of larger particles. it is recommended to use masks especially for patients. the use of masks may reduce exposure to droplet nuclei, which is the main mode of transmission of most respiratory tract infections ( ) . in a study by deris et al. on malaysian hajj pilgrims it was stated that wearing masks was significantly associated with sore throat and longer duration of sore throat and fever ( ) . on the contrary, in another study by al-jasser et al. on saudi arabian hajj pilgrims it was showed that occurrence of urti among the pilgrims who were wearing face mask most of the time was lower than those pilgrims who were wearing them only at some times ( ) . the effects of the following factors require further investigations.  indiscriminate use of disinfectants such as chlorine compounds in caravans  population density of the rooms in caravans  distances between the beds in the rooms of the caravans  mask usage  the number of attendances at crowded locations per day  use of antiseptic lozenges before attendance at crowded locations  repeated hand washing  exposure to cold air  use of the personal prayer mat  repeated consumption of banana or the other substances producing histamine. in this paper, we reviewed types, frequencies, etiologies, and epidemiologic fac- tors of respiratory diseases among iranian hajj pilgrims and suggested some applied points for prevention, treatment, and correction of common malpractices in the treatment of respiratory diseases of the pilgrims. pattern of diseases among visitors to mina health centers during the hajj season, h ( g) protective practices and respiratory illness among us travelers to the hajj the association between pre-morbid conditions and respiratory tract manifestations amongst malaysian hajj pilgrims comparison of mortality and morbidity rates among iranian pilgrims in hajj surveying respiratory infections among iranian hajj pilgrims pattern of admission to hospitals during muslim pilgrimage (hajj) pattern of medical diseases and determinants of prognosis of hospitalization during muslim pilgrimage hajj in a tertiary care hospital.a prospective cohort study trend of diseases among iranian pilgrims during five consecutive years based on a syndromic surveillance system in hajj titration of serum antibodies against mycoplasma pneumoniae, chlamydia pneumoniae and legionella pneumophila in iranian pilgrims during the fungal flora in the accommodation of iranian pilgrims and their role in respiratory diseases in hajj persian) . razavi sm, dabiran s, ziaee ardekani h. the incidence of influenza like illness and determination of the efficacy of flu vaccine in iranian pilgrims during hajj pilgrimage the comparison of influenza vaccine efficacy on respiratory disease among iranian pilgrims morbidity and mortality among iranian hajj pilgrims in . faculty of medicine journal what is syndromic surveillance? mmwr respiratory tract infections during the annual hajj: potential risks and mitigation strategies influenza viral infections among the iranian mjiri hajj pilgrims returning to shiraz, fars province, iran. influenza other respi viruses the prevalence of acute respiratory symptoms and role of protective measures among malaysian hajj pilgrims principles and practice of infectious diseases wilder-smith a, earnest a, ravindran s, paton ni. high incidence of pertussis among hajj pilgrims chronic obstructive pulmonary disease and acute exacerbations principles and practice of infectious diseases protective effects of the -valent pneumococcal polysaccharide vaccine in the elderly population protective measures against acute respiratory symptoms in french pilgrims participating in the hajj of prevention of influenza at hajj: applications for mass gatherings the hajj: updated health hazards and current recommendations for preventive effect of garlic extract against influenza patterns of diseases and preventive measures among domestic hajjis from central, saudi arabia we would like to express our gratitude to the physicians of caravans, specialist physicians in hospitals of mecca and medina, researchers in departments of microbiology, virology, immunology, mycology, social medicine, statistics and epidemiology of tehran university of medical sciences and the staff of hajj medical centre for their support and participation. key: cord- -lpmsalux authors: alqahtani, amani s.; bindhim, nasser f.; tashani, mohamed; willaby, harold w.; wiley, kerrie e.; heywood, anita e.; booy, robert; rashid, harunor title: pilot use of a novel smartphone application to track traveller health behaviour and collect infectious disease data during a mass gathering: hajj pilgrimage date: - - journal: j epidemiol glob health doi: . /j.jegh. . . sha: doc_id: cord_uid: lpmsalux this study examines the feasibility of using a smartphone application (app) to conduct surveys among travellers during the hajj pilgrimage, where the use of apps has not been evaluated for infectious disease surveillance. a longitudinal study was conducted among pilgrims at the hajj using an iphone app with separate questionnaires for three study phases covering before, during, and after hajj. forty-eight pilgrims from countries downloaded the app. respondents were aged between and (median ) years and . % ( / ) were male. of these, % ( / ) completed the first phase, % ( / ) completed both the second and third phases, and of these reported meningococcal vaccination, with % ( / ) receiving other vaccines. all ( ) reported hand hygiene use and % ( / ) wore a facemask at some point during the pilgrimage. four ( %) reported close contact with camels. respiratory symptoms commenced from the th day of hajj, with sore throat ( %) and cough ( %) being the most common. three participants ( %) reported respiratory symptoms after returning home. conducting a prospective survey using a smartphone app to collect data on travel-associated infections and traveller compliance to prevention is feasible at mass gatherings and can provide useful data associated with health-related behaviour. pilot use of a novel smartphone application to track traveller health behaviour and collect infectious disease data during a mass gathering: hajj pilgrimage the annual hajj pilgrimage to mecca, saudi arabia, is a striking example of intensely crowded human activity where - million pilgrims assemble from over countries. incidence of acute respiratory tract infections (ari) is high [ , ] . moreover, emergence of middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia and other countries poses a new public health challenge [ ] . in order to reduce the risk of ari among hajj pilgrims, the saudi arabian health authority recommends a range of infection control measures [ ] , however, compliance to these measures is highly variable [ ] [ ] [ ] [ ] . several studies have addressed pilgrim knowledge, attitude, and practice (kap) towards preventive measures and infectious diseases, finding that their understanding about the potential severity of respiratory infection and the need for protective measures was inadequate [ ] [ ] [ ] [ ] [ ] [ ] . gautret et al. [ ] found that < % of french pilgrims were aware of social distancing, available treatment options, and facemask use as precautionary measures against the spread of respiratory infections. other studies assessed pilgrim knowledge of emerging infections, such as mers-cov and ebola, and found that % of pilgrims were not aware of mers-cov circulation in arabia and about % had no accurate knowledge of ebola transmission. however, longitudinal studies examining these questions before, during, and after travel are lacking. conducting longitudinal studies among travellers during mass gatherings involves many challenges, including requirements of a large sample size and high response rate, as well as continuous follow up throughout the course of travel with real-time data capturing. conducting such studies using conventional ''pen and paper"-based methods requires significant time and resources. smartphones are increasingly becoming an integral part of modern life, making it possible to conduct prospective surveys among hajj pilgrims through their use. several studies have demonstrated their usefulness in conveying health messages in a variety of contexts and audiences, with high response and retention rates and fewer dataentry errors during descriptive studies and randomised controlled trials [ , ] . thus, smartphones may provide better platforms to conduct prospective surveys among hajj pilgrims than conventional ''pen and paper"-based methods [ ] [ ] [ ] [ ] [ ] . additional advantages include constant internet connection, location-detection services, and user proximity making it an ideal tool for collecting infectious disease data during mass gatherings. data concerning smartphone usefulness in infectious disease research at mass gatherings are very limited [ ] . therefore, we conducted a pilot study using a smartphone app to examine its feasibility to track not only hajj pilgrim kap regarding preventive measures, but also symptom onset and participation in high-risk activities before, during, and after hajj . a prospective cohort study was conducted among hajj pilgrims at three time points, including before, during, and after hajj (between september th and october th). this involved using three sets of questionnaires in english, including a pre-hajj questionnaire composed of questions, seven identical pages of hajj questionnaires (containing five questions per questionnaire) each to be completed daily over a week during the peak hajj period, and a post-hajj questionnaire composed of six questions. we developed an iphone application (app) called 'hajj health diary', utilising the 'health monitor' app template [ ] and released it in the apple app store on september , . users started by registering their device in our online secure research database and were assigned a unique identifier for their device. this method was used successfully in previous studies [ , , ] . the app determined user location through the smartphone location service and recorded it in our research database each time the participant used it. this study and the materials described below were approved by the human research ethics committee at the university of sydney (project no: / ). the terms and conditions of downloading the app were communicated before obtaining participant consent. participants aged years and older and participating in the hajj pilgrimage in mecca were included. attendance was confirmed by tracking their location during hajj. participants aged less than years or whose stay in mecca during the hajj period could not be confirmed through location-tracking services were excluded from the study. the app consists of three main screens ( fig. ) and an 'about' screen, which includes the participant information sheet and consent form. the first screen (first phase) is the pre-hajj questionnaire, including data on participant demographics, pre-existing chronic diseases, vaccinations received before travel, factors influencing vaccination decision and uptake, perception of the risk of respiratory infection during hajj, willingness to participate in highrisk activities, such as drinking unpasteurised milk, and awareness of official health recommendations provided by saudi arabian authorities. this phase lasted from september to , . the second screen (second phase) included the hajj questionnaire, which consisted of seven pages of identical questionnaires, one page for each day of the 'peak' hajj period. these questionnaires asked about development of respiratory symptoms and their adherence to preventive measures. given that the 'peak' hajj period in lasted from october to , the app pushed a local notification each day to the user to complete the questionnaire. if the user did not complete it on the same day, they were reminded to do it the next time they opened the app. therefore, the first default questionnaire needed to be completed first before going to the next. the participant could not start completing the hajj questionnaire before completing the pre-hajj questionnaire and not before october , . the third screen (third phase) includes a post-hajj questionnaire, including questions about participant use of infection prevention methods, involvement in high-risk activities, and development of ari symptoms week after the conclusion of hajj. as the hajj pilgrims usually spend up to weeks in saudi arabia before returning to their home countries, the app pushed a daily reminder to complete the post-hajj questionnaire from october to , . if the participant did not have an internet connection, data were stored locally on the device and automatically transferred to our database as soon as an internet connection was available. to understand usage behaviour, we also collected data entry date and time and transferred it to the database. participants had to complete all questions before submitting any of the questionnaires and could not submit any questionnaire more than once, even if they deleted and re-installed the app. we used both active and passive recruitment strategies. first, we recruited australian pilgrims through distribution of brochures during pre-hajj travel seminars in sydney. second, we released the app to the apple app store globally (and exclusively), expecting that some users searching for hajjrelated apps would find it. this was likely given that our app was the only one that would appear under the search term 'hajj health' in that outlet. in the pretravel questionnaire, we included a question on how the participants heard about the app. we identified a priori that there might be potential challenges, including loss of internet connection, app de-installation and re-installation, advertent or inadvertent omission of survey questions, and failure to follow the recommended order while completing the surveys. to minimise these pitfalls, the following measures were taken: if the participant lost the internet connection, the data would be stored locally on the device and transferred to our database as soon as the internet connection became available. if the participant de-installed the app and re-installed it, the app would not allow resubmission of the same questionnaire, requiring the participant to start from where they finished before de-installing the app. this would also maintain the sequence of questionnaire completion. to avoid any omission or delay in completing the questionnaires, the app would push a daily reminder to complete the current survey. the app was downloaded by pilgrims from countries (table ) . of them, % ( / ) completed the first phase (pre-hajj questionnaire) and of those, % ( / ) completed all three study phases (fig. ) . of the participants who completed the pre-hajj questionnaire, ( . %) opened the app in saudi arabia at least once while having internet connection. the respondents were aged between and (median ) years and . % ( / ) were male. a large portion ( . %, / ) was university educated and . % ( / ) were employed. sixteen ( %) participants had pre-existing chronic diseases, including five with diabetes ( . %), three each with hypertension, bronchial asthma, and hypercholesterolemia ( . %), and one with heart disease ( . %). the participants stayed in mecca for a median of days (range, - days), . % ( / ) attended hajj for the first time, and only . % ( / ) were aware of annual saudi arabian health recommendations for hajj pilgrims. in terms of how the participants heard about the app, . % ( / ) reported first seeing it in the apple app store, . % ( / ) heard about it in pre-hajj seminars, . % ( / ) from the study researchers, and . % ( / ) from other sources. regarding convenience of using the app, . % ( / ) found it very convenient, . % ( / ) found it slightly convenient, . % ( / ) found it a little inconvenient, and . % ( / ) found it very inconvenient. those who found it inconvenient (to any degree) left the survey incomplete. concerning usage behaviour, the number of participants who completed the hajj questionnaire on the day the reminder was pushed, i.e., the st day, was , but dropped to on the nd day and remained at from the rd day onward (fig. ) . those who did not complete the hajj questionnaire on the specified day completed it within the next - days. all participants who completed the hajj questionnaire subsequently also completed the post-hajj questionnaire. of those who completed the study phases, all reported receiving the compulsory meningococcal vaccine. the main factors driving meningococcal vaccine uptake were severity of the disease % ( / ) and effectiveness of the vaccine % ( / ). only ( %) pilgrims received other vaccines before hajj ( had influenza vaccine and one pneumococcal vaccine). three of these had comorbidities. forty-four percent ( / ) of participants were unconcerned about catching influenza while at hajj and % were unconcerned about developing a cough. forty percent ( / ) of respondents expressed concern about contracting mers-cov during hajj, at least to a modest extent, while the rest did not. however, % ( / ) of participants were willing to visit a camel farm during hajj and % ( / ) were willing to drink unpasteurised camel milk if offered in saudi arabia. in practice, % ( / ) of pilgrims ( american, canadian, and australian) actually reported coming into contact with camels, including visiting a camel farm, taking photographs with camels, and drinking their milk ( ) . the onset of respiratory tract symptoms began from the th day of the peak hajj period and continued over the next several days. sore throat ( %) and cough ( %) were the most frequently reported symptoms (fig. ) . after returning home from hajj, % ( / ) of participants reported developing a cough and sore throat within week and, among these, one pilgrim from australia reported having had contact with camels during hajj. sixty-four percent ( / ) reported wearing a facemask during hajj, with uptake highest on day ( table ). protection from infectious agents and air pollutants was the main reason for mask use. difficulty in breathing and a feeling of suffocation were commonly cited as barriers to the use of facemasks. on the other hand, all participants practiced hand hygiene at some point (mostly during the st days) during hajj. respondents stated that hand hygiene was easy to implement, convenient, and believed it to be effective in preventing infections. overall, this pilot study indicates that conducting a prospective survey using a smartphone app to collect data on travel-associated infections and traveller compliance to prevention is feasible, given that the response rate was > %. this survey also demonstrates that many pilgrims partake in activities that may increase risk of acquiring emerging infections. of the people who downloaded the app, ( %) participated in the first survey and of these, ( %) went on to complete it. previous paperbased cross-sectional surveys reported response rates ranging between < % and > % [ , , ] . the studies with high response rates involved recruitment with continuous follow up of worshippers throughout their pilgrimage. this approach requires significant resources and greater investment of time and cost [ , ] . other paper-based surveys where pilgrims were not followed up continuously had response rates as low as . % [ ] . the strengths of our study include its low cost, ability to reach far and wide to allow real-time analyses and longitudinal follow-up, and ability to capture data daily during the peak hajj period, something not accomplished in other studies. this pilot survey reveals that all pilgrims complied with hand hygiene. this is supported by a review by benkouiten et al. [ ] , which found that hand hygiene was the most popular nonpharmaceutical preventive measure among hajj pilgrims. ease of use and participant belief regarding its effectiveness against infection were important driving factors. in this study, we found that respiratory symptoms commenced on the th day of tent stay during hajj and continued thereafter, with cough and sore throat being the most commonly reported symptoms. this is likely because the incubation period of most commonly circulating respiratory viruses is about - days [ ] . used in combination with a geographic information system as a tool for syndromic surveillance, this novel method can be used to detect real-time clusters of respiratory infections at hajj and other mass gatherings. although mers-cov has been circulating in saudi arabia since , no case of hajj-associated mers-cov has been reported [ ] . evidence suggests that mers-cov can be transmitted to humans through close contact with an infected camel [ ] . interestingly, our study identified that some pilgrims had close contact with camels, including visiting camel farms, photo opportunities with camels, and drinking their raw milk. through this survey, we identified one australian pilgrim who had close contact with camels and subsequently developed respiratory symptoms within week of returning home. further follow up of the case was not possible, however, given that no mers-cov case was reported in australia, it is highly unlikely that the person had mers-cov. therefore, this pilot study suggests that smartphones could help detect patients with potential emerging infectious diseases. electronic surveillance to identify outbreaks of infectious diseases at a mass gathering has been attempted previously [ ] . for instance, surveillance using electronic medical records deployed during the winter olympic games helped detect an influenza outbreak, which was subsequently described with the aid of laboratory diagnosis [ , ] . digital interfaces, including smartphones, were applied at the london olympics to identify illnesses and injuries among athletes [ ] . our study, the first of its kind at hajj, demonstrates the feasibility of a smartphone app in a prospective survey of pilgrim illness and adherence to preventive measures throughout the course of travel. owing to delays in development, testing, and app store approval, the app was only released a few weeks before hajj, limiting the amount of time it was available to respondents prior to their journey. we speculate that earlier app release will result in greater numbers of participants. because this survey was conducted only in english, multilingual applications could have expanded participation into diverse language groups. data on pilgrim demographics show that - % of pilgrims are older than years of age [ , ] , while most smartphone users are aged - years [ ] , which might have impacted study outcomes. however, since smartphone use is gradually becoming ubiquitous, respondent demographics are likely to be less important in the future. finally, we designed the app only for iphone users, thus excluding users of other smartphone platforms, such as android or windows mobile. extending availability of this app to other platforms will likely increase participation rates. in conclusion, this pilot study demonstrates that smartphone apps can be used to conduct surveys to prospectively gather data concerning onset and progression of symptoms and location information during mass gatherings. such data collection can potentially reinforce education associated with disease prevention behaviours, thus improving public health. a larger study with multilingual apps for both iphone and android smartphones is planned for hajj . mass gathering medicine: hajj and umra preparation as a leading example prevention of influenza at hajj: applications for mass gatherings travel implications of emerging coronaviruses: sars and mers-cov health conditions for 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the case for effective post-hajj surveillance for infection evidence for camel-to-human transmission of mers coronavirus new digital technologies for the surveillance of infectious diseases at mass gathering events hospital electronic medical recordbased public health surveillance system deployed during the winter olympic games illness and injury in athletes during the competition period at the london paralympic games: development and implementation of a web-based surveillance system (web-iiss) for team medical staff causes of mortality for indonesian hajj pilgrims: comparison between routine death certificate and verbal autopsy findings digital industry association for australia. australian mobile phone lifestyle index professor robert booy has received funding from baxter, csl, gsk, merck, novartis, pfizer, roche, romark, and sanofi pasteur for the conduct of sponsored research and travel to present at conferences or consultancy work. all funding received is directed to research accounts at the children's hospital at westmead. dr. anita e. heywood has received grant funding for investigator-driven research from gsk and sanofi pasteur. dr. harunor rashid received fees from pfizer and novartis for consulting or serving on an advisory board. the other authors have no competing interests to declare. key: cord- - tzbvgyr authors: pane, masdalina; kong, fiona yin mei; purnama, tri bayu; glass, kathryn; imari, sholah; samaan, gina; oshitani, hitoshi title: indonesian hajj cohorts and mortality in saudi arabia from to date: - - journal: j epidemiol glob health doi: . /jegh.k. . sha: doc_id: cord_uid: tzbvgyr the hajj is an annual pilgrimage that – million muslims undertake in the kingdom of saudi arabia (ksa), which is the largest mass gathering event in the world, as the world’s most populous muslim nation, indonesia holds the largest visa quota for the hajj. all hajj pilgrims under the quota system are registered in the indonesian government’s hajj surveillance database to ensure adherence to the ksa authorities’ health requirements. performance of the hajj and its rites are physically demanding, which may present health risks. this report provides a descriptive overview of mortality in indonesian pilgrims from to . the mortality rate from to ranged from to per , hajj pilgrims, equivalent to the actual number of deaths ranging between and cases. the top two mortality causes were attributable to diseases of the circulatory and respiratory systems. older pilgrims or pilgrims with comorbidities should be encouraged to take a less physically demanding route in the hajj. all pilgrims should be educated on health risks and seek early health advice from the mobile medical teams provided. over - million muslims globally partake in the annual hajj pilgrimage to and in the kingdom of saudi arabia (ksa) [ ] . this is the largest annual global temporary migration and gathering of muslims during a short period. the largest hajj quota is allocated to indonesia, the world's most populous muslim nation. performance of the hajj and its rites are physically demanding, together with overcrowding owing to the large number of pilgrims. health risks during the hajj include sun exposure, extreme temperatures (depending on the season when the hajj falls-summer or winter), dehydration, crowding, steep inclines, and traffic congestion [ ] [ ] [ ] [ ] . as the hajj is fairly expensive for pilgrims from indonesia, a middle-income developing country, the pilgrims tend to be older with medical comorbidities [ , ] , which may increase the risk of severe infections especially influenza [ ] , neisseria meningitis [ ] , gastroenteritis [ ] , cardiovascular, [ , ] , and respiratory episodes [ ] . furthermore, there is also the probability of stampedes in certain areas despite several measures taken by the ksa authorities [ ] . iran is one of the very few countries that have published pilgrim morbidity [ ] and mortality rates on a cohort basis [ ] . a study of iranian pilgrims over a -year period estimated a mortality rate of per , pilgrims in , whereas it was per , pilgrims in [ ] . however, compared with the available information, the indonesian mortality rate is much higher [ ] . an estimated % of indonesians perform the hajj once in their lifetime, due to cost and priority allocation for first time hajj pilgrims. the hajj's period follows the lunar calendar, so that sometimes it falls between spring/summer (extreme heat) and autumn/ winter seasons (extreme low temperatures) in the arid desert climate of mecca and medinah [ ] . this report uses data extracted from the indonesian hajj surveillance to provide a descriptive overview of mortality patterns in each cohort of pilgrims from to (winter hajj season) to identify health issues of pilgrims for further research planning. the duration of the government-sponsored travel for pilgrims to the ksa is days, of which days are spent in mecca, - days in arafat-mina, - days in medinah, and - days in jeddah (for transit). there are two routes available to pilgrims who may travel from airports within indonesia ( figure ). route is more physically demanding as pilgrims proceed to mecca directly after a long flight (~ hours or more) and then to arafat-mina. route is less demanding as pilgrims can stop over in jeddah/medinah after the flight prior to the -hour journey to mecca. since , medical services have been provided by the government of indonesia to their hajj pilgrims. some services, such as predeparture health screening, meningococcal vaccination as well as temporary clinics staffed by indonesian doctors in the ksa, have been introduced progressively over the years. for all pilgrims > years old, tuberculosis (tb) screening is done additionally by any registered medical doctor or general practitioner prior to departure from indonesia. this is because indonesia has a high burden of tb [ ] . for the hajj [ ] , there is specialised surveillance conducted for morbidity and mortality in hajj pilgrims by a team of doctors and nurses who accompany the pilgrims to saudi arabia. the purpose of this surveillance is to identify possible interventions for mortality reduction and assist in life insurance claims [ ] . the surveillance begins from the moment the pilgrims leave their residence to embark on their journey until they return home or they pass away. there is a -day follow-up after they return to indonesia if an infectious disease is detected in either ksa or indonesian healthcare facilities. the surveillance data hold individual records of pilgrim demographics, hospitalisation, morbidity, and mortality data coded according to the broad international classification of diseases (currently icd- ) coding due to limited resources in ksa to do a full autopsy. reports of hospitalisations and deaths are recorded either by hospital death certificate (issued by ksa) or general cause of death (with verbal autopsy results since ). verbal autopsy allows for the systematic investigation of probable causes of death where only a fraction of deaths occur in hospitals or in absence of vital registration systems. all these reports are sent daily to a central indonesian public health team based in ksa during the hajj. the data obtained from hajj medical service records also include hospital death certificates or flight doctor's records if a death occurred in the community. demographic variables collected include name, age, sex, home address, employment, flight group, travel route, date of arrival into saudi arabia, and cause of death (if any), according to the hospital medical record or flight doctor death certificate. prior to departure, pilgrims have to undergo a medical test to confirm that they are fit for travel and to receive the meningococcal vaccine as mandated by the saudi arabian authorities. they are in - , > . million indonesians undertook the pilgrimage during hajj. the pilgrims who joined one of the governmentsponsored hajj pilgrimage travel services had days of travel. all the pilgrims were divided into - flight groups, the minimum number of pilgrims in each flight group was pilgrims, and the maximum was pilgrims. one doctor and two nurses accompanied each flight group and conducted health services, except in - , when there was only one doctor and one nurse in the flight group. public health surveillance was conducted as the morbidity and mortality surveillance in hajj by the indonesian public health authorities accompanying pilgrims to saudi arabia with daily reporting of hospitalizations and deaths. one indonesian doctor and two nurses accompanied each flight group of ~ - pilgrims to conduct morbidity and mortality surveillance. for deaths, the indonesian public health team maintains a database of demography, hospitalization, morbidity, and mortality data. data were obtained from the hajj medical service records such as the hospital death certificate or the flight doctor's records if a death occurred in the community. database variables included name, age, sex, home address, employment, flight group, travel route, date of arrival into saudi arabia, and cause of death as obtained from the hospital medical record or flight doctor's death certificate. predeparture, pilgrims undertake a medical test to confirm fitnessfor-travel and to receive a meningitis vaccine. pilgrims who were aged > years and had at least one preexisting medical condition (e.g., diabetes mellitus, heart conditions, hypertension) were classified as high risk. for the purpose of this study, they were categorized into the high-risk group. pilgrims were mandated to receive meningococcal vaccines and were advised to receive the influenza vaccine before their departure. these healthcare workers treated, triaged, and conducted health surveillance for pilgrims. hospitalizations and any incidental deaths occurring outside a healthcare facility were notified daily to the indonesian public health team based in saudi arabia. mortality data collected by the indonesian public health team were entered into a database for data analysis. standard variables in the database included name, age, sex, home address, employment, flight group, time and place of death, date of arrival into saudi arabia, and cause of death as per the hospital or flight doctor's death certificate. we used counts and proportions to describe demographic characteristics of indonesian pilgrims and fatalities. the description for the trend was used for the analysis of categorical and numerical data. to show the consistency of the data by years, we compared the percentages and rates for each variable and used logistic regression to analyze factors associated with deaths outside health services. ethics approval for the study was obtained from the ministry of health (moh), national institute of health research and development ethics review committee with the approval number lb. . /ke/ / . each year, from to , ~ , indonesians joined hajj ( table ). all pilgrims were aged ≥ years and the majority ( . - . %) were aged between and years. most pilgrims were female ( . %). one-fifth of hajj pilgrims had higher education and the majority of them were business employees and housewives. according to the pre-embarkation medical assessment, . - . % of pilgrims were classified as high risk due to underlying health conditions such as diabetes, hypertension, other chronic diseases, or if they were aged years or older. the top two causes of mortality were diseases of the circulatory system (cardiovascular disease) and those of the respiratory system. both contribute . - . % and . - . % of deaths from to , respectively ( table ) . the mortality rate for the mentioned years ranged from to per , hajj. most deaths occurred in mecca, followed by medinah and jeddah (table ) . it is mainly because of different periods of stay: mecca ( days), medinah ( . days), and jeddah ( hours). figure a shows deaths during the entire years according to age and sex; as age increased, the proportion of male deaths increased. the proportion of female deaths are higher in individuals less than years of age, but % of deaths were among males aged ≥ years. there were reports of women between the ages of and years who were diagnosed in ksa with a terminal illness. although the doctors' reports were checked generally before departure, this group slipped through the net. this will need to be investigated further and to determine whether stricter checks need to be in place. thus, the proportion of female deaths is skewed due to this underlying factor. this trend may change in the future as the pilgrim queue system has changed. during - , terminally ill individuals could be provided priority hajj opportunity. however, in more recent years, the queue system is less flexible to provide priority to the terminally ill. weekly mortality rates exceeded the ) was an experimental approach to centralizing healthcare workers in mecca so that pilgrims could go to a center rather than access the healthcare provided by the workers nearby. as can be seen from table , the number of deaths (n = ) in in mecca was very high ( % more than those in other years). mortality rates for pilgrims travelling on route peaked earlier during the hajj period than those travelling on route (figure c ). this is likely due to less time for acclimatization to the surrounds, heat, and the intense physical activity during hajj. figure d shows the risk of death per , pilgrims hour-by-hour throughout the day for and all other years combined. in , a stampede occurred that led to mass causalities during the middle of the day. this is indicated by the spike in deaths at noon in . figure shows death rate from the time of arrival for routes and and for each year. route consistently peaks earlier than route . this highlights the need to instigate more public health interventions for route on their arrival. this may include predeparture health education and physical preparation. the same pattern was observed in each year except in , wherein no difference was observed. there was a stampede situation in mina tunnels, which caused > hajj deaths at that time. one of the success indicators for health services is that % of deaths should not occur outside the healthcare facilities. the average of proportion of deaths occurring outside healthcare facilities was . %, there was a decreasing trend in that proportion ( (table ) and fewer deaths occurred outside healthcare facilities in mecca. the period from to was selected because hajj during these years fell within the winter season where temperatures in mecca are not as extreme as in summer. during the hajj, there is a period where pilgrims are exposed to the elements of the arafat desert; hence, heat strokes, especially in summers, might play a role in the cause of death [ ] . furthermore, the crowds during the hajj period create human traffic congestion, especially in mina, where stampedes tend to occur. in , a stampede in mina occurred that led to mass causalities during the middle of the day. more than hajj pilgrims of different nationalities died in the stampede, and an estimated quarter of the deaths were indonesians. anecdotally, there is also a cultural-religious belief that results in young terminally ill women coming to hajj prior to their death. thus, the proportion of female deaths could be possibly skewed due to this underlying factor. women, especially older ones, were also found to be more likely to present underlying chronic cardiovascular disorder and diabetes compared with men during the hajj, and thus posing a high risk for the hajj [ , , ] . management of cardiovascular risks, especially relating to other factors (e.g., heat stroke, strenuous activities) for both men and women are required during the hajj because cardiovascular disease is identified by this and other studies as the most important cause of deaths [ , [ ] [ ] [ ] [ ] . most health programs tend to target the reduction of disease transmission while neglecting the chronic diseases and comorbidities that may affect the hajj pilgrims [ ] . respiratory diseases are also another common health problem encountered by hajj pilgrims in the other studies, and our study also identified this as an important cause of deaths [ , ] . infectious diseases such as severe pneumonia [ , ] , common cold [ ] , tb [ ] , meningococcal disease, and influenza could be an issue in mass gatherings, where large crowds assemble [ , [ ] [ ] [ ] . the surveillance and updated information can inform the preparedness for emerging respiratory diseases such as the middle east respiratory syndrome. increased laboratory confirmation of infectious diseases would be helpful to prevent and limit the transmission of such infectious diseases. terminally ill individuals were a priority for hajj opportunity from to . this trend may change in future as the pilgrim selection system becomes stricter and the priority is no longer allocated to the terminally ill because of changing ksa hajj regulations. in , the government of the republic of indonesia changed a policy for health services in flight groups. earlier, there was one medical doctor and two nurses, but in , only one medical doctor and one nurse were assigned to each flight group. in addition, one medical doctor was assigned as health services in "polimaktab" (hotel's clinic) in mecca. polimaktab provided medical services for - flight groups ( - hajj pilgrims). the peak of the hajj season falls between weeks and , where crowding and physical activity are most intense. interventions during these weeks are most needed to ensure that pilgrims seek healthcare early, so that deaths outside healthcare facilities can be prevented. significantly more deaths were found to occur in healthcare facilities in mecca. this is likely due to the availability of seven free saudi hospitals in mecca as well as the ksa-based indonesianoperated clinics, specifically for indonesian pilgrims (one central and on average satellite clinics). the moh, republic of indonesia, aims to decrease the proportion of deaths occurring outside healthcare facilities. investments have been made annually in raising pilgrim health awareness to seek early treatment and conducting reviews to ensure the availability of health services to indonesian pilgrims. a major limitation of this report is that it is the available aggregated data. this is the first time that long-term hajj health data pertaining to indonesia from to were described in an effort to offer some insight into the risks that indonesian pilgrims face on the hajj pilgrimage. the other major limitation is the reporting of deaths under a broad icd- category due to the verbal autopsy methods and hospitalization death certification [ ] . however, it does not differ from other reports on pilgrims of different nationalities, which indicate cardiovascular and respiratory diseases as well as other comorbidities as a main cause of hajj pilgrims' mortality and morbidity [ , , ] . the icd- coding used in the cause of death remains an important source of data for hajj health evaluation. there are other identified sources of individual health data, once linked, that can assist in the identification of potential improvement of the hajj surveillance database and fill the gaps, which need to be investigated for interventional purposes. this report has provided a preliminary assessment of whether there is a need for health education/advocacy research and measures required to enforce vaccinations. second, there are studies planned on analyzing the effectiveness of indonesian health capacities and coordination for indonesian hajj pilgrims to relieve the burden on the ksa healthcare system. future studies will provide the frameworks for analyzing deaths on an individual level to predict health risks and to formulate health intervention capacities required to reduce the health burden resulting from the hajj 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services clinical and temporal patterns of severe pneumonia causing critical illness during hajj trend of diseases among iranian pilgrims during five consecutive years based on a syndromic surveillance system in hajj comparison of mortality and morbidity rates among iranian pilgrims in hajj health risks at the hajj incidence of hajj-associated febrile cough episodes among french pilgrims: a prospective cohort study on the influence of statin use and risk factors how to reduce cardiovascular mortality and morbidity among hajj pilgrims: a multiphasic screening, intervention, and assessment cardiovascular disease in hajj pilgrims electrocardiographic abnormalities in patients with heat stroke etiology of severe community-acquired pneumonia during the hajj-part of the mers-cov surveillance program tuberculosis infection during hajj pilgrimage. the risk to pilgrims and their communities public health considerations for mass gatherings in the middle east and north africa (mena) region mass gatherings and infectious diseases: prevention, detection, and control diseases pattern among patients attending holy mosque (haram) medical centers during hajj the hajj: communicable and non-communicable health hazards and current guidance for pilgrims public health. pandemic h n and the hajj pattern of admission to hospitals during muslim pilgrimage (hajj) the authors have no conflicts of interest to declare. key: cord- - xi lqf authors: albarrak, ali; alotaibi, badriah; yassin, yara; mushi, abdulaziz; maashi, fuad; seedahmed, yassein; alshaer, mohamed; altaweel, abdulaziz; elshiekh, husameddin; turkistani, abdulhafiz; petigara, tanaz; grabenstein, john; yezli, saber title: proportion of adult community-acquired pneumonia cases attributable to streptococcus pneumoniae among hajj pilgrims in date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: xi lqf background: the hajj mass gathering is a risk for pneumococcal disease. this study was performed to evaluate the proportion of adult community-acquired pneumonia (cap) cases attributable to streptococcus pneumoniae among hajj pilgrims in . to add sensitivity to etiological attribution, a urine antigen test was used in addition to culture-based methods. methods: adult subjects hospitalized with x-ray-confirmed cap were enrolled prospectively from all general hospitals designated to treat hajj pilgrims in the holy cities of mecca and medina. patients were treated according to local standard of care and administered the binaxnow s. pneumoniae urine antigen test. results: from august to september , , a total of patients with cap were enrolled in the study, . % of whom were admitted to hospitals in mecca; % of the cases were admitted after the peak of hajj. patients originated from countries. their mean age was . years and the male to female ratio was : . just over % of the cases had diabetes, % declared that they were smokers, and . % of cases were treated in the intensive care unit (icu). the overall case-fatality rate was . %, but was higher among those treated in the icu and in those with invasive disease. the proportion of cap cases positive for s. pneumoniae, based on culture or urine antigen test, was . % ( % confidence interval . – . %). conclusions: cap during hajj has an important clinical impact. a proportion of cap cases among hajj pilgrims were attributable to s. pneumoniae, a pathogen for which vaccines are available. additional studies to determine the serotypes causing pneumococcal disease could further inform vaccine policy for hajj pilgrims. the hajj religious mass gathering hosted by the kingdom of saudi arabia (ksa) is attended by millions of muslims annually from all over the globe (yezli et al., ) . the event can facilitate the acquisition and transmission of infectious agents, including those responsible for respiratory tract infection, and has been linked to both local and international outbreaks of diseases (ahmed et al., ; memish et al., a,b; yezli et al., a) . examples include meningococcal disease and influenza (salmon-rousseau et al., ; yezli et al., a) . experience from hajj shows that the implementation of appropriate prevention measures such as vaccination can significantly reduce the incidence of disease and outbreaks associated with this mass gathering. of note is the prevention of meningococcal disease outbreaks since , after the introduction of compulsory vaccination with the quadrivalent meningococcal vaccine and targeted chemoprophylaxis (yezli et al., b) . streptococcus pneumoniae is a common cause of pneumonia and an important cause of morbidity and mortality worldwide (feldman and anderson, ; varon et al., ) . hajj presents many risk factors for pneumococcal disease acquisition and transmission. many pilgrims are elderly with pre-existing underlying health conditions and worship under crowded conditions that promote respiratory disease transmission and infection . crowding in particular has been associated with pneumococcal disease outbreaks (banerjee et al., ; mercat et al., ) . the acquisition and transmission of s. pneumoniae is well documented during hajj, independent of clinical status (memish et al., , a , and the organism is a leading cause of pneumonia-related hospitalizations and intensive care unit (icu) admissions during the event (al-tawfiq and memish et al., ) . vaccines against pneumococcal disease are available and are recommended for those at risk (such as the elderly and those with underlying health conditions) in many countries, including countries in the gulf states such as bahrain, kuwait, oman, qatar, and the united arab emirates (feldman et al., ; tomczyk et al., ) . the saudi thoracic society has also recently published guidelines on pneumococcal vaccination for hajj pilgrims (alharbi et al., ) . however, there is no official ksa recommendation for vaccination for hajj pilgrims (saudi ministry of health, ) . appropriate evidence-based policies regarding vaccination for pilgrims require a better understanding of the clinical burden of the disease associated with the event (al-tawfiq and . the evidence currently available for the burden of hajjassociated pneumococcal disease is suggestive, but limited by the insensitivity of bacterial cultures as a means of diagnosing the full burden of invasive or non-invasive pneumococcal pneumonia (bartlett, ) . the addition of urine antigen testing for adult pneumonia patients is expected to add sensitivity to the etiological attribution, without inappropriately minimizing specificity (mandell et al., ) . the sensitivity and specificity of this test in the diagnosis of community-acquired pneumonia (cap) due to s. pneumoniae have been reported to be in the range of %- % and %- %, respectively (gutierrez et al., ; klugman et al., ; molinos et al., ; song et al., ) . the aim of this study was to evaluate the proportion of hospitalized, x-ray-confirmed cap attributable to s. pneumoniae among adult hajj pilgrims in , using the urine antigen test as well as standard culture-based tests, in order to determine the clinical burden of disease associated with hajj and inform vaccination policy-making. this was a prospective case-series study conducted in hospitals in the holy cities of mecca and medina, ksa. the study was conducted over a -month period from august to september , ( dull qida to dull hija h in the islamic calendar) around the date of the hajj peak of september . the study was therefore able to capture three time periods: pre-hajj (august to september ), hajj (september to september ), and post-hajj (september to september ). patients were enrolled from all general hospitals (excluding specialty hospitals such as obstetrics and gynecology hospitals and pediatric hospitals) designated to treat hajj pilgrims. these included four general hospitals and seven temporary (holy sites) hospitals in mecca and four general hospitals in medina. the study population comprised adult pilgrim patients aged years old diagnosed with x-ray-confirmed cap. for this protocol, cap was defined in accordance with the us food and drug administration (fda) (us food and drug administration, ) as an acute infection of the pulmonary parenchyma associated with symptoms such as fever or hypothermia, chills, rigors, cough, chest pain, or dyspnea, accompanied by the presence of a new lobar or multilobar infiltrate on a chest radiograph within h of hospital admission. patients with known or suspected active tuberculosis (tb; defined as smear-positive after three acidfast bacilli tests), those < years old, non-hajj pilgrims, and patients admitted to the study hospitals with suspected cap patients excluded (not pilgrims or under years of age) patients excluded (did not fit the definition of cap, confirmed tb cases, refused to participate) patients excluded (missing crfs, no urine test performed (missed or patient unable to provide sample)), and no culture based tests performed x-ray confirmed cap cases fulfilling the inclusion criteria with crfs and urine and/or culture tests performed patients who did not consent to participate were excluded from the study. based on the above criteria, patients were enrolled in the study. following informed consent, x-ray-confirmed cap patients were treated according to local standard of care and administered a urine antigen test for s. pneumoniae (alere binaxnow s. pneumoniae urine antigen test; alere, waltham, ma, usa). a case report form (crf) containing patient demographic and clinical characteristics was filled out by trained investigators (to ensure consistency across sites) for each patient using the patient's medical chart and information from the patient or a family member. a case of x-ray-confirmed cap was recorded as positive or negative for s. pneumoniae on the crf based on findings from any one of the following microbiological tests: alere binaxnow s. pneumoniae urine antigen test, culture from a normally sterile site if conducted during routine investigation (i.e., blood, bone, cerebrospinal fluid, joint fluid, pericardial fluid), culture from a respiratory specimen if conducted during routine investigation and obtained by any of the following means (us food and drug administration, ): ( ) endotracheal aspiration in intubated patients; ( ) bronchoscopy with bronchoalveolar lavage or table demographic and other characteristics of the pilgrim population enrolled. number ( protected-brush sampling; ( ) sputum obtained by deep expectoration. the urine antigen test was performed at the patient's bedside as soon as possible after enrolment using the alere binaxnow s. pneumoniae test as per the manufacturer's recommendation. other samples were handled and processed in the same hospital as per the hospital's standard procedures. the results of microbiological investigations were collected and recorded on the crfs once available. characteristics of the study population were summarized as frequencies and percentages for categorical variables and as means with the range for quantitative variables. the association between explanatory variables and outcomes was evaluated by chi-square test or fisher's exact test, as appropriate. in addition, odds ratios (or) and their % confidence intervals (ci) were calculated in multivariate analyses. all tests for significance were two-sided, and a p-value of < . was considered statistically significant. all analyses were performed using ibm spss statistics version . (ibm corp., armonk, ny, usa). over the study period, patients with suspected cap were admitted to the hospitals included in this study. of these patients, had x-ray-confirmed cap and were enrolled in the study (figure ). demographic and other characteristics of the enrolled study population are shown in table . patients originated from countries, with the most represented being indonesia (n = , . %), egypt (n = , . %), and india (n = , . %). all but one case entered ksa between august and september , . most patients were elderly males (mean age . years, range - years; male to female ratio : ). the majority of cases (n = , . %) were admitted to hospitals in the city of mecca, the main site of the hajj pilgrimage, including cases admitted to the four temporary hospitals at the mecca holy sites. the pattern of admission shows that the number of cases admitted to hospitals increased over the study period and that most cases of cap occurred post hajj (figure , table ). cough and difficulty breathing were the most common symptoms and were present in % (n = ) and . % (n = ) of the cases, respectively. similarly, fever and tachypnea were the most common vital sign abnormalities, recorded in . % (n = ) and . % (n = ) of the cases, respectively. at least one clinical or laboratory abnormality was recorded for % of cases. only . % (n = ) of cases were initially admitted to the icu upon arrival at the hospital, but . % (n = ) of cases were treated in the icu during their hospital stay. diabetes mellitus was reported by . % (n = ) of the study population, and % (n = ) declared that they were cigarette smokers. only . % (n = ) of the cases acknowledged having used antibiotics in the days prior to their admission, although antibiotic use was unknown in a further . % (n = ) of the cases. all but one of the cases who had used antibiotics prior to hospital admission had been on a single antibiotic. one person had taken both ceftriaxone and clarithromycin prior to hospital admission. the most common antibiotics used prior to hospital admission were cephalosporins (mainly third-generation) and penicillins. culture-based methods (sterile sites or respiratory specimens) were performed in . % (n = ) of the cases, with the etiology determined in . % ( / ) of these cases. s. pneumoniae was identified in % (n = ) of the samples and in % (n = ) of samples from normally sterile sites. other pathogens were identified in six samples, including staphylococci (n = ) and klebsiella pneumoniae (n = ). urine antigen tests to detect s. pneumoniae infection were performed in . % (n = ) of cap cases; . % (n = ) were positive. the overall proportion of cap cases with a positive result for s. pneumoniae (based on either culture-based tests or the urine antigen test) was % (n = ). valid test results for both culture-based methods and the urine antigen test were available for cases. overall, agreement in results (both negative and positive) between the two methods was figure . general pattern of community-acquired pneumonia (cap) case admissions to hospitals during the study period. found in cases ( . %). based on these results, the sensitivity and specificity of the urine antigen test compared to the culturebased methods were calculated to be . % and . %, respectively. hospital location and treatment in the icu were significantly associated with s. pneumoniae cap cases (p = . ). cap patients admitted to medina hospitals were less likely to have s. pneumoniae-attributable cap than those admitted to mecca hospitals (or . , % ci . - . ). cap patients treated in the icu were . times more likely to be s. pneumoniae cap cases than those not treated in the icu (or . , % ci . - . ). no significant association was observed between s. pneumoniae-attributable cap and age, gender, pilgrim's country of origin, antibiotic use in the days prior to hospital admission, smoking, or diabetes status (table ) . disposition at discharge was recorded for cap cases. twenty-four patients died, resulting in an overall case-fatality rate of . %. the case-fatality rate among cap patients treated in the icu was nearly nine times that of non-icu patients ( . % vs. . %). the case-fatality rate among all s. pneumoniae-positive cases was . %, among s. pneumoniae-positive urine antigen test cases was . %, and among blood culture-positive s. pneumoniae cases was %. only admission to the icu on arrival and treatment in the icu were significantly associated with mortality in cap cases. patients with cap treated in the icu were over times more likely to die than those not treated in the icu (or . , % ci . - . ). this study is the first to systematically enroll cases of x-rayconfirmed cap among pilgrims during the whole hajj season and from hospitals in the two holy cities of mecca and medina, giving the best estimate of the burden of cap associated with hajj. as there was active triaging of all cases of suspected cap admitted to hospitals during hajj (due to middle east respiratory syndrome coronavirus (mers-cov) screening), the study is likely to have captured almost all cap cases admitted to hospitals. cap patients originated from a wide variety of countries with a sizable proportion being older males, which is reflective of the general population of hajj. a number of other studies have reported that pneumonia is a leading cause of hospital admission (accounting for - % of hospital admissions) during the pilgrimage (al-ghamdi et al., ; khan et al., ; madani et al., ; shirah et al., ) . however, most of these studies were limited to mecca city alone, specific hospital(s), or to the hajj rituals days only or a few days around that period. hence, previous studies have likely underestimated the true burden of hajj-associated pneumonia. it was found that % of hospitalized x-ray-confirmed cap cases among adult hajj pilgrims in were attributable to s. pneumoniae. the organism is commonly isolated from hajj pilgrims treated in clinics or hospitals during their pilgrimage. several studies have found s. pneumoniae to be the cause of pneumonia in up to % of cases during hajj (alzeer et al., ; asghar et al., ; mandourah et al., ; shirah et al., ) , while one study found that among patients treated for severe cap at facilities during the hajj, s. pneumoniae was found in %, using the randox respiratory multiplex array (memish et al., ) . other important causative pathogens reported in these studies have included other bacteria such as staphylococcus aureus, k. pneumoniae, haemophilus influenzae, and pseudomonas aeruginosa and viruses including human rhinovirus, influenza a virus, and human coronaviruses, as well as the fungus candida albicans. the results of this study are likely to be a more accurate reflection of the actual proportion of cap caused by s. pneumoniae during hajj, as the urine antigen test was used in addition to the standard culture-based methods. the test adds sensitivity to the etiological attribution without minimizing specificity (mandell et al., ) and overcomes many of the limitations and difficulties in culturing s. pneumoniae from clinical samples (bartlett, ) . although the test was highly specific in this study, it had lower sensitivity than that reported in other studies (mandell et al., ) . nearly half of the cap cases seen in this study were treated in the icu, reflecting the severity of the disease during hajj. admission to an icu was based on patient clinical assessment and the need for respiratory or hemodynamic support (arabi and alhamid, ) . pneumonia is a leading cause of icu admission during hajj, accounting for - % of icu admissions, and is a major cause of severe sepsis and septic shock in icus during the event (madani et al., ; mandourah et al., ; shirah et al., ) . the case-fatality rate for cap patients in this study was . %, which is within the range of rates reported for cap internationally (drijkoningen and rohde, ; vila-corcoles et al., ) . also, case fatality was higher among those admitted/treated in an icu and among those with invasive disease. this is also in accordance with other reports, including those among hajj pilgrims (drijkoningen and rohde, ; mandourah et al., ; shirah et al., ) , and is likely because patients treated in the icu or those with invasive disease have a more severe illness and are at a higher risk of death. most cap cases in this study were admitted to mecca hospitals, and the number of cases increased over the study period, with the highest admission rate being after the hajj rituals days. this pattern is in accordance with the hajj journey and its characteristics. most pilgrims arrive in ksa a few days (or weeks) before the hajj ritual dates and spend time in the holy cities of mecca and/or medina. during the hajj dates, all pilgrims return to mecca to perform the hajj rituals, most of which take place at the mecca holy sites. hence, the pre-hajj period is characterized by a smaller number of pilgrims, living in less crowded environments, spread across both mecca and medina, and relatively free of stressors associated with performing the hajj rituals. during the hajj dates, the maximum numbers of pilgrims are located in a small area of mecca performing physically challenging hajj rituals in crowded conditions, under both physical and environmental stressors. these conditions facilitate disease transmission and render pilgrims more prone to infection. it is likely that many cap cases admitted after hajj were infected during the hajj dates. this may explain the increase in the number of cap cases post-hajj, while the number of pilgrims in mecca and medina was decreasing. most cap cases were elderly males and many had diabetes or were smokers. although no significant association was found between these factors and pneumococcal pneumonia in this study, age, co-morbidities, and smoking are established risk factors for cap, including pneumococcal pneumonia (almirall et al., ; lynch and zhanel, ). the latter is a vaccine-preventable disease and the above risk factors are indications for pneumococcal vaccination in adults (tomczyk et al., ) . the finding that a proportion of cap during hajj was caused by s. pneumoniae, and that most of it was among individuals at risk of the disease, is significant. currently, pneumococcal vaccination is not one of the officially recommended/compulsory vaccinations in the hajj health requirements set by the saudi authorities (saudi ministry of health, ). although some countries have recommended pneumococcal vaccination for their hajj pilgrims (feldman et al., ; mathai et al., ; rashid et al., ) , an evidence-based policy requires a better understanding of the clinical and economic burden of the disease associated with hajj. this study is a first step in providing such data, by defining the burden of the disease in the hajj season using a more reliable diagnostic test for pneumococcal pneumonia. however, further studies are warranted, including accurate estimations of the incidence of the disease during the mass gathering and determining the serotypes causing the illness. this study has some limitations. it was aimed to systematically enroll all hospitalized x-ray-confirmed cap cases among hajj pilgrims during the study period. however, very early pneumonia may not be apparent on chest radiographs and may have led to the exclusion of some cases from the study. not all cap cases were investigated using culture-based methods, which are not routinely conducted by hospitals during hajj due to feasibility. some of the information collected from pilgrims was self-reported (e.g., smoking status) and hence may be subject to underreporting. also, information on the pneumococcal disease vaccination status of the cases was not collected, so it was not possible to investigate the effect of vaccination. in addition, as no accurate data on the adult population at risk during the study period were available, it was not possible to accurately estimate the incidence of cap during hajj. in conclusion, s. pneumoniae-attributable cap during hajj has an important clinical burden. further studies, including investigations of the incidence of the disease and s. pneumoniae serotypes involved in the disease, as well as the identification of the population at risk, are warranted to provide a comprehensive evidence base for appropriate policy-making regarding vaccination of hajj pilgrims. this study was funded by merck & co., inc. the study was approved by the king fahad medical city ethics committee and the institutional review board. all participants gave verbal consent before enrolment and the study was conducted in accordance with the guidelines of the ethics committee. tanaz petigara and john grabenstein are full-time employees of merck & co., inc. the other authors have no conflicts of interest to declare. health risks at the hajj pattern of admission to hospitals during muslim pilgrimage (hajj) prevention of pneumococcal infections during mass gathering the saudi thoracic society pneumococcal vaccination guidelines- risk factors for community-acquired pneumonia in adults: a systematic review of observational studies tuberculosis is the commonest cause of pneumonia requiring hospitalization during hajj (pilgrimage to makkah) emergency room to the intensive care unit in hajj. the chain of life profile of bacterial pneumonia during hajj outbreak of pneumococcal pneumonia among military recruits diagnostic tests for agents of community-acquired pneumonia pneumococcal infection in adults: burden of disease pneumococcal disease in the arabian gulf: recognizing the challenge and moving toward a solution epidemiology, virulence factors and management of the pneumococcus evaluation of the immunochromatographic binax now assay for detection of streptococcus pneumoniae urinary antigen in a prospective study of community-acquired pneumonia in spain pattern of medical diseases and determinants of 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the mers-cov surveillance program impact of the hajj on pneumococcal transmission mass gathering and globalization of respiratory pathogens during the hajj an outbreak of pneumococcal pneumonia in two men's shelters sensitivity, specificity, and positivity predictors of the pneumococcal urinary antigen test in community-acquired pneumonia the potential for pneumococcal vaccination in hajj pilgrims: expert opinion hajj-associated infections saudi ministry of health. health requirements for travellers to saudi arabia for pilgrimage to makkah mass gathering medicine (hajj pilgrimage in saudi arabia): the clinical pattern of pneumonia among pilgrims during hajj diagnosis of pneumococcal pneumonia: current pitfalls and the way forward use of -valent pneumococcal conjugate vaccine and -valent pneumococcal polysaccharide vaccine among adults aged >/= years: recommendations of the advisory committee on immunization practices (acip) guidance for industry: community-acquired bacterial pneumonia: developing drugs for treatment streptococcus pneumoniae: still a major pathogen pneumococcal pneumonia in adults years or older: incidence, mortality and prevention meningococcal disease during the hajj and umrah mass gatherings prevention of meningococcal disease during the hajj and umrah mass gatherings: past and current measures and future prospects an opportunity for mass gatherings health research we thank the mecca and medina regional general directorate of health affairs for their contribution to the study. key: cord- -j psma i authors: ahmed, qanta a.; memish, ziad a. title: the cancellation of mass gatherings (mgs)? decision making in the time of covid- date: - - journal: travel med infect dis doi: . /j.tmaid. . sha: doc_id: cord_uid: j psma i our recommendation, as experts who have monitored health hazards at the hajj for over years, especially if the situation with covid- continues to escalate globally is that hajj will be at risk of being suspended and a means for muslims to fulfill their rights in the future either personally or even by proxy need to be announced. the same holds true for the summer olympics in japan and for many other mgs and large gatherings. decisions in the time of covid- will be closely followed and will be a blueprint for other mass gatherings. the world has been put "on hold" by the emerging coronavirus outbreak which has now surpassed the combined toll of the severe acute respiratory syndrome (sars) and middle east respiratory syndrome (mers) outbreaks in terms of deaths. the public health burden of the novel coronavirus disease (covid- ) is set to increase and it is a time for urgent decisions [ , ] . two major mass gatherings (mg) -events attracting more than people in one location, -are on the horizon, with little sign of containment of the current outbreak [ ] . in july, the south east asian nation japan hosts the summer olympics, shortly after the world's largest mg, the hajj, receives pilgrims to mecca, kingdom of saudi arabia (ksa) from all over the world [ , ] . drawing muslims from over nations, hajj is the single most international mg in the world. ksa, acutely aware of its international pilgrim-travelers has been vigilant of the coronavirus outbreak from its inception. while the summer olympics is at least seven years in planning, the hajj is an annual event based on the lunar calendar, for which the ksa prepares annually with a much more compressed schedule-no more than a -month lead time, with the dates moving days in advance of the gregorian calendar annually. in , hajj is scheduled to fall close to august th and to last up to days. while the olympics will gather hundreds of thousands of attendees both in terms of competing athletes and domestic and international visitors, the hajj is islam's defining pilgrimage, a pivotal act of worship in a muslim's lifetime and one they often wait decades to fulfill. each hajj draws over . million attendees and, in some years, almost million 'guests of god" as the ksa regards them. safeguarding the lives of millions of pilgrims is the cardinal duty and honor of the custodian of the two holy cities in islam. keeping hajj safe and sacrosanct are the overriding national priorities of the ksa and the ruling monarch. protecting the lives of pilgrims during hajj however is not only a matter of governing national policy for the ksa and its monarch, but a divinely ordained duty. the stakes for protecting hajj are therefore extremely high, not only in scale but also in terms of the religious mandate. while the ksa annually hosts . million religious' visitors-muslims can perform an abbreviated pilgrimage known as umrah any time of the year for which the ksa issues visas year-round. in the months leading up to ramadan-beginning this year on april rd and later the hajj -anticipated in august this year, the ksa attracts longer term religious pilgrims often in ksa for some weeks to months before the pinnacle act of hajj, one of the five pillars of islamic belief. with such huge number of pilgrims from almost every nation on earth, hajj planners and the ksa government have been focused on ways to contain the coronavirus through the lens of an international perspective. because the potential for both mgs-the olympics and the hajj-to be jeopardized by the outbreak is significant, huge efforts in the ksa are underway to assess and mitigate the risks to travelers, the vast majority of whom are religious pilgrims. we predict hajj may be suspended in the interests of global safety as well as a precaution for domestic containment in the ksa [ ] . while almost unprecedented-the last time https://doi.org/ . /j.tmaid. . received march ; accepted march hajj was canceled predates the formation of the modern ksa, islam mandates that the sanctity of human life be placed above all other rights including the right of god to demand worship by mankind. with this in mind, the ksa in canceling hajj well in advance of the events would be very much in line with islamic ideals and would contribute greatly to the safety of humanity in doing so [ ] . we also predict that hajj planners and the saudi authorities will very much set the tone for the international community in addressing many forthcoming mass gatherings including the forthcoming olympics in japan (see fig. ). if public health planners fail to anticipate coronavirus outbreaks during these remarkably international mg events, the ramifications will be global [ ] . this is because mgs are effectively massive 'hubs' with the potential to disseminate infection. the mg participants, religious pilgrims and olympics spectators and participants can act as 'spokes' enabling spread of disease. mg facilitated spread of covid- could overshadow even the epicenter of the outbreak in wuhan, china. fortunately, public health experts and the field of mg medicine are seasoned at managing outbreaks and preparations are already underway and hajj planners have a uniquely intense and informed travel medicine and infectious disease xxx (xxxx) xxxx experience which is of enormous international value at this time. the hajj has handled the sars-cov outbreak, the ebola virus disease (evd) outbreaks, the rift valley fever (rvf) outbreak, zika virus, pandemic influenza h n and the mers-cov outbreak all in the last decade [ ] [ ] [ ] [ ] [ ] . management of these outbreaks involved close collaboration with multiple agencies both domestically across ksa and international intergovernmental collaboration [ ] . immigration restrictions even for religious reasons were put in place and affected areas were categorically embargoed from sending pilgrims to mecca [ ] . very early on thermal screening was incorporated across all ports of entry into the ksa. strongly worded guidelines were provided to travel and other physicians advising pilgrims in their countries of origin with the firm message that the elderly, the very young, and those with serious comorbidities-including diabetes and renal disease -were strongly discouraged from attending the hajj mass gathering in acknowledgement of the increased risk of respiratory infection [ ] . basic precautions remain paramount and must be emphasized including cough etiquette, rigorous and frequent hand hygiene and the use of facemask when in contact with patients with upper respiratory tract symptoms. while health care workers (hcws) will be familiar with these measures, and hajj pilgrims are always escorted by hajj tour agencies who also provide basic education in infection control, the umrah pilgrim (the traveler making the mini-pilgrimage to mecca sometimes on the spur of the moment and at any time of the year) and the general public will not have experience in hand hygiene education. the public must be informed to wash hands with soap and water frequently, as well as before and after visits to the lavatory and before and after eating. the public must learn to wash their hands for at least - s -and when hands are not overtly soiled, to use an alcohol hand rub. while alcohol is forbidden for ingestion to the observing muslim, it is permitted for all medical purposes including as both a vehicle for medications and in topical form as alcohol hand hygiene agents. the ksa has been very far sighted in issuing religious fatwahs for such medical practices for over two decades with ksa's scholars issuing fatwas to reassure muslim patients and the wider public of the acceptability of the use of alcohol hand rub for the muslim without violating any principles of islam [ ] . in this time of covid- outbreaks, religious authorities would do well to remind the muslim public of the legitimacy of alcohol hand rubs as safe and indeed preferred mode of hand hygiene and coronavirus containment. less well known is the enormous semi-permanent and highly mobile healthcare system that is activated in the hajj season, the months leading from ramadan to after the hajj ends. this provides on-site acute medical care including acute care for critical illness at all the hajj sites. the enormous effort of this temporary but massive and sophisticated healthcare system that ksa engages and operates for the purposes of the religious pilgrim visiting in hajj season means that many thousands of hcws must travel to the hajj sites as well. sometimes they are hired from outside the country, many international volunteer doctors and other personnel seek to serve the 'guests of god'. these workers are also at risk should hajj be allowed to continue in the face of an accelerating covid- outbreak. the impact would be two-fold. not only of more health care personnel exposed to active disease with the threat of severe infection in localized pockets and then transmission to others seeking medical care, but also a twofold burden on the hcws-caring for patients afflicted by the outbreak or compromised by it somehow and managing fellow colleagues sickened by the intensification of exposure. the semi-permanent health services at hajj are already siphoning off critical healthcare staff from their usual responsibilities throughout the ksa managing a population of close to million including million expatriates. in a scenario with colleagues falling ill and on some occasions dying, the wider saudi healthcare system could be singularly more impacted by the covid- crisis during hajj than any other healthcare workforce yet to date. the long-term impact of such an outcome is as yet unknown and difficult to predict. facemasks could mitigate aerosolized transmission especially in areas of high-density during mgs-where crowd densities in hajj can reach persons per square meter. as the public starts to purchase supplies, mass purchasing can cause shortages for masks which would be best used by hcws in the healthcare setting. many hospitals have removed all n masks from open access on medical floors and units to be reserved for an acute outbreak when these masks will be needed to provide protection for hcws in close contact to exposed persons. in line with containment, the saudi cdc has recommended the avoidance of travel to outbreak nations, and for persons returning from these regions, -day quarantine periods at home-excluding the hcw or hospital employee from the workplace-are now in force. globally, purveyors have been legally prohibited from price hiking facemasks and gloves which have sold in an unprecedented fashion both in high volume and-until the restriction -exorbitant pricing [ ] . we are already learning that what is much more challenging in terms of sars-cov- is the asymptomatic status. this allows infected persons without symptoms to move freely in society infecting others and therefore the opportunity for detection is very low [ ] [ ] [ ] [ ] [ ] . there is evidence that the impact of large gatherings on disease transmission is also reaching the awareness of other governments. switzerland has announced a ban on events expected to draw gatherings of over people. france has issued a temporary ban of all public gatherings of over people. it is increasingly likely that massive international events will be postponed or canceled entirely until we begin to see regression and ultimately resolution of this outbreak. a secondary and perhaps more palpable impact of the outbreak has been panic. panic has impacted the global market. china rightly prolonged the closure of the chinese stock market, the largest market in the world, trading over % of the global market-as the outbreak became apparent. this was a wise move to avoid volatile reverberations across global markets as panic concerning the outbreak set in [ ] . the economic impact of the coronavirus on china has been much greater already than the impact of the swine flu. this is because china's economy is now seven-fold bigger than it was then in and china is much more integrated in global supply chains now than it was then. thus, a greater impact on china translates as more significant reverberations in the global markets. sars reduced china's gdp by % in -then billion renmibi at a time when china represented only % of the global gdp. today the losses are already far greater. last week witnessed the biggest market correction in the us stockmarket since and the fastest correction in history. this correction comes at a time of one of the most fundamentally strong periods of economic growth in us history. with the outbreak likely to reach the united states in more substantial scale than the initial handful of cases that are now being reported there is real risk of a market correction developing into an economic recession and with a general election imminent the domestic political ramifications here in the us are enormous. because of all the aforementioned reasons, curtailing mgs at this time is crucial. tragically china's experience has been telling in this regard too and we must learn from the events there. wuhan officials allowed over million people to leave wuhan where they were exposed to and some of them incubating the coronavirus weeks before the city was quarantined on january nd. the virus was thus rapidly propagated across china and then globally. today all provinces of china have reported outbreaks in large cities. both outbreak management and mg management require clear communication and responsive political approaches. much has been learned from the experience with sars and the chinese authorities have been much more transparent than in the past. the stakes are extremely high. china is also sharing its data widely and engaging international experts with valuable and timely insights. china must be commended for many aspects of disease management at this time of crisis. similarly when ksa has faced the extremely delicate balance of welcoming religious pilgrims for both hajj and umrah this year many of whom have waited a life time to enact their religious rites, and weighing the impact of propagating outbreaks, difficult and unpopular decisions have to be made to safeguard not only the mass gathering but also the wider global community. one clearly impact the other. ksa has made an unprecedented and courageous decision by temporarily banning the umrah by curtailing religious tourism from all international destinations in addition to local umra and suspending the recently introduced tourism e-visa (recently launched for nations) for all nations now at-risk countries. this is in addition to banning travel of saudi's to affected countries and closing land borders with uae, bahrain, kuwait and jordan. these bans while impeding the rights of millions of muslims to fulfil religious islamic rites have been widely supported by the organization of the islamic cooperation, world health organization and also by other individual muslim governments including egypt which indicated the ban was indeed in line with sharia principles of holding sacrosanct the right to human life above all else, a right that muslims must preserve for all humanity irrespective of creed or belief. while some optimistic reports suggest the outbreak is slowing, and china is now reporting fewer cases daily while cases outside of china are rising, public health officials everywhere will be vigilant of the forthcoming mass gatherings in the arabian peninsula and se asia. hajj planners, public health experts and mass gathering medicine experts must collaborate intensely in advance of these events for the best possible outcomes. while smaller events such as the formula one race to be held in china in april have already been postponed, a final decision for postponing the olympics and the hajj has not been made awaiting more data on how this infection evolves over time. our recommendation as experts who have monitored health hazards at the hajj for over years, especially if the situation with covid- continues to escalate globally is that hajj will be at risk of being suspended and a means for muslims to fulfill their rights in the future either personally or even by proxy must be rapidly announced. while that decision will be heartbreaking for individual muslims and both spiritually and economically damaging for the kingdom, solace will be obtained in knowing the muslim majority world can contribute to the wellbeing of humanity. further, the kingdom has the opportunity to lead the world in acknowledging that even the most beloved and long-awaited mass gathering events including the olympics must sometimes be suspended, postponed or canceled. hajj planners frequently consult on the management of mass gatherings including the us inauguration, the olympics and the world cup. their preemptive management of the coronavirus crisis in the setting of the world's largest and most diverse mass gathering is being closely followed and will be a blueprint for other mass gatherings soon following. while the approaches are myriad, the time for international geopolitical and public health collaboration and solidarity is now, we must save no resources to protect 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patient safety challenge muslim health-care workers and alcohol-based handrubs challenges to the system of reserve medical supplies for public health emergencies: reflections on the outbreak of the severe acute respiratory syndrome coronavirus (sars-cov- ) epidemic in china asymptomatic coronavirus infection: mers-cov and sars-cov- (covid- ) presumed asymptomatic carrier transmission of covid- the novel coronavirus pneumonia emergency response epidemiology team. the epidemiological characteristics of an outbreak of novel coronavirus disease (covid- ) -china. china cdc weekly protecting health-care workers from subclinical coronavirus infection asymptomatic cases in a family cluster with sars-cov- infection. pii: s - lancet infect coronavirus set to weaken china's ailing economy: business. downturn deadly outbreak forces banks, shops and factories to shut as growth rate hits -year low [usa region] weinland. london (uk) [london (uk): don. financial times key: cord- -cd wttk authors: benkouiten, samir; charrel, rémi; belhouchat, khadidja; drali, tassadit; nougairede, antoine; salez, nicolas; memish, ziad a.; al masri, malak; fournier, pierre-edouard; raoult, didier; brouqui, philippe; parola, philippe; gautret, philippe title: respiratory viruses and bacteria among pilgrims during the hajj date: - - journal: emerg infect dis doi: . /eid . sha: doc_id: cord_uid: cd wttk pilgrims returning from the hajj might contribute to international spreading of respiratory pathogens. nasal and throat swab specimens were obtained from pilgrims in before they departed from france and before they left saudi arabia, and tested by pcr for respiratory viruses and bacteria. overall, . % and . % of pre-hajj and post-hajj specimens, respectively, were positive for ≥ virus (p = . ). one third ( . %) of the participants acquired ≥ virus, particularly rhinovirus ( . %), coronavirus e ( . %), and influenza a(h n ) virus ( . %) while in saudi arabia. none of the participants were positive for the middle east respiratory syndrome coronavirus. in addition, . % and . % of pre-hajj and post-hajj specimens, respectively, were positive for streptococcus pneumoniae (p = . ). one third ( . %) of the participants had acquired s. pneumoniae during their stay. our results confirm high acquisition rates of rhinovirus and s. pneumoniae in pilgrims and highlight the acquisition of coronavirus e . m ore than million muslims gather annually in saudi arabia for a pilgrimage to the holy places of islam known as the hajj. the hajj presents major public health and infection control challenges. inevitable overcrowding within a confined area with persons from > countries in close contact with others, particularly during the circumambulation of the kaaba (tawaf) inside the grand mosque in mecca, leads to a high risk pilgrims to acquire and spread infectious diseases during their time in saudi arabia ( ), particularly respiratory diseases ( ) . respiratory diseases are a major cause of consultation in primary health care facilities in mina, saudi arabia, during the hajj ( ). pneumonia is a leading cause of hospitalization in intensive care units ( ) . numerous studies have shown a high prevalence of respiratory symptoms among pilgrims ( ) ( ) ( ) . respiratory viruses, especially influenza virus, are the most common cause of acute respiratory infections among pilgrims ( ) ( ) ( ) ( ) . we recently reported the acquisition of rhinovirus ( ) and streptococcus pneumoniae infections ( ) by french pilgrims during the hajj season and highlighted the potential for spread of these infections to home countries of pilgrims upon their return. however, none of the french pilgrims were positive for middle east respiratory syndrome coronavirus (mers-cov) in ( ) and ( ) . in this study, we collected paired nasal and throat swab specimens from adult pilgrims departing from marseille, france to mecca, saudi arabia, for the hajj season. the primary objective was to determine the prevalence of the most common respiratory viruses and bacteria upon return of pilgrims from the hajj. the secondary objective was to evaluate the potential yearly variation of the acquisition of these respiratory pathogens by comparing results from the and hajj seasons. pilgrims who planned to participate in the hajj were recruited on september , , at a private specialized travel agency in marseille, france, which organizes travel to mecca. potential participants were asked to participate in the study on a voluntary basis if they were ≥ years of age and were able to provide consent. in this prospective cohort study, participants were sampled and followed up before departing from france (on october , ) and immediately before leaving saudi arabia (on october , ) . upon inclusion in the study, participants were interviewed by arabic-speaking investigators who used a standardized pre-travel questionnaire that collected information on the demographic characteristics and medical history of each participant. a post-travel questionnaire that collected clinical data and information respiratory viruses and bacteria among pilgrims during the hajj on vaccination status and compliance with preventive measures was completed during a face-to-face interview days before the pilgrims returned to france by a single investigator who joined the pilgrims after the hajj. health problems that occurred during the pilgrims' stay were also recorded by a physician who traveled with them during the entire stay in saudi arabia, including during the rituals. subjective fever was defined as a feverish feeling according to the pilgrims' report. influenza-like illness (ili) was defined as the presence of cough, sore throat, and subjective fever ( ) . the study protocol was approved by the aix marseille université institutional review board (july , ; reference no. -a - ) and by the saudi ministry of health ethical review committee. the study was performed in accordance with the good clinical practices recommended by the declaration of helsinki and its amendments. all participants gave written informed consent. paired nasal and throat swab specimens were collected from each participant by using rigid cotton-tipped swab applicators (medical wire and equipment, corsham, uk) days (september , ) before participants departed from france (pre-hajj specimens) and only day (october , ) before they left saudi arabia (post-hajj specimens). nasal and throat swab specimens collected from participants were placed in viral transport media (virocult and transwab, respectively; sigma, st. louis, mo, usa) at the time of collection and kept at °c before being transported to a laboratory in marseille for storage at − °c within h of collection. nasal swab samples were independently tested as described ( ) for influenza virus a/h n ( ), influenza b virus ( ), influenza c virus ( ) , and a(h n )pdm virus ( ) ; human adenovirus ( ) ; human bocavirus ( ) , human cytomegalovirus ( ) ; human coronaviruses (hcovs); human enterovirus ( ) ; human metapneumovirus ( ); human parainfluenza viruses (hpivs); human parechovirus ( ); human respiratory syncytial virus ( ) ; and human rhinovirus (hrv) ( ) by using real-time reverse transcription pcrs. hcovs and human hpivs were detected by using an hcov/hpiv r-gene kit (argene/biomérieux, marcy l'etoile, france) ( ) . hcov-positive samples were then genotyped by using the ftd respiratory pathogens kit (fast track diagnostics, luxembourg, luxembourg). throat swab samples were independently tested as described ( ) by using quantitative real-time pcrs for streptococcus pneumoniae, neisseria meningitidis, bordetella pertussis, and mycoplasma pneumoniae. sequences of all primers and probes have been reported ( ) . in the present study, reactions were performed by using a ht fast real-time pcr system (applied biosystems, foster city, ca, usa). the pearson χ and fisher exact tests, as appropriate, were used to analyze categorical variables. statistical analyses were performed by using spss software package version (spss inc., chicago, il, usa). p values ≤ . were considered significant. a total of persons were invited to participate in the study. all persons agreed to participate in the study and responded to the pre-travel questionnaire. the participants were women ( . %) and men ( . %) who had a mean (sd) age of . ( . ) years (age range - years) ( table ) . although most ( . %) participants were born in northern africa, most ( . %) had lived for years in marseille or the surrounding cities. more than half of the participants ( . %) reported having ≥ chronic disease, as described ( ) . all post-travel questionnaires were completed. during the -week stay in saudi arabia (october - , ), most ( . %) pilgrims had ≥ respiratory symptom, including cough ( . %), sore throat ( . %), rhinorrhea ( . %), myalgia ( . %), fever ( . %), and dyspnea ( . %), and . % met the criteria for self-reported ili ( . % in vs. . % in ; p = . ). onset of respiratory symptoms peaked in the second week (week ) after the arrival of the pilgrims in mecca and decreased thereafter. however, ( . %) pilgrims still had respiratory symptoms before leaving saudi arabia at the time of sampling (week ). only pilgrim ( . %) was hospitalized during the stay in saudi arabia (for undocumented pneumonia). no deaths occurred. regarding preventive measures, . % of participants reported receiving pneumococcal vaccination (pneumo ) in the past years, which was significantly higher than the rate in ( . % in vs. . % in ; p = . ). none had received the influenza vaccine before departing for the hajj, but . % reported having received the seasonal influenza vaccine in ( . % among participants < years of age vs. . % among participants > years of age; p = . ). during the stay in saudi arabia, . % of pilgrims reported either frequent use ( . %) or occasional use ( . %) of facemasks; . % used disposable handkerchiefs; . % reported frequent handwashing; and . % used hand sanitizer. ili symptoms were less frequently reported by persons who reported receiving the influenza vaccine in compared with reports by unvaccinated persons ( . % vs. . %, respectively; p = . ) (odds ratio . , % ci . - . ). in contrast, none of the other preventive measures was found to be effective in preventing ili symptoms during the stay in saudi arabia. pre-hajj and post-hajj nasal swab specimens were obtained from ( . %) and ( %) participants, respectively. a total of ( . %) of pre-hajj specimens tested were positive for ≥ virus compared with ( . %) of post-hajj specimens tested (p = . ) ( table ) . moreover, ( . %) participants had acquired ≥ virus during the stay in saudi arabia (figure ). the prevalence of human coronavirus e (hcov-e ) was significantly higher in post-hajj specimens than in pre-hajj specimens ( . % vs. %; p< . ). a high prevalence of hrv was observed in pre-hajj and post-hajj specimens ( . % and . %, respectively; p = . ). of participants whose post-hajj specimens were positive for hrv, ( . %) had acquired the infection during their stay in saudi arabia (figure ). the prevalence of influenza a and b viruses was significantly higher in post-hajj specimens than in pre-hajj specimens ( . % vs. %; p = . ); further details are described elsewhere ( ) . coronaviruses hku , nl , and oc ; human enterovirus; human metapneumovirus; hpiv; and human respiratory syncytial virus were also acquired during the stay in saudi arabia by a low proportion of participants (table ) . of participants whose post-hajj specimens were positive for ≥ respiratory virus, ( . %) reported ≥ respiratory symptom during their stay in saudi arabia, of whom ( . %) still had respiratory symptoms at the time of sampling. also, of participants whose post-hajj specimens were negative for respiratory viruses, ( . %) reported ≥ respiratory symptom during their stay saudi arabia, of whom ( . %) still had respiratory symptoms at the time of sampling. none of the preventive measures was found to be effective in preventing respiratory viruses in post-hajj specimens. pre-hajj and post-hajj throat swab specimens were obtained from ( . %) and ( %) participants, respectively. none of the participants were positive for n. meningitidis, b. pertussis, or m. pneumoniae at any point in the study period (table ) . a total of ( . %) of pre-hajj specimens tested and ( . %) of post-hajj specimens tested were positive for s. pneumoniae (p = . ) (table ; figure ). of participants whose post-hajj specimens were positive for s. pneumoniae, ( . %) had acquired the infection during their stay in saudi arabia (figure ). in addition, of participants whose pre-hajj specimens were positive for s. pneumoniae, ( . %) subsequently had post-hajj specimens that were negative for s. pneumoniae ( figure ), of whom ( . %) reported having received antimicrobial drugs during their stay in saudi arabia: received amoxicillin, received amoxicillin and ciprofloxacin, and received azithromycin. of participants whose post-hajj specimens were positive for s. pneumoniae, ( . %) reported ≥ respiratory symptom during their stay in saudi arabia, of whom ( . %) still had respiratory symptoms at the time of sampling. among participants who reported having received a pneumococcal vaccination in the years before traveling to saudi arabia, ( . %) had post-hajj specimens that were positive for s. pneumoniae. the prevalence of s. pneumoniae in post-hajj specimens was significantly lower in persons who reported using hand sanitizer during their stay in saudi arabia than in remaining participants ( . % vs. . %; p = . ) (odds ratio . , % ci . - . ) and slightly lower in persons who reported more frequent handwashing than usual during their stay in saudi arabia than in persons who reported usual handwashing ( . % vs. . %; p = . ). of participants whose post-hajj specimens were positive for s. pneumoniae, ( . %) were co-infected with ≥ virus (figure ). of participants whose post-hajj specimens were negative for s. pneumoniae, ( . %) were infected with ≥ virus ( . % vs. . %; p = . ) (figure ). for the second consecutive year, we conducted a prospective longitudinal study of respiratory viruses and bacteria in respiratory specimens collected from a single cohort of pilgrims before departing from marseille, france, to mecca, saudi arabia, for the hajj and immediately before leaving saudi arabia. by collecting samples from pilgrims before their departure from saudi arabia, we were able to rule out acquisition of infections acquired as a result of travel through the international airports of jeddah, saudi arabia, and istanbul, turkey, as part of the return trip to marseille. close monitoring for respiratory symptoms and compliance with preventive measures was also performed by the investigators accompanying the group. in this study, we confirmed that performing the hajj pilgrimage is associated with an increased occurrence of respiratory symptoms in most pilgrims; of pilgrims showed nasal or throat acquisition of respiratory pathogens. this acquisition may have resulted from humanto-human transmission through close contact within the group of french pilgrims because many of them were already infected with hrv or s. pneumoniae before departing from france. alternatively, the french pilgrims may pre-hajj samples ( . %) were collected on the day of departure from france (at the airport) and were stored at ambient temperature for d after collection before being transported to a laboratory in marseille for storage at  °c. in , all samples collected during the study were kept at ambient temperature before being transported to a laboratory in marseille for storage at  °c within h of collection. na, not applicable; nd, not determined. †statistically significant difference. ‡in the study, nasal swab specimens were collected from participants instead of throat swab specimens, which were used in the present study conducted in . have acquired these respiratory pathogens from other pilgrims, given the extremely high crowding density to which persons from many parts of the world are exposed when performing hajj rituals. finally, contamination originating from an environmental source might have played a role. sequencing of these pathogens would be required to determine how often new infections were acquired during the stay in saudi arabia. however, detection of nasal carriage of coronaviruses other than mers-cov and influenza a and b viruses in only the post-hajj specimens supports the hypotheses that infection occurred during the hajj. we confirmed the predominance of hrv and s. pneumoniae among pathogens acquired during the pilgrims' stay ( , ) . we also highlighted acquisition of coronaviruses other than mers-cov, most notably hcov-e , by pilgrims during the hajj pilgrimage. in and , results of screening for mers-cov infection in different cohorts of pilgrims, including the present cohort, were negative ( , , ) . finally, we found that compared with acquisition of hrv and hcov-e , influenza viruses were acquired at a lower frequency among pilgrims. the present study is a continuation of our previous study in ( ) . we extended the investigation to additional viruses, including human bocavirus, human cytomegalovirus, coronaviruses, human parechoviruses, and hpiv, and showed a high frequency of hcov-e infection in pilgrims returning from the hajj. the prevalence of hrv was lower in than in , both before departing from france ( . % in vs. . % in ; p = . ) and before leaving saudi arabia ( . % in vs. . % in ; p = . ). however, samples that were obtained from pilgrims before departing from france during the study were stored at room temperature ( °c) for ≤ days before being processed. this protocol may have resulted in degradation of genetic material, which probably contributed to underestimation of frequencies of infection in . in , all samples collected during the study period were stored at − °c within h of collection. the prevalence of s. pneumoniae was also significantly lower in than in before pilgrims departed from france ( . % vs. . %; p< . ) and before they left saudi arabia ( . % vs. . %; p< . ). however, in the study, nasal swab specimens were collected from participants instead of throat swab specimens, which were used in the study. in addition, the period of the storage of samples before freezing differed between the and the studies, as mentioned earlier in this report. our results confirm that various respiratory viruses might be acquired by pilgrims during their stay in saudi arabia and introduced into home countries of pilgrims on their return, thus contributing to potential international spread of these viruses. however, detection of other human coronaviruses does not enable any conclusions regarding mers-cov, for which the available data to date, although limited, indicate different epidemiologic characteristics. we could not demonstrate whether pathogens detected in respiratory specimens were responsible for observed symptoms because nasal carriage was observed in asymptomatic pilgrims in certain instances, and symptoms might have resulted from infection by pathogens that were not investigated in our study. in future studies, checking pilgrims at more frequent intervals might provide useful information. nevertheless, we believe that hajj cough likely results from infection of the respiratory tract by various respiratory viruses, including hrv and hcov-e , which are known to cause mild or serious lower respiratory tract infections ( , ) . however, our results cannot be extrapolated to all pilgrims. a large-scale study based on a similar design and conducted in a large number of pilgrims from many countries would be useful. we found that pilgrims who had received influenza vaccine in were less likely to report ili symptoms during their stay in saudi arabia in . thus, availability of seasonal influenza vaccine for all persons attending the hajj is crucial. vaccination with a conjugate pneumococcal vaccine should be considered for persons with medical risk factors for invasive pneumococcal disease. in addition, use of hand sanitizer during the stay in saudi arabia was reported by more than two thirds of pilgrims in our survey and was associated with a lower prevalence of s. pneumoniae carriage. interventional studies are urgently needed that evaluate efficacy of influenza and pneumococcal vaccines and use of hand sanitizer and closely monitor respiratory symptoms and carriage of respiratory pathogens in large cohorts of pilgrims. it is expected that results of such studies will lead to implementation of evidence-based recommendations about preventive measures during the hajj. health risks at the hajj respiratory tract infection during hajj pattern of diseases among visitors to mina health centers during the hajj season, h ( g) clinical and temporal patterns of severe pneumonia causing critical illness during hajj circulation of respiratory viruses among pilgrims during the hajj pilgrimage comparison of mortality and morbidity rates among iranian pilgrims in hajj the prevalence of acute respiratory symptoms and role of protective measures among malaysian hajj pilgrims influenza a common viral infection among hajj pilgrims: time for routine surveillance and vaccination influenza and respiratory syncytial virus infections in british hajj pilgrims influenza viral infections among the iranian hajj pilgrims returning to shiraz, fars province, iran. influenza other respir viruses detection of respiratory viruses among pilgrims in saudi arabia during the time of a declared influenza a(h n ) pandemic acquisition of streptococcus pneumoniae carriage in pilgrims during the hajj pilgrimage lack of nasal carriage of novel corona virus (hcov-emc) in french hajj pilgrims returning from the hajj , despite a high rate of respiratory symptoms lack of mers coronavirus but prevalence of influenza virus in french pilgrims after influenza and the hajj: defining influenza-like illness clinically simultaneous detection of influenza viruses a and b using real-time quantitative pcr influenza type c. pcr methodology pandemic a(h n ) influenza virus detection by real time rt-pcr: is viral quantification useful? pring-akerblom p. rapid and quantitative detection of human adenovirus dna by real-time pcr real-time pcr assays for detection of bocavirus in human specimens quantification of human cytomegalovirus dna in bone marrow transplant recipients by real-time pcr a retrospective overview of enterovirus infection diagnosis and molecular epidemiology in the public hospitals of marseille real-time reverse transcriptase pcr assay for detection of human metapneumoviruses from all known genetic lineages rapid simultaneous detection of enterovirus and parechovirus rnas in clinical samples by onestep real-time reverse transcription-pcr assay applicability of a real-time quantitative pcr assay for diagnosis of respiratory syncytial virus infection in immunocompromised adults real-time reverse transcription-pcr assay for comprehensive detection of human rhinoviruses comparative evaluation of six commercialized multiplex pcr kits for the diagnosis of respiratory infections revolutionizing clinical microbiology laboratory organization in hospitals with in situ point-of-care prevalence of mers-cov nasal carriage and compliance with the saudi health recommendations among pilgrims attending the hajj human rhinoviruses a decade after sars: strategies for controlling emerging coronaviruses key: cord- -v t b ca authors: benkouiten, samir; charrel, rémi; belhouchat, khadidja; drali, tassadit; salez, nicolas; nougairede, antoine; zandotti, christine; memish, ziad a.; al masri, malak; gaillard, catherine; parola, philippe; brouqui, philippe; gautret, philippe title: circulation of respiratory viruses among pilgrims during the hajj pilgrimage date: - - journal: clin infect dis doi: . /cid/cit sha: doc_id: cord_uid: v t b ca background. the hajj is the oldest and largest annual mass gathering in the world and may increase the risk of spread of respiratory viruses. methods. we performed a prospective survey among a cohort of pilgrims departing from marseille, france, to mecca in the kingdom of saudi arabia (ksa) for the hajj season. nasal swabs were collected from participants and tested for respiratory viruses by real-time reverse transcription polymerase chain reaction. results. of participants sampled before departing to the ksa, ( . %) were positive for at least virus ( rhinovirus, influenza c, adenovirus, and enterovirus). seventy symptomatic pilgrims underwent additional nasal swabs during their pilgrimage in the ksa, of which ( . %) were positive for at least virus ( rhinovirus, influenza a, influenza c, respiratory syncytial virus b, metapneumovirus, adenovirus, and enterovirus). this was significantly higher than the . % who were positive before departing for the ksa (p < . ). of pilgrims sampled before leaving the ksa, ( %) were positive for at least virus ( rhinovirus, adenovirus, influenza b, and enterovirus), which was also significantly higher than the percentage of positive pilgrims ( . %), before departing for the ksa (p = . ). conclusions. this study suggests a rapid acquisition of respiratory viruses among pilgrims during their stay in the ksa, most notably rhinovirus, and highlights the potential of spreading these infections in the pilgrims' home countries upon their return. the hajj and its rituals are physically demanding and usually last for week, but the period of pilgrimage is up to month. on arrival in mecca, the holiest city in islam, hajj pilgrims start their pilgrimage by visiting the grand mosque for the circumambulation (tawaf ) of the kaaba. the pilgrims then move, during subsequent days, to different sacred places located around the city of mecca, including mina, arafat, and the muzdalifah valleys, where they reside for several nights in tent camps [ ] (figure ). later, most pilgrims leave mecca for the city of medina to visit islam's secondholiest site, the mosque of the prophet. the hajj presents major public health and infection control challenges. in addition to fatigue and extreme weather conditions [ ] (in mecca, during october the average temperature is > °c during the day and > °c at night, with a monthly rainfall averaging mm), which increase the susceptibility of pilgrims to airborne infections, inevitable overcrowding within a confined area of individuals from different parts of the world and close contact with others greatly increase the risk of acquiring or spreading infectious diseases during the pilgrims' stay [ ] ; in particular, acute respiratory infections, which are among the leading cause of acute illnesses worldwide, can spread among the pilgrims. respiratory tract infections are very common during the hajj [ , ] and account for most of the hospital admissions during this period [ , ] . it has been estimated that more than one-third of pilgrims will experience respiratory symptoms during their stay [ ] . a range of pathogens can cause acute respiratory infections, but respiratory viruses were found to be the most common etiology of upper respiratory tract infections among pilgrims in several surveys [ ] . this study, including sample collection and laboratory methods, was conducted among a cohort of pilgrims departing from marseille, france, to mecca in the ksa for the hajj season. they were tested for the most common respiratory viruses, with the aim of elucidating the dynamics of viral circulation among pilgrims. participants were recruited between august and october from a private specialized travel agency in the city of marseille, france, which organizes travel to mecca. pilgrims who planned to take part in the hajj season were asked to participate in the study on a voluntary basis if they were years of age or older and were able to provide consent. we conducted a cohort survey of participants who were followed up and sampled before departing to the ksa, during their pilgrimage in the ksa, and just before leaving the ksa. upon inclusion, the participants were questioned by arabicspeaking investigators using a standardized pretravel questionnaire, which included demographic data and medical history. a posttravel questionnaire, which collected travel-associated diseases, vaccination status, and compliance with protective behaviors, was completed by a french muslim arabic-speaking medical doctor who traveled with the pilgrims. this survey was administered during a face-to-face interview just prior to returning to france or via telephone after returning to france. if we were unable to contact the pilgrim after attempts, we considered the pilgrim lost to follow-up. health problems that occurred during the stay in the ksa were monitored and recorded by the medical doctor. a cough was defined as the occurrence of a cough with or without sputum. subjective fever was defined as a pilgrim's report of feeling feverish. for the purpose of this study, influenza-like illness (ili) was defined according to the presence of the triad of a cough, sore throat, and subjective fever [ ] . this study was approved by our local ethics committee under number - and by the saudi ethics committee. it was performed in accordance with the good clinical practices recommended by the declaration of helsinki and its amendments. all participants gave written informed consent. anterior nare swabs were systematically collected from each participant using a commercial rigid cotton-tipped swab applicator (sigma virocult, mw s, wiltshire, england), in the month before departing from france and in the days before leaving the ksa. in a number of cases, the medical doctor also collected additional nasal samples at the onset of symptoms during the pilgrimage in the ksa (within weeks after their arrival). all the samples collected during the study were placed in viral transport media (virocult virus transport medium) at the point of collection and kept at room temperature (stabilized by air conditioning to °c, in france and in the ksa) before being transported to the marseille laboratory for storage in a − °c freezer. each sample was tested for the following viruses by real-time reverse transcription polymerase chain reaction (rrt-pcr): influenza a (flua) [ ] , influenza b (flub) [ ] , influenza c (fluc), and a/ /h n [ ] viruses; human respiratory syncytial virus a and b (rsvb) [ ] ; human metapneumovirus (hmpv) [ ] ; human rhinovirus (hrv) [ ] ; ms bacteriophage; human adenovirus (hadv) [ ] ; and human enterovirus (hev) [ ] . total nucleic acids were purified from a -μl sample volume and were spiked with ms + t bacteriophage as an internal control [ ] , using the biorobot ez xl with the virus mini kit v . (both from qiagen, courtaboeuf, france) according to the manufacturer's instructions. each sample was tested independently in a -μl reaction containing μl of rna, . μl of × buffer (iscripttm one-step rt-pcr kit for probes, bio-rad), μl of reverse transcriptase/taq, nm concentration of each primer, and nm of probe. the reactions were performed using a c tm thermal cycler (cfx tm real-time system, bio-rad, marnes-la-coquette, france). the following cycling conditions were applied: °c for minutes, followed by °c for minutes; and then cycles of °c for seconds and °c for seconds. the presence of inhibitors was determined using ms and t bacteriophage-specific detection systems, as previously reported [ ] . we hypothesized that several factors may influence the outcome of respiratory symptoms or virus portage during the stay, including age, preventive measures, and underlying chronic diseases. the pearson χ test and fisher exact test, as appropriate, were applied to analyze the categorical variables. p values of ≤. were considered significant. statistical analyses were performed using spss software, version . . a total of participants were recruited to take part in the study, of whom responded to the pretravel questionnaire. table summarizes their baseline demographics and characteristics. participants' mean age was . years (sd, . ; range, - years), with a male-to-female sex ratio of . to . they were predominately born in north africa ( . %), and most of the foreign-born individuals reported living in france for > years. most of the participants reported living in marseille and the surrounding cities. more than half of the participants ( . %) reported suffering from at least chronic disease, including diabetes ( . %), hypertension ( . %), chronic respiratory disease ( . %), and chronic cardiac disease ( . %). a total of posttravel questionnaires were completed, representing a total response rate of . %, and . % of these were telephone-administered. the mean time between return from the ksa and administration of the questionnaire by telephone was days (range, - days). before departing to the ksa, none of the pilgrims presented acute respiratory symptoms at the time they were sampled. pilgrims stayed in the ksa for weeks, and the vast majority ( . %) of them suffered from at least respiratory symptom during their stay. a cough was the most frequently reported complaint ( . % of respondents), followed by sore throat ( . %), rhinorrhea ( . %), myalgia ( . %), feverishness ( . %), dyspnea ( . %), conjunctivitis ( . %), and diarrhea ( . %). of the pilgrims who reported respiratory symptoms during their stay in the ksa, . % met the criteria for selfreported ili. the onset of respiratory symptoms peaked at - days after the arrival of the pilgrims in mecca and declined thereafter. a second peak of smaller amplitude occurred on days and after arrival in mina, shortly after moving from arafat and muzdalifah. both peaks immediately occurred after performing the tawaf in mecca. finally, only % of the pilgrims who were systematically sampled before leaving the ksa reported respiratory symptoms during the days prior to leaving the ksa. regarding preventive measures, . % of participants reported receiving a seasonal influenza vaccination in the past year and . % reported receiving a pneumococcal vaccination in the past years. during their stay in the ksa, . % of pilgrims reported using facemasks, . % using disposable handkerchiefs, . % frequent hand-washing, and . % using hand sanitizer. pilgrims who reported frequent hand-washing during their stay, compared with those who reported using typical handwashing habits, more frequently reported feverishness ( . % vs . %; odds ratio [or], . ; % confidence interval [ci], . - . ; p = . ) and ili symptoms ( . % vs . %; or, . ; % ci, . - . ; p = . ). rhinorrhea was more frequently reported by pilgrims who declared that they were not vaccinated against influenza in compared to vaccinated pilgrims ( . % vs . %; or, . ; % ci, . - . ; p = . ). dyspnea was more frequently reported by those with chronic respiratory disease compared to other pilgrims ( . % vs . %; or, . ; % ci, . - . ; p = . ). the majority of pilgrims ( . %) sought healthcare from a doctor during their stay in the ksa, and . % consulted a doctor after their return to france. four pilgrims ( %) were hospitalized ( in the ksa and upon returning to france), for respiratory tract infection, for ili symptoms, for nephritic colic, and for vomiting. no deaths occurred. of the participants enrolled in the study, ( . %) underwent a systematic pre-hajj nasal swab before traveling to the ksa, and ( . %) underwent a systematic post-hajj nasal swab in the days before leaving the ksa ( . % underwent both pre-and post-hajj nasal swabs). a total of pilgrims ( . %) also underwent an additional nasal swab at the onset of acute respiratory symptoms during their pilgrimage in the ksa. the collection dates of the samples and results are shown in figures , , and . before departing to the ksa, participants ( . %) were positive for at least virus ( hrv, fluc, hadv, and hev), without coinfection. during the pilgrimage in the ksa, among the symptomatic pilgrims who were sampled, ( . %) were positive for at least virus ( hrv, flua, fluc, rsvb, hmpv, hadv, and hev), and there were double infections (flua/fluc, rsvb/hrv, and hrv/hev). this was significantly higher than the . % of pilgrims who were positive before departing to the ksa (p < . ). the prevalence of hrv was significantly higher during the hajj than before ( . % vs %; p < . ). of the pilgrims positive for hrv during their pilgrimage, were positive before traveling to the ksa. among the pilgrims ( . %) who met criteria for self-reported ili during the hajj, ( . %) were sampled, of whom ( . %) were virus-positive. the overall prevalence of respiratory viruses during the pilgrimage was significantly higher in pilgrims who reported more frequent hand-washing than usual during their stay compared to those who reported usual hand-washing ( . % vs . %; or, . ; % ci, . - . ; p = . ). no respiratory symptoms reported during the stay in the ksa were significantly associated with specific viral detection. before leaving the ksa, pilgrims ( %) were positive for at least virus ( hrv, hadv, flub, and hev), with double infections (hrv/hadv and hrv/hev), and this was significantly higher than the . % of pilgrims who were positive before departing to the ksa (p = . ). the prevalence of hrv was significantly higher before leaving the ksa than before departing to the ksa ( . % vs %; p = . ). of the pilgrims positive for hrv before leaving the ksa, were positive during their pilgrimage. the overall prevalence of respiratory viruses before leaving the ksa was significantly higher in individuals who reported using hand sanitizer during their stay compared to the remaining pilgrims ( . % vs . %; or, . ; % ci, . - . ; p = . ). all the pilgrims who were viruspositive before leaving the ksa complained of at least respiratory symptom during their stay. this is the first prospective longitudinal study investigating respiratory viruses from nasal specimens taken before departing for the ksa, during the pilgrimage in the ksa, and just before leaving the ksa in a single cohort of pilgrims, whether symptomatic or not. other studies have been conducted either among symptomatic pilgrims recruited in the ksa [ , ] , among separate populations of arriving and departing pilgrims [ ] , and in returned pilgrims only [ ] , or were limited to the influenza virus [ ] [ ] [ ] . nine pilgrims out of experienced respiratory symptoms during their stay in the ksa, with a cough and sore throat as the most common symptoms. ili symptoms were reported by . % of total pilgrims. an increase of respiratory symptoms was observed twice, following the tawaf, which is performed in the grand mosque in mecca in highly overcrowded conditions. an -fold increase in the overall prevalence of respiratory viruses was observed between samples obtained before departing from france ( . % of pilgrims) and samples obtained from ill pilgrims after performing their first tawaf in mecca ( . % of pilgrims). in our study, hrv was the most frequent virus detected from symptomatic pilgrims ( %). this result is in accordance with studies conducted worldwide where hrv has been recognized as the most frequent virus responsible for the common cold in adults [ , ] . this is not unexpected, as rhinoviruses are nonenveloped viruses that are more resistant in the environment than enveloped viruses. symptoms of hrv infection are generally mild and limited to the upper respiratory tract. in contrast, lower respiratory symptoms associated with hrv infection are prominent in patients who have underlying asthma or other chronic lung disease [ ] . in the present study, . % of pilgrims reported chronic respiratory diseases; therefore, prevention must be reinforced in this high-risk population. there have been arguments [ ] regarding whether rhinoviruses are spread chiefly from infected person to healthy individuals by direct contact to the fingers of healthy individuals by a handshake or indirect contact from the hands of an infected person to an intermediary surface [ ] , or through the aerosol route [ ] . our findings showed that more frequent hand-washing was significantly associated with feverishness and symptoms of ili and with a higher prevalence of respiratory viruses. however, these results may indicate a reverse causation, as pilgrims with symptoms or who believe themselves to be at greater risk may have washed their hands more frequently. a recent study found that hand disinfection did not reduce hrv infection or hrv-related common cold illnesses [ ] . the prevalence of hrv paralleled the increase of respiratory clinical symptoms, with a higher prevalence in pilgrims sampled in mecca city during the first week of the pilgrimage. influenza viruses ranked second after hrv among symptomatic pilgrims ( . %), and patients with influenza virus infection reported receiving a seasonal influenza vaccination prior to the hajj pilgrimage. other viruses were rarely found in our study. we previously reported that the novel coronavirus middle east respiratory syndrome (mers-cov; formerly known as hcov-emc) was not detected during the hajj season among the cohort pilgrims described here [ ] . other coronaviruses and parainfluenza viruses were not considered in this study and should be investigated in future studies. more than out of pilgrims tested positive for overall respiratory viruses just before leaving the ksa, which indicates a high potential for spreading viral pathogens into pilgrims' home countries. given that a significant proportion of french pilgrims also travel to their country of birth in north africa immediately after returning to france from the hajj [ ] , there is also a potential for spreading these viruses beyond france. the main limitation of this study is that, although the vast majority of pilgrims reported respiratory symptoms during their stay in ksa, the sampling by the medical doctor was limited to those who sought medical consultation from her. however, some symptomatic pilgrims were found to be negative for respiratory viruses. for those sampled at mina and medina, this was likely due to delayed medical consultation, as the specimen was collected several weeks after the onset of symptoms. second, symptom occurrence was collected retrospectively and was based on self-reporting; thus, the date of the medical consultation did not necessarily correspond to the selfreported date of the onset of respiratory symptoms. third, samples that were obtained at the beginning of the pilgrimage in the ksa were stored at room temperature ( °c) for periods up to days before being processed, which may have been resulted in the degradation of genetic material. this may have likely contributed to underestimating the frequencies of infection. alternative strategies to better preserve the samples must be considered, among which ethanol or nucleic acid lysis buffer [ ] could be used. fourth, a technical point is that hrv sequencing was not performed to determine how often new hrv infections were acquired during the stay in the ksa. finally, we cannot demonstrate that the viruses detected from nasal swabs were responsible for the symptoms, as nasal carriage in asymptomatic pilgrims was observed in some cases, and symptoms may have resulted from infection by other viruses [ ] , or possibly bacteria [ ] , that were not investigated in our study. although our results cannot be extrapolated to all pilgrims, our study illustrates the rapid acquisition of respiratory viruses among pilgrims during their stay in the ksa, particularly rhinovirus, and demonstrates the potential for spreading these infections to pilgrims' home countries upon their return. financial support. this work was supported by the marseille public 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bacteria and viruses that cause respiratory tract infections during the pilgrimage (haj) season in makkah, saudi arabia key: cord- - nrejsgr authors: alqahtani, amani s.; wiley, kerrie e.; tashani, mohamed; willaby, harold w.; heywood, anita e.; bindhim, nasser f.; booy, robert; rashid, harunor title: exploring barriers to and facilitators of preventive measures against infectious diseases among australian hajj pilgrims: cross-sectional studies before and after hajj date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: nrejsgr objective: for reasons that have yet to be elucidated, the uptake of preventive measures against infectious diseases by hajj pilgrims is variable. the aim of this study was to identify the preventive advice and interventions received by australian pilgrims before hajj, and the barriers to and facilitators of their use during hajj. methods: two cross-sectional surveys of australians pilgrims aged ≥ years were undertaken, one before and one after the hajj . results: of pilgrims who completed the survey (response rate %), % had the influenza vaccine, % the pneumococcal vaccine, and % the pertussis vaccine. concern about contracting disease at hajj was the most cited reason for vaccination ( . %), and not being aware of vaccine availability was the main reason for non-receipt ( %). those who obtained pre-travel advice were twice as likely to be vaccinated as those who did not seek advice. of pilgrims surveyed upon return, % reported practicing hand hygiene during hajj, citing ease of use ( %) and belief in its effectiveness ( . %) as the main reasons for compliance; university education was a significant predictor of hand hygiene adherence. fifty-three percent used facemasks, with breathing discomfort ( %) and a feeling of suffocation ( %) being the main obstacles to compliance. conclusion: this study indicates that there are significant opportunities to improve awareness among australian hajj pilgrims about the importance of using preventive health measures. the transmission of infectious diseases is high at mass gatherings such as the annual hajj pilgrimage in makkah, saudi arabia. hajj is the largest annual mass gathering on the planet, with around two to three million people attending from over countries. intense congestion, shared accommodation, air pollution, and compromised hygiene all contribute to the transmission of infections at hajj, most notably acute respiratory infections (aris). , hajj presents a public health challenge for saudi arabia, as the authorities need to cater for an increasing number of pilgrims and respond to emerging infections such as the middle east respiratory syndrome coronavirus (mers-cov). , it is also challenging for the countries sending pilgrims, since these pilgrims can import epidemic diseases to their home countries upon return. in an effort to reduce the risk of infectious diseases at hajj, an array of preventive measures have been recommended by the saudi arabian ministry of health (moh), which include vaccination and hygiene measures (table ) . however, studies have demonstrated that vaccine uptake and compliance with hygiene and protective measures are highly variable among pilgrims, , and the reasons behind this variability remain unclear. to date few studies have assessed the knowledge, attitudes, and beliefs in relation to preventive measures among hajj pilgrims. a recent qualitative study of australian pilgrims found that considerable misconceptions about preventive measures and the risk of respiratory infections prevail among hajj pilgrims. a french study demonstrated that less than half of pilgrims were aware of social distancing and facemask use as precautions against respiratory infections, but no study has explored the barriers to and facilitators of the uptake of preventive measures. to address these questions, two cross-sectional surveys were conducted among australian pilgrims, one before and one after the hajj , to identify what preventive advice and interventions pilgrims received before travel, and what factors influenced their compliance with these measures while they were there. two cross-sectional self-administered questionnaires were distributed among australian hajj pilgrims aged ! years in . the first survey was conducted on a group of departing pilgrims approximately month before hajj (pre-hajj study). the second survey was conducted on a second, separate group of pilgrims immediately after their return to australia (post-hajj study). the pre-hajj survey collected data on socio-demographic characteristics, hajj itinerary details, and the receipt of pre-travel advice, including vaccinations. the questionnaire also assessed the pilgrims' knowledge of and attitudes towards preventive measures, and their risk perception of diseases occurring at hajj, including influenza, pneumonia, and blood-borne diseases. the post-hajj questionnaire assessed the actual compliance with infection control measures (such as the use of facemasks, hand disinfectants, and handkerchiefs) during hajj, and the barriers to and facilitators of the use of those preventive measures while at hajj. the surveys were primarily in english, with arabic translations available for those who preferred to complete the survey in arabic. muslims residing in the greater sydney area, new south wales (nsw) were the target population for the study. nsw has the largest muslim population ( %) of any state in australia with the majority living in greater sydney. australian hajj pilgrims aged years and over who were planning to attend the hajj were eligible for recruitment. potential participants were approached through hajj tour operators. the list of accredited hajj travel agents in australia, including their location/address, was obtained from the saudi arabian embassy in canberra, australia. the selection of participants was based on the number of hajj visas allocated for a given travel agent: travel agents with the highest quota of hajj visas were approached first, and the travel agents who dealt with diverse ethnic groups, including arabs, africans, indians, and malays, were prioritized to ensure a diverse sample. for the pre-hajj survey, departing pilgrims were approached at weekly pre-hajj seminars run by travel agents between august and mid-september . all pilgrims attending the seminars were invited to take part in the study. for the post-hajj survey, a second group of pilgrims (separate to the first) were approached in person at community gatherings and events within weeks of returning home from hajj (between mid-october and the end of december ). the study was promoted using a number of methods, including the distribution of brochures at mosques and community centres and by word of mouth. a consecutive sampling plan was used to ensure a sample that was representative of pilgrims residing in nsw. assuming that at least % of respondents will have a general knowledge of infection control measures, and considering an error margin of % to be acceptable for this anonymous survey, a sample of was considered to be sufficient for this study; assuming a noncompletion rate of the survey of - %, a total of participants were targeted. the sample size of this study represents approximately % of australian pilgrims to hajj (which is approximately ). previous works studying the uptake of vaccinations among australian hajj pilgrims showed that a convenience sample of % of the target population is sufficient. the data collected were entered into an excel spreadsheet. the statistical analysis was performed using ibm spss statistics version . (ibm corp., armonk, ny, usa). pearson correlation coefficients and chi-square tests were used to assess variables and determine associations and correlations. univariate factors with p-values of < . were entered into multivariable regression analyses. twotailed p-values of . were considered statistically significant in the multivariable models. this study was reviewed and approved by the human research ethics committee (hrec) at the university of sydney (project no. / ). a total of respondents agreed to participate in the study, of whom ( %) completed the survey questionnaires. their demographic details are presented in table . eighty-two percent of pilgrims ( / ) were attending hajj for the first time, and the median duration of their stay in saudi arabia was (range - ) days. all respondents reported receiving meningococcal vaccine; the majority ( %, / ) also received one or more other recommended vaccines (table ) . factors influencing vaccine uptake are listed in table . being aged > years was significantly associated with the uptake of recommended vaccines (odds ratio (or) . , % confidence interval (ci) . - . , p = . ), as was having a university education (or . , % ci . - . , p = . ). approximately two thirds ( / ) obtained 'professional travel health advice' from one or more sources before hajj, including % ( / ) from general practitioners (gps), % ( / ) from a specialist travel clinic, % ( / ) from a specific hajj website (e.g., moh website ), and % ( / ) from the 'smartraveller' website. of those who received professional pretravel advice, % ( / ) reported a positive experience with the advice, while the rest described a negative experience. one third ( / ) did not seek any 'professional travel health advice' before hajj. reasons for not seeking pre-travel advice included not recognizing the need to seek such advice ( %, / ), preference for other sources, i.e., friends, family members, and travel agents ( %, / ), reliance on previous experience/ knowledge ( %, / ), and previous negative experience of seeking pre-travel advice ( %, / ). being within the age band of to years was the only factor associated with receiving professional pre-travel advice (or . , % ci . - , p = . ). additional pre-travel health advice sources were also reported, including hajj travel leaders ( %, / ), family members and friends who had previous experience of performing hajj ( %, / ), and 'general websites' on the internet ( %, / ). fortysix percent ( / ) were aware of the annual hajj health recommendations issued by the saudi moh. additionally, pilgrims who sought pre-travel advice from gps (or . , % ci - . , p = . ) or tour group leaders (or . , % ci . - . , p = . ) before travelling to hajj were twice as likely to be vaccinated as those who did not. pilgrims were reportedly concerned about food poisoning ( %, / ), diarrhoea ( %, / ), influenza ( %, / ), blood-borne diseases ( %, / ), skin diseases ( %, / ), and pneumonia ( %, / ). however, there was no association between the level of concern about influenza, pneumonia, and blood-borne diseases and the uptake of the influenza, pneumococcal, and hepatitis b vaccines, respectively (all p-values > . ). a total of returned pilgrims were surveyed. their demographic characteristics are presented in table . a large proportion of pilgrims ( %, / ) had performed hajj for the first time. they had stayed for a median duration of (range - ) days. the majority of participants, % ( / ), believed hand washing (with water only) to be the most effective measure to protect oneself from respiratory infections, while the uses of alcoholic hand rubs ( %, / ) and facemasks ( %, / ) were considered to be less effective. only beliefs about the effectiveness of facemasks and hand washing with water and soap were significantly associated with their actual use (p < . ) ( table ). half of the pilgrims ( %, / ) used facemasks to protect themselves from infectious diseases during hajj at least three times a day. participants described three major reasons for facemask use: protection from disease ( %, / ), protection from air pollution ( %, / ), and belief that facemasks are effective in preventing aris ( %, / ). less than half ( %, / ) did not use a facemask. the reasons for non-compliance were breathing discomfort ( %, / ), feeling of suffocation ( %, / ), and thinking it was not necessary ( %, / ). in addition, none of the demographic characteristics were associated with facemask compliance (all p-values > . ) and therefore these were not entered into multivariable regression analyses. a subgroup of women (n = ) answered questions on their use of the niqab (traditional face veil); of those who responded, % ( / ) used only facemasks, % ( / ) used only the niqab, and % ( / ) used both a facemask and the niqab. of those who used the niqab (either alone or with a facemask), % ( / ) reported that they did so because it is 'airy' and easier to breathe and % ( / ) felt that it was comfortable to use. almost all ( %, / ) practised some kind of hand hygiene during hajj. this included hand washing with soap ( %, / ), hand washing with water only ( %, / ), and alcoholic hand disinfectant ( %, / ). reasons influencing the pilgrims' decision to use these methods included belief in the effectiveness of hand hygiene in preventing infectious diseases ( %, / ) and convenience and ease of use ( . %, / ). additionally, those with a university education were more likely to use hand hygiene measures than those without (or . , % ci . - . , p = . ). respondents reported using other preventive measures including disposable handkerchiefs ( %, / ), avoiding dense crowding ( %, / ), avoiding contact with symptomatic people ( %, / ), and practicing hand washing after touching the ill ( %, / ). this appears to be the first in-depth quantitative study comparing the health knowledge attitudes, beliefs, and practices of departing and returning hajj pilgrims regarding preventive measures against infectious diseases. this study found that and france where the vaccination rate for was zero due to vaccine non-availability, and compares well with the overall vaccination rates among international pilgrims over recent decades, which range between . % and %. , influenza vaccine aside, the uptake of other recommended vaccines was low. for instance, the uptake of pneumococcal vaccine was only %. previous australian and international surveys have reported coverage rates ranging from . % to %. , this is concerning because pneumonia is the leading cause of hospital admission and an important cause of mortality at hajj. [ ] [ ] [ ] furthermore, surveys have shown that many pilgrims were not aware that pneumonia is transmissible and preventable by vaccination. there is currently no formal guidance from the saudi moh on the use of pneumococcal vaccine for hajj pilgrims, which may partly explain this apparent lack of awareness (table ) . the uptake of pertussis vaccine was %, compared with . % among french hajj pilgrims in . additionally, the coverage for hepatitis a and b vaccines were each %, which is higher than the . % uptake for hepatitis a reported among french pilgrims in , and the % each for hepatitis a and b among saudi pilgrims in . while a large proportion of hajj pilgrims are from countries with intermediate to high hepatitis b virus (hbv) prevalence, the risk of contracting hbv at hajj is not well studied. , it is known that a significant proportion of pilgrims engage in high-risk behaviours; for example it was found that about % of male pilgrims shaved their heads with reused razors, or had their heads shaved by non-professional (unlicensed) barbers. other studies have also reported high-risk behaviours that increase the risk of hepatitis a, including buying and eating food from street vendors. despite this, hepatitis a and b vaccines are not listed in the saudi moh recommendations for hajj pilgrims (table ) . in this study, polio vaccine uptake was %, which is low compared with the uptake among french pilgrims in ( %), and the uptake among pilgrims from other non-endemic countries in ( %). typhoid vaccine coverage was % in this study, which compares well with the uptake rate of % among international pilgrims in . the present study appears to report mmr (measles, mumps, and rubella) vaccine uptake ( %) for the first time. the participants cited several reasons for not receiving the recommended vaccines, the most common being that they were unaware that the vaccines were recommended. these results are consistent with the findings of memish et al., who reported a lack of knowledge to be a significant factor for poor uptake of the seasonal influenza vaccine among pilgrims. conversely, previous australian studies have reported reliance on natural immunity as the main reason for not being vaccinated against influenza in , while low risk perception of contracting influenza was the main reason in . a unique finding of this study is that pilgrims who received pretravel advice from gps and hajj tour group leaders were twice as likely to be vaccinated as those who did not receive such advice. barasheed et al. found that receiving advice from hajj group leaders was the main motivator for the uptake of influenza vaccine among australian hajj pilgrims in . this survey also revealed that older pilgrims (aged > years) were more likely to take up the recommended vaccines. similarly, gautret et al. demonstrated that influenza vaccine coverage increased with age in french pilgrims. this could be due to the fact that older people are more aware of their health, or it could be due to an increasing number of pre-existing illnesses as people age. another study among french pilgrims found that 'at risk' pilgrims were significantly more likely to be advised to receive pneumococcal vaccine than those who were not 'at risk'. this may explain why vaccine uptake has been found to increase with age in some studies. , although respiratory infections are the most common diseases during hajj, the participants in this study were more concerned about food-borne illness than aris. limited knowledge and perception of diseases among pilgrims has been found in other studies; an australian study found that % of pilgrims in were not aware that pneumonia can be transmissible. similarly, french pilgrims in did not perceive pneumonia as a severe condition, and were not aware of the existence of a vaccine against it. no association was found between the disease risk perception for influenza, pneumonia, and hepatitis b and the uptake of the respective vaccines. this contradicts other data, which demonstrated that an increased risk perception of pandemic influenza a (h n ) was significantly associated with influenza vaccine uptake among us pilgrims in . almost all of the participants in the present study used some kind of hand hygiene; this was higher compared with french pilgrims in ( %). more than half of the pilgrims used facemasks in this study, similar to french pilgrims in . nevertheless, previous studies have reported that only half of the participants were aware of the availability of non-pharmaceutical preventive measures against respiratory infections. , belief that hand hygiene is easy to use and effective in preventing infections were the main reasons for uptake among the present sample. conversely, facemasks were less accepted. among non-users, discomfort and difficulty in breathing were barriers to their use. those who used facemasks believed that they were effective in preventing infectious diseases. similar quantitative findings have been reported among members of the general singaporean community, but not previously among hajj pilgrims. another important factor identified as a driver for the use of facemasks was protection from air pollution. a recent study found that the air pollution level in makkah during the hajj consistently exceeds internationally acceptable standards, and therefore this perception is probably justified and could inform health promotion policy. thirty-four percent of female pilgrims in the present sample preferred to use a traditional face cover (niqab) to a facemask during hajj. in contrast, other studies found that higher proportions (over %) of saudi women preferred the niqab over facemasks at hajj and . , in the exploration of why some women prefer using the niqab, it was found that comfort and breathability were contributing factors. in this study, two thirds of pilgrims sought pre-travel advice from health professionals; this is similar to the results of a survey that found that % of arab pilgrims received health advice before departing to hajj. gps were the most cited sources, followed by specialist travel clinics. this result is supported by a study that found gps to be the most trusted sources of health advice among australian pilgrims in . interestingly, only % of the present sample sought advice from the saudi moh website. this is different to the findings of a study that showed the saudi moh to be the main source of health information among pilgrims from arab countries ( %). this difference may be due to language barriers. not recognizing the need to seek pre-travel health advice and the preference for other information sources (i.e., friends, family members, and travel agents) were the main barriers to seeking professional pre-travel advice. these results support the findings of a recent australian study, which also demonstrated a high level of confidence in advice from non-health professional sources such as family, friends, and travel agents. the present study identified that being aged between and years was the only factor significantly associated with seeking pre-travel health advice. therefore, enhancing awareness among other groups of hajj pilgrims, especially elderly adults and those with pre-existing illnesses, about the importance of seeking professional pre-travel advice could be an important strategy to improve the uptake of preventive measures. moreover, providing gps with culturally appropriate health information on hajj and the preventive measures recommended by the saudi moh could also facilitate uptake. this study has some limitations. two different groups were surveyed and the groups showed significant differences in demographic characteristics, particularly in sex, education level, and country of birth. also, the sample size of the post-hajj group was smaller than intended. these could limit the generalizability of the findings of one group to the other. these limitations are being addressed by a second, larger cohort study among australian pilgrims during hajj , and a qualitative study among gps and tour group leaders is underway. despite these limitations this study has uniquely identified the barriers to and facilitators of the uptake of preventive measures among australian hajj pilgrims, providing important preliminary data upon which to build. this study shows that there are significant opportunities to improve awareness among hajj pilgrims about the importance of using preventive health measures and indicates the need for better communication of official health information from the saudi moh to a broader international audience. conflict of interest: professor robert booy has received funding from baxter, csl, gsk, merck, novartis, pfizer, roche, romark, and sanofi pasteur for the conduct of sponsored research, travel to present at conferences, or consultancy work; all funding received is directed to research accounts at the children's hospital at westmead. dr anita e. heywood has received grant funding for investigator driven research from gsk and sanofi pasteur. dr harunor rashid received fees from pfizer and novartis for consulting or serving on an advisory board. the other authors have no competing interests to declare. burden of vaccine preventable diseases at large events. vaccine respiratory tract infections during the annual hajj: potential risks and mitigation strategies travel implications of emerging coronaviruses: sars and mers-cov imported cases of middle east respiratory syndrome: an update health conditions for travellers to saudi arabia for the pilgrimage to mecca (hajj)- vaccinations against respiratory tract infections at hajj non-pharmaceutical interventions for the prevention of respiratory tract infections during hajj pilgrimage australian hajj pilgrims' infection control beliefs and practices: insight with implications for public health approaches hajj pilgrims' knowledge about acute respiratory infections australian department of 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declared influenza a (h n ) pandemic predictors for the uptake of recommended vaccinations in mecca travelers who visited the public health service amsterdam for mandatory meningitis vaccination predictors of protective behaviors among american travelers to the hajj respiratory viruses and bacteria among pilgrims during the hajj the use of facemasks to prevent respiratory infection: a literature review in the context of the health belief model air quality in mecca and surrounding holy places in saudi arabia during hajj: initial survey incidence of hajj-related acute respiratory infection among hajjis from riyadh hajj-associated acute respiratory infection among hajjis from riyadh sources of health education for international arab pilgrims and the effect of this education on their practices towards health hazards in hajj time for patient leaflets on the hajj key: cord- -m choyr authors: hoang, van-thuan; gautret, philippe; memish, ziad a.; al-tawfiq, jaffar a. title: hajj and umrah mass gatherings and covid- infection date: - - journal: curr trop med rep doi: . /s - - -x sha: doc_id: cord_uid: m choyr purpose of review: we discuss the risk of covid- in religious mass gathering events including hajj and umrah pilgrimages. recent findings: the risk of transmission of respiratory viruses including covid- is particularly high due to the overcrowding conditions at the hajj and umrah. the profile of the hajj pilgrims who tend to be older and with multiple comorbidities corresponds to that of individuals at risk for severe covid- . in order to avoid a covid- outbreak with potential spreading to many countries through returning pilgrims, saudi arabia suspended the umrah, and access to the hajj was very limited. summary: a clear relation between early suspension of religious mass gatherings and lower occurrence of covid- transmission in countries that took such measures promptly was noticed. there are lessons to national and international health organizations for other mass gatherings in the context of the pandemic. the hajj in makkah, kingdom of saudi arabia (ksa), is one of the largest annual religious mass gatherings (mgs) in the world with a strong international component. each year, two to three million muslims from more than countries around the world flock to makkah for the hajj pilgrimage [ •] . this is one of the five pillars of islam. it is compulsory, at least once in lifetime, for all responsible adult muslims who have the physical and financial capacities necessary to accomplish it. the hajj takes place every year between the th and the th of dhul hijjah, the th and last month of the islamic calendar. in contrast, the umrah is another islamic pilgrimage to makkah (shorter than the hajj) that can be undertaken at any time of the year. the umrah is not compulsory, but is still highly recommended [ ] . umrah during ramadan is equal to hajj in terms of religious value, according to a statement that is attributed to the prophet mohammad [ ] . together, the hajj and umrah involve over million participants each year [ •] . the presence of a large number of pilgrims from many parts of the world in congested and crowded areas greatly increases the risk of spreading infectious diseases [ •, ] . respiratory tract infections (rtis) are the most frequent infections transmitted between pilgrims [ •, ] . most of pilgrims develop rtis early after their arrival in makkah with prevalence up to % [ ] . this article is part of the topical collection on massive gathering events and covid - in december , an outbreak of respiratory infectious disease (covid- ) due to a novel coronavirus (officially named sars-cov- ) emerged in the city of wuhan, in the chinese province of hubei. the virus is easily transmitted between humans, and the outbreak was declared a public health emergency of international concern on january , , and then a pandemic on march , [ ] . this pandemic is posing serious risks to public health worldwide including in the ksa. all possible measures against lethal covid- were applied in the country, but one of the most important questions asked in the islamic world in the context of covid- was about approaching umrah and hajj pilgrimages. we review viral respiratory infections at the hajj and umrah mass gatherings with a focus on covid- . acute rtis are a major problem of public health that affects over million individuals (more than %) of the ksa population in [ ] . respiratory viruses are the most frequent cause of these infections [ , ] . the epidemiology of respiratory viruses in ksa is likely affected by the gathering of more than million muslims in the holy sites of makkah and medina during the umrah and hajj seasons [ ] . in pilgrims, human rhinovirus (hrv), common human coronaviruses (hcov), and influenza virus were the respiratory viruses most frequently acquired at the hajj [ , , , [ ] [ ] [ ] [ ] [ ] . hrv is a highly contagious respiratory virus. it is a frequent cause of rtis in humans of all age range. immunosuppressed individuals or persons with congenital heart disease and bronchopulmonary dysplasia are exposed to severe hrv infection [ ] . in cohorts of pilgrims sampled after participation in the hajj, carriage of hrv ranged from . to . % and was significantly higher before the hajj [ ] . as an example, a paired survey realized among international hajj pilgrims showed that over % pilgrims acquired hrv after the hajj season [ ] . more recently ( to ), in a -year cohort of french pilgrims, . % participants acquired hrv after their pilgrimage [ ] . the dynamic of hrv acquisition during the pilgrimage was recently described in french pilgrims [ ] . the authors showed an early increase in hrv carriage during the first days of the pilgrimage with a prevalence times higher than that of pre-travel samples. then, hrv carriage decreased progressively in subsequent samples but was still eight times higher in post-hajj samples compared to pre-hajj [ ] . in november , a pandemic due to the novel hcov named sars-cov started in guangdong, china. the virus spread to several countries with confirmed cases reported, and the mortality was nearly . % [ ] . ten years later, a sars-like cov identified as mers-cov was isolated from a saudi patient. an outbreak quickly spread to neighboring countries, followed by a wider spread to geographically distant countries [ ] . as of september , it involved countries with laboratory-confirmed cases and deaths (mortality rate was . %). the majority of cases occurred in the ksa with cases reported and deaths ( . % case fatality rate) [ ] . the largest numbers of mers-cov cases were reported in and with and cases, respectively [ ] . however, no cases of sars coronavirus and mers coronavirus were documented in hajj pilgrims until now [ ] , and only a few cases of mers have been reported among umrah pilgrims [ ] . by contrast, other common hcovs were acquired by pilgrims during their pilgrimage. acquisition rate of hcov e calculated from a large paired cohort survey ( international pilgrims) in was . % [ ] . in paired cohorts of french pilgrim (n = ) investigated during the hajj - , the overall hcov acquisition rate was . % (with hcov e the most frequent ( . %)) [ ] with a marked peak during the hajj season with a . % hcov e acquisition rate [ , - , •] . in april , an outbreak due to a novel h n influenza virus (influenza a(h n )pdm ) was first identified in mexico and became rapidly pandemic with more than million cases reported in with usa [ ] . the ksa was one of the countries affected by the virus, with , laboratory-confirmed cases, including deaths on december , [ ] . the first cases in ksa involved travelers at four airports during june [ ] . the hajj took place in the last week of november, during the outbreak that had been declared as a global pandemic by the world health organization on june , [ ] . the acquisition rate of influenza a(h n )pdm among returning iranian pilgrims after the hajj season was . % [ ] . koul et al. conducted a study among indian pilgrims returning from the hajj and umrah in - . their qpcr result showed that % were positive for influenza virus, including cases of influenza a(h n )pdm , cases of influenza a/h n , and cases of influenza b [ ] . in another study realized among international pilgrims after the hajj season, a total of . % participants were positive for influenza a by qpcr. of whom, cases were positive for influenza a(h n )pdm [ ] . overall, these results show that acquisition of respiratory viruses following the hajj is very frequent with high carriage rates on leaving ksa and a potential for further transmission on returning to home country. this strongly suggests that the hajj and possibly the umrah may contribute to the globalization of common respiratory viruses. the first covid- case in ksa was detected on march , , in the qatif region among an individual who had traveled to an endemic region in iran [ •] . the outbreak then began to spread throughout the country in early april . as of august , , a total of death out of , confirmed cases covid- ( cases/ m population) were reported in ksa [ ] . a dynamic epidemiological model estimated that the hajj season could coincide with the peak or deceleration leg of the covid- pandemic curve [ ] . interestingly, the covid- epidemic in ksa was partly related to another pilgrimage (shiite pilgrimage) with saudi pilgrims returned from pilgrimage sites in iraq and iran being an early source of community seeding of sars-cov- in ksa contributing to global total cases. the annual number of pilgrims in the last years varied between , , and , , ( fig. ) [ ] . the incidence of confirmed cases of covid- in top countries which send hajj pilgrims in varied from / m population to / m population [ ] (table ) . thus, it was expected that the hajj and umrah will be suspended [ ] . during the hajj and umrah pilgrimages, the risk of transmission of respiratory viruses including covid- is particularly high due to the overcrowding as pilgrims gather in sacred crowded places where rituals take place such as during tawaaf (circumambulating the ka'ba) or within the housing structures. by example, these is up to persons per m at the grand mosque in makkah during rituals, and - pilgrims are housed per tent at mina encampment [ , ] . even when the reproduction rate of an outbreak is low, the over density during the hajj tends to amplify the spread of transmission [ ] . the sri petaling mg, a muslim missionary movement with , participants, including foreigners from countries, in the suburb of kuala lumpur, malaysia, that took place from february to march , , accounted for > % of the covid- cases in the country [ ••] . in february , . % ( / ) of the ship's population on the diamond princess cruise ship were infected by sars-cov- [ ] . the shincheonji christian religious group with approximately , participants gathering in the city of daegu, south korea, took an important role in the covid- epidemic in the country. on march , , nearly related cases were reported out of cases in whole south korea [ ] . a high attack rate of sars-cov- was observed during a large wedding in jordan with a total of / ( . %) participants tested positive [ ] . in february , pilgrims had returned to different cities of pakistan from qom city in iran where a pilgrimage of shia muslims took place. at the end of march , a total of confirmed cases were reported in pakistan, of whom, % were pilgrims returning from iran [ •] . in early march , a cluster of / ( . %) covid- cases was documented in greek pilgrims after a christian pilgrimage in jerusalem, israel [ ] . in late march , six pilgrims who attended a pilgrimage at a masjid in pakistan were detected positive for sars-cov- in china. during their -month stay, they had close contact with thousands of masjid pilgrims without face mask [ ] . finally, in march , the covid- outbreak started in arkansas, usa, with two index cases who participated to a christian event in a rural county [ •] . a total of / ( %) attendees were confirmed for the sars-cov- , including deaths. in addition, at least additional patients who had contact with these participants were likely infected by them. several risk factors for covid- infection and critical covid- cases were described [ •] . persons with organ transplant, cancers, severe lung condition, and serious heart condition or pregnant woman are at high risk. older persons, having lung condition that is not severe, heart disease, diabetes, chronic kidney or liver disease, or obesity are at moderate risk [ ] . in a meta-analysis of patients from studies showed multiple factors to be associated with sars-cov- infection [ •] . being male and smoking were associated with a twofold increased risk of severe disease. age older than years was associated with a sixfold increased risk of disease progression in patients with covid- [ •] . in addition, the proportion of chronic diseases was significantly higher in critical and among those who died compared to others, including hypertension (odds ratio (or) = . ), [ ] . international travel has already been shown to play a central role in the spreading of covid- and international mgs like the hajj or umrah, if maintained may well have contributed to the globalization of sars-cov- through returned participants. [ ] [ ] [ ] . a few cases of covid- occurred in umrah pilgrims before international travel was banned. as an example, the first patient who died of covid- in pakistan was a returned umrah pilgrim [ ] . in addition, most of hajj and umrah pilgrims are from countries with suboptimal disease surveillance or travel health counseling service [ ] . to date, no specific preventive measures or vaccines are available for covid- . furthermore, health systems are still overloaded in many places. the overcrowding during the hajj and umrah is inevitable, and it is difficult to prevent the transmission of contagious diseases in this context. the ksa ministry of health recommends individual preventive measures such as use of face mask and disposable handkerchiefs and hand hygiene to mitigate the risk of rtis. however, the efficacy of these measures against rtis is debated [ ] , and there have been no reliable controlled studies investigating their efficacy on the incidence of hajj-related rtis. the use of face masks may not provide optimal protection from infection, but that may reduce the spread of smallsized saliva droplets around when coughing or sneezing which is the main mode of transmission of most rtis. mandatory use of face mask in public places is considered one of the effective measures in controlling the covid- pandemic [ ] [ ] [ ] , but no investigation has been conducted in the context of mgs so far. in addition, the practice of social distancing, hand hygiene, and contact avoidance was associated with reduced risk of spreading this outbreak [ , ] . the ksa ministry of health annually publishes the recommendations for required immunization such as influenza vaccine and meningococcal vaccine for the hajj. in , specific individual preventive measures were also recommended against mers [ ] . on may , , who published the key planning recommendations for mass gatherings in the context of covid- [ ] . there are several factors to consider when determining the need to cancel or postpone a mass gathering event. these factors include the number of attendees and the proportion at greater risk of covid- transmission, the density of attendees within a confined place, the level of transmission in the host area, and the community to which the participants will return [ ] . who also recommended canceling gatherings of more than persons for organizations that serve higher-risk populations or community-wide mgs with more than participants [ ] . if a mg is to be held, prevention supplies are needed to be provided to event staff and participants, such as hand sanitizer with at least % alcohol, disposable tissues, trash baskets, disposable facemasks, and surface disinfectants ( table ) [ ] . since the ksa has been affected by the covid- pandemic, several measures were applied, including in the holy cities makkah and madinah, to protect people from further infection [ •] . in order to prevent the spread of covid- and for avoiding super spreader events, saudi arabia suspended the umrah on march , [ ] . the government also closed the grand mosque and the kaaba on march , , for over months. the shipping services and all international flights were also suspended [ ] . this year, the hajj took place from july , , to august , . because the spread of infection has not been controlled worldwide and in the country, on june , , the ksa government announced complete ban of international visitors for the annual hajj pilgrimage to makkah, and access for the domestic population was denied to pilgrims with chronic diseases or aged years and older [ ••] . the hajj pilgrimage has not been canceled since saudi arabia's foundation in [ ••] . in addition, the hajj pilgrimage has faced no significant limits on attendance since the outbreaks of cholera and plague in second half of the nineteenth century [ ••] . more recently, during the influenza a(h n )pdm , the population groups with the highest risk of influenza complications, including pregnant women, patients with chronic diseases, and individuals under years or over years of age, were invited to voluntarily refrain from performing the hajj to decrease the transmission of the virus [ ] . the hajj season was successfully ended on august , , with no major public health incident [ ••] . although the holy sites in makkah and medina remain open, access to the holy sites was limited for no more than persons (already resident in saudi arabia). wearing of facemasks was mandatory during the pilgrimage. the participants were checked for fever and quarantined if required. disinfectant measures were also implemented. a social distance of . m between pilgrims was applied. no pilgrims were allowed to touch the kaaba. and after the pilgrimage, pilgrims were quarantined for days. [ ] who key planning recommendations for mass gatherings in the context of covid- planning phase ✓ establishing direct links of communication between event organizers and health authorities ✓ ensuring alignment of the event plan with wider national emergency preparedness and response plans ✓ making provisions for detecting and monitoring event-related cases of covid- ✓ reducing the spread of the virus ✓ treating ill persons ✓ disseminating public health messages specific to covid- in culturally appropriate ways and in languages used by participants ✓ establishing a clear line of command and control and enabling efficient situation analysis and decision-making or developing a risk communication strategy and a community engagement plan for the event ✓ making provisions for human resources, procurement of personal protective equipment and other medical consumables operational phase • related to the venue ✓ hosting the event, at least partially, online/remotely/virtually ✓ hosting the event outdoors rather than indoors ✓ adjusting the official capacity of the venue ✓ ensuring availability of hand washing facilities with soap and water and/or hand rub dispensers ✓ ensuring regular and thorough cleaning and disinfection of the venue by designated staff ✓ regulating the flow and density of people entering, attending, and departing the event • related to the participants ✓ advising people to observe physical distancing, respiratory/cough etiquette, and hand hygiene practices ✓ advising people with higher risk of transmitting covid- that they should not attend the event ✓ advising people with higher risk of developing severe illness from covid- and individuals in contact with higher-risk patients that they should not attend the event, or making special arrangements for them • duration of event ✓ keeping the duration of the event to a minimum to limit contact among participants • risk communication ✓ ensuring coordination and consistency in crafting and delivering culturally appropriate and language specific messages to participants and the public ✓ disseminating key messages in line with national health policies • surveillance of participants, aimed at detecting and managing individuals developing symptoms during the event ✓ detection and management of event-related covid- cases should be conducted in accordance with national policies and regulations, within the framework of national health systems ✓ isolation facilities should be made available at the event site ✓ arrangements with national and local health authorities regarding diagnosis and treatment of covid- cases identified during the event post-event phase liaison between event organizers and health authorities, along the following lines: ✓ in case participants or staff develop symptoms during the event, event organizers should liaise with national and local health authorities, as well with those of the participant's home city or country, and facilitate sharing of information ✓ individuals who develop symptoms upon returning to their home city or country should be advised to contact public health authorities about their potential exposure ✓ liaison between event organizers and health authorities is required to ensure that systems are in place to detect cases arising the level of covid- outbreak had been linked to large religious mgs in several countries. a clear relation between early suspension of such events and lower occurrence of covid- transmission in countries that took such measures promptly was noticed [ ] . there are lessons to national and international health organizations for other mgs in the context of a pandemic. the saudi decision to drastically restrict the hajj pilgrimage and to cancel the umrah, two events with super spreader potential, offers impetus and precedence for other stakeholders and countries facing similar challenges amidst the reports of worsening covid- global pandemic. as a global community, in the absence of a vaccine, the 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countries this study funds a high attack rate ( %) of sars-cov- infection at a mass gathering event risk factors of critical & mortal covid- cases: a systematic literature review and meta-analysis who's at higher risk from coronavirus (covid- ) antibiotic use for respiratory infections among hajj pilgrims: a cohort survey and review of the literature an evaluation of health policy implementation for hajj pilgrims in indonesia outbreak dynamics of covid- in europe and the effect of travel restrictions observations of the global epidemiology of covid- from the prepandemic period using web-based surveillance: a crosssectional analysis religious tourism and mass religious gatherings -the potential link in the spread of covid- . current perspective and future implications hajj in the time of covid- covid- : preparing for superspreader potential among umrah pilgrims to saudi arabia controlling the covid- pandemic: useful lessons from vietnam efficacy of face mask in preventing respiratory virus transmission: a systematic review and meta-analysis masks and medical care: two keys to taiwan's success in preventing covid- spread the hajj: updated health hazards and current recommendations for key planning recommendations for mass gatherings in the context of the current covid- outbreak saudi arabia's drastic measures to curb the covid- outbreak: temporary suspension of the umrah pilgrimage pausing super spreader events for covid- mitigation: international hajj pilgrimage cancellation this paper shows that the hajj ended successfully with no major public health incident thanks to preventive measures and mitigation decisions taken by saudi authorities establishment of public health security in saudi arabia for the hajj in response to pandemic influenza a h n covid- and religious congregations: implications for spread of novel pathogens publisher's note springer nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations key: cord- -mucatzaa authors: shafi, shuja; dar, osman; khan, mishal; khan, minal; azhar, esam i.; mccloskey, brian; zumla, alimuddin; petersen, eskild title: the annual hajj pilgrimage—minimizing the risk of ill health in pilgrims from europe and opportunity for driving the best prevention and health promotion guidelines date: - - journal: int j infect dis doi: . /j.ijid. . . sha: doc_id: cord_uid: mucatzaa mass gatherings at religious events can pose major public health challenges, particularly the transmission of infectious diseases. every year the kingdom of saudi arabia (ksa) hosts the hajj pilgrimage, the largest gathering held on an annual basis where over million people come to ksa from over countries. living together in crowded conditions exposes the pilgrims and the local population to a range infectious diseases. respiratory and gastrointestinal tract bacterial and viral infections can spread rapidly and affect attendees of mass gatherings. lethal infectious disease outbreaks were common during hajj in the th and th centuries although they have now been controlled to a great extent by the huge investments made by the ksa into public health prevention and surveillance programs. the ksa provides regular updated hajj travel advice and health regulations through international public health agencies such as the who, public health england, the centers for disease control and prevention, and hajj travel agencies. during the hajj, an additional health workers are deployed; there are eight hospitals in makkah and mina complete with state-of-the-art surgical wards and intensive care units made specifically available for pilgrims. all medical facilities offer high quality of care, and services are offered free to hajj pilgrims to ensure the risks of ill health to all pilgrims and ksa residents are minimal. a summary of the key health issues that arise in pilgrims from europe during hajj and of the ksa hajj guidelines, together with other factors that may play a role in reducing the risks to pilgrims and to wider global health security, is provided herein. mass gathering sporting and religious events pose important public health challenges, including the transmission of infectious diseases, exacerbation of non-communicable diseases, and disorders related to climate change. [ ] [ ] [ ] [ ] [ ] every year, the kingdom of saudi arabia (ksa) hosts the hajj pilgrimage, which is the largest mass gathering in the world held on a recurrent annual basis. the hajj occurs annually from the eighth to the th of dhul al-hijah, the last ( th ) month of the islamic calendar, and two to three million people perform the pilgrimage during this period. a further seven million complete a 'mini' pilgrimage, known as umrah, outside the hajj period throughout the year. mass gatherings at religious events can pose major public health challenges, particularly the transmission of infectious diseases. every year the kingdom of saudi arabia (ksa) hosts the hajj pilgrimage, the largest gathering held on an annual basis where over million people come to ksa from over countries. living together in crowded conditions exposes the pilgrims and the local population to a range infectious diseases. respiratory and gastrointestinal tract bacterial and viral infections can spread rapidly and affect attendees of mass gatherings. lethal infectious disease outbreaks were common during hajj in the th and th centuries although they have now been controlled to a great extent by the huge investments made by the ksa into public health prevention and surveillance programs. the ksa provides regular updated hajj travel advice and health regulations through international public health agencies such as the who, public health england, the centers for disease control and prevention, and hajj travel agencies. during the hajj, an additional health workers are deployed; there are eight hospitals in makkah and mina complete with state-of-the-art surgical wards and intensive care units made specifically available for pilgrims. all medical facilities offer high quality of care, and services are offered free to hajj pilgrims to ensure the risks of ill health to all pilgrims and ksa residents are minimal. a summary of the key health issues that arise in pilgrims from europe during hajj and of the ksa hajj guidelines, together with other factors that may play a role in reducing the risks to pilgrims and to wider global health security, is provided herein. in light of the huge number of pilgrims from all around the worldof which thousands come from low-income countries with minimal access to healthcare -mixing closely for several days in a difficult terrain, it is remarkable that the majority of pilgrims complete the hajj without experiencing any major health issues. infectious disease outbreaks were common during hajj in the th and th centuries and have been controlled to a great extent, although proactive surveillance of the transmission of potential epidemic threats at hajj is critical to preserving global health security. , crush injuries and stampedes, which can pose major risks at mass gatherings, are infrequent during the hajj relative to its size and logistical complexity. a summary of the key health issues that arise in pilgrims from europe during hajj and of the ksa hajj guidelines, together with other factors that may play a role in reducing the risks to pilgrims and to wider global health security, is provided herein. respiratory and gastrointestinal tract bacterial and viral infections spread rapidly and affect almost all pilgrims during hajj. [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] respiratory tract infections -whose spread through coughing and sneezing is exacerbated by the crowded hajj conditions -include community-acquired pneumonia, influenza, and tuberculosis (tb). while bacterial and viral pneumonia are well-documented causes of hospital admission in pilgrims, quantifying the increase in risk of tb transmission is more challenging owing to the longer time period between infection and the development of symptoms. the elderly and those with comorbid diseases such as diabetes are particularly vulnerable to morbidity from respiratory illnesses. acute food poisoning is common during the hajj and is caused by toxins produced by staphylococcus aureus and bacillus cereus. gastroenteritis due to salmonella spp and viruses such as rotavirus and norovirus are common during hajj. , factors responsible for increasing the spread of gastrointestinal diseases during hajj include contamination of food through unhygienic preparation, prolonged storage of food, drinking from contaminated water sources, and a shortage of water for hand washing. the risks of dehydration are heightened when hajj occurs during summer months, owing to the extremely hot climate in saudi arabia. other infectious disease risks include meningococcal disease, which caused outbreaks during hajj in the early s owing to overcrowding and high carrier rates of neisseria meningitidis among pilgrims. , [ ] [ ] [ ] mosquito species responsible for the transmission of malaria and the arbovirus that causes dengue are present in the ksa, although the country has been classified by the world health organization (who) as a low, geographically restricted malaria transmission area since . historically, infectious diseases were the largest cause of morbidity and mortality during hajj, but non-communicable diseases are now a major burden. many pilgrims both elderly and young have existing non-communicable diseases such as diabetes, hypertension, arthritis, epilepsy, liver and kidney disease, which can be worsened by strenuous hajj conditions or if regular medications are neglected during the spiritual activities. in addition to cardiovascular disease, heat exhaustion and heatstroke are important causes of death; again health-related morbidity is exacerbated when hajj occurs during the summer months. the risk of injury from fires has been reduced since tents were replaced with fibreglass and cooking in tents was prohibited following a fire in . however, risks from stampedes and crush injuries remain due to the overcrowding. as the events of the falling cranes and the stampede in the hajj illustrate, trauma can be a major cause of injury and death during hajj. furthermore, many pilgrims who walk long distances as part of the rituals invariably are injured by motor vehicles. (table ) table the ksa government employs a well-coordinated, intersectoral approach to the planning, communication, public health, and safety issues of the hajj. during the hajj, an additional health workers are deployed; there are eight hospitals in makkah and mina complete with state-of-the-art surgical wards and intensive care units made specifically available for pilgrims. all medical facilities offer high quality of care, and services are offered free to hajj pilgrims to ensure the risks of ill health to all pilgrims and ksa residents are minimal. in terms of preventative measures, in addition to the vaccination requirements described below, measures are put in place to ensure food safety and the ministry of health ensures strict enforcement of the regulation that pilgrims are not allowed to bring fresh food or agricultural products into the country. other coordinated activities include targeted insecticide spraying to control mosquito populations, the distribution of health promotion materials to pilgrims, and electronic surveillance of infectious diseases. the health requirements for pilgrimage to mecca (hajj and umrah) are published annually by the ksa government. information for pilgrims is made available on the saudi arabia ministry of health website. [ ] [ ] [ ] meningococcal vaccine is a prerequisite for all pilgrims; hajj visas cannot be issued without proof of meningococcal vaccination. all adults and children aged > years must have received a single dose of quadrivalent a/c/y/w- vaccine and must show proof of vaccination on a valid international certificate of vaccination or prophylaxis. children between months and years of age must show proof of vaccination with two doses of meningococcal a monovalent vaccine with a -month interval between the doses. hajj pilgrims need to have had the meningococcal vaccine years and days before arriving in saudi arabia. other vaccination requirements for hajj pilgrims entering from specific countries include yellow fever and polio vaccines. the yellow fever vaccine is mandatory for all travellers arriving from countries listed by the who as being a yellow fever risk. polio vaccine is required for travellers arriving from countries that have polio virus circulating, or from countries at high risk of reimportation of polio virus, regardless of age and vaccination status. those who do not have evidence certificates are immunized at the port of entry. the saudi ministry of health recommends seasonal influenza vaccine for those at increased risk, such as the elderly and those with chronic comorbidities. however, there is conflicting evidence about the efficacy of influenza vaccine in protecting hajj pilgrims. , pneumonia is among the most common causes of hospital admission during hajj, and thus the prevention of pneumococcal infection is crucial. pneumococcal polysaccharide vaccine is recommended for pilgrims aged years and for younger pilgrims with comorbidities. finally, with regard to measles and rubella vaccines, updating immunization against vaccine-preventable diseases in all travellers is strongly recommended. the prevention and management of threats to global health security and protecting the health and lives of pilgrims requires effective cooperation between numerous agencies within and outside the ksa. the hajj can therefore provide important lessons for setting up and maintaining inter-sectoral collaborations, for example between agencies responsible for health, transport, border control, and environmental health. the value of the hajj experience to planners of mass gatherings in sharing best practices is evident, but lessons can go beyond mass gatherings to inform other areas of public health that require inter-sectoral engagement, such as one health and the control of antimicrobial resistance. the hajj also provides an opportunity for research, not only into all aspects of mass gatherings, but also into faith-based health promotion and electronic disease surveillance capacity building. conflict of interest: all authors have an interest in infectious diseases transmission at mass gatherings. european football championship finals: planning for a health legacy olympic and paralympic games: public health surveillance and epidemiology hajj: infectious disease surveillance and control hajj: health lessons for mass gatherings mass gatherings medicine and global health security emerging respiratory tract viral infections bacteria and viruses that cause respiratory tract infections during the pilgrimage (hajj) season in makkah, saudi arabia respiratory tract infections during the annual hajj: potential risks and mitigation strategies viral respiratory infections at the hajj: comparison between uk and saudi pilgrims influenza and respiratory syncytial virus infections in british hajj pilgrims influenza and the hajj: defining influenza-like illness clinically diarrhea at the hajj and umrah causes of hospitalization of pilgrims in the hajj season of the islamic year sun protection during the hajj massgathering- physiological studies on heat exhaustion victims among mecca pilgrims health at hajj and umra research group. meningococcal vaccine coverage in hajj pilgrims prevention of meningococcal disease during the hajj and umrah mass gatherings: past and current measures and future prospects world health organization. health conditions for travelers to saudi arabia for the pilgrimage to mecca (hajj) middle east respiratory syndrome middle east respiratory syndromeadvancing the public health and research agenda on mers-lessons from the south korea outbreak spread of mers to south korea and china emerging novel and antimicrobial-resistant respiratory tract infections: new drug development and therapeutic options mass gathering medicine: hajj and umra preparation as a leading example kingdom of saudi arabia: ministry of health saudi arabia: ministry of health saudi arabia: ministry of health influenza vaccine in hajj pilgrims: policy issues from field studies influenza vaccine uptake among british muslims attending hajj prevention of pneumococcal infections during mass gathering mass gatherings medicine: international cooperation and progress key: cord- -uo ah authors: hashem, anwar m.; al‐subhi, tagreed l.; badroon, nassrin a.; hassan, ahmed m.; bajrai, leena hussein m.; banassir, talib m.; alquthami, khalid m.; azhar, esam i. title: mers‐cov, influenza and other respiratory viruses among symptomatic pilgrims during hajj season date: - - journal: j med virol doi: . /jmv. sha: doc_id: cord_uid: uo ah more than two million muslims visit makkah, saudi arabia, annually to perform the religious rituals of hajj where the risk of spreading respiratory infections is very common. the aim here was to screen symptomatic pilgrims for middle east respiratory syndrome coronavirus (mers‐cov) and other viral etiologies. thus, nasopharyngeal samples were collected from pilgrims presenting with acute respiratory symptoms at the healthcare facilities in the holy sites during the days of the hajj season. samples were tested using real‐time reverse transcription polymerase chain reactions and microarray. demographic data including age, sex, and country of origin were obtained for all participants. while we did not detect mers‐cov in any of the samples, several other viruses were detected in . % of the cases. among the detected viruses, . % of the cases were due to a single‐virus infection and . % were due to the coinfections with up to four viruses. the most common respiratory virus was influenza a, followed by non‐mers human coronaviruses, rhinoviruses, and influenza b. together, we found that it was not mers‐cov but other respiratory viruses that caused acute respiratory symptoms among pilgrims. the observed high prevalence of influenza viruses underscores the need for more effective surveillance during the hajj and adoption of stringent vaccination requirements from all pilgrims. at the jamaraat pillars in mina. finally, they finish their hajj ritual by going back to the holy mosque in makkah to perform "tawaf". overcrowding of individuals in such confined settings leads to inevitable prolonged close contact and increases the risk of spreading and acquiring respiratory pathogens among pilgrims, which raises global and public health concerns due to the high potential of international spread of such pathogens. [ ] [ ] [ ] [ ] another important driver of spreading and acquiring respiratory pathogens during hajj is the great diversity of inbound viruses from around the world that can potentially spread among the immunologically naive hosts. in fact, acute respiratory infections are very common during hajj and represent the leading cause of the most hospitalizations. [ ] [ ] [ ] [ ] [ ] it has been suggested that more than one-third of pilgrims will suffer from respiratory symptoms during hajj mostly due to the respiratory viruses. , [ ] [ ] [ ] [ ] [ ] [ ] most commonly isolated viruses from symptomatic patients during hajj were human rhinoviruses (hrvs), influenza virus and non-mers human coronaviruses (hcovs). , [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] [ ] the emergence of the novel middle east respiratory syndrome coronavirus (mers-cov) in saudi arabia, its endemicity, and high mortality rates ( %- %) clearly represent another major public health concern, especially during hajj. since , mers-cov caused more than confirmed cases in countries in the arabian peninsula, africa, asia, europe, and north america as of december . , furthermore, multiple hospitals and household outbreaks have been reported mostly in the saudi arabia. rna extraction was performed using the qiaamp viral rna mini kit (qiagen, hilden, germany) according to manufacturerʼs instructions. extracted rna from all samples was tested for mers-cov using realtime reverse transcription polymerase chain reactions targeting upstream region of the e-gene as described previously. positive and negative (no template) controls were included in all runs. remaining np samples were used for complementary dna (cdna) synthesis and microarray testing as described previously. plus analyzer (autogenomics inc., carlsbad, ca) according to manu-facturerʼs instructions and as previously described. samples were considered positive when the ratio between the virus and background signals was above the calculated threshold. the data were analyzed using the statistical package for the social science software (spss v . ; spss inc, chicago, il). the χ and fisher exact tests were used to compare the proportions and a twotailed probability value of p < . was considered statistically significant. table ). as shown in table , although a majority of positive patients were older than years, this difference was not significant. no statistical significance was found for comparisons of infection rates among males and females or the different age groups. one hundred and twenty-nine of the patients in this study were from countries mostly from asia and africa followed by europe and north america. nationalities of three individuals were unknown. as (table ) . coinfections with more than two viruses were not uncommon. in fact, four patients had triple concurrent infections, and one patient had a quadruple concurrent infection ( table ). the remaining nine coinfections were due to the unique combination of respiratory viruses (table ) . not surprisingly, flu a, flu b, and hcov oc were the most frequently detected viruses in the most age groups ( coinfections with multiple viruses in symptomatic pilgrims were very common in our study and represented more than % of the positive cases and more than % of the total number of patients. this rate is markedly higher than the previously reported. [ ] [ ] [ ] [ ] , , furthermore, while most of these reports have identified hrvs as the most coinfecting viruses during hajj, our data showed hcov oc as the most prevalent coinfecting virus followed by flu a and hrvs. [ ] [ ] [ ] [ ] , , these marked differences most probably were due to technical and methodological differences. however, it is clear that enhanced surveillance using detection assays with high sensitivity and coverage such as microarray and multiplex pcr could enhance our understanding of pathogens involved in respiratory infections during mass gatherings and ultimately lead to better infection control. , or hrv c, which could represent a significant number of potential rhinovirus infections among symptomatic pilgrim. in conclusion, we investigated the etiology of acute respiratory infections in symptomatic pilgrims attending hajj. while mers-cov was not detected in any of the patients, a variety of other respiratory viruses has been found in more than half of the patients with many coinfections with multiple viruses. our observation as well as the previous reports from hajj indicate that enhanced and active surveillance during hajj seasons is critical to recognize the wide variety of pathogens that might be involved in hajj epidemics and to implement proper infection control measures. importantly, there is an evident risk of influenza infection among pilgrims underscoring the need for targeted, active and continuous surveillance for influenza viruses not only to monitor viral circulation but also to characterize circulating viruses to better understand vaccine effectiveness and to recognize the need to improve current influenza vaccination strategies during hajj. hajj: infectious disease surveillance and control hajj-associated viral respiratory infections: a systematic review health risks at the hajj respiratory tract infection during hajj causes of hospitalization of pilgrims in the hajj season of the islamic year infections in travellers returning to turkey from the arabian peninsula: a retrospective cross-sectional multicenter study respiratory tract infections during the annual hajj: potential risks and mitigation strategies the prevalence of acute respiratory symptoms and role of protective measures among malaysian hajj pilgrims influenza a common viral infection among hajj pilgrims: time for routine surveillance and vaccination high prevalence of common respiratory viruses and no evidence of middle east respiratory syndrome coronavirus in hajj pilgrims returning to ghana circulation of respiratory viruses among pilgrims during the hajj pilgrimage respiratory viruses and bacteria among pilgrims during the influenza and respiratory syncytial virus infections in british hajj pilgrims patterns of reported respiratory symptoms and detected respiratory viruses during hajj days. a, bar graph showing the number of pilgrims presented with respiratory symptoms and tested for respiratory viruses with numbers of those tested positive or negative for any virus during daily. b, bar graph showing the number of viruses detected from positive cases during the days of hajj. day , makkah then mina in the afternoon; day , arafat in the morning then muzdalifah at night; day , muzdalifah then mina in the morning detection of respiratory viruses among pilgrims in saudi arabia during the time of a declared influenza a(h n ) pandemic influenza viral infections among the iranian hajj pilgrims returning to shiraz, fars province, iran. influenza other respir viruses mers-cov but positive influenza viruses in returning hajj pilgrims, china acute respiratory infections among returning hajj pilgrims-jordan active screening and surveillance in the united kingdom for middle east respiratory syndrome coronavirus in returning travellers and pilgrims from the middle east: a prospective descriptive study for the period - etiology of severe community-acquired pneumonia during the hajj-part of the mers-cov surveillance program viral respiratory infections among hajj pilgrims in isolation of a novel coronavirus from a man with pneumonia in saudi arabia middle east respiratory syndrome coronavirus (mers-cov) multifacility outbreak of middle east respiratory syndrome in taif, saudi arabia critically ill patients with middle east respiratory syndrome coronavirus infection middle east respiratory syndrome coronavirus (mers-cov) outbreak in south korea, : epidemiology, characteristics, and public health implications lack of nasal carriage of novel corona virus (hcov-emc) in french hajj pilgrims returning from the hajj , despite a high rate of respiratory symptoms lack of mers coronavirus but prevalence of influenza virus in french pilgrims after prevalence of mers-cov nasal carriage and compliance with the saudi health recommendations among pilgrims attending the hajj cross-sectional survey and surveillance for influenza viruses and mers-cov among egyptian pilgrims returning from hajj during - . influenza other respir viruses influenza not mers cov among returning hajj and umrah pilgrims with respiratory illness influenza a and b viruses but not mers-cov in hajj pilgrims middle east respiratory syndrome coronavirus (mers-cov) infections in two returning travellers in the netherlands evidence for camel-to-human transmission of mers coronavirus patterns of human respiratory viruses and lack of mers-coronavirus in patients with acute upper respiratory tract infections in southwestern province of saudi arabia influenza virus but not mers coronavirus circulation in iran, - : comparison between pilgrims and general population an opportunistic pathogen afforded ample opportunities: middle east respiratory syndrome coronavirus acute respiratory viral infections among tamattu'-hajj pilgrims in iran viral etiology of acute respiratory infections among iranian hajj pilgrims meningococcal, influenza virus, and hepatitis b virus vaccination coverage level among health care workers in hajj pandemic (h n ) and hajj pilgrims who received predeparture vaccination pandemic influenza a (h n ) infection among hajj pilgrims from southern iran: a realtime rt-pcr-based study. influenza other respir viruses mismatching between circulating strains and vaccine strains of influenza: effect on hajj pilgrims from both hemispheres respiratory tract samples, viral load, and genome fraction yield in patients with middle east respiratory syndrome mers-cov, influenza and other respiratory viruses among symptomatic pilgrims during hajj season the authors declared that there is no conflict of interests. http://orcid.org/ - - - key: cord- -nku kt authors: hoang, van-thuan; gautret, philippe title: infectious diseases and mass gatherings date: - - journal: curr infect dis rep doi: . /s - - - sha: doc_id: cord_uid: nku kt purpose of review: mass gatherings (mgs) are characterized by a high concentration of people at a specific time and location. infectious diseases are of particular concern at mgs. the aim of this review was to summarize findings in the field of infectious diseases with a variety of pathogens associated with international mgs in the last years. recent findings: in the context of hajj, one of the largest religious mgs at mecca, saudi arabia, respiratory tract infections are the leading cause of infectious diseases in pilgrims with a prevalence of – %. the most commonly acquired respiratory viruses were human rhinovirus, followed by human coronaviruses and influenza a virus, in decreasing order. haemophilus influenzae, staphylococcus aureus, and streptococcus pneumoniae were the predominant bacteria. the prevalence of hajj-related diarrhea ranged from . to . % and etiologies included salmonella spp., and escherichia coli, with evidence of acquisition of antimicrobial-resistant bacteria. in other mgs such as muslim, christian, and hindu religious events, sports events, and large-scale open-air festivals, outbreaks have been reported less frequently. the most common outbreaks at these events involved diseases preventable by vaccination, notably measles and influenza. gastrointestinal infections caused by a variety of pathogens were also recorded. summary: because social distancing and contact avoidance are difficult measures to implement in the context of many mgs, individual preventive measures including vaccination, use of face mask, disposable handkerchief and hand hygiene may be recommended. nevertheless, the effectiveness of these measures has been poorly investigated in the context of mgs. the who defines mass gatherings (mgs) as a "concentration of people at a specific location for a specific purpose over a set period of time which has the potential to strain the planning and response resources of the country or community" [ ] . mgs can be either planned or spontaneous and recurrent or sporadic [ ] . planned mgs may include sporting, social, cultural, religious, and political events. examples include music festivals, the olympic games, and the hajj [ ] . spontaneous mgs, given their nature, are more difficult to plan for and may include events, such as funerals of religious and political figures [ , ] . mgs may also include the gatherings of displaced populations due to natural disasters, conflicts, and wars [ ] . diverse health risks are associated with mgs, including transmission of infectious disease, non-communicable disease, trauma and injuries (occupational or otherwise), environmental effects (such as, heatrelated illnesses, dehydration, hypothermia), illnesses related to the use of drugs and alcohol, and deliberate acts, such as terrorist attacks [ ] . infectious diseases are of particular concern at mgs [ ] . in this review, we summarize recent findings in the field of infectious diseases associated with international mgs. the hajj (table ) the hajj, an annual muslim pilgrimage to mecca, saudi arabia, is one of the largest religious mgs in the world with about two million pilgrims from countries [ ] . as part of the hajj rituals, pilgrims visit various sacred places around the city of mecca. most of them also travel to the city of medina to visit the second holiest site of islam, the prophet's mosque containing the tomb of the prophet muhammad. the presence of a large number of pilgrims from different countries of the world and overcrowded condition considerably increases the risk of occurrence of infectious diseases, particularly respiratory and gastrointestinal diseases [ ] . furthermore, a vast majority of pilgrims are elderly people with a high prevalence of chronic diseases. in the past, hajj-related cholera has been a public health problem and the main cause of morbidity and mortality among pilgrims, leading to major epidemics and international spread. due to improved sanitary conditions in saudi arabia in general and at religious sites, large-scale cholera outbreaks have not been recorded during the last decades [ , ] . similarly, invasive meningococcal disease has been a hajj-related public health concern with its last outbreaks (serogroup w- ) in the s. however, with the strengthening of prevention through mandatory vaccination, no case of meningococcal disease has been reported in mecca since [ , ] . while gastrointestinal diseases and diarrhea have changed towards a lower prevalence, respiratory tract infections (rtis) now account for the vast majority of health problems during the hajj [ , ] . the inevitable overcrowding conditions at the grand mosque in mecca and the accommodation in tents in mina with an average of to people per tent are likely responsible for the high rate of respiratory infections among hajj pilgrims [ ] . over the last years, a significant number of publications from different countries based on both syndromic surveillance and pcr-based investigation of respiratory pathogen carriage were made available. studies were conducted in out-and inpatients at health structures in saudi arabia or on return in pilgrim's country of origin and in cohorts of pilgrims regardless of symptoms (table ) . rtis are among the leading causes of admission to hospitals in mina, mecca, and medina during the hajj period (table ). most cases are upper respiratory tract infections [ ] [ ] [ ] [ ] [ ] [ ] [ ] , but severe respiratory tract infections [ ] and pneumonia are not uncommon among pilgrims [ , , •] . respiratory diseases were the second cause of mortality in indonesian pilgrims during the hajj (following cardiovascular diseases) [ ] . among pathogens detected by pcr methods in ill pilgrims, the most common viruses were human rhinovirus (hrv), followed by human coronaviruses (hcov) and influenza a virus (iav). haemophilus influenzae, staphylococcus aureus, and streptococcus pneumoniae were the predominant bacteria isolated by culture [ , ] . cross-sectional and longitudinal cohort studies have recorded - . % prevalence of rti symptoms among hajj pilgrims [ - , •, , , •] . the rate of ili varied from . to . % [ , , •, , , - ] . cohort surveys allow evaluating the acquisition rate of respiratory pathogens regardless of symptoms. the most commonly acquired viruses were human rhinovirus (hrv) ( . - . %), followed by human coronavirus e (hcov-e ) ( . - . %) and influenza virus (iav) ( . - . %) [ , , , , , •, ] . the most commonly acquired bacteria were s. pneumoniae ( . to . %) and s. aureus ( . to . %) and h. influenzae ( . %) [ , , , •, •] . bordetella pertussis, mycoplasma pneumoniae, and chlamydia pneumoniae have not been detected in pilgrims in recent studies [ , , •] . middle east respiratory syndrome coronavirus (mers-cov) that emerged in the arabian peninsula in is associated with severe acute respiratory infection with high [ - , , , , , , , , - ] . tuberculosis (tb) transmission is another concern at the hajj, but there are no large-scale, specific studies to determine its prevalence among pilgrims [ ] . a prospective crosssectional study was conducted in mecca, during the hajj period in september . one thousand one hundred sixty-four pilgrims with cough were selected from five countries in africa and south asia that are endemic for tb and . % had active previously undiagnosed tb [ [ ] . in the latter study, escherichia coli was the predominant pathogen isolated from pilgrims by pcr. enteropathogenic e. coli, enteroaggregative e. coli, and shiga-like toxin-producing e. coli were acquired by . %, . %, and . % pilgrims, respectively [ ] . among persons infected during the - hajj and hospitalized in saudi hospitals, the pathogens responsible for enteric infection were mostly bacteria, with a prevalence of salmonella spp. of . %, while that of diarrhea associated e. coli ranged between . and . % according to pathotypes [ ] . two cases of tropheryma whipplei were recorded in a cohort of french pilgrims during the hajj [ ] . the frequency of infectious diseases during the hajj results in a significant demand for antibiotic use. [ ] . a prospective study conducted among pilgrims from marseille, france, during the periods of hajj in - showed that . % of the population used antibiotics because of respiratory diseases and . % because of diarrhea [ ] . although the dispensing of antibiotics without a prescription has been banned in saudi arabia for more than years [ ] , % of australian pilgrims used antibiotics either delivered in saudi arabia without prescription or purchased in australia before traveling [ ] . the predominance of bacterial pathogens in hajj-related gastrointestinal infections poses a major risk to public health through the potential emergence and transmission of antimicrobial-resistant bacteria [ ] . methicillin-resistant s. aureus had been isolated in % of pilgrims with acute sinusitis in [ ] and % of pilgrims with communityacquired infections hospitalized during the hajj in [ •] . one study addressed the carriage of resistant s. pneumoniae in a multinational cohort of pilgrims and showed that % of isolates were resistant to multiple antibiotics (resistant to three or more classes of antibiotics) [ ] . extended spectrum beta-lactamase enterobacteriaceae are also common among hospitalized pilgrims. during the - hajj, % of pilgrims attending hospitals for urinary tract infections showed blactx-m genes in e. coli isolates [ ] . during the and hajj seasons, studies were conducted using rectal samples obtained before and after the hajj in cohorts of french pilgrims to assess the carriage of the blactx-m gene. acquisition rates of . - . % were observed [ , ] . there was also a significant increase in the number of pilgrims harboring e. coli resistant to ceftriaxone and ticarcillin-clavulanic acid [ ] . the prevalence of c g-resistance was observed in . % acinetobacter baumannii isolates in a cohort of french pilgrims in [ ] and in . % of isolates obtained from hospitalized pilgrims suffering from community-acquired infections in [ •] . two french pilgrims carried s. enterica, resistant to ceftriaxone, gentamycin, and colistin after the hajj [ ] . mrc- resistance gene screening from rectal swabs was conducted in french pilgrims in - and found an acquisition rate of . % after hajj [ ] . risk factors for the spread of antibiotic-resistant bacteria at the hajj include international travel, misuse of antibiotics, and availability of over-the-counter antibiotics [ ] . however, gastrointestinal diseases and diarrhea continue to occur in pilgrims, outbreaks of food poisoning are reported, and the acquisition of multi-resistant bacteria is emerging. the ongoing monitoring of these diseases is part of the public health response regarding the hajj [ •, ] . currently, meningococcal vaccination (a, c, y, w- ) is mandatory for all pilgrims, national and international, as well as local residents of holy cities and workers in contact with pilgrims; however, polysaccharide vaccine which does not prevent meningococcal carriage is still in use in many countries. mandatory oral ciprofloxacin prophylaxis is provided upon arrival to all the pilgrims coming from the "meningitis belt" of sub-saharan africa [ , , , ] . a cross-sectional study among pilgrims arrived at king abdul aziz international airport, in jeddah for the hajj in showed antibody titers under the level of protection against serogroups a, c, w, and y of only . %, . %, . %, and . %, respectively. most of them ( . %) had received meningococcal vaccination in the three previous years [ ] . in a prospective cohort study conducted in turkish hajj pilgrims during , the carriage prevalence of neisseria meningitides, assessed by culture method, was % before and . % after the hajj with the majority being serogroup w- [ ] . in a prospective culture-based cohort study conducted among iranian pilgrims in , . % acquired n. meningitides at the hajj [ ] . a prospective study conducted in among international pilgrims at king abdul aziz international airport showed . % n. meningitides carriage by culture method upon arrival and . % upon departure, with the majority of typable isolates being serogroup b [ ] . outbreaks of the disease including those due to serogroups not included in the required vaccines, such as serogroups b and x, are therefore possible at the hajj. despite the wide use of polysaccharide vaccine, it does not prevent the carriage of serogroup w- and subsequent transmission to unvaccinated individuals by returning pilgrims. the grand magal of touba, the largest muslim pilgrimage in senegal, has specific features. besides its setting in a tropical environment, its population is characterized by a large range of age groups since most pilgrims travel with their family, including young children. a preliminary survey in has showed a high rate of febrile systemic illnesses and malaria ( . %), diarrheal diseases ( . %), and rtis ( . %) among ill pilgrims consulting at health care structures during the pilgrimage. the overall hospitalization rate was . % including gyneco-obstetric cases ( . %) and confirmed malaria ( . %) [ ••] . the kumbh mela in india is the largest mg in the world with about million visitors. it posed an exciting challenge to the provision of healthcare services. increased population density, reduced sanitation, and exposure to environmental pollutants open the way for easy transmission of pathogens [ ] . during kumbh mela in , , patients consulted at hospitals. respiratory infections accounted for % of illnesses and diarrheal diseases for %. in total, ( . %) were hospitalized. gastrointestinal disease risk, including cholera, is high because of potential contamination of water and food. in addition, vaccination against cholera is no longer considered adequate or even feasible in this context [ ] . the ashura mg at karbala is an increasingly popular religious event in iraq with about three to four million muslims from within and outside iraq. in , a cross-sectional study conducted in three public hospitals at karbala city showed that about % of the , consultations were at emergency rooms. febrile illness was recorded seven times more frequently during this event compared to previous events, in relation to an eight-fold increase in the population in the area during the event [ ] . other notable events include the moulay abdellah amghar moussem, an -day annual gathering in morocco, that documented an increase of gastrointestinal diseases from to % between and [ ] . during the anniversary of the death (urs) of baba farid, an annual mg in pakpattan, pakistan, % of people seen at healthcare facilities were affected by communicable diseases, including % gastrointestinal illnesses and % rtis [ ] . also in , a cross-sectional study of , attendees to the -day eid al adha holiday, aqaba (one of the largest muslim mgs in jordan), identified % and % increases in emergency department attendance and hospital admissions, respectively; however, no food poisoning outbreaks were reported [ ] . unlike the syndromic surveillance data mentioned above that lacked reliable identification of the responsible pathogen, s. enterica serotype typhimurium was determined to cause cases of gastrointestinal illness among participants in a christian religious festival in hamilton county, ohio; the outbreak was associated with the consumption of pulled pork prepared in a private house and sold at the festival [ ] . (table ) although numerous gastrointestinal and respiratory outbreaks have been documented at large-scale open-air festivals, particularly music festivals, with thousands of participants, these events are probably neglected, in terms of public health attention, as well as surveillance and prevention of infectious disease strategies, compared to other categories of mgs [ ] . since this review was published, several outbreaks were reported in the context of festivals. between july and , , during the annual independence celebrations in kiribati, the kiribati syndromic surveillance system reported an increase in children presenting with severe diarrhea due to rotavirus. in total, cases of gastroenteritis were reported and ( . %) died among ( . %) hospitalized. most of them ( . %) were younger than years of age [ ] . an outbreak of measles with cases identified at an international dog show occurred in november in slovenia, where measles virus had not been circulating for many years. twenty-three persons were infected there and were presumable secondary and tertiary cases. most cases ( ) were adults. five were unvaccinated children [ ] . also, a multistate measles outbreak that caught global attention occurred at the disney theme parks in california, usa [ ] . the rd world scout jamboree (wsj) in yamagushi, japan, from july to august , , was a mg attended by more than , participants from countries. the event is designed for scouts aged to years to live together, experience diverse cultures, and take part in recreational activities. in this event, six cases of invasive meningococcal disease related to the wsj were reported, affecting . per , wsj attendees, far exceeding the annual incidence rate in japan in ( . per , population) [ •] . finally, an outbreak of measles ( cases) was reported at music and art festivals in england and wales between june and october . almost half of the cases occurred in participants aged to years. several people who contracted measles at a festival later attended another festival when they were contagious, resulting in multiple, interconnected outbreaks. only one confirmed case was fully vaccinated. forty-two were not vaccinated. nine cases were not fully vaccinated, or their immunization status was unknown [ ] . an epidemic of measles occurred during the xxi olympic winter games that were held in february - , , in vancouver, canada, with cases [ ] . another epidemic of measles was noted during the th edition of the italia super cup, international junior football tournament in rimini, italy, from june nd to th, . most ill individuals had not been vaccinated [ ] . during the london olympic and paralympic games, no major public health incidents occurred. only a few outbreaks of gastrointestinal and respiratory infections were recorded during this period. no food-borne illness was directly linked to a games venue, despite the tendency for those reporting them to label them as such [ ] . during this event, olympic visitors were followed for sexually transmitted infections (sti), new sti diagnoses were made including non-specific genital infection, eight chlamydia, and eight genital warts (first episode) diagnoses. there were no new hiv or syphilis diagnoses [ ] . during euro european football, according to national data from ukraine, cases of acute gastroenteritis occurred in host cities, but daily notifications remained consistently below the epidemic threshold determined by ukraine. similarly, measles cases were reported in the host cities during the tournament, only one of which occurred in a foreign visitor. this number represented about % of the new cases reported throughout ukraine during the same period [ ] . during the european youth olympic festival in utrecht, the netherlands, in , a prospective cohort study was conducted among participants from countries. forty-six cases of diseases were reported. infection was the most commonly reported cause of illness ( . % overall) with . % patients reporting gastrointestinal symptoms and . % respiratory symptoms [ ] . among the athletes in the sochi olympic winter games, a total of illnesses were reported, resulting in an incidence of . illnesses per athletes ( % ci . to . ). most ill athletes suffered from respiratory symptoms ( . %), followed by gastrointestinal symptoms ( %) with % caused by infections [ ] . only three cases of dengue fever were confirmed at the fifa world cup [ ] . a recent multinational salmonella outbreak was reported at an international youth ice hockey competition in riga, lativa in [ ] . among , athletes from countries participating to the rio de janeiro olympic summer games, illnesses were reported, resulting in . illnesses per athletes. two hundred two individuals ( %) presented with respiratory symptoms and (n = ; %) gastrointestinal symptoms with % (n = ) due to infections [ ] . dengue case count was negligible and no case of zika virus was detected [ , ] . more recently, the pyeong ghang winter olympiad may have been hindered by a norovirus outbreak days before the event commenced. this outbreak affected mainly security staff for the games rather than athletes or visitors [ ] . this review has some limitations. it was limited to articles written in english, which may have been a source of bias. there was a significant heterogeneity in the studies in relation to the populations studied, the clinical criteria for syndromic surveillance and the diagnostic methods applied. infectious diseases at mgs are dominated by respiratory tract and gastrointestinal infections. meningitis outbreaks were also reported in some instances. inter-human transmission of airborne diseases is favored by the temporal and spatial concentration of people. because social distancing and contact avoidance are difficult measures to implement in the context of many mgs, individual preventive measures such as cough etiquette, the use of face mask and disposable handkerchiefs and hand hygiene may be recommended. nevertheless, the effectiveness of these measures has been poorly investigated in the context of mgs. most available data come from hajj studies and results are contradictory [ ] . non-compliance with hygiene rules and inadequate sanitation are responsible for fecal-oral transmission of gastrointestinal infections. public health measures aiming at provision of safe water and food supplies with rigorous quality control are likely the best way to limit the occurrence of gastrointestinal outbreaks at mgs. planned organization by highly specialized teams of staff is a key element. it should be noted that many mg-associated diseases are vaccine-preventable, including influenza, measles, mumps, meningococcal, and pneumococcal disease. mandatory vaccination against meningitis has proven effective in the context of the hajj. measles and mumps and meningococcal vaccination status should certainly be verified and updated if needed in young people attending mgs. influenza and pneumococcal vaccination should be recommended in at-risk individuals participating to mgs. this particularly applies to elderly people participating to religious mgs. finally, because of the evidence of circulation of resistant bacteria, at least in the hajj context, rationalization of antibiotic consumption should be promoted. unfortunately, official recommendations for prevention at mgs are lacking, with the exception of the hajj [ ] . conflict of interest philippe gautret and van-thuan hoang declare that they have no conflict of interest. human and animal rights and informed consent this article does not contain any studies with human or animal subjects performed by any of the authors. world health organization. public health for mass gatherings: key considerations world health organization. communicable disease alert and response for mass gatherings: key considerations mass gatherings and infectious diseases: prevention, detection, and control hajj: infectious disease surveillance 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